11-Oxygenated C19 Steroids Do Not Decline with Age in Women.

Context: The ovaries and adrenals are sources of androgens in women. While dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and testosterone (T) all decline with age, these C19 steroids correlate poorly with parameters of androgen action in postmenopausal women.

Objective: To comprehensively compare androgen profiles in pre- and post-menopausal women.

Methods: We quantified 19 steroids, including DHEA, DHEAS, T, androstenedione (A4), and the adrenal-specific 11-oxygenated C19 steroids (11oxyandrogens) 11β-hydroxytestosterone (11OHT), 11-ketotestosterone (11KT), 11β-hydroxyandrostenedione (11OHA4) and 11-ketoandrostenedione (11KA4) using liquid chromatography-tandem mass spectrometry in morning serum obtained from 100 pre- (age 20-40 years) and 100 post-menopausal (age ≥ 60 years) women. Double immunofluorescence of 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) with either cytochrome b5 (CYB5A) or sulfotransferase 2A1 (SULT2A1) was performed in normal adrenal glands obtained from 8 pre- and 8 post-menopausal women.

Results: DHEA, DHEAS, A4 and T were significantly higher in pre- vs. post-menopausal women (fold pre/post 2.9, 2.8, 2.9 and 1.6, 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.