11-Oxygenated C19 Steroids Do Not Decline With Age in Women

Context: The ovaries and adrenals are sources of androgens in women. Although dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and testosterone (T) all decline with age, these C-19 steroids correlate poorly with parameters of androgen action in postmenopausal women. Objective: To comprehensively compare the androgen profiles of pre-and postmenopausal women. Methods: We quantified 19 steroids-including DHEA; DHEAS; T; androstenedione (A4); and the following adrenal-specific 11-oxygenated C-19 steroids (11oxyandrogens): 11 beta-hydroxytestosterone (11OHT), 11-ketotestosterone (11KT), 11 beta-hydroxyandrostenedione (11OHA4), and 11-ketoandrostenedione (11KA4)-using liquid chromatography-tandem mass spectrometry in morning serum obtained from 100 premenopausal (age 20 to 40 years) and 100 postmenopausal (age >= 60 years) women. Double immunofluorescence of 3 beta-hydroxysteroid dehydrogenase type 2 (HSD3B2) with cytochrome b(5) (CYB5A) or sulfotransferase 2A1 (SULT2A1) was performed in normal adrenal glands obtained from eight premenopausal and eight postmenopausal women. Results: DHEA, DHEAS, A4, and T were significantly higher in pre- than in postmenopausal women (2.9, 2.8, 2.9, and 1.6-fold, respectively; P < 0.0001). In contrast, the 11-oxyandrogens did not decrease with aging, and the 11OHT/T and 11OHA4/A4 ratios showed strong positive correlations with age (r = 0.5 and 0.8, respectively; P < 0.0001). Double immunofluorescence analysis showed that with the involution of the zona reticularis in the old adrenals, the sharp zonal segregation of HSD3B2 and CYB5A becomes less distinct, and areas of HSD3B2 and CYB5A overlap are observed. Conclusions: Unlike DHEA, DHEAS, A4, and T, the 11oxyandrogens do not decline in aging women. Structural changes within the adrenal cortex might explain the evolution of androgen profiles in aging women.