Loci at chromosomes 13, 19 and 20 influence age at natural menopause.

We conducted a genome-wide association study for age at natural menopause in 2,979 European women and identified six SNPs in three loci associated with age at natural menopause: chromosome 19q13.4 (rs1172822; -0.4 year per T allele (39%); P = 6.3 × 10(-11)), chromosome 20p12.3 (rs236114; +0.5 year per A allele (21%); P = 9.7 × 10(-11)) and chromosome 13q34 (rs7333181; +0.5 year per A allele (12%); P = 2.5 × 10(-8)). These common genetic variants regulate timing of ovarian aging, an important risk factor for breast cancer, osteoporosis and cardiovascular disease.

Fat mass rather than muscle strength is the major determinant of physical function and disability in postmenopausal women younger than 75 years of age.

OBJECTIVE: Few studies have investigated the relationships between body composition, functional ability, and age-related disability in postmenopausal women. We investigated the relative role of fat mass, lean mass, and muscle strength in the development of disability in a group of healthy postmenopausal women younger than 75 years. DESIGN: We performed a cross-sectional study among 396 independently living women aged 56-73 years, randomly selected between 8 and 30 years after menopause. Lean mass and fat mass were assessed by dual-energy x-ray absorptiometry. Muscle strength (grip and leg extensors) was assessed using dynamometry. Functional ability was estimated by Physical Performance Score, physical activity during the preceding year, and impairment in activities of daily living. RESULTS: Of the participants, 43.7 % were overweight (25 > or = BMI < 30 kg/m2), and 17.7% were obese (BM I > or = 30 kg/m2). Higher muscle strength was observed with increasing lean body mass, and participants with higher muscle strength scored better in the physical performance score and activities of daily living. Higher fat mass was significantly associated with a lower physical performance score, lower physical activity, and a higher frequency of disability. Increasing fat mass was associated with increasing lean mass and decreasing lean/fat ratio. The increase in lean mass and muscle strength associated with higher fat mass was mainly localized in the legs. CONCLUSIONS: Our results support the role of fat mass as the primary risk marker for disability, which might later accelerate by the age-related decrease in lean mass and the development of sarcopenia after the age of 75 years.

Relations between body composition, functional and hormonal parameters and quality of life in healthy postmenopausal women.

OBJECTIVE: To investigate whether body composition, functional status and serum hormone levels are associated with quality of life in healthy postmenopausal women. DESIGN: A cross-sectional study among 402 women aged 56-73 years, 8-30 years postmenopausal. Quality of life (QoL) was assessed using the questionnaire on life satisfaction (QLS), with two modules directed at general factors (QLS-general) and health factors (QLS-health). Muscle strength was measured using dynamometry. Functional ability was estimated by physical performance (PPS), physical activity during the preceding year, and impairment in activities of daily living (ADL). Bone mineral density, lean mass and fat mass were assessed by dual-energy X-ray absorptiometry. Fasting levels of serum oestradiol, oestrone, and sex hormone-binding globulin (SHBG), testosterone, cortisol, androstenedione, DHEA and DHEAS, insulin-like growth factor (IGF-1), its binding proteins (IGFBP-1 and -3) and insulin, were determined. RESULTS: Both QLS modules did not decrease with age. The major positive predictor of QLS-general module was the presence of a partner. Higher physical performance and higher educational level of participants' partners were significantly related to higher QLS-general, while smoking and presence of co-morbidities were significantly associated with a lower QLS-general. The determinants studied were mostly related to the QLS-health module, the major negative predictor of QLS-health being the presence of co-morbidities, followed by physical activity, physical performance and grip strength. Higher educational level of participants was related with higher QLS-health module, while higher BMI, fat mass and presence of disability were associated with significantly lower QLS-health. No consistent relation was found between serum levels of hormones measured and both QLS modules. CONCLUSIONS: The most important and specific determinant for psychological well-being was having a partner. Physical and psychological well-being are further strongly associated in this population of healthy postmenopausal women below 75 years of age, while increasing fat mass was related to decreased well-being. Our results suggest that in elderly and late postmenopausal women hormonal factors do not predict quality of life.

Endogenous oestrogens are related to cognition in healthy elderly women.

OBJECTIVE: To investigate whether levels of endogenous hormones, in particular circulating oestrogens and SHBG, are associated with cognition in healthy postmenopausal women. DESIGN: Cross-sectional study. PATIENTS: Four hundred and two healthy postmenopausal women aged 50-74 years between 8 and 30 years after menopause, none taking oestrogen. MEASUREMENTS: Serum concentration of oestradiol, oestrone, and sex hormone binding globulin (SHBG) determined by immunoassay. Cognition assessed using the mini-mental state examination questionnaire (MMSE). RESULTS: In this group, 149 individuals had a MMSE score < 27, while only 89 individuals had a MMSE score < 26, indicating a relatively healthy population with regard to cognitive ability. Cognition decreased with age, time since menopause and blood pressure, and was better with higher age at menopause. Serum oestrogens and SHBG levels were not related to age, age at menopause, or time since menopause, and oestrogen levels were positively associated with blood pressure. After adjustment for mean arterial pressure and SHBG, the frequency of mild cognitive impairment decreased significantly with higher oestradiol and oestrone serum levels [ORs Q5 vs. Q1: 0.41 (95% CI 0.20-0.84) and 0.51 (95% CI 0.20-0.99) for oestradiol and oestrone, respectively]. CONCLUSIONS: Postmenopausal women with higher remaining circulating oestradiol levels appear less likely to suffer from cognitive impairment. This effect is independent of age at menopause, time since menopause and BMI. These findings support the hypothesis that endogenous oestrogens may protect against cognitive decline with ageing.

