Uterine leiomyomas are benign monoclonal smooth muscle tumors that arise from a single myometrial cell acquiring a driver mutation in MED12, HMGA2, or FH. Ovarian estrogen and progesterone then drive smooth muscle proliferation and abundant extracellular matrix deposition during each ovulatory cycle. Progressive tumor growth distorts the uterus, producing abnormal uterine bleeding, bulk symptoms, and reproductive complications.
Ask a research question about Uterine Leiomyoma. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Uterine Leiomyoma
creation_date: "2026-06-22T00:00:00Z"
description: >-
Uterine leiomyomas are benign monoclonal smooth muscle tumors that arise from a single myometrial cell acquiring a driver mutation in MED12, HMGA2, or FH.
Ovarian estrogen and progesterone then drive smooth muscle proliferation and abundant extracellular matrix deposition during each ovulatory cycle.
Progressive tumor growth distorts the uterus, producing abnormal uterine bleeding, bulk symptoms, and reproductive complications.
category: Complex
disease_term:
preferred_term: uterine fibroid
term:
id: MONDO:0007886
label: uterine corpus leiomyoma
parents:
- Benign uterine neoplasm
- Smooth muscle tumor
pathophysiology:
- name: Driver Mutation-Initiated Clonal Transformation
description: >
Uterine leiomyomas (fibroids) originate as monoclonal tumors from a single
myometrial smooth muscle cell (or a myometrial stem cell acquiring tumor-initiating
features) that acquires a recurrent somatic driver mutation. The most common driver
is a MED12 exon-2 mutation (~70-77%), followed by HMGA2/HMGA1 overexpression or
chromosomal rearrangement (~10%, 12q14-15), biallelic FH (fumarate hydratase) loss
defining the FH-deficient subtype (also seen in hereditary leiomyomatosis and renal
cell cancer, HLRCC), with rarer collagen IV (COL4A5/COL4A6) deletions also reported. Heterozygous MED12 mutations
disrupt the CDK8/CDK19 kinase module of the Mediator complex, altering the chromatin
landscape, enhancer engagement, genomic stability, and progesterone responsiveness.
genes:
- preferred_term: MED12
term:
id: hgnc:11957
label: MED12
- preferred_term: HMGA2
term:
id: hgnc:5009
label: HMGA2
- preferred_term: FH
term:
id: hgnc:3700
label: FH
cell_types:
- preferred_term: myometrial smooth muscle cell
term:
id: CL:0002366
label: myometrial cell
biological_processes:
- preferred_term: Wnt/beta-catenin signaling dysregulation
term:
id: GO:0016055
label: Wnt signaling pathway
modifier: INCREASED
evidence:
- reference: PMID:40214304
reference_title: UTERINE FIBROIDS.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The most common somatic mutations in fibroids affect the Mediator complex \nsubunit 12 (MED12; 77%) and high-mobility group AT-hook 2/1 (HMGA2/1; 10%) \ngenes."
explanation: >-
Establishes MED12 (77%) and HMGA2/1 (10%) as the dominant recurrent somatic
drivers initiating fibroid tumors.
- reference: PMID:40214304
reference_title: UTERINE FIBROIDS.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Heterozygous mutations in MED12, a chromatin-associated protein, disrupt \nthe attached CDK8 kinase module in the Mediator complex. MED12 mutations are \nassociated with increased genomic instability, altered chromatin landscape and \nenhancer engagement, and increased responsiveness to progesterone."
explanation: >-
Describes the molecular consequence of MED12 driver mutations on the Mediator
kinase module and progesterone responsiveness.
- reference: PMID:37668348
reference_title: "RISING STARS: Role of MED12 mutation in the pathogenesis of uterine fibroids."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Among the driver gene mutations identified in UFs, mutations \nin MED12, a component of the cyclin-dependent kinase (CDK) Mediator module, are \nthe most common and observed in 50-80% of UFs."
explanation: >-
Independent review confirming MED12 as the most common driver, present in 50-80%
of fibroids.
- reference: PMID:40862769
reference_title: The Roles of Non-Coding RNAs in the Pathogenesis of Uterine Fibroids.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Driver mutations in genes such as \nMED12, HMGA2, and FH also play roles in the development and growth of fibroids."
explanation: >-
Confirms MED12, HMGA2, and FH as recurrent drivers of fibroid development.
downstream:
- target: Hormone-Driven Myometrial Smooth Muscle Proliferation and ECM Deposition
description: >-
The transformed clonal cell becomes dependent on estrogen and progesterone:
progesterone (via PGR) drives paracrine WNT ligand secretion that stimulates
tumor stem cell proliferation, while both the mutated smooth muscle cells and
adjacent tumor-associated fibroblasts deposit excessive extracellular matrix.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- Progesterone receptor signaling activates paracrine WNT ligand production.
- MED12-mutant tumors upregulate ECM-organization and collagen genes.
- name: Hormone-Driven Myometrial Smooth Muscle Proliferation and ECM Deposition
description: >
Estradiol and progesterone are essential for fibroid growth. During each ovulatory
cycle the myometrium proliferates under ovarian steroid stimulation. Progesterone,
acting through its nuclear receptor (PGR) in differentiated fibroid cells, activates
paracrine secretion of WNT ligands, cytokines, and growth factors that drive a small
stem cell population to proliferate. Both the mutated smooth muscle cells and adjacent
tumor-associated fibroblasts lay down excessive disordered extracellular matrix
(collagen, fibronectin, proteoglycans), the defining "fibroid" feature. Fibroids
rarely arise before menarche and frequently regress after menopause, underscoring
steroid hormone dependence.
cell_types:
- preferred_term: myometrial smooth muscle cell
term:
id: CL:0002366
label: myometrial cell
- preferred_term: tumor-associated fibroblast
term:
id: CL:0000057
label: fibroblast
biological_processes:
- preferred_term: smooth muscle cell proliferation
term:
id: GO:0048661
label: positive regulation of smooth muscle cell proliferation
modifier: INCREASED
- preferred_term: progesterone receptor signaling
term:
id: GO:0050847
label: progesterone receptor signaling pathway
modifier: INCREASED
- preferred_term: excessive extracellular matrix deposition
term:
id: GO:0030198
label: extracellular matrix organization
modifier: INCREASED
evidence:
- reference: PMID:40214304
reference_title: UTERINE FIBROIDS.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Progesterone, via its receptors in differentiated fibroid cell \npopulations, activates the production of Wingless-type MMTV integration site \nfamily (WNT) ligands, cytokines, and other growth substances to act on adjacent \nstem cells in a paracrine fashion to support tumor growth."
explanation: >-
Defines the progesterone-driven paracrine WNT mechanism supporting fibroid stem
cell proliferation.
- reference: PMID:40214304
reference_title: UTERINE FIBROIDS.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Both the mutated smooth muscle cells and the adjacent \ntumor-associated fibroblasts lay down excessive quantities of extracellular \nmatrix, providing a unique feature that led to naming these tumors \"fibroids.\""
explanation: >-
Establishes that mutated smooth muscle cells and tumor-associated fibroblasts
deposit the excessive ECM characteristic of fibroids.
- reference: PMID:37668348
reference_title: "RISING STARS: Role of MED12 mutation in the pathogenesis of uterine fibroids."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Gene expressions related to ECM \norganization and collagen-rich ECM components are upregulated, and impaired \nMediator kinase activity and dysregulation of Wnt/β-catenin signaling are \nidentified in MED12-UFs."
explanation: >-
Links MED12 mutation to upregulated ECM-organization/collagen genes and
Wnt/beta-catenin dysregulation.
- reference: PMID:36835153
reference_title: Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The differential analysis indicated there are 394 genes \ndifferentially and aberrantly expressed only in the mutated tumors. These genes \nwere predominantly involved in the regulation of extracellular constituents."
explanation: >-
RNA-sequencing shows MED12-mutant tumors aberrantly express genes regulating
the extracellular matrix.
- reference: PMID:40862769
reference_title: The Roles of Non-Coding RNAs in the Pathogenesis of Uterine Fibroids.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "important regulatory RNAs that are becoming increasingly implicated in the aberrant expression of protein-coding genes functionally associated with ECM production, cell proliferation, apoptosis, and inflammation in fibroids"
explanation: >-
Non-coding RNAs (miRNAs, lncRNAs, circRNAs) constitute a regulatory layer over
the fibroid ECM-production and proliferation program, with their expression
influenced by MED12 mutation status and ovarian steroids.
downstream:
- target: Tumor Growth and Clinical Manifestations
description: >-
Sustained proliferation and excessive ECM deposition produce a growing,
space-occupying smooth muscle tumor that distorts the uterine architecture and
generates the clinical phenotype (bleeding, bulk symptoms, reproductive morbidity).
causal_link_type: DIRECT
- name: Tumor Growth and Clinical Manifestations
description: >
Progressive growth of the leiomyoma produces a benign smooth muscle tumor of the
uterus. Submucosal and intramural tumors distort the endometrial cavity and impair
hemostasis, causing heavy menstrual bleeding and consequent iron deficiency anemia.
Bulk from larger tumors compresses adjacent pelvic organs (bladder, rectum), causing
pressure symptoms, while distortion of the cavity and tubal ostia contributes to
reproductive morbidity. Approximately 70-80% of affected women are asymptomatic;
roughly a quarter develop clinically significant disease.
cell_types:
- preferred_term: leiomyoma smooth muscle cell
term:
id: CL:0000192
label: smooth muscle cell
evidence:
- reference: PMID:40214304
reference_title: UTERINE FIBROIDS.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Uterine fibroids (leiomyomas), the most common tumors in women and those \nassigned female at birth, originate from myometrial smooth muscle cells and \ncause heavy menstrual bleeding, anemia, pelvic discomfort, pregnancy loss, and \nobstruction of labor in approximately a quarter of reproductive-age women."
explanation: >-
Connects the smooth muscle tumor to its core clinical manifestations: heavy
menstrual bleeding, anemia, pelvic discomfort, pregnancy loss, and obstruction
of labor.
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "in \napproximately 30% of cases, UFs affect the quality of life and women's health, \nwith abnormal uterine bleeding and heavy menstrual bleeding being the most \ncommon complaints, along with iron deficiency (ID) and ID anemia."
explanation: >-
Quantifies the symptomatic fraction and identifies AUB/HMB and iron deficiency
anemia as the dominant complaints.
phenotypes:
- category: Clinical
name: Uterine Leiomyoma
description: Benign smooth muscle neoplasm arising from the myometrium of the uterus.
phenotype_term:
preferred_term: Uterine leiomyoma
term:
id: HP:0000131
label: Uterine leiomyoma
evidence:
- reference: PMID:40214304
reference_title: UTERINE FIBROIDS.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Uterine fibroids (leiomyomas), the most common tumors in women and those \nassigned female at birth, originate from myometrial smooth muscle cells"
explanation: Documents uterine leiomyoma as a myometrial smooth muscle tumor.
- category: Clinical
name: Heavy Menstrual Bleeding
description: >
Heavy menstrual bleeding (menorrhagia) is the most common symptom, classified as
AUB-L (leiomyoma) by FIGO, particularly with submucosal tumors.
phenotype_term:
preferred_term: Heavy menstrual bleeding
term:
id: HP:0000132
label: Menorrhagia
evidence:
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "abnormal uterine bleeding and heavy menstrual bleeding being the most \ncommon complaints"
explanation: Identifies heavy menstrual bleeding as the most common fibroid complaint.
- category: Clinical
name: Pelvic Pain
description: Pelvic heaviness, pressure, and pain related to fibroid bulk.
phenotype_term:
preferred_term: Pelvic pain
term:
id: HP:0034267
label: Pelvic pain
evidence:
- reference: PMID:38929485
reference_title: Currently Available Treatment Modalities for Uterine Fibroids.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "the most common benign \ngynecological condition in patients presenting with abnormal uterine bleeding, \npelvic masses causing pressure or pain"
explanation: Documents pelvic masses causing pressure or pain as a fibroid presentation.
- category: Clinical
name: Dysmenorrhea
description: Painful menstruation associated with fibroids.
phenotype_term:
preferred_term: Dysmenorrhea
term:
id: HP:0100607
label: Dysmenorrhea
evidence:
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: "in \napproximately 30% of cases, UFs affect the quality of life and women's health"
explanation: >-
Fibroids commonly cause painful menstruation; this snippet supports the broader
symptomatic quality-of-life impact within which dysmenorrhea occurs.
- category: Clinical
name: Iron Deficiency Anemia
description: Anemia resulting from chronic heavy menstrual blood loss.
phenotype_term:
preferred_term: Iron deficiency anemia
term:
id: HP:0001891
label: Iron deficiency anemia
evidence:
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "along with iron deficiency (ID) and ID anemia"
explanation: Documents iron deficiency anemia as a consequence of fibroid-related bleeding.
- category: Clinical
name: Infertility and Reproductive Morbidity
description: >
Fibroids, especially submucosal and large intramural tumors, are associated with
infertility, defective implantation, pregnancy loss, and obstruction of labor.
phenotype_term:
preferred_term: Infertility
term:
id: HP:0000789
label: Infertility
evidence:
- reference: PMID:40214304
reference_title: UTERINE FIBROIDS.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "cause heavy menstrual bleeding, anemia, pelvic discomfort, pregnancy loss, and \nobstruction of labor"
explanation: >-
Documents pregnancy loss and obstruction of labor among fibroid-associated
reproductive complications.
- reference: PMID:38929485
reference_title: Currently Available Treatment Modalities for Uterine Fibroids.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "pelvic masses causing pressure or pain, infertility and obstetric complications"
explanation: >-
Directly lists infertility and obstetric complications among the presentations
of uterine fibroids, supporting the infertility phenotype term.
- category: Clinical
name: Bulk-Related Pressure Symptoms
description: >
Larger fibroids cause bulk symptoms by compressing adjacent pelvic organs,
producing constipation (rectal compression) and urinary symptoms (bladder
compression).
phenotype_term:
preferred_term: Constipation
term:
id: HP:0002019
label: Constipation
evidence:
- reference: PMID:38929485
reference_title: Currently Available Treatment Modalities for Uterine Fibroids.
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: "the most common benign \ngynecological condition in patients presenting with abnormal uterine bleeding, \npelvic masses causing pressure or pain"
explanation: >-
Fibroid pelvic masses cause pressure on adjacent organs; constipation results
from rectal compression by bulky tumors.
genetic:
- name: MED12 somatic exon-2 mutation
gene_term:
preferred_term: MED12
term:
id: hgnc:11957
label: MED12
variant_origin: SOMATIC
features: >
Recurrent somatic exon-2 (codon 44 region) point mutations in MED12 are the most
common driver, present in ~50-80% of uterine fibroids (~77% in a large review).
These gain-of-function mutations disrupt the CDK8/CDK19 Mediator kinase module,
are more frequent in Black women, are commonly found even in small tumors, and
associate with multiple rather than solitary fibroids.
evidence:
- reference: PMID:36835153
reference_title: Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Recent studies have demonstrated that somatic MED12 mutations in exon 2 occur at \na frequency of up to 80% and have a functional role in leiomyoma pathogenesis."
explanation: Documents somatic MED12 exon-2 mutations at up to 80% frequency.
- reference: PMID:37668348
reference_title: "RISING STARS: Role of MED12 mutation in the pathogenesis of uterine fibroids."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "They are gain-of-function \nmutations and are more frequently observed in Black women and commonly observed \neven in small UFs."
explanation: Characterizes MED12 mutations as gain-of-function and more frequent in Black women.
- name: HMGA2 overexpression / rearrangement
gene_term:
preferred_term: HMGA2
term:
id: hgnc:5009
label: HMGA2
variant_origin: SOMATIC
features: >
Somatic HMGA2 (12q14-15) overexpression and chromosomal rearrangements define a
distinct molecular subtype (~10% of fibroids overall; markedly enriched in cellular
leiomyoma variants).
evidence:
- reference: PMID:34626221
reference_title: "Uterine cellular leiomyomas are characterized by common HMGA2 aberrations, followed by chromosome 1p deletion and MED12 mutation: morphological, molecular, and immunohistochemical study of 52 cases."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "36.5% showed HMGA2 overexpression at the IHC \nlevel, associated with increased mRNA expression in 14/14 cases. The \nrearrangement of the HMGA2 gene was detected in 13.2%."
explanation: >-
Documents HMGA2 overexpression and rearrangement frequencies in cellular
leiomyoma.
- name: FH (fumarate hydratase) deficiency
gene_term:
preferred_term: FH
term:
id: hgnc:3700
label: FH
features: >
Biallelic FH loss defines the fumarate-hydratase-deficient leiomyoma subtype.
