Serum Sex Steroid Levels and Longitudinal Changes in Bone Density in Relation to the Final Menstrual Period

Context: The associations of serum sex steroid and FSH levels with change of bone mineral density (BMD) across the complete menopausal transition are incompletely understood. Objective: The objective of the study was to examine the associations of annual serum levels of FSH, estradiol (E-2), T, and SHBG with the rates of bone loss in 3 phases: pretransmenopausal [baseline to 1 year before the final menstrual period (FMP)], transmenopausal (1 year before to 2 years after the FMP), later postmenopausal (>= 2 years after the FMP). Design: The design of the study was a repeated-measures, mixed-effects regression. Setting: This was a community-based observational study, with a 10-year follow-up. Participants: A total of 720 participants of the Study of Women's Health Across the Nation Bone Study participated in the study. Outcome Measures: Annualized lumbar spine (LS) and femoral neck (FN) BMD decline was measured. Results: The mean annual change in BMD was slowest in pretransmenopause (0.27%/year in FN) and fastest in transmenopause (2.16%/year in LS). In the pretransmenopausal phase, for every doubling of FSH level, LS BMD change was faster by -0.32%/year (P < .0001). In the transmenopausal phase, for every doubling of FSH level, LS BMD change was -0.35%/year faster (P < .0001); for every doubling of SHBG level, LS BMD change was -0.36%/year faster (P < .0001). In the later postmenopausal phase, for each doubling of the E-2 level, the LS BMD change was slower by +0.26%/year (P = .049); for each SHBG doubling, the LS BMD change was 0.21%/year slower (P = .048). The FN associations were weaker and inconsistent. Conclusions: Higher E-2 levels and lower FSH levels were associated with lower rates of LS bone loss in some but not all menopausal transition phases. (J Clin Endocrinol Metab 98: E654-E663, 2013)