Dexamethasone suppressibility and adrenal and ovarian venous effluents of 5α-reduced C19 conjugates in hyperandrogenic women

Abstract

Several C19 conjugates, derived via 5α-reductase activity, are putative markers of peripheral androgen action and have been shown to correlate well with various clinical manifestations of androgen excess. While no ovarian vein gradient has been found for androsterone sulfate (ADT-S), androsterone glucuronide (ADT-G), 5α-androstane-3α,17β-diol sulfate (3α-diol-S), and 5α-androstane-3α,17β-diol glucuronide (3α-diol-G), the contribution of the adrenal gland to these conjugates has been unclear. Ten hirsute women were treated with 2mg/day dexamethasone (dex) for 7 days to determine the effect of adrenal androgen suppression on 5α-reduced androgen conjugate production. In addition, 11 women with mixed ovarian and adrenal androgen excess of non-neoplastic origin underwent ovarian and adrenal vein catheterization studies in order to assess gradients for the various C19 steroids. These women had significantly higher levels of both unconjugated and conjugated androgens, except for ADT-S, compared to 8 matched normal ovulatory women. After dex treatment, total testosterone (TT), unbound T (UT), androstenedione (A) and DHEAS, all decreased by 31–75%. ADT-S, ADT-G, 3α-diol-S and 3α-diol-G decreased by 48%, 71%, 46% and 68%, respectively. The suppression of the unconjugated androgens correlated highly and significantly with ADT-G. In the 11 patients undergoing adrenal venous catheterization, all patients exhibited a substantial adrenal gradient for TT and A. Of significance, in paired samples of peripheral venous and glandular effluents, no adrenal or ovarian gradient was found for any of the conjugated androgens. The data suggest that because dex suppression significantly decreases levels of the conjugated androgens, they are highly substrate dependent. However, since no adrenal or ovarian vein gradient exists, these markers of the manifestations of androgen excess largely reflect peripheral androgen metabolism.