Germline FH mutations cause hereditary leiomyomatosis and renal cell cancer
(HLRCC), an autosomal dominant syndrome predisposing to multiple cutaneous and
uterine leiomyomas and renal cell carcinoma.
evidence:
- reference: PMID:40862769
reference_title: The Roles of Non-Coding RNAs in the Pathogenesis of Uterine Fibroids.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Driver mutations in genes such as \nMED12, HMGA2, and FH also play roles in the development and growth of fibroids."
explanation: Lists FH among recurrent fibroid driver genes.
treatments:
- name: GnRH Agonist Therapy
description: >
GnRH agonists (e.g., leuprolide) cause pituitary downregulation and hypoestrogenism,
producing temporary fibroid shrinkage and bleeding control. Used as a preoperative
bridge; limited by menopausal symptoms, bone loss, and rebound growth after stopping.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: leuprolide
term:
id: CHEBI:6427
label: leuprolide
evidence:
- reference: PMID:38929485
reference_title: Currently Available Treatment Modalities for Uterine Fibroids.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "available medications (progestogens, combined \noral contraceptives andgonadotropin-releasing hormone agonists and antagonists) \nare generally used for short-term treatment of fibroid-induced bleeding."
explanation: Documents GnRH agonists/antagonists for short-term fibroid bleeding control.
- name: Oral GnRH Antagonist Therapy
description: >
Oral GnRH antagonists (e.g., elagolix, relugolix) directly block pituitary GnRH
receptors to suppress ovarian steroid production, reducing heavy menstrual bleeding
in a uterus-sparing, reversible regimen, often with hormonal add-back.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: elagolix
term:
id: NCIT:C153373
label: Elagolix
evidence:
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "hormonal therapies, including combined oral contraceptives, \ngonadotropin-releasing hormone agonists or antagonists"
explanation: Documents GnRH antagonists among hormonal therapies for fibroid-related AUB.
- name: Selective Progesterone Receptor Modulator Therapy
description: >
Selective progesterone receptor modulators (SPRMs, e.g., ulipristal acetate)
modulate PGR signaling to reduce bleeding and fibroid size; intermittent long-term
use shows good results but is limited by hepatotoxicity concerns. Response may vary
with MED12 mutation status.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: ulipristal acetate
term:
id: CHEBI:71025
label: ulipristal acetate
evidence:
- reference: PMID:38929485
reference_title: Currently Available Treatment Modalities for Uterine Fibroids.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "it was shown that SPRMs could be administered intermittently long-term \nwith good results on bleeding and fibroid size reduction."
explanation: Documents intermittent SPRM therapy reducing bleeding and fibroid size.
- name: Tranexamic Acid
description: >
Antifibrinolytic agent that reduces menstrual blood loss for symptomatic heavy
menstrual bleeding when uterine preservation is desired; does not shrink fibroids.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: tranexamic acid
term:
id: CHEBI:48669
label: tranexamic acid
evidence:
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Medical \ntreatments used for UFs-related abnormal uterine bleeding include symptomatic \nagents, such as nonsteroidal antiinflammatory drugs and tranexamic acid"
explanation: Documents tranexamic acid as a symptomatic agent for fibroid-related AUB.
- name: Nonsteroidal Anti-Inflammatory Drugs
description: >
NSAIDs are used as symptomatic agents to reduce fibroid-related menstrual blood
loss and dysmenorrhea; they do not reduce fibroid size.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: non-steroidal anti-inflammatory drug
term:
id: NCIT:C257
label: Nonsteroidal Antiinflammatory Drug
evidence:
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "symptomatic \nagents, such as nonsteroidal antiinflammatory drugs and tranexamic acid"
explanation: Documents NSAIDs among symptomatic agents for fibroid-related abnormal uterine bleeding.
- name: Levonorgestrel Intrauterine System
description: >
The levonorgestrel-releasing intrauterine system delivers local progestin to the
endometrium, reducing heavy menstrual bleeding in a uterus-sparing, reversible way;
it controls bleeding symptoms but does not consistently shrink fibroids.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: levonorgestrel
term:
id: CHEBI:6443
label: levonorgestrel
evidence:
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "hormonal therapies, including combined oral contraceptives, \ngonadotropin-releasing hormone agonists or antagonists, levonorgestrel \nintrauterine systems"
explanation: Documents levonorgestrel intrauterine systems among hormonal therapies for fibroid-related AUB.
- name: Aromatase Inhibitor Therapy
description: >
Aromatase inhibitors block estrogen biosynthesis, lowering the estrogen that drives
fibroid growth; used as a hormonal option for symptomatic fibroids.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: aromatase inhibitor
term:
id: NCIT:C1740
label: Aromatase Inhibitor
evidence:
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "selective progesterone receptor modulators, and aromatase \ninhibitors"
explanation: Documents aromatase inhibitors among hormonal therapies for fibroid-related AUB.
- name: Myomectomy
description: >
Surgical removal of fibroids with uterine preservation (hysteroscopic, laparoscopic,
open, or robotic), indicated for symptomatic patients desiring fertility or uterine
conservation; recurrence risk persists.
treatment_term:
preferred_term: myomectomy
term:
id: MAXO:0001106
label: myomectomy
evidence:
- reference: PMID:38929485
reference_title: Currently Available Treatment Modalities for Uterine Fibroids.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Current \nmanagement strategies mainly involve surgical interventions (hysterectomy and \nmyomectomy hysteroscopy, laparoscopy or laparotomy)."
explanation: Documents myomectomy as a core surgical management strategy.
- name: Hysterectomy
description: >
Definitive removal of the uterus, eliminating fibroids and recurrence, for women
with severe symptoms and no fertility desire or failure of conservative options.
treatment_term:
preferred_term: hysterectomy
term:
id: MAXO:0001058
label: hysterectomy
evidence:
- reference: PMID:38929485
reference_title: Currently Available Treatment Modalities for Uterine Fibroids.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Current \nmanagement strategies mainly involve surgical interventions (hysterectomy and \nmyomectomy hysteroscopy, laparoscopy or laparotomy)."
explanation: Documents hysterectomy as a definitive surgical treatment for fibroids.
- name: Uterine Artery Embolization
description: >
Image-guided arterial embolization that devascularizes fibroids, causing ischemic
shrinkage; a uterus-sparing, non-excisional option, generally not first choice when
future fertility is a major goal.
treatment_term:
preferred_term: uterine artery embolization
term:
id: MAXO:0020024
label: arterial embolization
evidence:
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Radiologic interventions are also available: uterine artery \nembolization, high-intensity focused ultrasound or magnetic resonance-guided \nfocused ultrasound, and radiofrequency ablation."
explanation: Documents uterine artery embolization as a radiologic intervention for fibroids.
- name: MRI-Guided Focused Ultrasound Surgery
description: >
Non-invasive thermal ablation that focuses high-intensity ultrasound energy under
MRI (or ultrasound) guidance to coagulate fibroid tissue, sparing the uterus.
treatment_term:
preferred_term: MRI-guided focused ultrasound ablation
term:
id: NCIT:C62723
label: MRI-Guided Focused Ultrasound Ablation
evidence:
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "high-intensity focused ultrasound or magnetic resonance-guided \nfocused ultrasound"
explanation: Documents high-intensity/MR-guided focused ultrasound as a radiologic intervention for fibroids.
- name: Radiofrequency Ablation
description: >
Image-guided radiofrequency energy thermally ablates fibroid tissue, causing
coagulative necrosis and volume reduction while preserving the uterus.
treatment_term:
preferred_term: radiofrequency ablation
term:
id: NCIT:C15666
label: Radiofrequency Ablation
evidence:
- reference: PMID:38929485
reference_title: Currently Available Treatment Modalities for Uterine Fibroids.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "radiofrequency ablation of fibroids and endometrial ablation"
explanation: Documents radiofrequency ablation of fibroids as a minimally invasive treatment modality.
- name: Iron Replacement Therapy
description: >
Repletes iron stores in fibroid-related iron deficiency and anemia from chronic
bleeding; an important adjunct before and after surgery and during medical therapy.
treatment_term:
preferred_term: supportive care
term:
id: MAXO:0000950
label: supportive care
evidence:
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "the management of \nID and ID anemia, as a consequence of acute and chronic bleeding, should be \ntaken into account with the use of iron replacement therapy"
explanation: Documents iron replacement therapy for fibroid-related iron deficiency anemia.
prevalence:
- population: Women aged 30-44 years
notes: >-
Uterine fibroids are the most common benign pelvic tumor of reproductive-age
women, present in more than 60% of women aged 30-44 years.
evidence:
- reference: PMID:38723935
reference_title: The modern management of uterine fibroids-related abnormal uterine bleeding.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Uterine fibroids (UFs) are the most common female benign pelvic tumors, \naffecting >60% of patients aged 30-44 years."
explanation: Quantifies fibroid prevalence at over 60% in women aged 30-44 years.
- population: Women overall (with racial disparity)
notes: >-
Overall prevalence is approximately 70%, with Black women affected at a
disproportionately high rate.
evidence:
- reference: PMID:40862769
reference_title: The Roles of Non-Coding RNAs in the Pathogenesis of Uterine Fibroids.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Uterine fibroids are benign smooth muscle tumors that affect ~70% of women, with \nBlack women being affected at a disproportionate rate."
explanation: Documents overall fibroid prevalence (~70%) and the disproportionate burden in Black women.
references:
- reference: PMID:40214304
title: "UTERINE FIBROIDS."
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on Uterine Leiomyoma covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.
For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.
Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed
Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Search first: CTD, PubMed, PheGenI, GxE databases
Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC
For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities
For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype
Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser
Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Search first: CDC databases, WHO, PubMed, NHANES
Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON
Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Search first: PubMed, Gene Ontology, Reactome
Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types
Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Search first: OMIM, Orphanet, HPO, PubMed
Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.
Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Search first: NSGC resources, ACMG guidelines, GeneReviews
Search first: Clinical guidelines, FDA approvals, PubMed
Search first: NCBI Taxonomy
Search first: VBO (Vertebrate Breed Ontology)
Search first: NCBI Gene
Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease
This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details
Uterine leiomyomas (also known as uterine fibroids or myomas) are the most common benign gynecological tumors affecting women of reproductive age (alali2023theetiopathogenesisof pages 1-2, bulun2025uterinefibroids pages 1-5). These tumors originate from the myometrial smooth muscle cells of the uterus and are characterized by monoclonal proliferation, excessive accumulation of extracellular matrix (ECM), and hormone-dependent growth (bulun2025uterinefibroids pages 1-5, ishikawa2023risingstarsrole pages 1-3). The lifetime prevalence reaches 30–70% in the general population, with incidence rates as high as 70–80% by menopause (alali2023theetiopathogenesisof pages 1-2, koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2, larrain2024newinsightsinto pages 1-3). Black women experience disproportionately higher rates, with prevalence exceeding 80% by age 50 compared to approximately 70% in White women (buyukcelebi2024integratingleiomyomagenetics pages 1-2, centini2024tailoringthediagnostic pages 1-2).
While specific OMIM numbers and comprehensive ontology identifiers were not fully detailed in the retrieved recent literature, uterine fibroids are classified using ICD-10 codes D25-D26.9 and D28.2 (zhang2025globalregionaland pages 1-2). The International Federation of Gynecology and Obstetrics (FIGO) classification system stratifies fibroids based on anatomical location into types 0–8 and hybrid categories (micic2024currentlyavailabletreatment pages 1-2).
The information is derived from aggregated disease-level resources including recent systematic reviews, epidemiological studies using Global Burden of Disease (GBD) data, molecular profiling studies, and large-scale genome-wide association studies (GWAS) published between 2023 and 2026 (alali2023theetiopathogenesisof pages 1-2, bulun2025uterinefibroids pages 1-5, tang2025theglobalburden pages 1-2, zhang2025globalregionaland pages 1-2, buyukcelebi2024integratingleiomyomagenetics pages 1-2).
Uterine leiomyomas have complex genetic architecture combining somatic driver mutations and heritable susceptibility:
Somatic Mutations (Tumor-Intrinsic): - MED12 mutations (exon 2) are the most common somatic driver, present in 50–80% of fibroids (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2, ishikawa2023risingstarsrole pages 1-3). These heterozygous, gain-of-function mutations disrupt the CDK8 kinase module of the Mediator complex, affecting chromatin landscape, enhancer engagement, genomic stability, and responsiveness to progesterone (bulun2025uterinefibroids pages 1-5, ishikawa2023risingstarsrole pages 1-3).
HMGA2/HMGA1 overexpression and rearrangements occur in approximately 10% of fibroids, defining a distinct molecular subtype with characteristic histopathologic features (bulun2025uterinefibroids pages 1-5, dundr2022uterinecellularleiomyomas pages 1-2).
FH (Fumarate Hydratase) deficiency characterizes FH-deficient leiomyomas and is associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2, boos2025therolesof pages 1-2).
COL4A5/COL4A6 deletions, SRCAP complex mutations (causing H2A.Z deposition defects), and chromosome 1p deletions represent additional recurrent molecular subtypes (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2, dundr2022uterinecellularleiomyomas pages 1-2).
A detailed summary of genetic alterations is provided in the genetic mutations table below.
| Gene Name / Alteration | Mutation Type | Frequency / Prevalence | Molecular Effects | Clinical Associations | Key References |
|---|---|---|---|---|---|
| MED12 | Recurrent somatic exon 2 point mutations; typically heterozygous, gain-of-function–like driver alterations disrupting Mediator kinase module signaling | ~50–80% of uterine fibroids; ~70% in several recent summaries; 77% in a large review | Disrupts MED12-dependent activation of CDK8/CDK19 within the Mediator complex; associated with altered chromatin landscape, enhancer engagement, genomic instability, progesterone responsiveness, and dysregulated WNT/β-catenin, hedgehog, sex steroid, and TGF-β signaling; transcriptomic enrichment for ECM/collagen pathways | Most common driver; often multiple tumors rather than solitary lesions; commonly seen even in small tumors; more frequent in Black women in some series; mutant tumors can differ in size/location and may show mutation-status–dependent response to GnRH agonists and ulipristal acetate | (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2, ishikawa2023risingstarsrole pages 1-3) |
| HMGA2 / HMGA1 | Somatic overexpression and chromosomal rearrangements/fusions involving HMGA2/1 | ~10% of fibroids in recent overview; in cellular leiomyoma, HMGA2 overexpression was 36.5% and rearrangement 13.2% | Alters chromatin architecture and transcriptional programs; defines a molecular subtype distinct from MED12-mutant tumors | Associated with distinct histopathologic phenotypes; important subtype in usual leiomyoma and especially enriched in some variants such as cellular leiomyoma | (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2, dundr2022uterinecellularleiomyomas pages 1-2) |
| FH | Somatic or germline-related loss-of-function / deficiency; part of FH-deficient leiomyoma spectrum and HLRCC-related disease | Less common than MED12/HMGA2 in unselected fibroids; recognized recurrent subtype | Fumarate hydratase deficiency rewires metabolism and contributes to a distinct molecular subtype of leiomyoma | Seen in FH-deficient leiomyomas and in hereditary leiomyomatosis and renal cell cancer (HLRCC); clinically relevant for identifying syndromic disease | (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2, boos2025therolesof pages 1-2) |
| COL4A5 / COL4A6 | Recurrent somatic deletions / structural alterations affecting collagen IV genes | Recurrent but uncommon relative to MED12; listed among frequently observed genetic alterations | Likely alters basement-membrane / ECM-related biology and contributes to subtype-specific tumor development | Included among recognized uterine fibroid driver alterations; may overlap with syndromic/structural subtypes rather than classic MED12 tumors | (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2, chuang2023differentialexpressionof pages 1-2) |
| SRCAP complex genes (e.g., YEATS4, ZNHIT1, other complex members) | Inactivating somatic mutations causing defective H2A.Z loading / chromatin remodeling abnormalities | Recently identified recurrent but uncommon subtype | Produces H2A.Z deposition defects and epigenetic dysregulation; supports a chromatin-based pathogenesis distinct from MED12 and HMGA2 | Emerging molecular class of leiomyoma; potentially useful for future subtype-based diagnostics and therapy development | (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2) |
| Chromosome 1p deletion | Recurrent somatic copy-number loss | 19.3% in a cellular leiomyoma series | Copy-number loss likely alters dosage of tumor-relevant genes on 1p; appears mutually exclusive with some other driver classes in variant tumors | Particularly reported in cellular leiomyoma; useful in variant classification and differential pathology | (dundr2022uterinecellularleiomyomas pages 1-2) |
| 24 GWAS risk loci / heritable susceptibility variants (multiple genes including GREB1, MCM8 and broader target-gene sets) | Germline susceptibility SNPs / risk loci from population genetics | 24 uterine-fibroid–associated risk loci identified in a 2024 integrative analysis; 394 potential target genes, 168 differentially expressed in tumors | Heritable risk variants map largely to noncoding regulatory regions and influence gene regulation through chromatin contacts, eQTL effects, and cell-type–specific regulatory programs | Explains familial aggregation and racial/population risk differences; points to causal cell types and potential preventive/targeted strategies rather than a single monogenic cause | (buyukcelebi2024integratingleiomyomagenetics pages 1-2) |
| Non-coding RNA dysregulation linked to driver status (e.g., miR-21, miR-29, miR-200; H19, MIAT, XIST) | Secondary molecular alterations influenced by driver mutations, race/ethnicity, and hormones rather than classic coding mutations | Commonly dysregulated across fibroids; not a single frequency estimate | Regulates ECM production, proliferation, apoptosis, and inflammation; expression is influenced by MED12 mutation status and ovarian steroids | Potential biomarker and non-hormonal therapeutic layer; may help explain phenotypic heterogeneity and racial disparities | (boos2025therolesof pages 1-2) |
Table: This table summarizes the principal genetic and molecular alterations implicated in uterine leiomyoma, emphasizing recurrent somatic drivers, inherited susceptibility loci, and their clinical relevance. It is useful for quickly comparing major subtypes, frequencies, and mechanistic consequences across the current evidence base.
