No Evidence for Hepatic Conversion of Dehydroepiandrosterone (DHEA) Sulfate to DHEA: In Vivo and in Vitro Studies

Dehydroepiandrosterone (DHEA) sulfate (DHEAS) is the most abundant steroid in the human circulation and is thought to be the circulating hydrophilic storage form of DHEA. It is generally accepted that DHEA and DHEAS interconvert freely and continuously via hydroxysteroid sulfotransferases and steroid sulfatase and that only desulfated DHEA can be converted downstream to sex steroids. Here we analyzed DHEA/DHEAS interconversion in vivo and in vitro. We administered oral DHEA (100 mg) and iv DHEAS (25 mg) to eight healthy young men, resulting in similar increases in serum DHEAS compared with baseline. However, although DHEA administration significantly increased serum DHEA (P < 0.05), no such increase was observed after DHEAS. Similarly, DHEA but not DHEAS was converted downstream to androstenedione, estrone, and androstanediol glucuronide. The striking absence of conversion of DHEAS to DHEA was mirrored by our in vitro findings in HepG2 cells, revealing dose-dependant conversion of DHEA (0.1–2 μm) to DHEAS but no conversion of DHEAS (0.1–2 μm). These results clearly illustrate a lack of hepatic conversion of DHEAS to DHEA, challenging the concept of free interconversion of DHEA and DHEAS. DHEAS does not seem to represent a circulating storage pool for DHEA regeneration, and therefore serum DHEAS is unlikely to reflect bioavailable DHEA.

Comparison of finasteride versus flutamide in the treatment of hirsutism

OBJECTIVE: To compare the effectiveness of finasteride and flutamide in the treatment of hirsutism in patients with polycystic ovary syndrome (PCOS) and with idiopathic hirsutism. DESIGN: Randomized study. PATIENTS: One hundred and ten hirsute patients were selected: 64 women with PCOS and 46 with idiopathic hirsutism. METHODS: Patients were assigned randomly to receive 5mg finasteride once daily or 250mg of flutamide twice daily, for 12 consecutive months. Hirsutism was evaluated at 12 months of therapy, with the Ferriman-Gallwey score and with measurement of the terminal hair diameters (microm) taken from four different body areas. Blood samples were taken for assessment of endocrine and hematochemical parameters. Side effects were monitored during the treatment. RESULTS: Both finasteride and flutamide induced a significant decrease in the hirsutism scores and hair diameters at the end of 12 months. Finasteride reduced the Ferriman-Gallwey score by 31.4% in the PCOS cases and by 34.2% in the idiopathic hirsutism cases, and hair diameter by 27.0-34.1% in PCOS and by 29.6-37.9% in idiopathic hirsutism. Flutamide reduced the Ferriman-Gallwey score by 56.7% in PCOS and by 50.9% in idiopathic hirsutism, and hair diameter by 50. 3-60.0% in PCOS and by 47.7-56.5% in idiopathic hirsutism. Flutamide did not induce hormone variations, while finasteride increased testosterone levels by 40% in PCOS and by 60% in idiopathic hirsutism and decreased 3alpha-androstanediol glucuronide (3alpha-diolG) by 66.7% in PCOS and by 69.5% in idiopathic hirsutism. No important side effects or changes in the hematochemical parameters were observed with finasteride, while two patients (3.6%) in the flutamide group expressed abnormal transaminase levels after 6 months of treatment. Dry skin also appeared significantly more with flutamide (67.3%) than with finasteride (23.6%). CONCLUSIONS: Both drugs are effective in the treatment of hirsutism but flutamide is more effective than finasteride.

Serum levels of 3alpha-androstanediol glucuronide in hirsute and non hirsute women

This study has evaluated the behaviour of 3alpha-androstanediol glucuronide (3alpha-diol G) in 170 women of whom 85 had polycystic ovary syndrome (PCOS), 35 had idiopathic hirsutism (IH) and 50 had regular cycles (control group). Of the women with PCOS, 45 were hirsute (PCOS-H) and 40 were non hirsute (PCOS-NH). Women in the control group were not hirsute. Hirsutism was assessed by the same physician using the Ferriman-Gallway score. The body mass index (BMI) was estimated in all of the women. Plasma concentrations of 3alpha-diol G were elevated only in hirsute patients, both with PCOS and with IH. Even in PCOS-NH, concentrations of 3alpha-diol G were higher compared with controls (P < 0.001), but significantly lower (P < 0.001) than those of the PCOS-H and of the IH groups. The behaviour of 3alpha-diol G was not affected by BMI.