Effects of ethinyl estradiol on semen quality and various hormonal parameters in a eugonadal male

Abstract

Objective: To determine the influence of estrogens on male fertility.

Design: A 36-year-old eugonadal male was subjected to two different regimens of treatment with ethinyl estradiol (EE2). Sperm quality, immunoreactive luteinizing hormone (LH) and follicle-stimulating Hormone (FSH), testosterone (T), estrone (E1), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), prolactin (PRL) and sex hormone-binding globulin were determined at intervals of 2 weeks for 315 days.

Setting: A gender dysphoria clinic.

Patient: A transsexual male nurse.

Main outcome measures: It was hypothesized (and confirmed) that by comparing the effects of increasing and constant dose of EE2 on fertility parameters, differences in estrogen-sensitivity would show more clearly. Furthermore, this procedure served to find the minimal dose of EE2 for complete testicular suppression.

Results: Low doses of EE2 (20 micrograms/d) had no negative effect on sperm motility and density for a period of approximately 4 weeks, whereas high doses (60 micrograms/d) reduced motility already after a few days and led to a pronounced decrease in sperm density after 2 weeks. After discontinuation of therapy, motility normalized faster than sperm density. Under increasing doses of EE2 there was a constant decrease of FSH that occurred several weeks earlier than that of LH. Under constant dose of EE2 (60 micrograms/d) the decrease of LH was delayed (with respect to FSH) by only a few days. The decrease in T showed a stronger correlation with that of FSH than with that of LH. Volume and fructose content of the seminal fluid correlated with the decrease in T. Rebound effects were observed for FSH, LH, T, and fructose during the therapy-free interval. Ethinyl estradiol therapy had no influence on the serum concentrations of E1, E2, and PRL. Estrone was the dominant estrogen before and after therapy with EE2. Adrenal gland activity was markedly suppressed by EE2, as reflected by the decrease in DHEAS.

Conclusion: The suppressive effect of EE2 on FSH and sperm motility was more pronounced and consistent than on LH and sperm density. The T decrease appears to be mainly caused by a direct effect of EE2 on the testes.