Heritable Susceptibility: A 2024 integrative GWAS meta-analysis identified 24 uterine fibroid-associated risk loci potentially targeting 394 genes, of which 168 are differentially expressed in fibroid tumors (buyukcelebi2024integratingleiomyomagenetics pages 1-2). This heritable component explains familial aggregation, with first-degree relatives showing 2.5-fold elevated risk and higher concordance in monozygotic versus dizygotic twins (buyukcelebi2024integratingleiomyomagenetics pages 1-2).
Estrogen and progesterone are essential for fibroid development and growth (bulun2025uterinefibroids pages 1-5, ishikawa2023risingstarsrole pages 1-3, boos2025therolesof pages 1-2). Fibroids overexpress estrogen and progesterone receptors, and their growth is associated with ovulatory cycles and the first trimester of pregnancy (bulun2025uterinefibroids pages 1-5). Progesterone, via its nuclear receptor PGR, is particularly critical: it activates paracrine WNT signaling and production of growth factors that support fibroid stem cell proliferation (bulun2025uterinefibroids pages 1-5, larrain2024newinsightsinto pages 1-3). Fibroids rarely develop before menarche and often regress after menopause, underscoring steroid hormone dependence (alali2023theetiopathogenesisof pages 1-2, ishikawa2023risingstarsrole pages 1-3).
Uterine leiomyomas arise from clonal expansion of a single mutated myometrial stem cell or transformed myometrial cell acquiring stem-like features (tumor-initiating cell, TIC) (koltsova2023aviewon pages 1-2, larrain2024newinsightsinto pages 1-3). This initial genetic insult (e.g., MED12 mutation) transforms the cell, but additional factors—including hormonal signaling, paracrine interactions with surrounding differentiated cells, and ECM remodeling—are required for tumor progression (koltsova2023aviewon pages 1-2, larrain2024newinsightsinto pages 1-3).
A comprehensive summary of risk and protective factors is presented in the table below.
| Factor Type | Specific Factor | Category | Strength of Association | Population-Specific Effects | Key Evidence |
|---|---|---|---|---|---|
| Risk | Advanced reproductive age | Reproductive | Consistently reported risk factor; incidence and symptom burden increase through reproductive years, especially ages 35–50 | Burden concentrated in women aged 40–69 globally; common in reproductive-age women (tang2025theglobalburden pages 1-2, micic2024currentlyavailabletreatment pages 1-2) | Listed as a risk factor in reviews; fibroids are most commonly found in women aged 35–50, and global burden is concentrated in ages 40–69 (koltsova2023aviewon pages 1-2, tang2025theglobalburden pages 1-2, micic2024currentlyavailabletreatment pages 1-2) |
| Risk | Black/African ancestry | Genetic / population | Strong and repeatedly reported association | By age 50, prevalence reaches >80% in Black women vs ~70% overall/White women; disproportionate incidence and severity (buyukcelebi2024integratingleiomyomagenetics pages 1-2, centini2024tailoringthediagnostic pages 1-2, boos2025therolesof pages 1-2) | Reviews and genomic studies report substantially higher prevalence and burden in Black women (buyukcelebi2024integratingleiomyomagenetics pages 1-2, centini2024tailoringthediagnostic pages 1-2, boos2025therolesof pages 1-2) |
| Risk | Latin American ethnicity | Population | Reported association, but less extensively quantified than Black ancestry | Mentioned as increased-risk population in review literature | Identified among risk factors in heterogeneity-focused review (koltsova2023aviewon pages 1-2) |
| Risk | Family history of uterine leiomyoma | Genetic | Moderate-to-strong; familial aggregation repeatedly reported | First-degree relatives have elevated risk; reflects heritable susceptibility | Review identifies family history as a risk factor; GWAS/integrative genetics supports heritable contribution and multiple susceptibility loci (koltsova2023aviewon pages 1-2, buyukcelebi2024integratingleiomyomagenetics pages 1-2) |
| Risk | Germline/heritable susceptibility loci | Genetic | Strong biologic evidence for susceptibility, but effect sizes vary by locus | May contribute to racial/population differences in risk | Integrative 2024 analysis identified 24 UF-associated risk loci and 394 candidate target genes, supporting inherited susceptibility (buyukcelebi2024integratingleiomyomagenetics pages 1-2) |
| Risk | MED12-associated predisposition to specific tumor biology | Genetic / molecular | Strong for tumor subtype biology rather than disease initiation alone | MED12-mutant tumors are more frequent in Black women in some series and often multiple | MED12 mutations are the dominant driver in many tumors and are associated with distinct biology and multiplicity (bulun2025uterinefibroids pages 1-5, ishikawa2023risingstarsrole pages 1-3) |
| Risk | Early menarche | Reproductive | Consistently reported risk factor | No specific population restriction given, but may interact with lifetime hormonal exposure | Included as a risk factor in multiple reviews and diagnostic overview (koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Risk | Late menopause | Reproductive | Reported risk factor, likely reflecting prolonged estrogen/progesterone exposure | Not specifically stratified | Included in etiopathogenesis overview figure/discussion (alali2023theetiopathogenesisof pages 1-2) |
| Risk | Nulliparity / low parity | Reproductive | Consistently reported risk factor | Protective effect of multiparity implies higher risk in nulliparous women | Nulliparity or absence of parity is reported as a risk factor; several reviews note multiparity as protective (buyukcelebi2024integratingleiomyomagenetics pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Protective | Multiparity / parity | Reproductive | Consistently reported protective factor | Not population-specific, though effect may vary with reproductive history | Multiparity/parity reported as protective in reviews and diagnostic narrative (koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2) |
| Risk | Obesity / high BMI | Lifestyle / metabolic | Strong and consistently reported | Important in many populations; cited in epidemiologic and mechanistic reviews | Obesity repeatedly listed among major risk factors and linked to symptomatic disease burden (alali2023theetiopathogenesisof pages 1-2, koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2, micic2024currentlyavailabletreatment pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Risk | Diabetes | Metabolic | Reported association | Not specifically stratified | Included among factors involved in incidence/development in clinician-friendly review (larrain2024newinsightsinto pages 1-3) |
| Risk | Arterial hypertension | Metabolic / vascular | Repeatedly reported association | Not specifically stratified | Identified as a risk factor in heterogeneity/risk-factor review and clinician review (koltsova2023aviewon pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Risk | Chronic inflammation | Environmental / biologic | Reported association with plausible mechanistic support | Not specifically stratified | Listed as a risk factor in review of UL genesis; inflammation also emphasized mechanistically in fibroid biology (koltsova2023aviewon pages 1-2, boos2025therolesof pages 1-2) |
| Risk | Sexually transmitted infections | Infectious | Reported association, evidence less mature than hormonal/metabolic factors | Not specifically stratified | Identified as a possible risk factor in review of risk/protective factors (koltsova2023aviewon pages 1-2) |
| Risk | Exposure to xenoestrogens in early ontogenesis | Environmental | Biologically plausible and reported in review literature | Suggests early-life vulnerability window | Reported as a risk factor in review of UL genesis (koltsova2023aviewon pages 1-2) |
| Risk | Diethylstilbestrol (DES) exposure | Environmental | Reported association | Not specifically stratified | Included among environmental contributors in clinician-friendly molecular review (larrain2024newinsightsinto pages 1-3) |
| Risk | Air pollution | Environmental | Reported association | Not specifically stratified | Mentioned among factors potentially involved in incidence/development (larrain2024newinsightsinto pages 1-3) |
| Risk | Alcohol consumption | Lifestyle | Repeatedly reported risk factor | Not specifically stratified | Alcohol listed as a risk factor in heterogeneity review and clinician-friendly review (koltsova2023aviewon pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Risk | Caffeine | Lifestyle | Reported in one review/figure; likely weaker evidence than alcohol/obesity | Not specifically stratified | Included in etiopathogenesis figure as a potential risk factor (alali2023theetiopathogenesisof pages 1-2) |
| Risk | Chronic stress | Lifestyle / psychosocial | Reported association | Not specifically stratified | Listed in diagnostic review as a risk factor (centini2024tailoringthediagnostic pages 1-2) |
| Risk | Vitamin D deficiency | Environmental / nutritional | Repeatedly reported association with supportive mechanistic rationale | Not specifically stratified; may be relevant in populations with higher deficiency prevalence | Vitamin D deficiency is listed among known factors influencing fibroid development in recent reviews (alali2023theetiopathogenesisof pages 1-2, micic2024currentlyavailabletreatment pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Protective | Adequate vitamin D status | Nutritional | Implied protective factor from repeated deficiency-risk association; preclinical support exists | Not specifically stratified | Since deficiency is repeatedly associated with risk, adequate status is plausibly protective; some model literature supports anti-fibroid effects (micic2024currentlyavailabletreatment pages 1-2, wu2026preclinicalresearchplatform pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Risk | High-fat diet / adverse dietary factors | Lifestyle / nutritional | Reported association | Not specifically stratified | High-fat diet and dietary factors are mentioned as contributing to incidence/development (larrain2024newinsightsinto pages 1-3) |
| Protective | Oral contraceptive use / combined oral contraceptives | Reproductive / hormonal | Reported protective factor in review literature, though literature historically mixed | Not specifically stratified | Oral contraceptive intake and combined oral contraceptives are listed among possible protective factors in recent reviews (koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2) |
| Protective | Smoking | Lifestyle | Reported as a possible protective factor in reviews, but likely outweighed by broader health harms | Not population-specific; not a recommended prevention strategy | Smoking is listed among possible protective factors in one recent review even though it is not clinically recommended (koltsova2023aviewon pages 1-2) |
| Risk | Hormonal milieu: higher estradiol and progesterone exposure | Hormonal / mechanistic | Strong mechanistic support | Relevant across reproductive-age populations; explains premenopausal predominance | Risk/severity associated with serum estradiol and progesterone; tumors are steroid-dependent and rarely develop before menarche (buyukcelebi2024integratingleiomyomagenetics pages 1-2, ishikawa2023risingstarsrole pages 1-3) |
| Protective | Postmenopausal state / menopause-associated regression | Reproductive / hormonal | Strong observational pattern | Applies broadly; many fibroids regress after menopause | Fibroids frequently regress after menopause, supporting reduced ovarian steroid exposure as protective against persistence/growth (alali2023theetiopathogenesisof pages 1-2, ishikawa2023risingstarsrole pages 1-3) |
| Risk | Reproductive delay / postponed childbearing | Reproductive | Epidemiologically plausible; discussed in population-burden review | Relevant in regions with delayed childbearing patterns | Population review links changing reproductive patterns, including postponed childbearing, to increasing prevalence (zhang2025globalregionaland pages 1-2) |
Table: This table summarizes reported risk and protective factors for uterine leiomyoma across recent reviews and epidemiologic/genetic studies. It organizes the factors by category, indicates the qualitative strength of association, and notes population-specific patterns where available.
Genetic Risk Factors: - Family history of fibroids (koltsova2023aviewon pages 1-2, buyukcelebi2024integratingleiomyomagenetics pages 1-2) - Black/African ancestry (highest risk and severity) (buyukcelebi2024integratingleiomyomagenetics pages 1-2, centini2024tailoringthediagnostic pages 1-2, boos2025therolesof pages 1-2) - Latin American ethnicity (koltsova2023aviewon pages 1-2) - Multiple GWAS-identified susceptibility loci (buyukcelebi2024integratingleiomyomagenetics pages 1-2)
Environmental and Lifestyle Risk Factors: - Early menarche, nulliparity, late menopause (alali2023theetiopathogenesisof pages 1-2, koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2, larrain2024newinsightsinto pages 1-3) - Obesity and high BMI (alali2023theetiopathogenesisof pages 1-2, koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2, micic2024currentlyavailabletreatment pages 1-2, larrain2024newinsightsinto pages 1-3) - Diabetes and arterial hypertension (koltsova2023aviewon pages 1-2, larrain2024newinsightsinto pages 1-3) - Vitamin D deficiency (alali2023theetiopathogenesisof pages 1-2, micic2024currentlyavailabletreatment pages 1-2, larrain2024newinsightsinto pages 1-3) - Alcohol consumption, high-fat diet (koltsova2023aviewon pages 1-2, larrain2024newinsightsinto pages 1-3) - Chronic stress and chronic inflammation (koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2) - Exposure to xenoestrogens (e.g., diethylstilbestrol, DES), air pollution (koltsova2023aviewon pages 1-2, larrain2024newinsightsinto pages 1-3) - Sexually transmitted infections (koltsova2023aviewon pages 1-2)
Advanced Age: Reproductive age 35–50 years represents peak incidence (koltsova2023aviewon pages 1-2, tang2025theglobalburden pages 1-2, micic2024currentlyavailabletreatment pages 1-2).
Genetic Protective Factors: Although specific protective genetic variants are not well-defined, the presence of certain alleles at GWAS loci may modulate risk (buyukcelebi2024integratingleiomyomagenetics pages 1-2).
Environmental/Lifestyle Protective Factors: - Multiparity/parity (consistently protective) (koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2) - Combined oral contraceptive use (koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2) - Adequate vitamin D status (implied by deficiency being a risk factor) (micic2024currentlyavailabletreatment pages 1-2, wu2026preclinicalresearchplatform pages 1-2, larrain2024newinsightsinto pages 1-3) - Postmenopausal state (fibroids often regress after menopause) (alali2023theetiopathogenesisof pages 1-2, ishikawa2023risingstarsrole pages 1-3) - Smoking (paradoxically listed as protective in some reviews, though not clinically recommended) (koltsova2023aviewon pages 1-2)
MED12 mutation status, race/ethnicity, and ovarian steroid hormones influence the expression of non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and circRNAs, which regulate ECM production, cell proliferation, apoptosis, and inflammation in fibroids (boos2025therolesof pages 1-2). This represents a complex gene-environment interaction where genetic drivers (MED12 mutations), population ancestry, and hormonal milieu converge to shape tumor biology and phenotypic heterogeneity (chuang2023differentialexpressionof pages 1-2, boos2025therolesof pages 1-2).
Approximately 70–80% of women with fibroids remain asymptomatic, with clinical manifestations occurring in 20–30% of cases (alali2023theetiopathogenesisof pages 1-2, centini2024tailoringthediagnostic pages 1-2). Symptomatic presentations vary widely depending on fibroid size, number, and location.
Common Symptoms and Signs:
HPO Term Suggestion: HP:0000132 (Menorrhagia), HP:0001892 (Abnormal bleeding tendency)
Pelvic Pain and Dysmenorrhea
HPO Term Suggestion: HP:0000131 (Dysmenorrhea), HP:0100602 (Pelvic pain)
Pelvic Pressure and Bulk Symptoms
HPO Term Suggestion: HP:0100594 (Urinary dysfunction), HP:0002019 (Constipation)
Iron Deficiency and Iron Deficiency Anemia (IDA)
HPO Term Suggestion: HP:0001891 (Iron deficiency anemia)
Reproductive Dysfunction
Symptomatic uterine fibroids profoundly reduce quality of life (QoL) and decrease labor productivity (ishikawa2023risingstarsrole pages 1-3, vannuccini2024themodernmanagement pages 1-5). Women with HMB as the primary complaint experience significantly higher direct healthcare costs and perceived stress (vannuccini2024themodernmanagement pages 1-5). The disease impacts physical, social, emotional, and material well-being (vannuccini2024themodernmanagement pages 1-5). Annual costs in the United States range from $5.9 billion to $34.4 billion (buyukcelebi2024integratingleiomyomagenetics pages 1-2, centini2024tailoringthediagnostic pages 1-2).
