| 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 (pqac-00000003, pqac-00000007) | 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 (pqac-00000002, pqac-00000003, pqac-00000007) |
| 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 (pqac-00000005, pqac-00000006, pqac-00000014) | Reviews and genomic studies report substantially higher prevalence and burden in Black women (pqac-00000005, pqac-00000006, pqac-00000014) |
| 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 (pqac-00000002) |
| 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 (pqac-00000002, pqac-00000005) |
| 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 (pqac-00000005) |
| 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 (pqac-00000001, pqac-00000009) |
| 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 (pqac-00000002, pqac-00000006, pqac-00000013) |
| Risk | Late menopause | Reproductive | Reported risk factor, likely reflecting prolonged estrogen/progesterone exposure | Not specifically stratified | Included in etiopathogenesis overview figure/discussion (pqac-00000000) |
| 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 (pqac-00000005, pqac-00000013) |
| 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 (pqac-00000002, pqac-00000006) |
| 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 (pqac-00000000, pqac-00000002, pqac-00000006, pqac-00000007, pqac-00000013) |
| Risk | Diabetes | Metabolic | Reported association | Not specifically stratified | Included among factors involved in incidence/development in clinician-friendly review (pqac-00000013) |
| Risk | Arterial hypertension | Metabolic / vascular | Repeatedly reported association | Not specifically stratified | Identified as a risk factor in heterogeneity/risk-factor review and clinician review (pqac-00000002, pqac-00000013) |
| 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 (pqac-00000002, pqac-00000014) |
| 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 (pqac-00000002) |
| 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 (pqac-00000002) |
| Risk | Diethylstilbestrol (DES) exposure | Environmental | Reported association | Not specifically stratified | Included among environmental contributors in clinician-friendly molecular review (pqac-00000013) |
| Risk | Air pollution | Environmental | Reported association | Not specifically stratified | Mentioned among factors potentially involved in incidence/development (pqac-00000013) |
| Risk | Alcohol consumption | Lifestyle | Repeatedly reported risk factor | Not specifically stratified | Alcohol listed as a risk factor in heterogeneity review and clinician-friendly review (pqac-00000002, pqac-00000013) |
| 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 (pqac-00000000) |
| Risk | Chronic stress | Lifestyle / psychosocial | Reported association | Not specifically stratified | Listed in diagnostic review as a risk factor (pqac-00000006) |
| 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 (pqac-00000000, pqac-00000007, pqac-00000013) |
| 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 (pqac-00000007, pqac-00000011, pqac-00000013) |
| 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 (pqac-00000013) |
| 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 (pqac-00000002, pqac-00000006) |
| 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 (pqac-00000002) |
| 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 (pqac-00000005, pqac-00000009) |
| 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 (pqac-00000000, pqac-00000009) |
| 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 (pqac-00000004) |


*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.*