Evaluation of effects of an oral contraceptive containing ethinylestradiol combined with drospirenone on adrenal steroidogenesis in hyperandrogenic women with polycystic ovary syndrome

Objective: To investigate whether the administration of an oral contraceptive containing the new antiandrogenic drospirenone is associated with reduced adrenal androgen synthesis in hyperandrogenic women with diagnosis of polycystic ovary syndrome. Drospirenone, an analogue of spironolactone and aldosterone antagonist, is a novel progestin under clinical development that is similar to the natural hormone progesterone, combining potent progestogenic with antimineralocorticoid and antiandrogenic activities. Design: Prospective study. Setting: Healthy volunteers in University Department of Obstetrics and Gynecology. Patient(s): Fifteen women ages 18 to 28 years with the diagnosis of polycystic ovary syndrome. Intervention(s): Three months of contraceptive use (30 mcg ethinylestradiol, 3 mg drospirenone). Main Outcome Measure(s): An adrenocorticotropic hormone test was performed before and after the study. Result(s): Adrenal production of cortisol was unchanged after therapy with oral contraceptives. An interesting observation was reduced basal concentrations of androgens such as androstenedione, dehydroepiandrosterone sulfate, testosterone, and free testosterone during therapy. The ratios of the areas of substrates to products before and after oral contraceptive administration were compared for differences in 17-hydroxylase (17-hydroxyprogesterone/ progesterone) and 17,20-lyase (androstenedione/17-hydroxyprogesterone); activities were significantly reduced, indicating a reduction in the activities of these enzymes. Conclusion(s): The present results show for the first time that oral contraceptives containing drospirenone affect adrenal steroidogenesis by reducing synthesis and release of androgens in response to adrenocorticotropic hormone, leaving adrenal production of cortisol unchanged.