In-utero exposure to diethylstilbestrol (DES), a synthetic non- steroidal estrogen prescr...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-IATROGENIC-DES-EXPOSURE-PREVENTION`
Type	Red flag
Status	reviewed 2026-05-18 \| pending_clinical_signoff
Diseases	`DIS-CERVICAL` `DIS-VULVAR-VAGINAL-SCC`
Sources	`SRC-IARC-MONO-100B-2012` `SRC-NCCN-CERVICAL-2025`

Red Flag Origin

Definition	In-utero exposure to diethylstilbestrol (DES), a synthetic non- steroidal estrogen prescribed to pregnant women 1940s-1970s to prevent miscarriage and pregnancy complications (US peak 1947-1971; withdrawn for this indication 1971; smaller cohorts in Europe used through the late 1970s). Daughters of women who took DES during pregnancy ("DES daughters") have a markedly elevated risk of clear- cell adenocarcinoma of the vagina and cervix (CCA) — a rare cancer with a clear bimodal age distribution: peak at 15-25 years (historically detected during the first DES surveillance era) and a second elevated-risk window persisting through age 40+; cumulative lifetime CCA risk in DES-exposed cohort approximately 1 per 1000 (vs ~1 per million in unexposed) — IARC Group 1 carcinogen for this exact exposure. Additionally elevated: cervical intraepithelial neoplasia / carcinoma in situ (CIS), structural...
Clinical direction	investigate
Category	other

Trigger Logic

{
  "any_of": [
    {
      "finding": "in_utero_des_exposure_documented",
      "value": true
    },
    {
      "finding": "des_daughter_history",
      "value": true
    },
    {
      "finding": "maternal_pregnancy_des_use",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

Prevention-persona RedFlag for in-utero DES exposure. Engine routes to PreventionPlan recommending annual gynecologic exam with speculum + bimanual + careful palpation of vaginal walls (specific technique for DES daughters per ACOG), colposcopy with vaginal + cervical staining for early detection of CCA, cervical cytology / HPV co-test on routine cadence, breast surveillance per age- appropriate USPSTF cadence. Cohort is aging — bimodal-risk window extends past 40y; surveillance does NOT stop at any age cutoff. Cancer scope: anchored to DIS-VULVAR-VAGINAL-SCC (closest existing Disease entity for vaginal-tract anchor) + DIS-CERVICAL. DES- associated cancer is histologically clear-cell adenocarcinoma — NOT yet authored as a distinct DIS-VAGINAL-CLEAR-CELL entity; histology-specific surveillance considerations carried via the indication prose. Future authoring of DIS-VAGINAL-CLEAR-CELL recommended. Distinct from RF-IATROGENIC-LONG-TERM-HRMNL-CONTRACEPTION- PREVENTION (post-natal hormonal exposure, exposure-as-cofactor). This is a one-time in-utero developmental exposure — surveillance cohort is closed (no new DES daughters); known existing cohort remains at lifelong elevated risk.

Used By

Indications

IND-IATROGENIC-DES-EXPOSURE-PREVENTION-OBSERVATION - IND-IATROGENIC-DES-EXPOSURE-PREVENTION-OBSERVATION
IND-IATROGENIC-DES-EXPOSURE-PREVENTION-SURVEILLANCE - IND-IATROGENIC-DES-EXPOSURE-PREVENTION-SURVEILLANCE