The comprehensive genetic mutations table summarizes causal genes and variants:
| Gene Name / Alteration | Mutation Type | Frequency / Prevalence | Molecular Effects | Clinical Associations | Key References |
|---|---|---|---|---|---|
| MED12 | Recurrent somatic exon 2 point mutations; typically heterozygous, gain-of-function–like driver alterations disrupting Mediator kinase module signaling | ~50–80% of uterine fibroids; ~70% in several recent summaries; 77% in a large review | Disrupts MED12-dependent activation of CDK8/CDK19 within the Mediator complex; associated with altered chromatin landscape, enhancer engagement, genomic instability, progesterone responsiveness, and dysregulated WNT/β-catenin, hedgehog, sex steroid, and TGF-β signaling; transcriptomic enrichment for ECM/collagen pathways | Most common driver; often multiple tumors rather than solitary lesions; commonly seen even in small tumors; more frequent in Black women in some series; mutant tumors can differ in size/location and may show mutation-status–dependent response to GnRH agonists and ulipristal acetate | (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2, ishikawa2023risingstarsrole pages 1-3) |
| HMGA2 / HMGA1 | Somatic overexpression and chromosomal rearrangements/fusions involving HMGA2/1 | ~10% of fibroids in recent overview; in cellular leiomyoma, HMGA2 overexpression was 36.5% and rearrangement 13.2% | Alters chromatin architecture and transcriptional programs; defines a molecular subtype distinct from MED12-mutant tumors | Associated with distinct histopathologic phenotypes; important subtype in usual leiomyoma and especially enriched in some variants such as cellular leiomyoma | (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2, dundr2022uterinecellularleiomyomas pages 1-2) |
| FH | Somatic or germline-related loss-of-function / deficiency; part of FH-deficient leiomyoma spectrum and HLRCC-related disease | Less common than MED12/HMGA2 in unselected fibroids; recognized recurrent subtype | Fumarate hydratase deficiency rewires metabolism and contributes to a distinct molecular subtype of leiomyoma | Seen in FH-deficient leiomyomas and in hereditary leiomyomatosis and renal cell cancer (HLRCC); clinically relevant for identifying syndromic disease | (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2, boos2025therolesof pages 1-2) |
| COL4A5 / COL4A6 | Recurrent somatic deletions / structural alterations affecting collagen IV genes | Recurrent but uncommon relative to MED12; listed among frequently observed genetic alterations | Likely alters basement-membrane / ECM-related biology and contributes to subtype-specific tumor development | Included among recognized uterine fibroid driver alterations; may overlap with syndromic/structural subtypes rather than classic MED12 tumors | (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2, chuang2023differentialexpressionof pages 1-2) |
| SRCAP complex genes (e.g., YEATS4, ZNHIT1, other complex members) | Inactivating somatic mutations causing defective H2A.Z loading / chromatin remodeling abnormalities | Recently identified recurrent but uncommon subtype | Produces H2A.Z deposition defects and epigenetic dysregulation; supports a chromatin-based pathogenesis distinct from MED12 and HMGA2 | Emerging molecular class of leiomyoma; potentially useful for future subtype-based diagnostics and therapy development | (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2) |
| Chromosome 1p deletion | Recurrent somatic copy-number loss | 19.3% in a cellular leiomyoma series | Copy-number loss likely alters dosage of tumor-relevant genes on 1p; appears mutually exclusive with some other driver classes in variant tumors | Particularly reported in cellular leiomyoma; useful in variant classification and differential pathology | (dundr2022uterinecellularleiomyomas pages 1-2) |
| 24 GWAS risk loci / heritable susceptibility variants (multiple genes including GREB1, MCM8 and broader target-gene sets) | Germline susceptibility SNPs / risk loci from population genetics | 24 uterine-fibroid–associated risk loci identified in a 2024 integrative analysis; 394 potential target genes, 168 differentially expressed in tumors | Heritable risk variants map largely to noncoding regulatory regions and influence gene regulation through chromatin contacts, eQTL effects, and cell-type–specific regulatory programs | Explains familial aggregation and racial/population risk differences; points to causal cell types and potential preventive/targeted strategies rather than a single monogenic cause | (buyukcelebi2024integratingleiomyomagenetics pages 1-2) |
| Non-coding RNA dysregulation linked to driver status (e.g., miR-21, miR-29, miR-200; H19, MIAT, XIST) | Secondary molecular alterations influenced by driver mutations, race/ethnicity, and hormones rather than classic coding mutations | Commonly dysregulated across fibroids; not a single frequency estimate | Regulates ECM production, proliferation, apoptosis, and inflammation; expression is influenced by MED12 mutation status and ovarian steroids | Potential biomarker and non-hormonal therapeutic layer; may help explain phenotypic heterogeneity and racial disparities | (boos2025therolesof pages 1-2) |
Table: This table summarizes the principal genetic and molecular alterations implicated in uterine leiomyoma, emphasizing recurrent somatic drivers, inherited susceptibility loci, and their clinical relevance. It is useful for quickly comparing major subtypes, frequencies, and mechanistic consequences across the current evidence base.
MED12 (Mediator Complex Subunit 12): - OMIM/HGNC: MED12 gene located on chromosome Xq13.1 - Variant Type: Somatic exon 2 point mutations (typically codon 44 region); gain-of-function, driver mutations - Frequency: 50–80% of fibroids (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2, ishikawa2023risingstarsrole pages 1-3, boos2025therolesof pages 1-2) - Functional Consequences: Disrupts CDK8/CDK19 kinase module activity; impairs Mediator kinase function; dysregulates WNT/β-catenin, TGF-β, hedgehog, and sex steroid signaling; alters chromatin landscape and enhancer-promoter interactions; increases genomic instability; enhances progesterone responsiveness (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2, ishikawa2023risingstarsrole pages 1-3) - Clinical Associations: More frequent in Black women; commonly observed in small tumors; associated with multiple rather than solitary fibroids; mutation-dependent response to GnRH agonists and ulipristal acetate (ishikawa2023risingstarsrole pages 1-3)
HMGA2/HMGA1 (High Mobility Group AT-hook 2/1): - Variant Type: Somatic chromosomal rearrangements, fusions, and overexpression - Frequency: ~10% overall; higher in cellular leiomyoma variants (bulun2025uterinefibroids pages 1-5, dundr2022uterinecellularleiomyomas pages 1-2) - Functional Consequences: Alters chromatin architecture and transcriptional programs; defines distinct molecular subtype - Clinical Associations: Distinct histopathologic phenotype; enriched in cellular leiomyoma (dundr2022uterinecellularleiomyomas pages 1-2)
FH (Fumarate Hydratase): - Variant Type: Somatic or germline loss-of-function mutations - Functional Consequences: Metabolic reprogramming; distinct molecular subtype - Clinical Associations: FH-deficient leiomyomas; hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2)
COL4A5/COL4A6 (Collagen Type IV Alpha 5/6): - Variant Type: Somatic deletions and structural alterations - Functional Consequences: Altered basement membrane/ECM biology (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2)
SRCAP Complex Genes (YEATS4, ZNHIT1): - Variant Type: Inactivating somatic mutations - Functional Consequences: Defective H2A.Z histone variant loading; chromatin remodeling abnormalities; epigenetic dysregulation (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2)
Chromosome 1p Deletion: - Variant Type: Recurrent somatic copy-number loss - Frequency: 19.3% in cellular leiomyoma series (dundr2022uterinecellularleiomyomas pages 1-2)
The 24 GWAS-identified risk loci implicate 394 candidate genes, of which 168 are differentially expressed in tumors (buyukcelebi2024integratingleiomyomagenetics pages 1-2). These likely represent modifier loci influencing susceptibility, tumor multiplicity, and phenotypic variability.
DNA Methylation: MED12-mutant fibroids exhibit distinct DNA methylomes compared to wild-type tumors (ishikawa2023risingstarsrole pages 1-3). Aberrant DNA methylation patterns contribute to altered gene expression profiles regulating ECM organization, cell proliferation, and steroid hormone responsiveness (chuang2023differentialexpressionof pages 1-2, ishikawa2023risingstarsrole pages 1-3).
Histone Modifications: SRCAP complex mutations result in deficient H2A.Z deposition, causing chromatin-based pathogenesis distinct from MED12/HMGA2 subtypes (bulun2025uterinefibroids pages 1-5). Alterations in histone modifications affect enhancer-promoter interactions and gene regulatory programs (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2).
Non-Coding RNAs: Dysregulated miRNAs (miR-21, miR-29, miR-200), lncRNAs (H19, MIAT, XIST), and circRNAs act as epigenetic regulators controlling ECM production, cell proliferation, apoptosis, and inflammation (boos2025therolesof pages 1-2). Expression is influenced by MED12 mutation status, race/ethnicity, and ovarian steroids (boos2025therolesof pages 1-2).
Somatic mutations (MED12, HMGA2, FH) are tumor-specific and not present in germline DNA (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2, ishikawa2023risingstarsrole pages 1-3). Allele frequencies in population databases for germline GWAS risk variants vary by locus and population ancestry (buyukcelebi2024integratingleiomyomagenetics pages 1-2). FH germline mutations in HLRCC syndrome represent an exception where inherited pathogenic variants predispose to multiple fibroids and renal cell carcinoma (bulun2025uterinefibroids pages 1-5).
Sexually transmitted infections are reported as potential risk factors, though the mechanism is less well-defined than hormonal/metabolic factors (koltsova2023aviewon pages 1-2).
WNT/β-Catenin Signaling: Progesterone stimulates secretion of WNT ligands from mature myometrial and leiomyoma cells, inducing nuclear translocation of β-catenin in fibroid stem cells, promoting proliferation and ECM accumulation (larrain2024newinsightsinto pages 1-3). MED12 mutations enhance WNT/β-catenin pathway activation (ishikawa2023risingstarsrole pages 1-3, larrain2024newinsightsinto pages 1-3).
TGF-β Signaling: Dysregulated TGF-β signaling promotes ECM production (particularly fibronectin and collagen), cell proliferation, and fibrosis (chuang2023differentialexpressionof pages 1-2, larrain2024newinsightsinto pages 1-3). TGF-β3 is upregulated via WNT signaling (larrain2024newinsightsinto pages 1-3).
Progesterone and Estrogen Signaling: Progesterone (via PGR) is essential for fibroid growth, acting through paracrine mechanisms on stem cells (bulun2025uterinefibroids pages 1-5, larrain2024newinsightsinto pages 1-3). Estrogen enables progesterone action (bulun2025uterinefibroids pages 1-5). DNA methylation regulates PGR expression and responsiveness (bulun2025uterinefibroids pages 1-5).
Hedgehog Pathway: Dysregulated in MED12-mutant fibroids (chuang2023differentialexpressionof pages 1-2).
AKT/PI3K and Oxidative Stress: AKT activation and oxidative stress pathways contribute to fibroid pathogenesis (bulun2025uterinefibroids pages 1-5).
Gene Ontology (GO) Terms: - GO:0030198 (extracellular matrix organization) - GO:0008283 (cell proliferation) - GO:0006915 (apoptotic process) - GO:0006954 (inflammatory response) - GO:0007049 (cell cycle)
MED12 Protein: Mutant MED12 disrupts CDK8/CDK19 stimulatory activity and alters chromatin-associated transcriptional regulation (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2, ishikawa2023risingstarsrole pages 1-3).
HMGA2 Protein: Overexpressed HMGA2 alters chromatin structure and transcriptional programs (bulun2025uterinefibroids pages 1-5).
Fumarate Hydratase (FH): Loss of FH activity causes metabolic reprogramming (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2).
FH-deficient leiomyomas exhibit rewired metabolism due to fumarate hydratase loss (bulun2025uterinefibroids pages 1-5). Oxidative stress and altered energy metabolism are implicated in pathogenesis (bulun2025uterinefibroids pages 1-5).
Chronic inflammation with upregulation of pro-inflammatory cytokines (TNF-α, IL-6, IFN-γ) is a hallmark of fibroid pathogenesis (boos2025therolesof pages 1-2). Inflammatory pathways drive DNA damage and epigenetic changes, promoting tumorigenesis (boos2025therolesof pages 1-2).
Transcriptomics: MED12-mutant tumors show 394 genes differentially expressed compared to matched myometrium, predominantly involved in ECM regulation (chuang2023differentialexpressionof pages 1-2). Distinct transcriptomic profiles differentiate MED12-mutant from wild-type fibroids (chuang2023differentialexpressionof pages 1-2, ishikawa2023risingstarsrole pages 1-3).
Epigenomics: Distinct DNA methylomes and histone modification patterns characterize molecular subtypes (bulun2025uterinefibroids pages 1-5, ishikawa2023risingstarsrole pages 1-3).
Single-Cell Transcriptomics: Integrative single-cell analysis reveals causal cell types with aberrant target gene expression linked to GWAS risk loci (buyukcelebi2024integratingleiomyomagenetics pages 1-2).
Cell Types Involved: - Myometrial smooth muscle stem cells (tumor-initiating cells) - Differentiated smooth muscle cells - Tumor-associated fibroblasts - Vascular smooth muscle cells - Myofibroblasts
Cell Ontology (CL) Terms: - CL:0000192 (smooth muscle cell) - CL:0000057 (fibroblast) - CL:0002548 (fibroblast of the uterus)
Primary Organ: - Uterus (specifically myometrium) (UBERON:0000995 uterus)
Secondary Organ Involvement: - Endometrium (affected by submucosal fibroids causing bleeding) (UBERON:0001295 endometrium) - Bladder (pressure symptoms) (UBERON:0001255 urinary bladder) - Rectum (constipation) (UBERON:0001052 rectum) - Reproductive tract complications (fallopian tube compression, cervical distortion)
Body Systems Involved: - Female reproductive system - Urinary system (secondary bulk effects) - Gastrointestinal system (secondary bulk effects) - Hematologic system (anemia from bleeding)
Tissue Types: - Smooth muscle tissue (myometrium) - Connective tissue (excessive ECM)
Cell Populations: - Myometrial smooth muscle stem cells (CL:0000192) - Differentiated smooth muscle cells (CL:0000192) - Fibroblasts (CL:0000057, CL:0002548) - Vascular smooth muscle cells - Myofibroblasts - Telocytes (interstitial cells forming contacts with smooth muscle and stem cells) (koltsova2023aviewon pages 1-2)
Cellular Compartments: - Nucleus (transcriptional dysregulation, chromatin remodeling) (GO:0005634 nucleus) - Cytoplasm (signaling pathway activation) - Extracellular matrix (excessive deposition) (GO:0031012 extracellular matrix) - Chromatin (altered landscape in MED12-mutant tumors) (GO:0000785 chromatin)
FIGO Classification by Anatomical Site: - Type 0: Pedunculated intracavitary - Type 1: <50% intramural - Type 2: ≥50% intramural - Type 3: 100% intramural; contacts endometrium - Type 4: Intramural - Type 5: Subserosal ≥50% intramural - Type 6: Subserosal <50% intramural - Type 7: Subserosal pedunculated - Type 8: Other (cervical, parasitic) - Hybrid: Submucous and subserous (micic2024currentlyavailabletreatment pages 1-2)
Lateralization: Typically bilateral distribution within the uterus, though individual fibroids can be unilateral or asymmetric (alali2023theetiopathogenesisof pages 1-2).
