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)