Multiple androgenic abnormalities, including elevated free testosterone, in hyperprolactinemic women

Abstract

To investigate the basis of the hirsutism and elevated plasma dehydroepiandrosterone (DHA) and/or DHA sulfate (DHAS) in hyperprolactinemic women, we measured androgen binding parameters and an extensive profile of plasma androgens in normal (NL) and hyperprolactinemic women (HYPRL). ACTH tests and dexamethasone (dex) suppression tests were performed in subgroups. Free testosterone levels were higher in HYPRL (13.1 +/- 23.3 vs. 7.18 +/- 0.72 pg/ml; P less than 0.025), although total testosterone was comparable. This disparity was related to plasma testosterone-estradiol-binding globulin (TEBG) levels being one third lower in HYPRL (mean +/- SE, 27.4 +/- 4.0 nM) than in NL (41.2 +/- 3.7 nM; P less than 0.0125). Less striking elevations of plasma DHAS, androstenedione, and 11-deoxycortisol were found in HYPRL. Plasma total dihydrotestosterone [17 beta-hydroxy-5 alpha-androstan-3-one (tDHT)] was nearly 30% lower in HYPRL (11.2 +/- 2.6 ng/dl) than in NL (15.6 +/- 1.3 ng/dl; P less than 0.025), whereas free DHT was normal. Ratios of tDHT to precursors were lower in HYPRL (P less than 0.005). After ACTH stimulation, hyperresponsiveness of 17-hydroxyprogesterone and androstenedione were observed. Apparent adrenal enzyme efficiencies, judged from post-ACTH product to precursor ratios, were normal in HYPRL with one exception: the ratio of tDHT to total testosterone at 4 h was lower (P less than 0.05). Dex suppression normalized androgens and obliterated the abnormal tDHT to precursor ratios. These findings suggest an ACTH dependency of the abnormalities. In summary, we find that about 40% of HYPRL have an androgenic abnormality, and the most characteristic abnormality is an elevated free testosterone level (abnormal in 43%). Depressed TEBG and high DHAS levels were found with lesser frequency (19-21%). The plasma tDHT concentration was low, both in absolute terms and relative to its precursors. Dex suppressibility of the hyperandrogenemia was also observed. We postulate that PRL may exert multiple effects on steroid secretion and metabolism. Possibilities include the inhibition of the TEBG level.