Urinary Ovarian and Gonadotropin Hormone Levels in Premenopausal Women with Low Bone Mass

Abstract

We hypothesized that lower ovarian and gonadotropin hormone concentrations would be associated with lower levels of peak bone mineral density (BMD) in apparently normally menstruating women who did not exercise intensively and did not report anorexia or bulimia. This hypothesis was 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 percentile of the distribution, where controls were 34 premenopausal women with BMD between the 50th and 75th percentile. BMD was measured by dual-energy X-ray absorptiometry. In addition to their annual measurement, these 65 participants collected first-voided morning urine specimens daily through two consecutive menstrual cycles. The urine from alternating days of this collection was analyzed for estrone-3-glucuronide (E1G), pregnanediol glucuronide (PdG), testosterone, and follicle-stimulating hormone by radioimmunoassay and these values adjusted for daily creatinine excretion levels. Additionally, analyses of daily urine specimens for luteinizing hormone (uLH) was undertaken to better characterize the possible uLH surge. Cases had significantly lower amounts of E1G (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 under the curve, and after statistically controlling for body size. Further, when B-splines were used to fit lines to the E1G and PdG data across the menstrual cycle, the 95% confidence intervals (CIs) about the line for the controls consistently excluded and excluded and exceeded the 95% confidence bands for the cases in the time frame associated with the luteal phase in ovulatory cycles. Likewise, 95% CIs for the LH surge in controls exceeded the fitted line for cases around the time associates with the LH surge. The cases and controls were not different according to dietary intake (energy, protein, calcium), family history of osteoporosis, reproductive characteristics (parity, age at menarche, age of first pregnancy), follicular phase serum hormone levels, calciotropic hormone levels, or by evidence of perimenopause. We conclude that these healthy, 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 considering the role of body size. These data suggest that subclinical decreases in circulating gonadal steroids may impair the attainment and/or maintenance of bone mass in otherwise reproductively normal women.

A prospective investigation of the relations among cognitive dietary restraint, subclinical ovulatory disturbances, physical activity, and bone mass in healthy young women

“…Those other studies used the basal body temperature method, which has been shown to be an unreliable method of determining ovulation and which may have led to misclassification (48 -50). Indeed, those investigators reported a much higher prevalence of ovulatory disturbances (67-80% of participants had disturbances) (7, 10) than we and others (12,51) who used progesterone measurements have reported. Both salivary and urinary progesterone are highly correlated with serum progesterone, and measuring them is a reliable method of assessing ovarian function (28,30,52).…”

“…Prior et al (10) proposed that the observed bone loss was due to reduced luteal progesterone production in the presence of normal concentrations of estrogen, but this possibility has not been supported by other investigators. Sowers et al (51) found lower concentrations of both luteal phase estrogen and progesterone urinary metabolites in women with BMD in the bottom 10th percentile than in women with BMD in the 50 -75th percentile. DeSouza et al (11) observed lower luteal phase progesterone in women with short luteal phases (but found no difference in BMD) than in women with normal luteal phases.…”

Assessing menstrual cycles with urinary hormone assays

“…Correction of the urinary hormone value with creatinine excretion reduces within women variations in hormone concentrations, which can be considerable (25). Preservation of urine with glycerol is required to maintain gonadotropin activity in some (31) but not all (35) assays.…”

Principais causas de diminuição da massa óssea em mulheres na pré-menopausa encaminhadas ao ambulatório de doenças ósteo-metabólicas de um Hospital Terciário de Curitiba

“…Esta diminuição do estradiol foi anteriormente relatada por Sowers e cols. em um grupo de mulheres jovens, pré-menopausadas e com osteoporose de fêmur sem etiologia definida (12). Em um subgrupo de pacientes, nas quais foi realizado DMO por fazerem parte de grupos controle de outros estudos realizados em nosso serviço, nenhuma causa secundária foi identificada pela avaliação inicial.…”