Gail A. Greendale

Endogenous sex steroids and bone mineral density in older women and men: the Rancho Bernardo Study.

This study examines the associations between endogenous sex steroids and bone mineral density (BMD), using data from a geographically defined cohort in Rancho Bernardo, California. Participants were community‐dwelling women and men aged 50–89 years who took part in a study of endogenous sex steroid measurement between 1984–1987 and who had BMD measured in 1988–1991. Those taking corticosteroids or estrogen at the time of sex steroid determination were excluded. The main study outcomes were BMD of the ultradistal radius, midshaft radius, lumbar spine, and total hip by sex steroid level, adjusted for age, body mass index, cigarette smoking, alcohol consumption, leisure exercise, use of thiazides, thyroid hormones, and former estrogen use (women only). At the time of the hormone measurements, the mean age of the 457 women was 72.1 years and that of the 534 men was 68.6 years. A statistically significant positive relation was seen between bioavailable estradiol and BMD at all sites in women and men. Total estradiol was significantly associated with BMD at all sites in women and at all but the ultradistal radius in men. Estrone had a global effect on BMD in women and was not measured in men. Higher bioavailable (but not total) testosterone levels were associated with higher BMD of the ultradistal radius, spine, and hip in men and the ultradistal radius in women. Dehydroepiandrosterone was positively associated with BMD of the midradius, spine, and hip in women and was not associated with BMD at any site in men. Of the sex steroids tested, bioavailable estrogen was most strongly associated with BMD in both women and men. We conclude that endogenous sex steroid levels are significantly related to bone density in older women and men. Individual variation in age‐related bone loss may be partially accounted for by alterations in sex steroid levels with aging. Further study to elucidate safe environmental and medical methods to maintain optimal sex steroid levels in old age is needed.

Breast Cancer in Younger Women: Reproductive and Late Health Effects of Treatment

PURPOSE In 1997, we initiated a cohort study to evaluate quality of life (QOL) and reproductive health outcomes in younger female breast cancer survivors. MATERIALS AND METHODS Using listings from two tumor registries, we recruited women with stage 0, I, or II breast cancer who were 50 years or younger at diagnosis and were also disease-free survivors for 2 to 10 years. A mailed survey questionnaire assessed medical and demographic factors, health-related QOL, mood, outlook on life, and reproductive health outcomes. RESULTS We recruited 577 women, who ranged in age from 30 to 61.6 years (mean, 49.5 years) and were surveyed approximately 6 years after diagnosis. Almost three fourths had received some form of adjuvant therapy. Amenorrhea occurred frequently as a result of treatment in women > or = 40 years at diagnosis, and treatment-associated menopause was associated with poorer health perceptions. Across the cohort, physical functioning was quite good, but the youngest women experienced poorer mental health (P =.0002) and less vitality (energy; P =.03). Multiple regression analyses predicting QOL demonstrated better outcomes in African-American women, married or partnered women, and women with better emotional and physical functioning, whereas women who reported greater vulnerability had poorer QOL. CONCLUSION Overall QOL in younger women who survive breast cancer is good, but there is evidence of increased emotional disruption, especially among the youngest women. Factors that may contribute to poorer health perceptions and QOL include experiencing a menopausal transition as part of therapy, and feeling more vulnerable after cancer.

Longitudinal Analysis of the Association Between Vasomotor Symptoms and Race/Ethnicity Across the Menopausal Transition: Study of Women’s Health Across the Nation

OBJECTIVES We investigated whether vasomotor symptom reporting or patterns of change in symptom reporting over the perimenopausal transition among women enrolled in a national study differed according to race/ethnicity. We also sought to determine whether racial/ethnic differences were explained by sociodemographic, health, or lifestyle factors. METHODS We followed 3198 women enrolled in the Study of Womens Health Across the Nation during 1996 through 2002. We analyzed frequency of vasomotor symptom reporting using longitudinal multiple logistic regressions. RESULTS Rates of vasomotor symptom reporting were highest among African Americans (adjusted odds ratio [OR]=1.63; 95% confidence interval [CI]=1.21, 2.20). The transition to late perimenopause exhibited the strongest association with vasomotor symptoms (adjusted OR = 6.64; 95% CI = 4.80, 9.20). Other risk factors were age (adjusted OR=1.17; 95% CI=1.13, 1.21), having less than a college education (adjusted OR = 1.91; 95% CI = 1.40, 2.61), increasing body mass index (adjusted OR=1.03 per unit of increase; 95% CI=1.01, 1.04), smoking (adjusted OR=1.63; 95% CI=1.25, 2.12), and anxiety symptoms at baseline (adjusted OR=3.10; 95% CI=2.33, 4.12). CONCLUSIONS Among the risk factors assessed, vasomotor symptoms were most strongly associated with menopausal status. After adjustment for covariates, symptoms were reported most often in all racial/ethnic groups in late perimenopause and nearly as often in postmenopause.

