SAT-022 Adrenal Androgen Production Is Maintained While Ovarian Estrogens Fall Following the Final Menstrual Period in the Study of Women’s Health Across the Nation (SWAN)

Abstract

The aim of this study was to clarify changes in sex steroids at the final menstrual period (FMP). We have shown previously that estradiol (E2) declines substantially in the 4-year period around the FMP, but hypothesize that testosterone (T) declines modestly and adrenal Δ5 androgens dehydroepiandrosterone (DHEA) and androstenediol (Adiol) remain unchanged. Methods: Liquid chromatography tandem mass spectrometry (LC-MS/MS) and immunoassay was used in approximately annual samples collected before and following FMP in 1490 women. We estimated time-related changes in each log-transformed androgen using piecewise linear mixed modeling, with knots (slope changes) at FMP-2 yrs and FMP+2 yrs as seen for E2. These models then were re-estimated for subgroups with different time courses identified using group-based trajectory modeling. Results: In the full sample, T was generally stable, although time course varied by subgroup, with a significant decrease of 5%/year in T in [FMP-2yrs, FMP+2yrs] only in the lowest T women. For DHEA and Adiol, declines were similar across all 3 time segments and across subgroups. Mean circulating androgen concentration declined modestly (P> 0.05) from five years before to five years following FMP. However, when stratified only the lowest 7% of circulating T declined significantly (p< 0.05) in the four years surrounding FMP when mean circulating E2 declined. This trajectory divergence of the lower circulating T suggests a different, non-adrenal source that is decreased at FMP which may be useful in clarifying ovarian versus adrenal testosterone production during the post-menopause. Paired results from samples collected before and following FMP in the same subjects indicate mean circulating E2 is less than 5% of mean circulating T suggesting that a relatively large portion of circulating E2 may be largely a result of peripheral conversion of adrenal androgens. Longitudinal LC-MS/MS analyses of circulating E2 and T indicate that the principal change in sex steroid influence at menopause is largely a decrease and dampening of ovarian and not adrenal steroid production.