Osteoporosis and apolipoprotein E genotype in older adults: the Rancho Bernardo study.

Recent studies reported an association between apolipoprotein E (ApoE) 4 and osteoporosis. We examined the association of ApoE 4 genotype with bone mineral density (BMD), bone loss and fracture risk in 596 men and 332 community-dwelling women aged 45-95 years. Women were postmenopausal and not using estrogen. At the baseline visit, BMD was measured at the ultradistal and midshaft radius using single photon densitometry, and at the hip and lumbar spine using dual-energy X-ray absorptiometry. Hip and lumbar spine BMD levels were remeasured 4 years later. Self-reported fractures were confirmed by radiology reports in 95% of cases. ApoE allele distribution did not vary by age; 25% of men and 20% of women had one ApoE 4 allele. There were no differences in BMD at the lumbar spine, total hip, ultradistal or midshaft radius in men or women with the ApoE 4 allele compared with men or women without the ApoE 4 allele. After an average 4 year interval, there were also no differences in the annualized percent change in BMD at the hip or lumbar spine in men or women with or without an ApoE 4 allele. One or more clinical fractures were reported by 55 men and 109 women. Fewer, not more, clinical fractures were reported in men and women with an ApoE 4 allele; these differences were not statistically significant (p = 0.21 and p = 0.62, respectively). These data do not support the hypotheses that there is an association between ApoE genotype and BMD, bone loss or osteoporotic fractures in older community-dwelling men or women.

Vasomotor symptoms are not associated with reduced bone mass in postmenopausal women: the Rancho Bernardo Study.

The association of menopause-related vasomotor symptoms with later bone mineral density (BMD) at axial and appendicular sites was examined in community-dwelling older women. Subjects were 894 postmenopausal women from the Rancho Bernardo Study who had BMD measured in 1988-1991 and responded to a 1989 mailed survey that included questions about menopause symptoms. Mean age was 73 years (SE +/- 9.5, range 47-97), and mean age at menopause was 47 years (SD +/- 6.8, range 21-62). Vasomotor symptoms were recalled by two thirds (68%) and night sweats by 36% of all women, with no significant differences in symptom frequency by age or type of menopause. Postmenopausal estrogen (PME) had been used by 644 women (72%) for an average duration of 12.3 (+/-11) years. Among women who reported current estrogen use with a duration >3 years, those who experienced vasomotor symptoms had significantly higher BMD at the lumbar spine (p = 0.01), femoral neck (p = 0.05) and midshaft radius (p = 0.05) compared with women who did not experience symptoms. Vasomotor symptoms were not associated with BMD among past or never PME users or among women who reported current PME use for 3 or fewer years. Analyses stratified by age, type of menopause, or when PME use began showed similar results. Women who reported night sweats also had no difference in BMD compared with women without night sweats. In conclusion, vasomotor symptoms are not a marker for low BMD years after menopause in women with access to healthcare. Vasomotor symptoms significantly increased the likelihood of continued use of PME, which was in turn associated with higher BMD levels.

Low levels of estradiol are associated with vertebral fractures in older men, but not women: the Rancho Bernardo Study.

This longitudinal study included 288 postmenopausal women without estrogen use (median age, 72 yr) and 352 men (median age, 66 yr). All were community-dwelling, ambulatory, and Caucasian. Blood for hormone assays (total and bioavailable estradiol and testosterone, estrone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate) was obtained in 1984-1987, and vertebral fractures were diagnosed from lateral spine radiographs obtained in 1992-1996. At least one vertebral fracture was found in 21% of women and 8% of men. Among men, age-adjusted hormone levels differed by fracture status only for total (64.1 vs. 75.4 pmol/L, P = 0.012) and bioavailable (43.0 vs. 51.4 pmol/L, P = 0.008) estradiol. There was a graded association between higher concentrations of total and bioavailable estradiol and lower fracture prevalence (trend P<0.01 for both hormones). Men with total testosterone levels compatible with hypogonadism (<7 nmol/L) were not more likely to have vertebral fractures. In women, none of the measured sex hormones was associated with vertebral fractures. There was also no increased prevalence of fractures in women with estradiol levels below the assay sensitivity (<11 pmol/L). These data suggest that estrogen plays a critical role in the skeletal health of older men and confirm other studies showing no association of postmenopausal endogenous estrogen levels with vertebral fractures in older women.

Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study.

A cross-sectional population-based study examined the association between endogenous sex hormones and depressed mood in community-dwelling older men. Participants included 856 men, ages 50-89 yr, who attended a clinic visit between 1984-87. Total and bioavailable testosterone, total and bioavailable estradiol, and dihydrotestosterone levels were measured by radioimmunoassay in an endocrinology research laboratory. Depressed mood was assessed with the Beck Depression Inventory (BDI). Levels of bioavailable testosterone and bioavailable estradiol decreased with age, but total testosterone, dihydrotestosterone, and total estradiol did not. BDI scores increased with age. Low bioavailable testosterone levels and high BDI scores were associated with weight loss and lack of physical activity, but not with cigarette smoking or alcohol intake. By linear regression or quartile analysis the BDI score was significantly and inversely associated with bioavailable testosterone (both Ps = 0.007), independent of age, weight change, and physical activity; similar associations were seen for dihydrotestosterone (P = 0.048 and P = 0.09, respectively). Bioavailable testosterone levels were 17% lower for the 25 men with categorically defined depression than levels observed in all other men (P = 0.01). Neither total nor bioavailable estradiol was associated with depressed mood. These results suggest that testosterone treatment might improve depressed mood in older men who have low levels of bioavailable testosterone. A clinical trial is necessary to test this hypothesis.

A community-based study of menopause symptoms and estrogen replacement in older women.

This study examines the symptoms after a natural menopause recalled by women aged 50-89 years. We determined the frequency and clustering of symptoms, the effect of age on symptoms, and the relation of symptoms to the use of estrogen therapy in a cross-sectional, community-based study of 589 Caucasian, middle- to upper-middle-class women from Rancho Bernardo, California. At the time of menopause, 55% of the women reported that they felt life was getting better and 57% were more cheerful. The most frequently recalled symptoms were hot flushes (74%), propensity to weight gain (45%), night sweats (35%), tiredness (32%), and insomnia (28%). Irritability was reported by one-fourth, depression by one-fifth. Nearly 11% reported anxiety about looking older. The recalled prevalence of hot flushes, irritability, weepiness and tiredness did not vary by current age, but younger women were significantly more likely than older women to have experienced night sweats, visible flushes, depression, anxiety about looking older and insomnia. Principal components factor analysis yielded four main independent factors: psychological symptoms (21% of the variance), vasomotor symptoms (14%), positive feelings (11%), and negative self-image (8%). The four symptom groupings suggest different causal mechanisms. Forty-two percent reported past, and 27% reported current use of estrogen therapy. Both past and current hormone users were significantly more likely to report menopause symptoms than non-users. Estrogen use was not associated with positive feelings or self-image at the time of menopause. Although three-quarters experienced symptoms, the majority of women reported positive feelings about menopause.