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

• Published in: The journal of clinical endocrinology and metabolism Vol. 104; no. 7; pp. 2615 - 2622
• Main Authors: Nanba, Aya T, Rege, Juilee, Ren, Jianwei, Auchus, Richard J, Rainey, William E, Turcu, Adina F
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.07.2019; Copyright Oxford University Press; Oxford University Press
• Subjects: Adrenal cortex; Adrenal Cortex - metabolism; Adrenal glands; Adult; Age; Aged; Aging; Aging - blood; Aging - metabolism; Androgens; Androstenedione; Androstenes - blood; Androstenes - chemistry; Androstenes - metabolism; Clinical s; Cytochrome b5; Cytochromes b5 - metabolism; Dehydroepiandrosterone; Female; Hormone replacement therapy; Humans; Immunofluorescence; Liquid chromatography; Mass spectroscopy; Middle Aged; Ovaries; Oxygen - chemistry; Post-menopause; Postmenopause - blood; Postmenopause - metabolism; Progesterone Reductase - metabolism; Steroid hormones; Sulfates; Sulfotransferase; Sulfotransferases - metabolism; Testosterone; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2018-02527

Abstract 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 C19 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 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 premenopausal (age 20 to 40 years) and 100 postmenopausal (age ≥ 60 years) women. Double immunofluorescence of 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) with cytochrome b5 (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. This study of 100 pre- and 100 postmenopausal women shows that unlike other androgens, the adrenal 11-oxygenated C19 steroids do not decline with aging.