Impaired pregnenolone secretion after combined cyproterone acetate and ethynyl estradiol therapy in hirsute patients.

Abstract

6 women affected by hirsutism, either of idiopathic origin or due to polycystic ovary syndrome, have been treated with cyproterone acetate and ethynyl estradiol in combined therapy using, respectively, 100 mg and 50 micrograms/day, from the 5th to the 25th day of the cycle. The adrenal function was assessed before treatment and at the end of the 4th month of therapy, evaluating the peripheral plasma concentrations of pregnenolone (delta 5P), progesterone, 17-OH-progesterone, dehydro-epiandrosterone sulfate, androstenedione, testosterone, and cortisol in basal conditions and after dexamethasone suppression and an adrenocorticotropic hormone (ACTH) stimulation test. A group of healthy, untreated females were examined in the early follicular phase, as controls, Before therapy, the hirsute patient showed testosterone and androstenedione plasma levels, which were significantly higher than in the controls, and a significant reduction in pregnenolone response to ACTH. After 4 months of therapy with cyproterone acetate plus ethynyl estradiol, a significant decrease was found in testosterone and androstenedione plasma levels, and pregnenolone basal plasma levels, dexamethasone suppressibility, and response to ACTH were also markedly reduced, showing a significant difference versus the same patients before therapy and versus the control group. The existence of an impairment in adrenal function after cyproterone acetate plus ethynyl estradiol therapy at the given dose seems to be evident only in the case of directly ACTH-dependent adrenal enzymatic activities responsible for cholesterol cleavage to pregnenolone.