Embryology · Teratology and prenatal diagnosis
Androgens, diethylstilbestrol and other hormones !
- Teratogen
Sex hormones that reach the fetus can change the shape of the genitals and reproductive tract; the historical case is DES.
Updated 2026-11-01
See it in 3D: Clitoris · Labia majora · Vagina · Cervix · Body of uterus · Epididymis
What it is
The genitals and reproductive ducts differentiate according to the hormones present in the first trimester. External androgens (or older progestins with androgenic effects) virilize the genitals of a 46,XX fetus. Diethylstilbestrol (DES), a synthetic oestrogen used from 1940 to 1971 to prevent miscarriage, left reproductive tract malformations and a rare cancer in exposed daughters: the classic example of a teratogen whose effects show years later.
Key facts
- DES was used from 1940 to 1971; in 1971 it was linked to clear cell adenocarcinoma.
- Exposed daughters have about 40 times the risk of that cancer, though it remains rare.
- Endogenous androgen sources: fetal congenital adrenal hyperplasia and virilizing maternal tumours.
- Oral contraceptives have a low teratogenic potential.
- Environmental endocrine disruptors act on hormone receptors and are studied for reproductive tract effects.
Critical period and mechanism
- Critical period: first trimester, while the genital ducts and external genitalia differentiate.
- Androgens activate their receptors in the genital tubercle and folds and masculinize them even in a 46,XX fetus.
- DES crosses the placenta, binds sex hormone–binding globulin poorly and is converted to reactive metabolites.
- It disturbs differentiation of the Müllerian ducts (uterus, tubes and upper vagina).
Prevention
- Avoiding androgenic hormones in pregnancy unless the treating professional indicates them.
- Women exposed to DES in the womb receive regular gynaecological follow-up.
- Medicines in pregnancy are decided with the treating professional.
What it does to the embryo and fetus
- Ambiguous genitalia in a 46,XX fetus: large clitoris and fused labia.
- T-shaped uterus, abnormal cervix or vagina, vaginal adenosis.
- Clear cell adenocarcinoma in young exposed women.
- Cryptorchidism and epididymal cysts in exposed males.
Test yourself
Think of the answer, then tap the question to see it.
What do androgens do to a 46,XX fetus exposed in the first trimester?
They virilize the external genitalia: clitoromegaly and fusion of the labioscrotal folds.
Which cancer is linked to in-utero DES exposure?
Clear cell adenocarcinoma of the vagina and cervix.
Which embryonic structures does DES disturb in exposed women?
The Müllerian duct derivatives: uterus (T-shaped uterus), tubes, cervix and upper vagina.
See it in 3D
The structures of Durgical's 3D anatomy where it is found.
Related
- Differences of sex development: CAH, AIS and 5α-reductase
- External genitalia and their male–female homologues
- Genital ducts: Wolffian (mesonephric) and Müllerian (paramesonephric)
- Uterine anomalies: bicornuate, septate, didelphys, Müllerian agenesis
- Cryptorchidism
- Sex determination: SRY, anti-Müllerian hormone and testosterone
Related conditions
- Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
- Cryptorchidism (undescended testis)
- Ectopic pregnancy
- Preterm labour and birth
Educational content on embryonic development; not a guide to prenatal diagnosis or to medicines in pregnancy and no substitute for a health professional's advice. No doses are given.
Sources: Diethylstilbestrol (DES) Exposure and Cancer (National Cancer Institute, 2021); Teratogenic Medications (StatPearls Publishing (NCBI Bookshelf), 2024); Langman's Medical Embryology, 13th ed., ch. 9: Birth Defects and Prenatal Diagnosis (Wolters Kluwer, 2015).
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Representative model, for educational purposes only.