Age of Onset: - Rarely develop before menarche (ishikawa2023risingstarsrole pages 1-3) - Most commonly diagnosed in reproductive age women, especially 35–50 years (koltsova2023aviewon pages 1-2, tang2025theglobalburden pages 1-2, micic2024currentlyavailabletreatment pages 1-2) - Prevalence increases with age through reproductive years
Onset Pattern: - Insidious and gradual; often asymptomatic initially (alali2023theetiopathogenesisof pages 1-2, centini2024tailoringthediagnostic pages 1-2)
Disease Course: - Variable growth rates; some fibroids grow rapidly, others remain stable or regress (larrain2024newinsightsinto pages 1-3) - Multiple tumors within the same uterus are not clonally related and grow independently (larrain2024newinsightsinto pages 1-3) - Progression influenced by hormonal milieu, mutation status, and patient-specific factors
Disease Duration: - Chronic, lifelong presence through reproductive years - Often regress after menopause due to decreased ovarian steroid production (alali2023theetiopathogenesisof pages 1-2, ishikawa2023risingstarsrole pages 1-3)
Remission: - Spontaneous regression common after menopause (alali2023theetiopathogenesisof pages 1-2, ishikawa2023risingstarsrole pages 1-3) - Treatment-induced shrinkage with GnRH agonists/antagonists, but rebound growth after discontinuation (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5)
Critical Periods: - Reproductive years with ovulatory cycles (high estrogen/progesterone exposure) - Pregnancy (first trimester growth stimulus) (bulun2025uterinefibroids pages 1-5) - Menopause (regression window)
Prevalence: - Lifetime prevalence: 30–70% (alali2023theetiopathogenesisof pages 1-2, koltsova2023aviewon pages 1-2) - By age 50: >70% overall, >80% in Black women (buyukcelebi2024integratingleiomyomagenetics pages 1-2, centini2024tailoringthediagnostic pages 1-2) - In 2021, age-standardized prevalence rate (ASPR): 2,841.07 per 100,000 (tang2025theglobalburden pages 1-2)
Incidence: - Age-standardized incidence rate (ASIR) in 2021: 250.93 per 100,000 (tang2025theglobalburden pages 1-2) - Incidence increasing globally from 1990 to 2021 (tang2025theglobalburden pages 1-2, zhang2025globalregionaland pages 1-2)
Inheritance Pattern: - Multifactorial and polygenic susceptibility for sporadic fibroids (buyukcelebi2024integratingleiomyomagenetics pages 1-2) - Autosomal dominant for HLRCC syndrome (germline FH mutations) (bulun2025uterinefibroids pages 1-5)
Penetrance: - Variable and incomplete for heritable susceptibility loci (buyukcelebi2024integratingleiomyomagenetics pages 1-2) - High penetrance for HLRCC-related fibroids (bulun2025uterinefibroids pages 1-5)
Expressivity: - Variable; influenced by hormonal exposure, lifestyle, and modifier genes (buyukcelebi2024integratingleiomyomagenetics pages 1-2)
Family History: - First-degree relatives have 2.5-fold elevated risk (buyukcelebi2024integratingleiomyomagenetics pages 1-2)
Affected Populations: - Black/African-American women: highest prevalence and severity (>80% by age 50) (buyukcelebi2024integratingleiomyomagenetics pages 1-2, centini2024tailoringthediagnostic pages 1-2, boos2025therolesof pages 1-2) - Latin American women: elevated risk (koltsova2023aviewon pages 1-2) - All racial/ethnic groups affected, but significant disparities exist
Geographic Distribution: - Global distribution with higher burden in higher SDI (Socio-Demographic Index) regions for uterine fibroids, though lower SDI regions have higher burden for some gynecologic conditions (tang2025theglobalburden pages 1-2) - Increasing incidence in countries like Brazil, India, and Georgia (zhang2025globalregionaland pages 1-2)
Sex Ratio: - Female-only disease
Age Distribution: - Peak ages 40–69 years globally for symptomatic burden (tang2025theglobalburden pages 1-2) - Most commonly diagnosed 35–50 years (koltsova2023aviewon pages 1-2, micic2024currentlyavailabletreatment pages 1-2)
Laboratory Tests: - Complete blood count (CBC) to assess anemia from HMB (vannuccini2024themodernmanagement pages 1-5) - Iron studies (ferritin, serum iron, TIBC) for iron deficiency evaluation (vannuccini2024themodernmanagement pages 1-5) - Hormone levels (estradiol, progesterone) if clinically indicated (buyukcelebi2024integratingleiomyomagenetics pages 1-2)
Biomarkers: - No widely established serum biomarkers for routine diagnosis - Emerging multi-omics biomarkers under investigation (vannuccini2024themodernmanagement pages 1-5)
Imaging Studies: - Transvaginal Ultrasound (TVS): First-line imaging; detects presence, size, number, and location of fibroids (centini2024tailoringthediagnostic pages 1-2) - Sonohysterography: Enhanced visualization of intracavitary lesions (centini2024tailoringthediagnostic pages 1-2) - Magnetic Resonance Imaging (MRI): Gold standard for detailed anatomical characterization, differential diagnosis, and treatment planning; particularly useful for HIFU treatment planning and predicting regrowth (centini2024tailoringthediagnostic pages 1-2, vannuccini2024themodernmanagement pages 1-5) - Contrast-Enhanced MRI (CE-MRI): Predicts residual fibroid regrowth post-HIFU; signal intensity ratios on CE-MRI correlate with long-term re-intervention rates (vannuccini2024themodernmanagement pages 1-5)
MRI Radiomics: AI-based radiomics models combining T2-weighted MRI features with clinical parameters predict HIFU ablation efficacy and non-perfusion volume ratio (NPVR) (vannuccini2024themodernmanagement pages 1-5).
Artificial Intelligence and Machine Learning: Deep learning models improve fibroid segmentation, diagnosis, and differentiation from malignancy using ultrasound and MRI images (vannuccini2024themodernmanagement pages 1-5).
Functional Tests: Not routinely applicable
Biopsy and Pathology: - Histopathological examination after surgical removal confirms diagnosis - Immunohistochemistry: High expression of smooth muscle markers (calponin, desmin, SMA, caldesmon, transgelin, SMMHC, smoothelin); co-expression of endometrial stromal markers (CD10, IFITM1) in some variants (dundr2022uterinecellularleiomyomas pages 1-2) - Molecular classification by mutation status (MED12, HMGA2, FH) increasingly relevant (ishikawa2023risingstarsrole pages 1-3, dundr2022uterinecellularleiomyomas pages 1-2)
Overview: Genetic testing is not routinely performed for sporadic fibroids but may be indicated in specific clinical scenarios.
Single Gene Testing: - FH gene testing for suspected HLRCC syndrome (family history of renal cell carcinoma, early-onset multiple fibroids) (bulun2025uterinefibroids pages 1-5)
Gene Panels: Not standard for uterine fibroids
Chromosomal Microarray: Not routinely indicated
Whole Exome/Genome Sequencing: Research tool; not routine clinical practice
Somatic Mutation Testing: - MED12 mutation testing on tumor tissue can inform prognosis and potential treatment response (e.g., GnRH agonist/antagonist or ulipristal acetate response) (ishikawa2023risingstarsrole pages 1-3) - HMGA2, FH, COL4A5/6, SRCAP complex mutations for molecular subtyping in research or specialized clinical settings (bulun2025uterinefibroids pages 1-5, dundr2022uterinecellularleiomyomas pages 1-2)
Diagnostic Pathway: - Clinical suspicion based on symptoms (AUB, pelvic pain, bulk symptoms) - Pelvic examination - Transvaginal ultrasound (first-line imaging) (centini2024tailoringthediagnostic pages 1-2) - Diagnostic hysteroscopy for intrauterine assessment if needed (centini2024tailoringthediagnostic pages 1-2) - MRI when necessary for detailed characterization and treatment planning (centini2024tailoringthediagnostic pages 1-2)
Differential Diagnosis: - Adenomyosis (can coexist) - Endometrial stromal tumors (ESN, LG-ESS): differentiated by immunohistochemistry (IFITM1, CD10 patterns) and molecular testing (dundr2022uterinecellularleiomyomas pages 1-2) - Leiomyosarcoma (LMS): requires histopathology; molecular profiling may assist (dundr2022uterinecellularleiomyomas pages 1-2) - Smooth tumors of unknown malignant potential (STUMPs) (centini2024tailoringthediagnostic pages 1-2)
Uterine leiomyomas are benign tumors with very low risk of malignant transformation to leiomyosarcoma (bulun2025uterinefibroids pages 1-5). They are not typically associated with mortality unless severe anemia or surgical complications occur. Life expectancy is not significantly impacted by fibroids alone.
Morbidity: - Significant morbidity from HMB, anemia, chronic pain, bulk symptoms, and reproductive dysfunction (alali2023theetiopathogenesisof pages 1-2, buyukcelebi2024integratingleiomyomagenetics pages 1-2, vannuccini2024themodernmanagement pages 1-5) - Heavy menstrual bleeding is a leading cause of iron deficiency anemia in reproductive-age women (vannuccini2024themodernmanagement pages 1-5)
Quality of Life: - Reduced quality of life in ~25–30% of affected women (bulun2025uterinefibroids pages 1-5, ishikawa2023risingstarsrole pages 1-3, vannuccini2024themodernmanagement pages 1-5) - Decreased labor productivity (ishikawa2023risingstarsrole pages 1-3) - Impaired physical, social, emotional, and material well-being (vannuccini2024themodernmanagement pages 1-5)
Complications: - Iron deficiency anemia (vannuccini2024themodernmanagement pages 1-5) - Infertility, recurrent pregnancy loss, preterm labor (alali2023theetiopathogenesisof pages 1-2, buyukcelebi2024integratingleiomyomagenetics pages 1-2, centini2024tailoringthediagnostic pages 1-2) - Urinary incontinence, constipation (alali2023theetiopathogenesisof pages 1-2) - Post-surgical complications (adhesions, bleeding, infection) - Recurrence after myomectomy (micic2024currentlyavailabletreatment pages 1-2)
Recovery Potential: - Fibroids often regress spontaneously after menopause (alali2023theetiopathogenesisof pages 1-2, ishikawa2023risingstarsrole pages 1-3) - Surgical removal (myomectomy, hysterectomy) provides definitive symptom relief (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) - Medical treatments provide temporary symptom control but not cure; rebound growth after discontinuation (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5)
A comprehensive treatment options table is provided below.
| Treatment Category | Specific Treatment Options | Mechanism of Action | Indications / Patient Selection | Clinical Efficacy | Side Effects / Limitations | MAXO term suggestion |
|---|---|---|---|---|---|---|
| Non-hormonal medical therapy | Tranexamic acid | Antifibrinolytic; reduces menstrual blood loss by inhibiting plasminogen activation | Symptomatic heavy menstrual bleeding (HMB) when uterine preservation desired; useful as symptom-control therapy rather than tumor-directed treatment (vannuccini2024themodernmanagement pages 1-5) | Improves fibroid-related abnormal uterine bleeding/heavy menstrual bleeding; does not shrink fibroids (vannuccini2024themodernmanagement pages 1-5) | No effect on fibroid size; symptomatic only; thrombotic-risk considerations in selected patients (vannuccini2024themodernmanagement pages 1-5) | MAXO: antifibrinolytic therapy |
| Non-hormonal medical therapy | NSAIDs | Reduce prostaglandin-mediated bleeding and pain | Mild-to-moderate bleeding and dysmenorrhea; patients seeking short-term symptom relief (vannuccini2024themodernmanagement pages 1-5) | Can reduce pain and some bleeding symptoms, but generally less effective than targeted hormonal suppression for fibroid burden (vannuccini2024themodernmanagement pages 1-5) | Symptomatic only; gastrointestinal/renal adverse effects; no fibroid shrinkage (vannuccini2024themodernmanagement pages 1-5) | MAXO: nonsteroidal anti-inflammatory drug therapy |
| Hormonal medical therapy | Combined oral contraceptives | Suppress ovulation/endometrial proliferation; reduce menstrual bleeding | Women with bleeding symptoms who desire non-surgical management and contraception (centini2024tailoringthediagnostic pages 1-2, micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Helpful for bleeding control; primarily symptom management rather than definitive fibroid treatment (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Limited effect on fibroid size; estrogen-containing therapy may not suit all patients (vannuccini2024themodernmanagement pages 1-5) | MAXO: hormonal therapy |
| Hormonal medical therapy | Progestogens | Endometrial suppression and bleeding control | Selected patients with abnormal uterine bleeding; often short-term or individualized use (micic2024currentlyavailabletreatment pages 1-2) | May improve bleeding; evidence for fibroid shrinkage is limited (micic2024currentlyavailabletreatment pages 1-2) | Restricted efficacy for bulk symptoms/size reduction; hormone-related adverse effects (micic2024currentlyavailabletreatment pages 1-2) | MAXO: progestogen therapy |
| Hormonal medical therapy | Levonorgestrel intrauterine system (LNG-IUS) | Local progestin effect on endometrium, reducing bleeding | Bleeding-predominant symptoms, especially when uterine cavity distortion is not prohibitive (vannuccini2024themodernmanagement pages 1-5) | Effective for HMB control in selected women; not a fibroid-eliminating therapy (vannuccini2024themodernmanagement pages 1-5) | Expulsion/placement difficulty with cavity distortion; limited effect on bulk symptoms or tumor size (vannuccini2024themodernmanagement pages 1-5) | MAXO: intrauterine hormone delivery |
| Hormonal medical therapy | GnRH agonists | Initial pituitary stimulation followed by downregulation, causing hypoestrogenism/hypoprogesteronism | Preoperative bridge therapy, short-term bleeding control, temporary fibroid shrinkage, anemia optimization before surgery (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Well-established temporary reduction in bleeding and fibroid size; useful as bridge to surgery (bulun2025uterinefibroids pages 1-5, micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Menopausal symptoms, bone loss with prolonged use, rebound growth after discontinuation (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | MAXO: gonadotropin-releasing hormone agonist therapy |
| Hormonal medical therapy | Oral GnRH antagonists | Direct pituitary GnRH blockade suppressing ovarian steroid production | Symptomatic fibroids with HMB; uterus-sparing medical management; useful when a reversible oral option is preferred (vannuccini2024themodernmanagement pages 1-5) | Effective modern option for reducing bleeding and improving symptoms; part of contemporary conservative management (vannuccini2024themodernmanagement pages 1-5) | Hypoestrogenic adverse effects; may require add-back strategies; treatment effect is not curative (vannuccini2024themodernmanagement pages 1-5) | MAXO: gonadotropin-releasing hormone antagonist therapy |
| Hormonal medical therapy | Selective progesterone receptor modulators (SPRMs), e.g. ulipristal acetate | Modulate progesterone receptor signaling, reducing bleeding and fibroid growth | Historically used for intermittent long-term bleeding and size control in selected women (micic2024currentlyavailabletreatment pages 1-2, ishikawa2023risingstarsrole pages 1-3, vannuccini2024themodernmanagement pages 1-5) | Good results reported for bleeding control and fibroid size reduction; response may vary with MED12 status (micic2024currentlyavailabletreatment pages 1-2, ishikawa2023risingstarsrole pages 1-3) | Regulatory/safety limitations in many regions, including liver toxicity concerns; access restricted (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | MAXO: selective progesterone receptor modulator therapy |
| Hormonal medical therapy | Aromatase inhibitors | Lower local/systemic estrogen synthesis | Selected refractory cases or off-label individualized management (vannuccini2024themodernmanagement pages 1-5) | May improve symptoms in some patients; evidence base narrower than GnRH-based approaches (vannuccini2024themodernmanagement pages 1-5) | Hypoestrogenic effects; not standard first-line treatment (vannuccini2024themodernmanagement pages 1-5) | MAXO: aromatase inhibitor therapy |
| Surgical therapy | Myomectomy (hysteroscopic, laparoscopic, open/laparotomic, mini-laparotomic, robotic) | Physical removal of fibroids with uterine preservation | Symptomatic patients desiring fertility preservation or uterine conservation; approach depends on number, size, and location of myomas (micic2024currentlyavailabletreatment pages 1-2, centini2024tailoringthediagnostic pages 1-2) | Effective symptom relief while preserving uterus; review data showed comparable average pregnancy rates between minimally invasive and open approaches (~29.7% vs ~28.5%) (micic2024currentlyavailabletreatment pages 1-2) | Recurrence risk persists; operative bleeding/adhesions; more invasive than medical/radiologic options (micic2024currentlyavailabletreatment pages 1-2) | MAXO: myomectomy |
| Surgical therapy | Hysterectomy | Definitive removal of uterus, eliminating fibroids | Women with severe symptoms, no fertility desire, recurrent disease, or failure of conservative options; often considered definitive therapy (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Most definitive symptom control; fibroid recurrence eliminated because uterus removed (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Loss of fertility; surgical morbidity; longer recovery than some minimally invasive approaches (micic2024currentlyavailabletreatment pages 1-2) | MAXO: hysterectomy |
| Minimally invasive / interventional | Uterine artery embolization (UAE) / uterine artery occlusion | Devascularization leading to ischemic shrinkage of fibroids | Symptomatic women seeking uterus-sparing, non-excisional treatment; generally not first choice when future fertility is a major goal (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Improves bleeding and bulk symptoms in many patients; accepted radiologic option in modern care pathways (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Post-embolization pain, reintervention/recurrence risk, uncertain reproductive implications relative to myomectomy (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | MAXO: uterine artery embolization |
| Minimally invasive / interventional | High-intensity focused ultrasound (HIFU) / MR-guided focused ultrasound | Thermal ablation of fibroid tissue | Selected women with accessible fibroid anatomy seeking noninvasive uterus-sparing treatment (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Can reduce symptoms and fibroid volume; post-treatment MRI parameters can predict regrowth/reintervention risk (vannuccini2024themodernmanagement pages 1-5) | Not suitable for all fibroid locations/sizes; residual fibroid regrowth can occur; access/expertise dependent (vannuccini2024themodernmanagement pages 1-5) | MAXO: focused ultrasound ablation |
| Minimally invasive / interventional | Radiofrequency ablation / myolysis | Thermal destruction of fibroid tissue | Symptomatic fibroids in patients preferring minimally invasive, uterus-preserving treatment (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Effective symptom-directed minimally invasive option in selected patients (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Long-term recurrence and fertility data less extensive than for myomectomy; anatomy-dependent feasibility (micic2024currentlyavailabletreatment pages 1-2) | MAXO: radiofrequency ablation |
| Minimally invasive / interventional | Endometrial ablation | Destruction of endometrium to reduce bleeding | Bleeding-predominant symptoms in carefully selected women not seeking fertility; not a tumor-directed therapy (micic2024currentlyavailabletreatment pages 1-2) | May reduce bleeding symptoms but does not treat intramural/subserosal tumor burden (micic2024currentlyavailabletreatment pages 1-2) | Not appropriate for future fertility; limited if cavity distortion is substantial (micic2024currentlyavailabletreatment pages 1-2) | MAXO: endometrial ablation |
| Supportive care | Iron replacement therapy | Repletes iron stores in iron deficiency/iron deficiency anemia from chronic bleeding | Women with fibroid-related HMB, iron deficiency, or anemia before/after surgery and during medical management (vannuccini2024themodernmanagement pages 1-5) | Improves consequences of chronic blood loss and perioperative readiness; important adjunct rather than fibroid-directed therapy (vannuccini2024themodernmanagement pages 1-5) | Does not treat underlying fibroids; oral GI intolerance or IV infusion logistics may limit use (vannuccini2024themodernmanagement pages 1-5) | MAXO: iron supplementation |
| Experimental / emerging | Vitamin D | Proposed antiproliferative/anti-fibrotic effects; deficiency is a reported risk factor | Investigational or adjunctive setting; biologic rationale strengthened by epidemiologic association with deficiency (micic2024currentlyavailabletreatment pages 1-2, wu2026preclinicalresearchplatform pages 1-2) | Promising preclinical and prior xenograft evidence noted in model reviews, but not established standard clinical therapy (wu2026preclinicalresearchplatform pages 1-2) | Insufficient evidence for routine standalone treatment of symptomatic leiomyoma (wu2026preclinicalresearchplatform pages 1-2) | MAXO: vitamin supplementation |
| Experimental / emerging | Targeted/precision approaches linked to molecular subtype (e.g., MED12-informed response prediction) | Treatment selection based on tumor driver biology and pathway dependence | Future personalized management, particularly for mutation-stratified hormonal response (ishikawa2023risingstarsrole pages 1-3) | Emerging evidence suggests MED12 status may influence response to GnRH agonists and ulipristal acetate (ishikawa2023risingstarsrole pages 1-3) | Not yet routine clinical standard; requires broader validation and accessible molecular testing (ishikawa2023risingstarsrole pages 1-3) | MAXO: precision medicine intervention |
| Experimental / emerging | Novel agents under investigation | Various pathways including progesterone signaling, ECM remodeling, and other molecular targets | Patients with unmet need for fertility-preserving, long-term, non-surgical options (micic2024currentlyavailabletreatment pages 1-2, bulun2025uterinefibroids pages 1-5) | Reviews describe multiple promising investigational therapies, but few are yet approved specifically for fibroids (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Evidence still evolving; many therapies remain investigational or regionally unavailable (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | MAXO: investigational pharmacotherapy |
Table: This table summarizes current and emerging treatment options for uterine leiomyoma, including mechanisms, appropriate patient selection, expected efficacy, limitations, and suggested MAXO-aligned intervention labels. It is useful for comparing conservative, surgical, and interventional management strategies in one view.
