Cross-sectional studies suggest that the menopause is associated with changes in endocrine-metabolic function and body composition that may accelerate the development of osteoporosis. The hypotheses of this longitudinal study are that the menopausal transition is associated with change as described: 1) decreases in nocturnal secretory profile of growth hormone, that in combination with decreases in ovarian sex hormones, contribute to changes in body composition, specifically decreases in bone mass and increases in fat mass, 2) increases in biochemical markers of bone turnover that are measured in blood and urine that predict decreases in bone mass, and 3) increases in body fat mass and fat redistribution to the intra-abdominal area that are associated with adverse changes in lipid and lipoprotein profiles. The women are 100 healthy, nonsmoking famale participants of the Baltimore Longitudinal Study of Aging, ages 45-55 years who are experiencing monthly menses at enrollment. They receive quarterly GCRC outpatient visits until menses have ceased for 2 years.The visits include a menopausal symptom questionnaire, endocrine and blood lipid profiles, anthropometry, dual energy x-ray absorptiometry (DEXA), bone biochemistries, and dietary assessments. To date, 100 women have completed 740 outpatient visits. Preliminary analyses of body composition data have been performed for 21 women who remain premenopausal, as defined by having mid-follicular menstrual phase serum FSH levels <30mU/mL, who have completed a mean of 6.9 quarterly visits per womwn (range 3-12). Data are available for 24 women classified as perimenopausal, as defined by having at least one serum FSH level >/- 30 mU/mL, who have completed a mean of 8.5 quarterly visits per woman (range 4-15). Perimenopausal women, in contrast to the premenopausal group, exhibit significant increases in the estimates of fatness including total fat and percent fat by DEXA, p<0.03 by paired t-test of baseline visit to most recent visit, and in fat distribution (waist circumference and WHR, p<0.002), but not in weight or BMI. Similar analyses were performed for the DEXA data in 41 women classified as premenopausal, and 23 women classified as perimenopausal. Lumbar spine mean bone mineral density percent change per year (+/- SEM) was 0.01% +/- 0.3% for the premenopausal women versus - 0.9% +/- 0.5% for the perimenospusal women. These data suggest that changes in body composition may occur early in the menopausal transition as defined by a serum FSH level >/- 30 mU/mL. Future plans include the continued characterization of the biological antecedents and sequalae of the menopausal transition. Biochemical markers of bone and cardiovascular disease risk will be studied so as to target hormone replacement therapy to those women who are most likely to benefit. Moreover, the continued longitudinal assessment of the BLSA cohort beyond that provided in this proposal will permit an evaluation of the effects of the menopausal transition on age-related disease in women.
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