Endocrine Abstracts

Background: Daily injection of progesterone in men is reported to suppress the pituitary LH response to GnRH challenge. We hypothesized that the progesterone nuclear hormone receptor antagonist mifepristone (RU486) would reverse these effects.

Study design: Open–label randomised, three period crossover-over study in 12 healthy male subjects. Subjects were treated for 8 days with A/ progesterone 50 mg (IM) alone; B/ progesterone 50 mg + mifepristone 10 mg; C/ progesterone 50 mg + mifepristone100 mg with a 14 day washout between treatments. On days 1, 3 and 8 a GnRH challenge 1.4 μg/kg (IV), was carried out 2 h prior to study treatment administration. Blood samples were collected at -25, -15, -5, 15, 30, 60, 90 and 115 mins around the challenge and analysed for LH, FSH and testsoterone (T). Basal hormone levels and response to GnRH challenge (AUC0-2 h) were compared by ANOVA.

Results: Treatment with progesterone alone suppressed basal LH, FSH and T by 42, 43 and 64% on day 3 and 37, 46 and 62% on day 8 (relative to day 1). Concomitant treatment with RU486 dose dependently reversed the suppression of basal LH, FSH and T. In Group B (10 mg RU486), LH, FSH and T were increased by 16%, 35% and 126% on day 3, and by 18, 30 and 48% on day 8 compared to group A (no RU486). In group C (100 mg RU486), LH, FSH and T were increased by 34, 39 and 185% on day 3, and by 61, 36 and 108% on day 8 compared to group A (no RU486).

Progesterone treatment did not affect the LH, FSH or T response to GnRH challenge, and addition of RU486 had no affect on the response to GnRH.

Conclusions: Progesterone suppression of basal LH, FSH and T in men is mediated through the nuclear hormone receptor for progesterone.