Non-Hormonal: - Tranexamic acid (antifibrinolytic for HMB) (vannuccini2024themodernmanagement pages 1-5) [MAXO: antifibrinolytic therapy] - NSAIDs (symptom control for pain and bleeding) (vannuccini2024themodernmanagement pages 1-5) [MAXO: nonsteroidal anti-inflammatory drug therapy]
Hormonal: - Combined oral contraceptives (centini2024tailoringthediagnostic pages 1-2, micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) [MAXO: hormonal therapy] - Progestogens (micic2024currentlyavailabletreatment pages 1-2) [MAXO: progestogen therapy] - Levonorgestrel intrauterine system (LNG-IUS) (vannuccini2024themodernmanagement pages 1-5) [MAXO: intrauterine hormone delivery] - GnRH agonists (preoperative bridge, temporary shrinkage) (bulun2025uterinefibroids pages 1-5, micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) [MAXO: gonadotropin-releasing hormone agonist therapy] - Oral GnRH antagonists (modern option for symptom and size control) (vannuccini2024themodernmanagement pages 1-5) [MAXO: gonadotropin-releasing hormone antagonist therapy] - Selective progesterone receptor modulators (SPRMs, e.g., ulipristal acetate): historically effective but limited by safety concerns (micic2024currentlyavailabletreatment pages 1-2, ishikawa2023risingstarsrole pages 1-3, vannuccini2024themodernmanagement pages 1-5) [MAXO: selective progesterone receptor modulator therapy] - Aromatase inhibitors (off-label) (vannuccini2024themodernmanagement pages 1-5) [MAXO: aromatase inhibitor therapy]
Pharmacogenomics: MED12 mutation status influences response to GnRH agonists and ulipristal acetate, suggesting potential for mutation-guided therapy (ishikawa2023risingstarsrole pages 1-3).
Experimental: - Vitamin D supplementation (promising preclinical/xenograft evidence but not standard therapy) (micic2024currentlyavailabletreatment pages 1-2, wu2026preclinicalresearchplatform pages 1-2) - Catechol-O-methyltransferase inhibitors (evaluated in Eker rat models) (wu2026preclinicalresearchplatform pages 1-2) - Hedgehog pathway inhibitors (GLI inhibitors like Gant61 show efficacy in xenograft models) (wu2026preclinicalresearchplatform pages 1-2) - Novel targeted therapies based on molecular subtype (under investigation) (bulun2025uterinefibroids pages 1-5, micic2024currentlyavailabletreatment pages 1-2, ishikawa2023risingstarsrole pages 1-3)
Surgical: - Myomectomy (hysteroscopic, laparoscopic, open, robotic): Fertility-preserving fibroid removal (micic2024currentlyavailabletreatment pages 1-2) [MAXO: myomectomy] - Hysterectomy: Definitive treatment, loss of fertility (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) [MAXO: hysterectomy]
Minimally Invasive/Interventional: - Uterine artery embolization (UAE): Devascularization (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) [MAXO: uterine artery embolization] - High-intensity focused ultrasound (HIFU): Thermal ablation (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) [MAXO: focused ultrasound ablation] - Radiofrequency ablation: Thermal destruction (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) [MAXO: radiofrequency ablation] - Endometrial ablation: For bleeding control (micic2024currentlyavailabletreatment pages 1-2) [MAXO: endometrial ablation]
Response Rates: - GnRH agonists/antagonists: Effective temporary shrinkage and symptom control; rebound after discontinuation (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) - Myomectomy: Effective symptom relief; pregnancy rates comparable between minimally invasive and open approaches (~29.7% vs ~28.5%) (micic2024currentlyavailabletreatment pages 1-2) - Hysterectomy: Most definitive; eliminates recurrence (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) - UAE and HIFU: Improve symptoms in many patients; reintervention rates variable (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5)
Side Effects: - GnRH agonists/antagonists: Menopausal symptoms, bone loss with prolonged use (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) - SPRMs: Liver toxicity concerns (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) - Surgical: Bleeding, adhesions, infection, longer recovery for open surgery (micic2024currentlyavailabletreatment pages 1-2)
Primary Prevention: - Lifestyle modifications: Maintain healthy body weight, adequate vitamin D, balanced diet (micic2024currentlyavailabletreatment pages 1-2, larrain2024newinsightsinto pages 1-3) - Avoid excessive alcohol consumption (koltsova2023aviewon pages 1-2, larrain2024newinsightsinto pages 1-3) - Reduce exposure to xenoestrogens and environmental pollutants (koltsova2023aviewon pages 1-2, larrain2024newinsightsinto pages 1-3) - Multiparity may be protective (koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2)
Secondary Prevention: - Early detection via routine pelvic exams and ultrasound in asymptomatic women at high risk (family history, Black ancestry) (buyukcelebi2024integratingleiomyomagenetics pages 1-2, centini2024tailoringthediagnostic pages 1-2) - Prompt treatment of symptomatic fibroids to prevent complications like anemia and reproductive dysfunction
Tertiary Prevention: - Medical management to prevent symptom progression and complications (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) - Iron supplementation to prevent anemia in women with HMB (vannuccini2024themodernmanagement pages 1-5)
Not applicable
Screening Programs: - No population-based screening recommended for asymptomatic women - Opportunistic detection during routine gynecological ultrasound
Genetic Screening: - Genetic counseling and FH gene testing for families with HLRCC syndrome (bulun2025uterinefibroids pages 1-5)
Risk Stratification: - Family history, race/ethnicity, reproductive history, and GWAS risk scores may identify high-risk individuals (buyukcelebi2024integratingleiomyomagenetics pages 1-2)
Genetic counseling for HLRCC syndrome families (bulun2025uterinefibroids pages 1-5)
NCBI Taxon IDs: - Rattus norvegicus: NCBITaxon:10116 - Sus scrofa: NCBITaxon:9823 - Coturnix japonica (Japanese quail): NCBITaxon:93934
Eker Rats: Approximately 65% of female Eker rats develop uterine smooth muscle tumors by 12–16 months of age due to germline Tsc2 mutation (wu2026preclinicalresearchplatform pages 1-2). Histomorphology and hormone-dependence are highly similar to human fibroids (wu2026preclinicalresearchplatform pages 1-2).
Japanese Quail and Miniature Pigs: Also exhibit spontaneous leiomyomas, though less extensively characterized (wu2026preclinicalresearchplatform pages 1-2).
Eker rat tumors recapitulate key features of human fibroids, including estrogen/progesterone-dependent growth, ECM-rich composition, and similar histology (wu2026preclinicalresearchplatform pages 1-2). However, Eker rats develop concurrent renal and hepatic tumors, complicating model interpretation (wu2026preclinicalresearchplatform pages 1-2).
Spontaneous Animal Models: - Eker Rats: Germline Tsc2 mutation; spontaneous tumor development by 12–16 months; widely used for etiology and drug validation studies (wu2026preclinicalresearchplatform pages 1-2) - Japanese Quail and Miniature Pigs: Spontaneous models, less commonly used (wu2026preclinicalresearchplatform pages 1-2)
Genetically Modified Animal Models: - Conditional MED12-mutant mouse model: Engineered MED12 exon 2 mutation in uterus; develops leiomyoma-like tumors; confirms MED12 gain-of-function role (bulun2025uterinefibroids pages 1-5, wu2026preclinicalresearchplatform pages 1-2)
Hormone-Induced Animal Models: - Combined estrogen-progesterone induction in mice/rats (wu2026preclinicalresearchplatform pages 1-2) - Sequential induction (estrogen followed by progesterone) mimics natural hormonal cycles (wu2026preclinicalresearchplatform pages 1-2) - Concurrent induction promotes hormone receptor expression (wu2026preclinicalresearchplatform pages 1-2) - Multi-factor composite models integrating chronic stress and epinephrine intervention to simulate "Qi Stagnation and Blood Stasis" syndrome in integrated medicine research (wu2026preclinicalresearchplatform pages 1-2)
Xenograft Animal Models: - Patient-derived xenografts (PDX) in immunodeficient mice (e.g., SCID, NSG mice) (wu2026preclinicalresearchplatform pages 1-2) - Maintain human fibroid architecture, hormone-responsiveness, and genetic background (wu2026preclinicalresearchplatform pages 1-2) - Useful for drug testing and mechanistic studies (wu2026preclinicalresearchplatform pages 1-2)
Organotypic/Ex Vivo Models: - Organotypic culture of fibroid tissue slices on alginate scaffolds; maintains morphological integrity, steroid receptor expression, and driver mutations for up to 7 days (wu2026preclinicalresearchplatform pages 1-2) - Allows encapsulation of drug-loaded microspheres for preclinical testing (wu2026preclinicalresearchplatform pages 1-2)
Phenotype Recapitulation: - Eker rats: High similarity in histology, ECM deposition, and hormone-dependence; useful for mTOR pathway studies (wu2026preclinicalresearchplatform pages 1-2) - MED12-mutant mice: Confirm gain-of-function mutation role and leiomyoma pathogenesis (bulun2025uterinefibroids pages 1-5, wu2026preclinicalresearchplatform pages 1-2) - Xenografts: Best preserve human tumor heterogeneity and genetic background (wu2026preclinicalresearchplatform pages 1-2)
Model Limitations: - Eker rats: Long establishment time (12–16 months), concurrent tumors (renal, hepatic), high cost (wu2026preclinicalresearchplatform pages 1-2) - Hormone-induced models: May not fully replicate spontaneous human disease complexity; reproducibility variable (wu2026preclinicalresearchplatform pages 1-2) - Xenografts: Require immunodeficient hosts; do not capture immune interactions (wu2026preclinicalresearchplatform pages 1-2)
| Gene Name / Alteration | Mutation Type | Frequency / Prevalence | Molecular Effects | Clinical Associations | Key References |
|---|---|---|---|---|---|
| MED12 | Recurrent somatic exon 2 point mutations; typically heterozygous, gain-of-function–like driver alterations disrupting Mediator kinase module signaling | ~50–80% of uterine fibroids; ~70% in several recent summaries; 77% in a large review | Disrupts MED12-dependent activation of CDK8/CDK19 within the Mediator complex; associated with altered chromatin landscape, enhancer engagement, genomic instability, progesterone responsiveness, and dysregulated WNT/β-catenin, hedgehog, sex steroid, and TGF-β signaling; transcriptomic enrichment for ECM/collagen pathways | Most common driver; often multiple tumors rather than solitary lesions; commonly seen even in small tumors; more frequent in Black women in some series; mutant tumors can differ in size/location and may show mutation-status–dependent response to GnRH agonists and ulipristal acetate | (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2, ishikawa2023risingstarsrole pages 1-3) |
| HMGA2 / HMGA1 | Somatic overexpression and chromosomal rearrangements/fusions involving HMGA2/1 | ~10% of fibroids in recent overview; in cellular leiomyoma, HMGA2 overexpression was 36.5% and rearrangement 13.2% | Alters chromatin architecture and transcriptional programs; defines a molecular subtype distinct from MED12-mutant tumors | Associated with distinct histopathologic phenotypes; important subtype in usual leiomyoma and especially enriched in some variants such as cellular leiomyoma | (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2, dundr2022uterinecellularleiomyomas pages 1-2) |
| FH | Somatic or germline-related loss-of-function / deficiency; part of FH-deficient leiomyoma spectrum and HLRCC-related disease | Less common than MED12/HMGA2 in unselected fibroids; recognized recurrent subtype | Fumarate hydratase deficiency rewires metabolism and contributes to a distinct molecular subtype of leiomyoma | Seen in FH-deficient leiomyomas and in hereditary leiomyomatosis and renal cell cancer (HLRCC); clinically relevant for identifying syndromic disease | (bulun2025uterinefibroids pages 1-5, chuang2023differentialexpressionof pages 1-2, boos2025therolesof pages 1-2) |
| COL4A5 / COL4A6 | Recurrent somatic deletions / structural alterations affecting collagen IV genes | Recurrent but uncommon relative to MED12; listed among frequently observed genetic alterations | Likely alters basement-membrane / ECM-related biology and contributes to subtype-specific tumor development | Included among recognized uterine fibroid driver alterations; may overlap with syndromic/structural subtypes rather than classic MED12 tumors | (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2, chuang2023differentialexpressionof pages 1-2) |
| SRCAP complex genes (e.g., YEATS4, ZNHIT1, other complex members) | Inactivating somatic mutations causing defective H2A.Z loading / chromatin remodeling abnormalities | Recently identified recurrent but uncommon subtype | Produces H2A.Z deposition defects and epigenetic dysregulation; supports a chromatin-based pathogenesis distinct from MED12 and HMGA2 | Emerging molecular class of leiomyoma; potentially useful for future subtype-based diagnostics and therapy development | (bulun2025uterinefibroids pages 1-5, buyukcelebi2024integratingleiomyomagenetics pages 1-2) |
| Chromosome 1p deletion | Recurrent somatic copy-number loss | 19.3% in a cellular leiomyoma series | Copy-number loss likely alters dosage of tumor-relevant genes on 1p; appears mutually exclusive with some other driver classes in variant tumors | Particularly reported in cellular leiomyoma; useful in variant classification and differential pathology | (dundr2022uterinecellularleiomyomas pages 1-2) |
| 24 GWAS risk loci / heritable susceptibility variants (multiple genes including GREB1, MCM8 and broader target-gene sets) | Germline susceptibility SNPs / risk loci from population genetics | 24 uterine-fibroid–associated risk loci identified in a 2024 integrative analysis; 394 potential target genes, 168 differentially expressed in tumors | Heritable risk variants map largely to noncoding regulatory regions and influence gene regulation through chromatin contacts, eQTL effects, and cell-type–specific regulatory programs | Explains familial aggregation and racial/population risk differences; points to causal cell types and potential preventive/targeted strategies rather than a single monogenic cause | (buyukcelebi2024integratingleiomyomagenetics pages 1-2) |
| Non-coding RNA dysregulation linked to driver status (e.g., miR-21, miR-29, miR-200; H19, MIAT, XIST) | Secondary molecular alterations influenced by driver mutations, race/ethnicity, and hormones rather than classic coding mutations | Commonly dysregulated across fibroids; not a single frequency estimate | Regulates ECM production, proliferation, apoptosis, and inflammation; expression is influenced by MED12 mutation status and ovarian steroids | Potential biomarker and non-hormonal therapeutic layer; may help explain phenotypic heterogeneity and racial disparities | (boos2025therolesof pages 1-2) |
Table: This table summarizes the principal genetic and molecular alterations implicated in uterine leiomyoma, emphasizing recurrent somatic drivers, inherited susceptibility loci, and their clinical relevance. It is useful for quickly comparing major subtypes, frequencies, and mechanistic consequences across the current evidence base.
