How do androgens affect episodic gonadotrophin secretion in postmenopausal women?

In the absence of any significant ovarian oestrogen secretion, as in post-menopausal women, the hypothalamic-pituitary axis may still be influenced by the androgens which continue to be produced. The episodic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by postmenopausal women was accordingly assessed following short-term androgen antagonism induced by flutamide, a specific androgen receptor blocker. Blood samples were collected at 10-min intervals for 10 h in nine women before and during flutamide administration (750 mg/day for 6 days) for the determination of gonadotrophin and sex hormone concentrations by radioimmunoassay. On both occasions, 25 micrograms of gonadotrophin-releasing-hormone (GnRH) was injected intravenously 8 h after initiation of the blood collections. Flutamide administration decreased (P less than 0.01 or less) androgen concentrations (testosterone, androstenedione and dehydroepiandrosterone sulphate) in relation to baseline values, but did not alter oestrogen (oestrone and oestradiol) or sex-hormone-binding globulin levels. The LH and FSH pulse characteristics (frequency, amplitude, interpulse interval and transverse mean levels) determined by a cluster algorithm in the gonadotrophin secretory profiles did not differ before and during androgen blockade. By contrast, androgen antagonism increased LH (P less than 0.01) and tended to enhance FSH (P = 0.10) FSH release in response to GnRH stimulation. Hence, short-term androgen receptor blockade with flutamide did not greatly affect episodic gonadotrophin secretion. However, the combined evidence of the enhanced gonadotrophin release observed in response to GnRH stimulation and the unchanged gonadotrophin secretion during androgen antagonism suggests that alterations in the magnitude, but not the frequency, of hypothalamic GnRH release had occurred. Even in the presence of substantial serum androgen concentrations, the gonadotrophin pulse rhythm in hypogonadal women constitutes the maximal-rate GnRH-LH release pattern.