THE EFFECT OF ALPRAZOLAM ON SERUM CORTISOL AND LUTEINIZING-HORMONE PULSATILITY IN NORMAL WOMEN AND IN WOMEN WITH STRESS-RELATED ANOVULATION

Alprazolam, a benzodiazepine derivative, stimulates specific gamma-ami nobutyric acid(A) receptors and has been found to inhibit CRH activity in the brain. This study examined the effect of alprazolam on serum c ortisol and LH pulsatility in six women in the early follicular phase (EFP), six women in the midluteal phase (MLP), and six women with stre ss-related anovulation (SRA) of normal weight, but with a previous his tory of anorexia nervosa. Subjects were given alprazolam (2 mg, orally ) or an identical placebo capsule at 0900 h, and blood samples were co llected through an indwelling venous catheter every 10 min for 8 h in the SRA women and 10 h in EFP and MLP women. Women with SRA were also given clomiphene (100 mg/day) for 5 days before a further 8-h blood sa mpling session. As expected, there was a diurnal decline in serum leve ls of cortisol, which was significantly less in women with SRA (55 +/- 4%) than those in both EFP (76 +/- 4%) and MLP women (75 +/- 3%; P < 0.005). The food-related rise of cortisol that follows lunch in normal women was absent in women with SRA. Alprazolam accentuated the declin e in serum cortisol, and in all three groups, the mean serum cortisol level after alprazolam treatment was significantly less (P < 0.05) tha n that after placebo.