Metabolic clearance rate and interconversion of androgens and the influence of the free androgen fraction

Abstract

Using the continuous infusion technique, the conversion ratios (CR) of testosterone (T) to androstenedione (A) and dihydrotestosterone (DHT) and of A to T and DHT were determined in 12 normal males (aged 31-72 yr), 10 normal postmenopausal women, and 4 amenorrheic women with idiopathic hirsutism; in 4 additional males these studies were performed during infusion of cold T to increase plasma T to supraphysiological levels. It was observed that besides the MCR of T and DHT, the blood conversion ratios (CRBB) of T in A and to a lesser extent of T in DHT were also significantly correlated with either the free or the nontestosterone-estradiol-binding globulin-bound T fraction but not with total plasma T. In postmenopausal women, plasma A was by far the most important precursor of plasma DHT; the CRA/DHTBB was significantly higher than CRT/DHTBB. It is suggested that total plasma A, but only nonspecifically bound T, freely gains access into the cells where these conversions occur and that plasma A might be an important parameter of androgenicity. Less than 50% of plasma DHT could be accounted for by peripheral conversion of either A or T. Whereas in males this may be explained by direct DHT secretion, in (postmenopausal) women conversion of other precursors to plasma DHT should be considered.