Effect of Medroxyprogesterone Acetate (Provera) on the Metabolism and Biological Activity of Testosterone

Abstract

Oral administration of medroxyprogesterone acetate to 4 normal male and 3 normal female subjects was found to produce a significant increase in the metabolic clearance rate of testosterone in 6 of the 7 subjects. The plasma levels and production rates of testosterone decreased markedly in the males. The females tended to show a decrease in the plasma concentration of testosterone with no change in the production rate of the steroid. Although there was an over-all decrease in the percentage binding of testosterone for the group, individual responses were variable in degree and did not necessarily correlate with the alterations in the metabolic clearance rate of the steroid. Plasma LH levels fell during the administration of medroxyprogesterone acetate in 6 of the 7 subjects. Plasma FSH, however, decreased in only 1 subject (postmenopausal female). Medroxyprogesterone acetate increased rat hepatic testosterone A-ring reductase activity almost 4-fold. Moreover, the drug interfered with the growth-promoting effect of testosterone on rat ventral prostate. There was no evidence that the drug induced hepatic microsomal hydroxylases as evidenced by a negative zoxazolamine sleeping time study. The effect of medroxyprogesterone acetate on testosterone metabolism in human subjects is 2-fold: 1) it decreases the production rate of the steroid in males, presumably as a result of inhibition of pituitary secretion of LH, and 2) it increases the rate of removal of the steroid from the circulation, possibly by enhancing hepatic A-ring reductase activity.