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Hormone Predictors of Bone Mineral Density Changes during the Menopausal Transition

Departments of Epidemiology and Biostatistics (M.R.S., M.J., D.M., R.L.), School of Public Health, University of Michigan, Ann Arbor, Michigan 48104; Division of Geriatrics (G.A.G.), University of California, Los Angeles, School of Medicine, Los Angeles, California 90095; Endocrine Unit (J.S.F., R.M.N.), Massachusetts General Hospital, Boston, Massachusetts 02114; University of Pittsburgh (J.J.), Pittsburgh, Pennsylvania 15261; and Division of Research (B.E.), Kaiser Permanente Medical Care Program, Oakland, California 94611

Address all correspondence and requests for reprints to: MaryFran Sowers, Ph.D., Department of Epidemiology, School of Public Health, University of Michigan, 339 East Liberty Street, Suite 310, Ann Arbor, Michigan 48104. E-mail: mfsowers{at}umich.edu.

Objective and Context: Our objective was to examine predictability of reproductive hormone concentrations for bone mineral density (BMD) loss during the menopausal transition.

Design: We conducted a longitudinal (five annual examinations), multiple-site (n = 5) cohort study, the Study of Women’s Health Across the Nation (SWAN).

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

Main Outcome Measures: We assessed annual dual-energy x-ray absorptiometry lumbar spine and total hip BMD measures, with endogenous estradiol (E2), FSH, androgens, and self-reported menstrual bleeding patterns.

Results: Over the 4-yr period, lumbar spine 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-yr BMD loss. If baseline FSH was less than 25 mIU/ml, higher follow-up FSH (>70 mIU/ml) predicted a 4-yr 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-yr spine BMD loss. Charts show amounts of predicted BMD losses with combinations of baseline FSH values and FSH levels over time. E2 concentrations less than 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.

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