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Low Bone Mineral Density in the Early Menopausal Transition: Role for Ovulatory Function

Departments of Epidemiology (J.G., M.R.S., S.D.H.) and Biostatistics (X.L.), School of Public Health, and Department of Obstetrics and Gynecology (J.F.R.), University of Michigan, Ann Arbor, Michigan 48104

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

Objective and Context: The objective of the study was to determine whether luteal abnormalities or measures of sex steroid hormones collected across a menstrual cycle were associated with bone mineral density (BMD) at the total hip or lumbar spine.

Design and Setting: The Study of Women’s Health Across the Nation is a longitudinal, community-based study conducted at seven clinical sites. Study of Women’s Health Across the Nation includes a daily hormone study substudy in which daily urine samples are collected for one menstrual cycle (up to a maximum of 50 d) each year.

Participants: Participants included 643 pre- and perimenopausal women, aged 43–53 yr.

Main Outcome Measures: BMD of the lumbar spine and total hip was measured by dual-energy x-ray densitometry. Daily urine samples were assayed for estrone conjugates, pregnanediol glucuronide, LH, and FSH, and the information from across the menstrual cycle was expressed as area under the curve (AUC). BMD levels were evaluated in relation to three menstrual cycle attributes: 1) absence or presence of ovulation; 2) luteal phase length to menstrual cycle length ratio; and 3) ovulatory disturbances, defined as anovulatory cycles or cycles with short luteal phases (<10 d).

Results: Lower urine estrone conjugate AUC and higher urine FSH AUC were significantly associated with lower BMD. However, luteal abnormalities based on menstrual cycle attributes were not significantly associated with BMD at the total hip or lumbar spine after adjustment for age, body mass index, urinary hormone concentrations, menopausal status, and race/ethnicity.

Conclusions: Direct measures of urinary hormones, not menstrual cycle luteal abnormalities, were associated with lower levels of BMD.

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