Neurocognitive Performance in Breast Cancer Survivors Exposed to Adjuvant Chemotherapy and Tamoxifen

ABSTRACT The primary aim of the current study was to examine whether neurocognitive functioning among breast cancer survivors (BCS) exposed to systemic adjuvant chemotherapy differs from that seen among BCS who did not receive chemotherapy. The performance of each of these BCS groups was compared to a demographically matched comparison group without history of breast cancer, a group not included in the majority of previous cognitive functioning studies. We also sought to explore whether usage of the anti-estrogen drug tamoxifen, a common component of breast cancer treatment, was related to neurocognitive functioning. Finally, we wished to examine the relationship between subjective report of cognitive functioning and objective performance on neurocognitive measures among BCS. Fifty-three survivors of breast cancer (all between 2–5 years after diagnosis and initial surgical removal of cancerous tissue) and 19 healthy non-BCS comparison subjects were administered a comprehensive neurocognitive battery, and measures of mood, energy level, and self-reported cognitive functioning. Those BCS who received adjuvant chemotherapy performed significantly worse in the domains of verbal learning, visuospatial functioning, and visual memory than BCS treated with surgery only. Those who received both chemotherapy and tamoxifen showed the greatest compromise. Although patients who received chemotherapy (with and without tamoxifen) performed worse than those treated with surgery only on several domains, neither group was significantly different from demographically matched comparison subjects without a history of breast cancer. Finally, we found no relationship between subjective cognitive complaints and objective performance, although cognitive complaints were associated with measures of psychological distress and fatigue. We highlight ways in which these data converge with other recent studies to suggest that systemic chemotherapy, especially in combination with tamoxifen, can have adverse yet subtle effects on cognitive functioning.

Symptom Relief and Side Effects of Postmenopausal Hormones: Results From the Postmenopausal Estrogen/Progestin Interventions Trial

Objective To assess pair-wise differences between placebo, estrogen, and each of three estrogen-progestin regimens on selected symptoms. Methods This was a 3-year, multicenter, double-blind, placebo-controlled trial in 875 postmenopausal women aged 45–64 years at baseline. Participants were assigned randomly to one of five groups: 1) placebo, 2) daily conjugated equine estrogens, 3) conjugated equine estrogens plus cyclical medroxyprogesterone acetate, 4) conjugated equine estrogens plus daily medroxyprogesterone acetate, and 5) conjugated equine estrogens plus cyclical micronized progesterone. Symptoms were self-reported using a checklist at 1 and 3 years. Factor analysis reduced 52 symptoms to a set of six symptom groups. Results In intention-to-treat analyses at 1 year, each active treatment demonstrated a marked, statistically significant, protective effect against vasomotor symptoms compared with placebo (odds ratios [ORs] 0.17–0.28); there was no additional benefit of estrogen-progestin over estrogen alone. Only progestin-containing regimens were significantly associated with higher levels of breast discomfort (OR 1.92–2.27). Compared with placebo, women randomized to conjugated equine estrogens reported no increase in perceived weight. Those randomized to medroxyprogesterone acetate reported less perceived weight gain (OR 0.61–0.69) than placebo. Anxiety, cognitive, and affective symptoms did not differ by treatment assignment. Analyses restricted to adherent women were not materially different than those using intention-to-treat, except that women adherent to medroxyprogesterone acetate and micronized progesterone regimens reported fewer musculoskeletal symptoms (OR 0.62–0.68). Conclusion These results confirm the usefulness of postmenopausal hormone therapy for hot flashes, show convincingly that estrogen plus progestin causes breast discomfort, and demonstrate little influence of postmenopausal hormones on anxiety, cognition, or affect.

SWAN: A Multicenter, Multiethnic, Community-Based Cohort Study of Women and the Menopausal Transition

Study of Womens Health Across the Nation (SWAN) is the first national study to describe women at midlife, an understudied age group. Its multidisciplinary approach provides the opportunity to consider the contributions of both culture and biology so that one may better understand health of women. The SWAN employs a prospective design that includes sufficient pre- and postmenopausal observations to ensure the separation of menopause-related and age-related physiological changes. Other attributes include the comprehensive standardized data collection related to biological, behavioral, physiological, social, environmental, and cultural factors; specialized data collection methodologies suitable to address the monthly and yearly variation in behavioral and biological patterns; general ability to community-dwelling populations recruited from major United States population centers; sufficiently large sample size and numbers of data points to ensure reliable estimates of associations and relevant effect sizes; and inclusion of sufficient numbers of racial/ethnic minorities to provide comparative information with the non-Hispanic Caucasian population. Because of these attributes, SWAN can contribute new and substantive knowledge about womens health in general and the menopause transition in particular.

