androstane-3-17-diol-glucuronide and Hypogonadism

Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of dehydroepiandrosterone (DHEA).. In this randomized, double-blind, placebo-controlled study in 99 new COC starters (18-35 years old with body mass index range 18-34 kg/m²), a COC containing 30mcg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) was used for 3cycles, followed by 6cycles of the same COC combined with either 50 mg/day DHEA or placebo. Total T, albumin, sex hormone-binding globulin (SHBG), DHEA-sulfate (DHEA-S), Δ4-androstenedione (AD), 3α-androstanediol glucuronide (ADG) and estradiol (E₂) were measured, whereas free T and the free T index (FTI) were calculated. Assessments took place at baseline (no COC use), after the run-in period (COC use alone) and during the treatment period (DHEA or placebo).. During COC use alone, androgen levels decreased, especially total T by 62% and free T by 86%, and SHBG increased by 243%. Total T increased with DHEA compared to placebo (change from end of run-in period to end of treatment period -- 1.3±1.2 nmol/L vs. 0.0±0.4 nmol/L; p<.0001) -- and was restored to baseline levels. Free T and the FTI increased significantly (p<.0001), but the free T level was still 53% below baseline levels. DHEA-S, AD and ADG increased significantly to levels above baseline (p<.0001 for each). DHEA had no effect on SHBG, albumin and E₂.. An EE/DRSP containing COC strongly suppressed endogenous androgen concentrations in all users. The addition of 50 mg DHEA to a COC regimen containing EE/DRSP restored total T to baseline levels, but free T levels were restored by only 47% as most of the T remains bound to SHBG.. When using a COC that increases SHBG considerably, a daily dose of 50 mg DHEA is insufficient to normalize free T levels completely.

Topics: Adolescent; Adult; Androgen Antagonists; Androstane-3,17-diol; Androstenedione; Androstenes; Belgium; Contraceptives, Oral, Combined; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Double-Blind Method; Drug Combinations; Ethinyl Estradiol; Female; Humans; Hypogonadism; Sex Hormone-Binding Globulin; Solubility; Testosterone; Up-Regulation; Young Adult

Five hypogonadal men were treated with transdermal testosterone therapy, using a testosterone patch applied to the scrotal skin. Daily application of the patch, which contained 10 mg testosterone, produced an increase in serum testosterone concentrations from a pretreatment value of 45 +/- 12 (+/- SE; 1.5 +/- 0.4) to 436 +/- 80 ng/dL (15.1 +/- 2.8 nmol/L; P less than 0.001) after 4 weeks of treatment. Normal serum testosterone concentrations were achieved in all men after 6-8 weeks of therapy and were maintained during continued long term therapy for 9-12 months with a patch containing 15 mg testosterone. All men reported a subjective increase in libido and sexual function during therapy, and three men preferred it to testosterone injections. The serum testosterone and estradiol levels did not rise above the normal adult male range at any time during therapy. However, elevated serum dihydrotestosterone (DHT) concentrations occurred during treatment; the pretreatment DHT concentration was 95 +/- 3 ng/dL (3.3 +/- 0.1 nmol/L), and it increased to 228 +/- 40 ng/dL (7.8 +/- 1.4 nmol/L) after 4 weeks of treatment and remained elevated thereafter. The individual mean DHT to testosterone ratio increased from a pretreatment value of 0.2 (range, 0.1-0.3) to 0.6 (range, 0.4-0.7) after 2 weeks of therapy and remained high thereafter. Comparison of the serum DHT levels in patients during therapy with those in normal men who had similar testosterone concentrations [531 +/- 62 vs. 566 +/- 72 ng/dL (18.4 +/- 2.1 vs. 19.6 +/- 2.5 nmol/L); P greater than 0.05] revealed that the mean serum DHT concentration was significantly higher in the patients [315 +/- 69 vs. 87 +/- 6 ng/dL (10.8 +/- 2.4 vs. 2.9 +/- 0.2 nmol/L); P less than 0.001], as was the mean DHT to testosterone ratio [0.6 (range, 0.25- 1.1) vs. 0.16 (range, 0.09- 0.24); P less than 0.001]. The high serum DHT levels presumably were due to increased metabolism of testosterone to DHT by the 5 alpha-reductase in the scrotal skin. Serum 3 alpha-androstanediol glucuronide levels were not elevated in the patients. We conclude that transdermal testosterone therapy is an effective long term treatment for hypogonadism in men. It is, however, associated with high serum DHT levels, whose potential long term effects on the prostate and other tissues need to be investigated.

Topics: Administration, Cutaneous; Androstane-3,17-diol; Dihydrotestosterone; Estradiol; Humans; Hypogonadism; Male; Testosterone