Objective and Context: Examine predictability of reproductive hormone concentrations for bone mineral density (BMD) loss during the menopausal transition.

Design: Longitudinal (5 annual examinations), multiple site (n = 5) cohort study, the Study of Women's Health Across the Nation (SWAN).

Participants: At baseline, 2311 premenopausal or early perimenopausal African American, Caucasian, Chinese, and Japanese women.

Main Outcome Measures: Annual DEXA lumbar spine (LS) and total hip BMD measures, with endogenous estradiol (E2), follicle stimulating hormone (FSH), androgens, and self-reported menstrual bleeding patterns.

Results: Over the 4-year period, LS BMD loss was 5.6% in natural postmenopause, 3.9% in surgical postmenopause or 3.2% in late perimenopause. Baseline FSH concentrations, subsequent FSH levels, and their interaction predicted 4-year BMD loss. If baseline FSH was less than 25 mIU/ml, higher follow-up FSH (>70 mIU/ml) predicted a 4-year spine BMD loss of -0.05 g/cm². If baseline FSH values were more than 35-45 mIU/ml, lower follow-up FSH (i.e. 40-50 mIU/ml) predicted a -0.05 g/cm² 4-year spine BMD loss. Charts show amounts of predicted BMD losses with combinations of baseline FSH values and FSH levels over time. E2 concentrations <35 pg/ml were associated with lower BMD, but annual E2 measures and changes did not predict BMD loss. Testosterone, Free Androgen Index, and dehydroepiandrosterone-sulfate concentrations were not significantly associated with BMD loss.

Conclusions: Spine and hip BMD losses during the menopause transition were most strongly related to the interaction between initial FSH levels and longitudinal FSH changes and not to E2 or androgen levels or changes.