| Treatment Category | Specific Treatment Options | Mechanism of Action | Indications / Patient Selection | Clinical Efficacy | Side Effects / Limitations | MAXO term suggestion |
|---|---|---|---|---|---|---|
| Non-hormonal medical therapy | Tranexamic acid | Antifibrinolytic; reduces menstrual blood loss by inhibiting plasminogen activation | Symptomatic heavy menstrual bleeding (HMB) when uterine preservation desired; useful as symptom-control therapy rather than tumor-directed treatment (vannuccini2024themodernmanagement pages 1-5) | Improves fibroid-related abnormal uterine bleeding/heavy menstrual bleeding; does not shrink fibroids (vannuccini2024themodernmanagement pages 1-5) | No effect on fibroid size; symptomatic only; thrombotic-risk considerations in selected patients (vannuccini2024themodernmanagement pages 1-5) | MAXO: antifibrinolytic therapy |
| Non-hormonal medical therapy | NSAIDs | Reduce prostaglandin-mediated bleeding and pain | Mild-to-moderate bleeding and dysmenorrhea; patients seeking short-term symptom relief (vannuccini2024themodernmanagement pages 1-5) | Can reduce pain and some bleeding symptoms, but generally less effective than targeted hormonal suppression for fibroid burden (vannuccini2024themodernmanagement pages 1-5) | Symptomatic only; gastrointestinal/renal adverse effects; no fibroid shrinkage (vannuccini2024themodernmanagement pages 1-5) | MAXO: nonsteroidal anti-inflammatory drug therapy |
| Hormonal medical therapy | Combined oral contraceptives | Suppress ovulation/endometrial proliferation; reduce menstrual bleeding | Women with bleeding symptoms who desire non-surgical management and contraception (centini2024tailoringthediagnostic pages 1-2, micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Helpful for bleeding control; primarily symptom management rather than definitive fibroid treatment (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Limited effect on fibroid size; estrogen-containing therapy may not suit all patients (vannuccini2024themodernmanagement pages 1-5) | MAXO: hormonal therapy |
| Hormonal medical therapy | Progestogens | Endometrial suppression and bleeding control | Selected patients with abnormal uterine bleeding; often short-term or individualized use (micic2024currentlyavailabletreatment pages 1-2) | May improve bleeding; evidence for fibroid shrinkage is limited (micic2024currentlyavailabletreatment pages 1-2) | Restricted efficacy for bulk symptoms/size reduction; hormone-related adverse effects (micic2024currentlyavailabletreatment pages 1-2) | MAXO: progestogen therapy |
| Hormonal medical therapy | Levonorgestrel intrauterine system (LNG-IUS) | Local progestin effect on endometrium, reducing bleeding | Bleeding-predominant symptoms, especially when uterine cavity distortion is not prohibitive (vannuccini2024themodernmanagement pages 1-5) | Effective for HMB control in selected women; not a fibroid-eliminating therapy (vannuccini2024themodernmanagement pages 1-5) | Expulsion/placement difficulty with cavity distortion; limited effect on bulk symptoms or tumor size (vannuccini2024themodernmanagement pages 1-5) | MAXO: intrauterine hormone delivery |
| Hormonal medical therapy | GnRH agonists | Initial pituitary stimulation followed by downregulation, causing hypoestrogenism/hypoprogesteronism | Preoperative bridge therapy, short-term bleeding control, temporary fibroid shrinkage, anemia optimization before surgery (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Well-established temporary reduction in bleeding and fibroid size; useful as bridge to surgery (bulun2025uterinefibroids pages 1-5, micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Menopausal symptoms, bone loss with prolonged use, rebound growth after discontinuation (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | MAXO: gonadotropin-releasing hormone agonist therapy |
| Hormonal medical therapy | Oral GnRH antagonists | Direct pituitary GnRH blockade suppressing ovarian steroid production | Symptomatic fibroids with HMB; uterus-sparing medical management; useful when a reversible oral option is preferred (vannuccini2024themodernmanagement pages 1-5) | Effective modern option for reducing bleeding and improving symptoms; part of contemporary conservative management (vannuccini2024themodernmanagement pages 1-5) | Hypoestrogenic adverse effects; may require add-back strategies; treatment effect is not curative (vannuccini2024themodernmanagement pages 1-5) | MAXO: gonadotropin-releasing hormone antagonist therapy |
| Hormonal medical therapy | Selective progesterone receptor modulators (SPRMs), e.g. ulipristal acetate | Modulate progesterone receptor signaling, reducing bleeding and fibroid growth | Historically used for intermittent long-term bleeding and size control in selected women (micic2024currentlyavailabletreatment pages 1-2, ishikawa2023risingstarsrole pages 1-3, vannuccini2024themodernmanagement pages 1-5) | Good results reported for bleeding control and fibroid size reduction; response may vary with MED12 status (micic2024currentlyavailabletreatment pages 1-2, ishikawa2023risingstarsrole pages 1-3) | Regulatory/safety limitations in many regions, including liver toxicity concerns; access restricted (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | MAXO: selective progesterone receptor modulator therapy |
| Hormonal medical therapy | Aromatase inhibitors | Lower local/systemic estrogen synthesis | Selected refractory cases or off-label individualized management (vannuccini2024themodernmanagement pages 1-5) | May improve symptoms in some patients; evidence base narrower than GnRH-based approaches (vannuccini2024themodernmanagement pages 1-5) | Hypoestrogenic effects; not standard first-line treatment (vannuccini2024themodernmanagement pages 1-5) | MAXO: aromatase inhibitor therapy |
| Surgical therapy | Myomectomy (hysteroscopic, laparoscopic, open/laparotomic, mini-laparotomic, robotic) | Physical removal of fibroids with uterine preservation | Symptomatic patients desiring fertility preservation or uterine conservation; approach depends on number, size, and location of myomas (micic2024currentlyavailabletreatment pages 1-2, centini2024tailoringthediagnostic pages 1-2) | Effective symptom relief while preserving uterus; review data showed comparable average pregnancy rates between minimally invasive and open approaches (~29.7% vs ~28.5%) (micic2024currentlyavailabletreatment pages 1-2) | Recurrence risk persists; operative bleeding/adhesions; more invasive than medical/radiologic options (micic2024currentlyavailabletreatment pages 1-2) | MAXO: myomectomy |
| Surgical therapy | Hysterectomy | Definitive removal of uterus, eliminating fibroids | Women with severe symptoms, no fertility desire, recurrent disease, or failure of conservative options; often considered definitive therapy (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Most definitive symptom control; fibroid recurrence eliminated because uterus removed (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Loss of fertility; surgical morbidity; longer recovery than some minimally invasive approaches (micic2024currentlyavailabletreatment pages 1-2) | MAXO: hysterectomy |
| Minimally invasive / interventional | Uterine artery embolization (UAE) / uterine artery occlusion | Devascularization leading to ischemic shrinkage of fibroids | Symptomatic women seeking uterus-sparing, non-excisional treatment; generally not first choice when future fertility is a major goal (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Improves bleeding and bulk symptoms in many patients; accepted radiologic option in modern care pathways (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Post-embolization pain, reintervention/recurrence risk, uncertain reproductive implications relative to myomectomy (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | MAXO: uterine artery embolization |
| Minimally invasive / interventional | High-intensity focused ultrasound (HIFU) / MR-guided focused ultrasound | Thermal ablation of fibroid tissue | Selected women with accessible fibroid anatomy seeking noninvasive uterus-sparing treatment (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Can reduce symptoms and fibroid volume; post-treatment MRI parameters can predict regrowth/reintervention risk (vannuccini2024themodernmanagement pages 1-5) | Not suitable for all fibroid locations/sizes; residual fibroid regrowth can occur; access/expertise dependent (vannuccini2024themodernmanagement pages 1-5) | MAXO: focused ultrasound ablation |
| Minimally invasive / interventional | Radiofrequency ablation / myolysis | Thermal destruction of fibroid tissue | Symptomatic fibroids in patients preferring minimally invasive, uterus-preserving treatment (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Effective symptom-directed minimally invasive option in selected patients (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Long-term recurrence and fertility data less extensive than for myomectomy; anatomy-dependent feasibility (micic2024currentlyavailabletreatment pages 1-2) | MAXO: radiofrequency ablation |
| Minimally invasive / interventional | Endometrial ablation | Destruction of endometrium to reduce bleeding | Bleeding-predominant symptoms in carefully selected women not seeking fertility; not a tumor-directed therapy (micic2024currentlyavailabletreatment pages 1-2) | May reduce bleeding symptoms but does not treat intramural/subserosal tumor burden (micic2024currentlyavailabletreatment pages 1-2) | Not appropriate for future fertility; limited if cavity distortion is substantial (micic2024currentlyavailabletreatment pages 1-2) | MAXO: endometrial ablation |
| Supportive care | Iron replacement therapy | Repletes iron stores in iron deficiency/iron deficiency anemia from chronic bleeding | Women with fibroid-related HMB, iron deficiency, or anemia before/after surgery and during medical management (vannuccini2024themodernmanagement pages 1-5) | Improves consequences of chronic blood loss and perioperative readiness; important adjunct rather than fibroid-directed therapy (vannuccini2024themodernmanagement pages 1-5) | Does not treat underlying fibroids; oral GI intolerance or IV infusion logistics may limit use (vannuccini2024themodernmanagement pages 1-5) | MAXO: iron supplementation |
| Experimental / emerging | Vitamin D | Proposed antiproliferative/anti-fibrotic effects; deficiency is a reported risk factor | Investigational or adjunctive setting; biologic rationale strengthened by epidemiologic association with deficiency (micic2024currentlyavailabletreatment pages 1-2, wu2026preclinicalresearchplatform pages 1-2) | Promising preclinical and prior xenograft evidence noted in model reviews, but not established standard clinical therapy (wu2026preclinicalresearchplatform pages 1-2) | Insufficient evidence for routine standalone treatment of symptomatic leiomyoma (wu2026preclinicalresearchplatform pages 1-2) | MAXO: vitamin supplementation |
| Experimental / emerging | Targeted/precision approaches linked to molecular subtype (e.g., MED12-informed response prediction) | Treatment selection based on tumor driver biology and pathway dependence | Future personalized management, particularly for mutation-stratified hormonal response (ishikawa2023risingstarsrole pages 1-3) | Emerging evidence suggests MED12 status may influence response to GnRH agonists and ulipristal acetate (ishikawa2023risingstarsrole pages 1-3) | Not yet routine clinical standard; requires broader validation and accessible molecular testing (ishikawa2023risingstarsrole pages 1-3) | MAXO: precision medicine intervention |
| Experimental / emerging | Novel agents under investigation | Various pathways including progesterone signaling, ECM remodeling, and other molecular targets | Patients with unmet need for fertility-preserving, long-term, non-surgical options (micic2024currentlyavailabletreatment pages 1-2, bulun2025uterinefibroids pages 1-5) | Reviews describe multiple promising investigational therapies, but few are yet approved specifically for fibroids (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | Evidence still evolving; many therapies remain investigational or regionally unavailable (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5) | MAXO: investigational pharmacotherapy |
Table: This table summarizes current and emerging treatment options for uterine leiomyoma, including mechanisms, appropriate patient selection, expected efficacy, limitations, and suggested MAXO-aligned intervention labels. It is useful for comparing conservative, surgical, and interventional management strategies in one view.