Higher dietary intake of lignans is associated with better cognitive performance in postmenopausal women.

Data on the relation between phytoestrogens and cognitive function are still sparse. The purpose of this study was to examine the relation between the dietary intake of phytoestrogens and cognitive function in healthy postmenopausal women consuming a Western diet. We conducted a community-based survey among 394 postmenopausal women. Isoflavone and lignan intake was calculated from a validated FFQ. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Data were analyzed using logistic regression with intact cognitive function defined as a score >/= 26 as the outcome variable. After adjustment for confounders, increasing dietary lignans intake was associated with better performance on the MMSE [OR and (95%CI): 1.49 (0.94-2.38)]. Results were most pronounced in women who were 20-30 y postmenopausal [2.02 (1.11-3.71)]. Isoflavone intake was not related to cognitive function. From our results we conclude that higher dietary intake of lignans is associated with better cognitive function in postmenopausal women.

Alcohol consumption in relation to aortic stiffness and aortic wave reflections: a cross-sectional study in healthy postmenopausal women.

OBJECTIVE: Moderate alcohol consumption has been postulated to be cardioprotective. Such an effect might be reflected in large-artery properties, such as arterial stiffness and wave reflections. METHODS AND RESULTS: Three hundred seventy-one healthy postmenopausal women aged 50 to 74 years were sampled from a population-based study. Alcohol intake was calculated from a standardized questionnaire. Applanation tonometry was applied to assess the augmentation index and aortic pulse-wave velocity. Those drinking 1 to 3, 4 to 9, 10 to 14, and 15 to 35 glasses of alcoholic beverages per week had a 0.044 (95% CI -0.47 to 0.56), -0.085 (95% CI -0.59 to 0.43), -0.869 (95% CI -1.44 to -0.29), and -0.225 (95% CI -0.98 to 0.53) m/s difference in mean pulse-wave velocity compared with nondrinkers, respectively, which indicates a J-shaped relationship. Adjustment for potential confounders of pulse-wave velocity or alcohol intake did not materially change the strength of the association. Adjustment for HDL further attenuated the relationship. The augmentation index was not related to alcohol consumption when adjustments were made for physiological determinants such as age, height, and ejection duration. CONCLUSIONS: Among postmenopausal women, alcohol consumption is inversely associated with pulse-wave velocity. This supports the presence of a decreased risk of cardiovascular disease with moderate alcohol consumption, which may be mediated in part by HDL cholesterol.

Arterial stiffness in postmenopausal women: determinants of pulse wave velocity.

OBJECTIVE To investigate the degree and potential cardiovascular determinants of arterial stiffness, assessed by aortic pulse wave velocity (PWV) measurements, and to relate arterial stiffness to absolute 10-12-year risks of stroke, coronary heart disease and death, as estimated by available risk functions, in postmenopausal women. METHOD We performed a cross-sectional study among 385 postmenopausal women, aged 50-74 years, sampled from the general population. Arterial stiffness was assessed non-invasively by measurement of aortic PWV using applanation tonometry. Information on health was obtained by medical history, registration of current medication, and physical examination. Height, weight, waist and hip circumferences, fasting glucose, total and high-density lipoprotein (HDL) cholesterol, triglycerides, resting blood pressure, and heart rate were measured. Three risk scores were used to estimate, for each individual, the absolute risk of stroke, coronary heart disease, and death within 10-12 years as a function of their cardiovascular risk factor profile. The relationship between PWV and these risk scores was subsequently determined. RESULTS Significant positive relationships with PWV were found for body mass index, fasting glucose, diabetes mellitus, and triglycerides in analyses adjusted for age, mean arterial blood pressure, and heart rate. Height and HDL cholesterol were inversely related to PWV. The risks of stroke, coronary heart disease, and death increased with increasing PWV in a linear graded manner. CONCLUSIONS This cross-sectional study among postmenopausal women provides evidence that most of the established cardiovascular risk factors are determinants of aortic PWV. Increased PWV marks an increased risk of stroke, coronary heart disease, and death within 10-12 years.

Higher usual dietary intake of phytoestrogens is associated with lower aortic stiffness in postmenopausal women.

OBJECTIVE: Phytoestrogens have been postulated to protect against cardiovascular diseases, but few studies have focused on the effect of Western dietary phytoestrogen intake. METHODS AND RESULTS: Four hundred three women with natural menopause either between 1987 and 1989 or between 1969 and 1979 were selected from the baseline data of the PROSPECT study (n=17 395). Isoflavone and lignan intake was calculated from a food-frequency questionnaire. Aortic stiffness was noninvasively assessed by pulse-wave velocity measurement of the aorta. Linear regression analysis was used. After adjustment for age, body mass index, smoking, physical activity, mean arterial pressure, follow-up time, energy intake, dietary fiber intake, glucose, and high density lipoprotein cholesterol, increasing dietary isoflavone intake was associated with decreased aortic stiffness: -0.51 m/s (95% CI -1.00 to -0.03, fourth versus first quartile, P for trend=0.07). Increasing dietary intake of lignans was also associated with decreased aortic pulse-wave velocity: -0.42 m/s (95% CI -0.93 to 0.11, fourth versus first quartile, P for trend=0.06). Results were most pronounced in older women: for isoflavones, -0.94 m/s (95% CI -1.65 to -0.22, P for trend=0.02), and for lignans, -0.80 m/s (95% CI -1.85 to -0.05), fourth versus first quartile. CONCLUSIONS: The results of our study support the view that phytoestrogens have a protective effect on the risk of atherosclerosis and arterial degeneration through an effect on arterial walls, especially among older women.