Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and estrone over the menopausal transition

Women's Midlife Health, Oct 2017

Background Previous reports have noted that dehydroepiandrosterone-sulfate (DHEAS) increases prior to the final menstrual period (FMP) and remains stable beyond the FMP. How DHEAS concentrations correspond with other sex hormones across the menopausal transition (MT) including androstenedione (A4), testosterone (T), estrone (E1), and estradiol (E2) is not known. Our objective was to examine how DHEAS, A4, T, E1, and E2 changed across the MT by White vs. African-American (AA) race/ethnicity. Methods We conducted a longitudinal observational analysis of a subgroup of women from the Study of Women’s Health Across the Nation observed over 4 visits prior to and 4 visits after the FMP (n = 110 women over 9 years for 990 observations). The main outcome measures were DHEAS, A4, T, E1, and E2. Results Compared to the decline in E2 concentrations, androgen concentrations declined minimally over the MT. T (β 9.180, p < 0.0001) and E1 (β 11.365, p < 0.0001) were higher in Whites than in AAs, while elevations in DHEAS (β 28.80, p = 0.061) and A4 (β 0.2556, p = 0.052) were borderline. Log-transformed E2 was similar between Whites and AAs (β 0.0764, p = 0.272). Body mass index (BMI) was not significantly associated with concentrations of androgens or E1 over time. Conclusion This report suggests that the declines in E2 during the 4 years before and after the FMP are accompanied by minimal changes in DHEAS, A4, T, and E1. There are modest differences between Whites and AAs and minimal differences by BMI.

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Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and estrone over the menopausal transition

Kim et al. Women's Midlife Health Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and estrone over the menopausal transition Catherine Kim 0 Siobàn D. Harlow 2 Huiyong Zheng 2 Daniel S. McConnell 2 John F. Randolph Jr. 1 0 Departments of Medicine and Obstetrics & Gynecology, University of Michigan , 2800 Plymouth Road, Building 16, Room 430W, Ann Arbor, MI 48109 , USA 1 Department of Obstetrics & Gynecology, University of Michigan , Ann Arbor, MI , USA 2 Department of Epidemiology, University of Michigan , Ann Arbor, MI , USA Background: Previous reports have noted that dehydroepiandrosterone-sulfate (DHEAS) increases prior to the final menstrual period (FMP) and remains stable beyond the FMP. How DHEAS concentrations correspond with other sex hormones across the menopausal transition (MT) including androstenedione (A4), testosterone (T), estrone (E1), and estradiol (E2) is not known. Our objective was to examine how DHEAS, A4, T, E1, and E2 changed across the MT by White vs. African-American (AA) race/ethnicity. Methods: We conducted a longitudinal observational analysis of a subgroup of women from the Study of Women's Health Across the Nation observed over 4 visits prior to and 4 visits after the FMP (n = 110 women over 9 years for 990 observations). The main outcome measures were DHEAS, A4, T, E1, and E2. Results: Compared to the decline in E2 concentrations, androgen concentrations declined minimally over the MT. T (β 9.180, p < 0.0001) and E1 (β 11.365, p < 0.0001) were higher in Whites than in AAs, while elevations in DHEAS (β 28.80, p = 0.061) and A4 (β 0.2556, p = 0.052) were borderline. Log-transformed E2 was similar between Whites and AAs (β 0.0764, p = 0.272). Body mass index (BMI) was not significantly associated with concentrations of androgens or E1 over time. Conclusion: This report suggests that the declines in E2 during the 4 years before and after the FMP are accompanied by minimal changes in DHEAS, A4, T, and E1. There are modest differences between Whites and AAs and minimal differences by BMI. Dehydroepiandrosterone-sulfate; Androstenedione; Testosterone; Estrone; Menopause Background The menopausal transition (MT) represents a marked shift in women’s sex steroid profile, of which changes in estradiol (E2) are the best studied [ 1 ]. On average, women’s E2 concentrations begin to change more rapidly about 2 years prior to the final menstrual period (FMP) and stabilize several years after the FMP [ 2 ]. The rapidity of decline and average E2 levels may be predicted by race/ethnicity and body mass index (BMI) at the beginning of the transition [ 3, 4 ]. The most pronounced differences occur between African-American (AA) and White women, the former group having more gradual changes than the latter group [4]. Presumably in part due to adipose tissue production of E2, women with higher BMI have more gradual changes than women with lower BMI [ 3, 4 ]. The adrenal gland is the primary source of dehydroepiandrosterone-sulfate (DHEAS) and androstenedione (A4) and also contributes to circulating testosterone (T) [ 5 ]. Aromatase catalyzes A4 and T into estrogens, i.e. A4 into estrone (E1) and T into estradiol (E2). Previous reports have suggested that, prior to the FMP, adrenal DHEAS production increases even as peripheral E2 decreases [ 6–10 ]. As adrenal sex hormones exist in equilibrium with ovarian sex hormones in the peripheral circulation, it is plausible that adrenal hormone metabolism also changes over the MT [ 11 ]. This is consistent with the hypothesis that increasing adrenal sex hormone production and aromatization may be concurrent with decreasing ovarian estrogen production [ 12 ]. It is also possible that DHEAS production may also eventually decline over time resulting lower peripheral A4 and E1 concentrations. Few longitudinal studies examine changes in a comprehensive array of adrenal sex hormones across the MT. Since concentrations of circulating DHEAS increase in the 5th decade of life [ 6–10 ] and concentrations among women in their 8th decade of life are low [ 13 ], DHEAS must decline in the postmenopause. However, it is uncertain when in the postmenopause this might occur. In addition, few reports examine concentrations of A4 or E1 during the MT and whether ratios of A4:E1 change over the MT, consistent with changes in aromatase activity or consistent with increased A4 production and concomitant increases in aromatization. No reports examine whether E1 concentrations change across the MT. In addition, studies have not examined whether these patterns differ by BMI, as has been reported for E2, or between Whites and AAs. Therefore, using data from the Study of Women’s Health Across the Nation (SWAN), we characterized serum adrenal and ovarian sex steroid changes over the MT. We assessed concentrations of DHEAS, A4, T, E2, and E1 annually in the 4 years before and the 4 years after the FMP. We assessed whether concentrat (...truncated)


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Catherine Kim, Siobàn D. Harlow, Huiyong Zheng, Daniel S. McConnell, John F. Randolph Jr.. Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and estrone over the menopausal transition, Women's Midlife Health, 2017, pp. 9, Volume 3, Issue 1, DOI: 10.1186/s40695-017-0028-4