Hypermobile Ehlers-Danlos Syndrome <-> Endometriosis

name: com_Hypermobile_Ehlers-Danlos_Syndrome__Endometriosis
creation_date: '2026-09-18T02:57:53Z'
curation_status: CANDIDATE
notes: >-
  Despite a very high prevalence of gynecologic symptoms that clinically
  overlap with endometriosis (menorrhagia 76%, dysmenorrhea 72%, deep/
  intromission dyspareunia 38-43%), a French cohort study of 386 women with
  clinically diagnosed hEDS found endometriosis itself diagnosed in only 6%
  of the cohort -- essentially the same as the general-population range
  (3-6%) and well below rates in women with chronic pain generally. The
  authors explicitly propose that endometriosis may be over-diagnosed in
  hEDS patients because dysmenorrhea and bleeding symptoms mimic it. This
  entry therefore records a symptom overlap without a true excess prevalence
  of the underlying disease, honestly characterized as REFUTE for a genuine
  hEDS-endometriosis comorbidity signal. Directionality is UNKNOWN. No ICEES
  KG signal exists for this pair: hEDS (MONDO:0007523) is not a node in the
  ICEES KG snapshot at all (confirmed while curating the hEDS-POTS
  comorbidity entry).

disease_a:
  slug: Hypermobile_Ehlers-Danlos_Syndrome
  preferred_term: Ehlers-Danlos syndrome, hypermobility type
  term:
    id: MONDO:0007523
    label: Ehlers-Danlos syndrome, hypermobility type

disease_b:
  slug: Endometriosis
  preferred_term: endometriosis
  term:
    id: MONDO:0005133
    label: endometriosis

directionality: UNKNOWN

hypotheses:
- description: >-
    Hypothesis under test: connective-tissue laxity or altered peritoneal/
    uterine tissue mechanics in hEDS predisposes to endometriosis. The
    cited cohort study argues against this -- endometriosis prevalence in
    hEDS matches the general population, and the symptom overlap (chronic
    dysmenorrhea, dyspareunia, bleeding) that prompts clinical suspicion of
    endometriosis is itself attributable to hEDS-related connective-tissue
    and pain mechanisms rather than to true excess endometriosis.
  evidence:
  - reference: PMID:27619482
    reference_title: "Gynecologic symptoms and the influence on reproductive life in 386 women with hypermobility type ehlers-danlos syndrome: a cohort study."
    supports: REFUTE
    quote_role: PRIMARY_RESULT
    evidence_source: HUMAN_CLINICAL
    snippet: "The rate of endometriosis we found was the same as that for the general population (3–6 %) and much less than in women with chronic pain"
    explanation: >-
      Directly refutes a mechanistic hypothesis of true excess endometriosis
      prevalence in hEDS; the finding is that prevalence matches the general
      population.
  pathophysiology:
  - name: Chronic dysmenorrhea and dyspareunia mimicking endometriosis
    description: >-
      Connective-tissue laxity and generalized chronic-pain mechanisms in
      hEDS produce menorrhagia, dysmenorrhea, and dyspareunia that clinically
      resemble endometriosis and can prompt diagnostic suspicion or surgery,
      without a corresponding excess of confirmed endometriosis.
    biological_processes:
    - preferred_term: sensory perception of pain
      term:
        id: GO:0019233
        label: sensory perception of pain

association_signals:
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  signal_disorder_a_id: MONDO:0007523
  signal_disorder_b_id: MONDO:0005133
  population: >-
    Cohort of 386 women with clinically diagnosed hEDS, evaluated at a
    single French national referral center (2012-2014), including
    gynecologic examination and, where clinically indicated, pelvic
    sonogram/MRI.
  mapping_notes: >-
    Recorded as REFUTE for the population-level comorbidity claim: the study
    found endometriosis prevalence matching the general population despite a
    high burden of symptoms that clinically mimic it, and the authors
    explicitly caution against over-diagnosis.
  directionality: UNKNOWN
  statistics:
    metrics:
    - metric_type: PREVALENCE
      metric_value: 6.0
      notes: >-
        Endometriosis prevalence in the hEDS cohort (20/386), versus a
        cited general-population range of 3-6%.
    evidence:
    - reference: PMID:27619482
      reference_title: "Gynecologic symptoms and the influence on reproductive life in 386 women with hypermobility type ehlers-danlos syndrome: a cohort study."
      supports: REFUTE
      evidence_source: HUMAN_CLINICAL
      snippet: "Endometriosis was diagnosed in 6 % of the women."
      explanation: >-
        Quantifies endometriosis prevalence in a large clinically-diagnosed
        hEDS cohort at a level matching, not exceeding, the general
        population.
    - reference: PMID:27619482
      reference_title: "Gynecologic symptoms and the influence on reproductive life in 386 women with hypermobility type ehlers-danlos syndrome: a cohort study."
      supports: REFUTE
      quote_role: PRIMARY_RESULT
      evidence_source: HUMAN_CLINICAL
      snippet: "we suggest that endometriosis may be over-diagnosed in hEDS patients because of reports of chronic pain and bleeding"
      explanation: >-
        The study authors' own interpretation explicitly warns against
        inferring a true endometriosis excess from the symptom overlap.

- source: ICEES
  method: EHR_COHORT_ASSOCIATION
  signal_disorder_a_id: MONDO:0007523
  signal_disorder_b_id: MONDO:0005133
  population: ICEES KG snapshot 8-20-2024 (RENCI/UNC).
  mapping_notes: >-
    Searched: the local ICEES KG snapshot (rebuilt with `just icees-refresh`)
    contains only 226 nodes total, a small set of UNC-Health cohort-specific
    concepts. hEDS (MONDO:0007523) does not appear among them -- confirmed
    by grepping the decompressed node list directly (same check performed
    for the hEDS-POTS comorbidity entry). No ICEES signal exists for this
    pair in the current snapshot; recorded here rather than silently
    omitted.
  directionality: UNKNOWN