Exogenous testosterone does not influence 11-oxygenated C19 steroid concentrations in healthy postmenopausal women

Context: 11b-Hydroxyandrostenedione (11OHA4), 11b-hydroxytestosterone (11OHT), and their respective peripheral derivatives, 11-ketoandrostenedione (11KA4) and 11-ketotesosterone (11KT), have been implicated in androgen-related physiopathology. Little is known of these steroids in postmenopausal women or whether exogenous testosterone therapy influences their levels. Objective: The impact of exogenous testosterone on serum levels of 11-oxygenated steroids was determined in healthy postmenopausal women. Participants and Methods: Levels of 19-carbon (C19) steroids were measured by liquid chromatography-tandem mass spectrometry in serum obtained at baseline and at 12 and 26 weeks from 73 healthy postmenopausal women, aged 55 to 65 years, who participated in a randomized, double-blind, placebo-controlled clinical trial assessing the effects of transdermal testosterone on cognitive performance. Results: Of the 11-oxygenated androgens, 11OHA4 was the most abundant (median, 6.46 nmol/L; range, 1.51 to 23.82 nmol/L), with concentrations several fold greater than its precursor androstenedione (median, 1.38 nmol/L; range, 0.52 to 2.92 nmol/L). Baseline median (range) testosterone and 11KT levels were similar [0.56 (0.23 to 1.48) nmol/L; 0.85 (0.25 to 2.86) nmol/L, respectively). 11OHT was closely correlated with 11KT (Spearman rank correlation coefficient, 0.79; P, 0.001) and 11OHA4 correlated with 11KA4 (Spearman rank correlation coefficient, 0.73; P, 0.001). Testosterone therapy resulted in an increase in serum testosterone level, whereas all 11-oxygenated androgens remained unchanged throughout the 26 weeks of treatment. Conclusion: After menopause, the adrenal production of 11-oxygenated derivatives of androstenedione and testosterone contributes importantly to the total circulating androgen pool. Exogenous testosterone does not influence the circulating levels 11-oxygenated C19 steroids.