URINARY OVARIAN AND GONADOTROPIN HORMONE LEVELS IN PREMENOPAUSAL WOMEN WITH LOW BONE MASS

We hypothesized that lower ovarian and gonadotropin hormone concentrat ions would be associated with lower levels of peak bone mineral densit y (BMD) in apparently normally menstruating women who did not exercise intensively and did not report anorexia or bulimia. This hypothesis w as evaluated using a case-with-control study design (n = 65) which was nested within a population-based longitudinal study of peak bone mass (Michigan Bone Health Study) with annual assessment in women aged 25- 45 years (n = 582). Cases were 31 premenopausal women with BMD of the lumbar spine, femoral neck, and total body less than the 10th percenti le of the distribution, where controls were 34 premenopausal women wit h BMD between the 50th and 75th percentile. BMD was measured by dual-e nergy X-ray absorptiometry. In addition to their annual measurements, these 65 participants collected first-voided morning urine specimens d aily through two consecutive menstrual cycles. The urine from alternat ing days of this collection was analyzed for estrone-3-glucuronide (E1 G), pregnanediol glucuronide (PdG), testosterone, and follicle-stimula ting hormone by radioimmunoassay and these values adjusted for daily c reatinine excretion levels. Additionally, analyses of daily urine spec imens for luteinizing hormone (uLH) was undertaken to better character ize the possible uLH surge. Cases had significantly lower amounts of E 1G (p = 0.009) and PdG (p = 0.002) than did controls, whether amounts were characterized by a mean value, the highest value, or the area und er the curve, and after statistically controlling for body size. Furth er, when B-splines were used to fit lines to the E1G and PdG data acro ss the menstrual cycle, the 95% confidence intervals (CIs) about the l ine for the controls consistently excluded and exceeded the 95% confid ence bands for the cases in the time frame associated with the luteal phase in ovulatory cycles. Likewise, 95% CIs for the LH surge in contr ols exceeded the fitted line for cases around the time associated with the LH surge. The cases and controls were not different according to dietary intake (energy, protein, calcium), family history of osteoporo sis, reproductive characteristics (parity, age at menarche, age of fir st pregnancy), follicular phase serum hormone levels, calciotropic hor mone levels, or by evidence of perimenopause. We conclude that these h ealthy, menstruating women with BMD at the lowest 10th percentile from a population-based study had significantly lower urinary sex steroid hormone levels during the luteal phase of menstrual cycles as compared with hormone levels in premenopausal women with BMD between the 50th and 75th percentile of the same population-based study, even after con sidering the role of body size. These data suggest that subclinical de creases in circulating gonadal steroids may impair the attainment and/ or maintenance of bone mass in otherwise reproductively normal women.