ROLE OF ANDROGENS IN THE REGULATION OF THE HUMAN MENSTRUAL-CYCLE

Although previous investigations have examined the importance of andro gens in the regulation of the human menstrual cycle, no consensus has been reached, due to conflicting results. We have therefore used the n on-steroidal anti-androgen flutamide as a pharmacological probe to eva luate the role of androgens in the control of gonadotropin secretion i n normally cycling women. Eight women were studied during control and treatment cycles, during which either placebo (as control) or flutamid e (750 mg orally) was given daily. Blood was sampled every other day d uring the follicular and luteal phases and daily around the expected m idcycles for determination of luteinizing hormone (LH), follicle stimu lating hormone (FSH), estradiol, progesterone and androgens (testo-ste rone, androstenedione, dehydroepiandrosterone sulfate) by radioimmunia ssay and immunoradiometric assay. To establish unstimulated and gonado tropin releasing hormone (GnRH)-stimulated gonadotropin profiles, bloo d samples were frequently collected (every 10 min for 8 h, GnRH 25 mug i.v. after 7 h on day 10 in both the control and treatment cycles. Co mpared to control conditions, the durations of both the follicular and luteal phases did not change considerably during flutamide treatments . Serum androgen levels (testosterone, androstenedione dehydroepiandro sterone sulfate) were significantly (p < 0.01) reduced during androgen antagonism. Daily gonadotropin and estradiol levels did not differ be tween control and flutamide cycles, while progesterone secretion tende d to be attenuated (p = 0.2) during the luteal phases of the flutamide cycles. The LH and FSH secretory profiles and the GnRH-stimulated gon adotropin responses remained virtually unchanged during androgen antag onism. Thus, while androgen receptor blockade was capable of markedly reducing the circulating androgen concentrations, it failed to modify the temporal organization and endocrine characteristics of the menstru al cycles significantly. In particular, the dynamics of unstimulated e pisodic and GnRH-stimulated gonadotropin release remained unaffected. Within the limitations of the nature of a pharmacological experiment, we conclude that androgens may not critically participate in the neuro endocrine regulation of the human menstrual cycle.