diethylstilbestrol syndrome

Diethylstilbestrol syndrome is a malformation syndrome that develops following in utero exposure to the synthetic nonsteroidal estrogen diethylstilbestrol (DES), which was prescribed from the 1940s to the 1970s to prevent miscarriage. The condition primarily affects the reproductive system, with affected individuals exhibiting malformations that can impact fertility and increase the risk of certain cancers, clear cell carcinoma of the vagina and cervix in young women. Both females and males can be affected, with females experiencing uterine anomalies such as a small, T-shaped uterus and males showing reproductive tract abnormalities such as epididymal cysts or microphallus. Prevalence estimates are not well established, and the condition is considered uncommon in modern populations.

Individuals with diethylstilbestrol syndrome may present with a range of reproductive tract malformations. In females, common features include structural anomalies such as a small, T-shaped uterus and other uterotubal irregularities that can contribute to an increased risk of miscarriage and, later in life, an elevated risk of clear cell carcinoma of the vagina and cervix. Males exposed in utero might show features such as epididymal cysts, microphallus, cryptorchidism, or testicular hypoplasia. Not all individuals experience all features, and severity varies considerably.

Diethylstilbestrol syndrome is not caused by a genetic mutation but rather results from prenatal exposure to the synthetic estrogen diethylstilbestrol. The use of DES during pregnancy disrupted the normal development of the reproductive system, leading to the malformations observed in affected individuals. This condition is not inherited and does not run in families; the risk is specifically related to the environmental exposure during a critical period of fetal development. Genetic counseling may help families understand the nature of this exposure-related condition and discuss any concerns for future pregnancies.

Currently, management of diethylstilbestrol syndrome focuses on supportive care and symptom management, as no specific treatments have been established for reversing the malformations. For women, regular reproductive monitoring and cancer surveillance are critical given the increased risk of clear cell carcinoma, while men may require evaluation and management of any reproductive tract abnormalities. Treatment is tailored to the individual and typically involves a multidisciplinary team to address the range of possible complications. Patients should discuss treatment options with their healthcare team to determine the most appropriate strategies for their specific situation.

Outcomes for individuals with diethylstilbestrol syndrome vary depending on the nature and severity of the reproductive tract malformations and other individual factors. With current standards of care, many affected individuals maintain a good quality of life through appropriate surveillance and management. The condition may progress, stabilize, or present with a variable course in different individuals, and outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with specialists familiar with this condition and to consider genetic counseling for further guidance on long-term management and family planning.

Several clinical trials are currently investigating new treatment approaches for diethylstilbestrol syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team to learn more about eligibility and emerging therapies.