Longitudinal Patterns and Predictors of Alcohol Consumption in the United States

OBJECTIVES We examined demographic predictors of longitudinal patterns in alcohol consumption. METHODS We used mixed-effects models to describe individual alcohol consumption and change in consumption with age, as well as the associations between consumption and birth year, national alcohol consumption, and demographic factors, among 14 105 adults from the National Health and Nutrition Examination Survey I Epidemiologic Follow-Up Study. RESULTS Alcohol consumption declined with increasing age, and individual consumption mirrored national consumption. Higher consumption was associated with male gender, being White, being married, having a higher educational level, having a higher income, being employed, and being a smoker. Faster age-related decline in consumption was associated with earlier cohorts, being male, being married, having a lower educational level, and being a smoker. CONCLUSIONS Compared with alcohol consumption among earlier cohorts, that among recent cohorts declined more slowly with increasing age, suggesting that negative health effects of alcohol could increase in the future.

Disordered eating, menstrual irregularity, and Bone minéral Density in Female runners

PURPOSE To examine the relationships between disordered eating, menstrual irregularity, and low bone mineral density (BMD) in young female runners. METHODS Subjects were 91 competitive female distance runners aged 18-26 yr. Disordered eating was measured by the Eating Disorder Inventory (EDI). Menstrual irregularity was defined as oligo/amenorrhea (0-9 menses per year). BMD was measured by dual x-ray absorptiometry. RESULTS An elevated score on the EDI (highest quartile) was associated with oligo/amenorrhea, after adjusting for percent body fat, age, miles run per week, age at menarche, and dietary fat, (OR [95% CI]: 4.6 [1.1-18.6]). Oligo/amenorrheic runners had lower BMD than eumenorrheic runners at the spine (-5%), hip (-6%), and whole body (-3%), even after accounting for weight, percent body fat, EDI score, and age at menarche. Eumenorrheic runners with elevated EDI scores had lower BMD than eumenorrheic runners with normal EDI scores at the spine (-11%), with trends at the hip (-5%), and whole body (-5%), after adjusting for differences in weight and percent body fat. Runners with both an elevated EDI score and oligo/amenorrhea had no further reduction in BMD than runners with only one of these risk factors. CONCLUSION In young competitive female distance runners, (i) disordered eating is strongly related to menstrual irregularity, (ii) menstrual irregularity is associated with low BMD, and (iii) disordered eating is associated with low BMD in the absence of menstrual irregularity.

Late Physical and Functional Effects of Osteoporotic Fracture in Women: The Rancho Bernardo Study

OBJECTIVE: To examine the associations between osteoporotic fractures and difficulty performing selected physical and functional activities.

Correlates of sexual function among multi-ethnic middle-aged women: results from the Study of Women's Health Across the Nation (SWAN)

Objective:To examine sexual function in a cohort of Baby Boomer women of diverse racial/ethnic backgrounds; to compare differences between pre-and early perimenopausal women; and to identify sociodemographic, health-related, and psychosocial (including psychological, behavioral, and relationship) factors related to sexual function. Design:Six domains of sexual function were studied in 3,167 women in the baseline cohort of the Study of Womens Health Across the Nation (SWAN). Participants were 42 to 52 years old, pre-or early perimenopausal, and not using hormones. The study sample included non-Hispanic white, African American, Hispanic, Chinese, and Japanese women. Results:Early perimenopausal women reported greater pain with intercourse than premenopausal women (P = 0.01), but the two groups did not differ in frequency of sexual intercourse, desire, arousal, or physical or emotional satisfaction. Variables having the greatest association across all outcomes were relationship factors, the perceived importance of sex, attitudes toward aging, and vaginal dryness. Despite controlling for a wide range of variables, we still found ethnic differences for arousal (P < 0.0001), pain (P = 0.03), desire (P < 0.0001), and frequency of sexual intercourse (P = 0.0003). African American women reported higher frequency of sexual intercourse than white women; Hispanic women reported lower physical pleasure and arousal. Chinese women reported more pain and less desire and arousal than the white women, as did the Japanese women, although the only significant difference was for arousal. Conclusions:Relationship variables, attitudes toward sex and aging, vaginal dryness, and cultural background have a greater impact on most aspects of sexual function than the transition to early perimenopause.