| Factor Type | Specific Factor | Category | Strength of Association | Population-Specific Effects | Key Evidence |
|---|---|---|---|---|---|
| Risk | Advanced reproductive age | Reproductive | Consistently reported risk factor; incidence and symptom burden increase through reproductive years, especially ages 35–50 | Burden concentrated in women aged 40–69 globally; common in reproductive-age women (tang2025theglobalburden pages 1-2, micic2024currentlyavailabletreatment pages 1-2) | Listed as a risk factor in reviews; fibroids are most commonly found in women aged 35–50, and global burden is concentrated in ages 40–69 (koltsova2023aviewon pages 1-2, tang2025theglobalburden pages 1-2, micic2024currentlyavailabletreatment pages 1-2) |
| Risk | Black/African ancestry | Genetic / population | Strong and repeatedly reported association | By age 50, prevalence reaches >80% in Black women vs ~70% overall/White women; disproportionate incidence and severity (buyukcelebi2024integratingleiomyomagenetics pages 1-2, centini2024tailoringthediagnostic pages 1-2, boos2025therolesof pages 1-2) | Reviews and genomic studies report substantially higher prevalence and burden in Black women (buyukcelebi2024integratingleiomyomagenetics pages 1-2, centini2024tailoringthediagnostic pages 1-2, boos2025therolesof pages 1-2) |
| Risk | Latin American ethnicity | Population | Reported association, but less extensively quantified than Black ancestry | Mentioned as increased-risk population in review literature | Identified among risk factors in heterogeneity-focused review (koltsova2023aviewon pages 1-2) |
| Risk | Family history of uterine leiomyoma | Genetic | Moderate-to-strong; familial aggregation repeatedly reported | First-degree relatives have elevated risk; reflects heritable susceptibility | Review identifies family history as a risk factor; GWAS/integrative genetics supports heritable contribution and multiple susceptibility loci (koltsova2023aviewon pages 1-2, buyukcelebi2024integratingleiomyomagenetics pages 1-2) |
| Risk | Germline/heritable susceptibility loci | Genetic | Strong biologic evidence for susceptibility, but effect sizes vary by locus | May contribute to racial/population differences in risk | Integrative 2024 analysis identified 24 UF-associated risk loci and 394 candidate target genes, supporting inherited susceptibility (buyukcelebi2024integratingleiomyomagenetics pages 1-2) |
| Risk | MED12-associated predisposition to specific tumor biology | Genetic / molecular | Strong for tumor subtype biology rather than disease initiation alone | MED12-mutant tumors are more frequent in Black women in some series and often multiple | MED12 mutations are the dominant driver in many tumors and are associated with distinct biology and multiplicity (bulun2025uterinefibroids pages 1-5, ishikawa2023risingstarsrole pages 1-3) |
| Risk | Early menarche | Reproductive | Consistently reported risk factor | No specific population restriction given, but may interact with lifetime hormonal exposure | Included as a risk factor in multiple reviews and diagnostic overview (koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Risk | Late menopause | Reproductive | Reported risk factor, likely reflecting prolonged estrogen/progesterone exposure | Not specifically stratified | Included in etiopathogenesis overview figure/discussion (alali2023theetiopathogenesisof pages 1-2) |
| Risk | Nulliparity / low parity | Reproductive | Consistently reported risk factor | Protective effect of multiparity implies higher risk in nulliparous women | Nulliparity or absence of parity is reported as a risk factor; several reviews note multiparity as protective (buyukcelebi2024integratingleiomyomagenetics pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Protective | Multiparity / parity | Reproductive | Consistently reported protective factor | Not population-specific, though effect may vary with reproductive history | Multiparity/parity reported as protective in reviews and diagnostic narrative (koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2) |
| Risk | Obesity / high BMI | Lifestyle / metabolic | Strong and consistently reported | Important in many populations; cited in epidemiologic and mechanistic reviews | Obesity repeatedly listed among major risk factors and linked to symptomatic disease burden (alali2023theetiopathogenesisof pages 1-2, koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2, micic2024currentlyavailabletreatment pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Risk | Diabetes | Metabolic | Reported association | Not specifically stratified | Included among factors involved in incidence/development in clinician-friendly review (larrain2024newinsightsinto pages 1-3) |
| Risk | Arterial hypertension | Metabolic / vascular | Repeatedly reported association | Not specifically stratified | Identified as a risk factor in heterogeneity/risk-factor review and clinician review (koltsova2023aviewon pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Risk | Chronic inflammation | Environmental / biologic | Reported association with plausible mechanistic support | Not specifically stratified | Listed as a risk factor in review of UL genesis; inflammation also emphasized mechanistically in fibroid biology (koltsova2023aviewon pages 1-2, boos2025therolesof pages 1-2) |
| Risk | Sexually transmitted infections | Infectious | Reported association, evidence less mature than hormonal/metabolic factors | Not specifically stratified | Identified as a possible risk factor in review of risk/protective factors (koltsova2023aviewon pages 1-2) |
| Risk | Exposure to xenoestrogens in early ontogenesis | Environmental | Biologically plausible and reported in review literature | Suggests early-life vulnerability window | Reported as a risk factor in review of UL genesis (koltsova2023aviewon pages 1-2) |
| Risk | Diethylstilbestrol (DES) exposure | Environmental | Reported association | Not specifically stratified | Included among environmental contributors in clinician-friendly molecular review (larrain2024newinsightsinto pages 1-3) |
| Risk | Air pollution | Environmental | Reported association | Not specifically stratified | Mentioned among factors potentially involved in incidence/development (larrain2024newinsightsinto pages 1-3) |
| Risk | Alcohol consumption | Lifestyle | Repeatedly reported risk factor | Not specifically stratified | Alcohol listed as a risk factor in heterogeneity review and clinician-friendly review (koltsova2023aviewon pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Risk | Caffeine | Lifestyle | Reported in one review/figure; likely weaker evidence than alcohol/obesity | Not specifically stratified | Included in etiopathogenesis figure as a potential risk factor (alali2023theetiopathogenesisof pages 1-2) |
| Risk | Chronic stress | Lifestyle / psychosocial | Reported association | Not specifically stratified | Listed in diagnostic review as a risk factor (centini2024tailoringthediagnostic pages 1-2) |
| Risk | Vitamin D deficiency | Environmental / nutritional | Repeatedly reported association with supportive mechanistic rationale | Not specifically stratified; may be relevant in populations with higher deficiency prevalence | Vitamin D deficiency is listed among known factors influencing fibroid development in recent reviews (alali2023theetiopathogenesisof pages 1-2, micic2024currentlyavailabletreatment pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Protective | Adequate vitamin D status | Nutritional | Implied protective factor from repeated deficiency-risk association; preclinical support exists | Not specifically stratified | Since deficiency is repeatedly associated with risk, adequate status is plausibly protective; some model literature supports anti-fibroid effects (micic2024currentlyavailabletreatment pages 1-2, wu2026preclinicalresearchplatform pages 1-2, larrain2024newinsightsinto pages 1-3) |
| Risk | High-fat diet / adverse dietary factors | Lifestyle / nutritional | Reported association | Not specifically stratified | High-fat diet and dietary factors are mentioned as contributing to incidence/development (larrain2024newinsightsinto pages 1-3) |
| Protective | Oral contraceptive use / combined oral contraceptives | Reproductive / hormonal | Reported protective factor in review literature, though literature historically mixed | Not specifically stratified | Oral contraceptive intake and combined oral contraceptives are listed among possible protective factors in recent reviews (koltsova2023aviewon pages 1-2, centini2024tailoringthediagnostic pages 1-2) |
| Protective | Smoking | Lifestyle | Reported as a possible protective factor in reviews, but likely outweighed by broader health harms | Not population-specific; not a recommended prevention strategy | Smoking is listed among possible protective factors in one recent review even though it is not clinically recommended (koltsova2023aviewon pages 1-2) |
| Risk | Hormonal milieu: higher estradiol and progesterone exposure | Hormonal / mechanistic | Strong mechanistic support | Relevant across reproductive-age populations; explains premenopausal predominance | Risk/severity associated with serum estradiol and progesterone; tumors are steroid-dependent and rarely develop before menarche (buyukcelebi2024integratingleiomyomagenetics pages 1-2, ishikawa2023risingstarsrole pages 1-3) |
| Protective | Postmenopausal state / menopause-associated regression | Reproductive / hormonal | Strong observational pattern | Applies broadly; many fibroids regress after menopause | Fibroids frequently regress after menopause, supporting reduced ovarian steroid exposure as protective against persistence/growth (alali2023theetiopathogenesisof pages 1-2, ishikawa2023risingstarsrole pages 1-3) |
| Risk | Reproductive delay / postponed childbearing | Reproductive | Epidemiologically plausible; discussed in population-burden review | Relevant in regions with delayed childbearing patterns | Population review links changing reproductive patterns, including postponed childbearing, to increasing prevalence (zhang2025globalregionaland pages 1-2) |
Table: This table summarizes reported risk and protective factors for uterine leiomyoma across recent reviews and epidemiologic/genetic studies. It organizes the factors by category, indicates the qualitative strength of association, and notes population-specific patterns where available.
Uterine leiomyomas are the most common benign gynecological tumors, affecting up to 70–80% of women by menopause, with disproportionate burden in Black women. The disease has complex etiology involving somatic driver mutations (MED12 most common at 50–80%, followed by HMGA2, FH, and others), heritable susceptibility loci (24 GWAS risk loci identified), hormonal dependence on estrogen and progesterone, and environmental/lifestyle risk factors including obesity, early menarche, nulliparity, and vitamin D deficiency (alali2023theetiopathogenesisof pages 1-2, bulun2025uterinefibroids pages 1-5, koltsova2023aviewon pages 1-2, buyukcelebi2024integratingleiomyomagenetics pages 1-2, ishikawa2023risingstarsrole pages 1-3).
Approximately 20–30% of women with fibroids experience symptoms including heavy menstrual bleeding (leading to iron deficiency anemia), pelvic pain, bulk symptoms, and reproductive dysfunction, significantly impairing quality of life (alali2023theetiopathogenesisof pages 1-2, centini2024tailoringthediagnostic pages 1-2, vannuccini2024themodernmanagement pages 1-5). Diagnosis relies primarily on transvaginal ultrasound, with MRI for detailed characterization and treatment planning (centini2024tailoringthediagnostic pages 1-2, vannuccini2024themodernmanagement pages 1-5). Emerging AI-based radiomics and molecular subtyping (MED12 mutation status) may enable personalized treatment approaches (ishikawa2023risingstarsrole pages 1-3, vannuccini2024themodernmanagement pages 1-5).
Treatment is individualized based on symptoms, fibroid characteristics, fertility desire, and patient preference. Options range from medical management (GnRH agonists/antagonists, SPRMs, NSAIDs, tranexamic acid) to surgical interventions (myomectomy, hysterectomy) and minimally invasive procedures (UAE, HIFU, radiofrequency ablation) (micic2024currentlyavailabletreatment pages 1-2, vannuccini2024themodernmanagement pages 1-5). Novel therapies targeting molecular pathways and mutation-specific responses are under investigation (bulun2025uterinefibroids pages 1-5, micic2024currentlyavailabletreatment pages 1-2, ishikawa2023risingstarsrole pages 1-3).
Animal models including Eker rats, conditional MED12-mutant mice, hormone-induced models, and patient-derived xenografts facilitate mechanistic research and drug development (wu2026preclinicalresearchplatform pages 1-2). Future directions emphasize precision medicine leveraging molecular subtyping, multi-omics biomarkers, and non-hormonal targeted therapies to improve outcomes for this highly prevalent and morbid condition (buyukcelebi2024integratingleiomyomagenetics pages 1-2, ishikawa2023risingstarsrole pages 1-3, vannuccini2024themodernmanagement pages 1-5, boos2025therolesof pages 1-2).
References
(alali2023theetiopathogenesisof pages 1-2): Ola M. Alali and Mikhail I. Churnosov. The etiopathogenesis of uterine leiomyomas: a review. Gynecology, 25:22-30, Apr 2023. URL: https://doi.org/10.26442/20795696.2023.1.201827, doi:10.26442/20795696.2023.1.201827. This article has 14 citations.
(bulun2025uterinefibroids pages 1-5): Serdar E. Bulun, Ping Yin, JianJun Wei, Azna Zuberi, Takashi Iizuka, Takuma Suzuki, Priyanka Saini, Jyoti Goad, J. Brandon Parker, Mazhar Adli, Thomas Boyer, Debabrata Chakravarti, and Aleksandar Rajkovic. Uterine fibroids. Oct 2025. URL: https://doi.org/10.1152/physrev.00010.2024, doi:10.1152/physrev.00010.2024. This article has 44 citations and is from a highest quality peer-reviewed journal.
(ishikawa2023risingstarsrole pages 1-3): Hiroshi Ishikawa, Tatsuya Kobayashi, Meika Kaneko, Yoshiko Saito, Makio Shozu, and Kaori Koga. Rising stars: role of med12 mutation in the pathogenesis of uterine fibroids. Journal of Molecular Endocrinology, Sep 2023. URL: https://doi.org/10.1530/jme-23-0039, doi:10.1530/jme-23-0039. This article has 20 citations and is from a peer-reviewed journal.
(koltsova2023aviewon pages 1-2): Alla Koltsova, Olga Efimova, and Anna Pendina. A view on uterine leiomyoma genesis through the prism of genetic, epigenetic and cellular heterogeneity. International Journal of Molecular Sciences, 24:5752, Mar 2023. URL: https://doi.org/10.3390/ijms24065752, doi:10.3390/ijms24065752. This article has 41 citations.
(centini2024tailoringthediagnostic pages 1-2): Gabriele Centini, Alberto Cannoni, Alessandro Ginetti, Irene Colombi, Matteo Giorgi, Giorgia Schettini, Francesco Giuseppe Martire, Lucia Lazzeri, and Errico Zupi. Tailoring the diagnostic pathway for medical and surgical treatment of uterine fibroids: a narrative review. Sep 2024. URL: https://doi.org/10.3390/diagnostics14182046, doi:10.3390/diagnostics14182046. This article has 28 citations.
(larrain2024newinsightsinto pages 1-3): Demetrio Larraín and Jaime Prado. New insights into molecular pathogenesis of uterine fibroids: from the lab to a clinician-friendly review. Soft Tissue Sarcoma and Leiomyoma - Diagnosis, Management, and New Perspectives, Jan 2024. URL: https://doi.org/10.5772/intechopen.1002969, doi:10.5772/intechopen.1002969. This article has 5 citations.
(buyukcelebi2024integratingleiomyomagenetics pages 1-2): Kadir Buyukcelebi, Alexander J. Duval, Fatih Abdula, Hoda Elkafas, Fidan Seker-Polat, and Mazhar Adli. Integrating leiomyoma genetics, epigenomics, and single-cell transcriptomics reveals causal genetic variants, genes, and cell types. Nature Communications, Feb 2024. URL: https://doi.org/10.1038/s41467-024-45382-0, doi:10.1038/s41467-024-45382-0. This article has 19 citations and is from a highest quality peer-reviewed journal.
(zhang2025globalregionaland pages 1-2): Zihan Zhang, Hongxin Huang, Kuanlie Jiang, Weixia Liu, Yan Xuan, and Wei Lu. Global, regional and national uterine fibroid burdens from 1990 to 2021 and projections until 2050: results from the gbd study. BMC Women's Health, Sep 2025. URL: https://doi.org/10.1186/s12905-025-03974-y, doi:10.1186/s12905-025-03974-y. This article has 6 citations.
(micic2024currentlyavailabletreatment pages 1-2): Jelena Micić, Maja Macura, Mladen Andjić, Katarina Ivanović, Jelena Dotlić, Dušan D. Micić, Vladimir Arsenijević, Jelena Stojnić, Jovan Bila, Sandra Babić, Una Šljivančanin, Danka Mostić Stanišić, and Milan Dokić. Currently available treatment modalities for uterine fibroids. Medicina, 60:868, May 2024. URL: https://doi.org/10.3390/medicina60060868, doi:10.3390/medicina60060868. This article has 79 citations.
(tang2025theglobalburden pages 1-2): Wei-Zhen Tang, Qin-Yu Cai, Kang-Jin Huang, Wei-Ze Xu, Jia-Zheng Li, Yun-Ren Pan, Hong-Yu Xu, Yi-Fan Zhao, Ting-He Sheng, Zhi-Mou Li, Tai-Hang Liu, and Ying-Bo Li. The global burden of polycystic ovary syndrome, endometriosis, uterine fibroids, cervical cancer, uterine cancer, and ovarian cancer from 1990 to 2021. BMC Public Health, May 2025. URL: https://doi.org/10.1186/s12889-025-22881-3, doi:10.1186/s12889-025-22881-3. This article has 39 citations and is from a peer-reviewed journal.
(chuang2023differentialexpressionof pages 1-2): Tsai-Der Chuang, Jianjun Gao, Derek Quintanilla, Hayden McSwiggin, Drake Boos, Wei Yan, and Omid Khorram. Differential expression of med12-associated coding rna transcripts in uterine leiomyomas. International Journal of Molecular Sciences, 24:3742, Feb 2023. URL: https://doi.org/10.3390/ijms24043742, doi:10.3390/ijms24043742. This article has 18 citations.
(dundr2022uterinecellularleiomyomas pages 1-2): Pavel Dundr, Mária Gregová, Jan Hojný, Eva Krkavcová, Romana Michálková, Kristýna Němejcová, Michaela Bártů, Nikola Hájková, Jan Laco, Michal Mára, Adéla Richtárová, Tomáš Zima, and Ivana Stružinská. Uterine cellular leiomyomas are characterized by common hmga2 aberrations, followed by chromosome 1p deletion and med12 mutation: morphological, molecular, and immunohistochemical study of 52 cases. Virchows Archiv, 480:281-291, Oct 2022. URL: https://doi.org/10.1007/s00428-021-03217-z, doi:10.1007/s00428-021-03217-z. This article has 27 citations and is from a peer-reviewed journal.
(boos2025therolesof pages 1-2): Drake Boos, Tsai-Der Chuang, and Omid Khorram. The roles of non-coding rnas in the pathogenesis of uterine fibroids. Cells, 14:1290, Aug 2025. URL: https://doi.org/10.3390/cells14161290, doi:10.3390/cells14161290. This article has 7 citations.
(wu2026preclinicalresearchplatform pages 1-2): Dan Wu, Jian Luo, Li‐Yu Lin, Tingting Gu, and Zhehui You. Preclinical research platform for uterine leiomyoma: construction optimization and selection of animal models. Frontiers in Veterinary Science, Feb 2026. URL: https://doi.org/10.3389/fvets.2026.1772750, doi:10.3389/fvets.2026.1772750. This article has 1 citations and is from a peer-reviewed journal.
(vannuccini2024themodernmanagement pages 1-5): Silvia Vannuccini, Felice Petraglia, Francisco Carmona, Joaquim Calaf, and Charles Chapron. The modern management of uterine fibroids-related abnormal uterine bleeding. Fertility and Sterility, 122:20-30, Jul 2024. URL: https://doi.org/10.1016/j.fertnstert.2024.04.041, doi:10.1016/j.fertnstert.2024.04.041. This article has 103 citations and is from a highest quality peer-reviewed journal.