Hormone therapy and coronary heart disease risk by vasomotor menopausal symptoms.

OBJECTIVES: We examined whether the association between hormone therapy (HT) use and coronary heart disease (CHD) risk differed between women with and without vasomotor symptoms (VMS). STUDY DESIGN: We used data from a Dutch (EPOS) and Swedish (WHILA) population-based sample of 8865 women, aged 46-64 years, and free of CHD, stroke, venous thrombosis/pulmonary embolism or cancer at baseline. Data on HT use, VMS and potential confounders were collected by questionnaires. MAIN OUTCOME MEASURES: CHD endpoints, obtained via registries. RESULTS: 252 CHD cases occurred during 10.3 years of follow-up. Neither for women with nor for women without flushing or (night) sweats ever HT use was associated with CHD risk, compared with never HT use. Among women with intense VMS, ever HT use borderline significantly decreased CHD risk compared with never HT use (HR 0.48 [95% CI 0.20-1.03]). Among women without intense VMS, ever HT use was associated with a borderline significant increased CHD risk (HR 1.28 [95% CI 0.96-1.70]; P for interaction=0.02). However, after multivariate adjustment, as compared to never HT use, ever HT use was not associated with risk of CHD among women with or without intense VMS. CONCLUSIONS: In both groups of women with and without VMS, HT use does not seem to be associated with the risk of CHD. Hence, our findings do not support the view that HT use increases the CHD risk among women with an indication, i.e. VMS, but this needs to be confirmed in specifically designed studies.

Vasomotor menopausal symptoms are associated with increased risk of coronary heart disease.

OBJECTIVE: Emerging evidence suggests that women with vasomotor menopausal symptoms (VMS) may have an adverse cardiovascular disease (CVD) risk profile. We investigated whether VMS are related to an increased risk of future coronary heart disease (CHD) and whether possible associations can be explained by CVD risk factors. METHODS: Data used were from a Dutch and Swedish population-based sample of 10,787 women enrolled between 1995 and 2000, aged 46 to 64 years, and free of CVD at baseline. Data on VMS were collected by questionnaires. Body mass index and blood pressure were measured in all women, and total cholesterol levels were measured in a subgroup of the population. Multivariable Cox regression models were used to analyze the data. RESULTS: After a mean ± SD follow-up period of 10.3 ± 2.1 years, 303 women were diagnosed with CHD. Symptoms of flushing were not associated with risk of CHD. However, the presence of night sweats was associated with a significantly modest increased risk of CHD, with a multivariable-adjusted hazard ratio of 1.33 (95% CI, 1.05-1.69). This association was attenuated but not eliminated after correction for body mass index, blood pressure, and total cholesterol (hazard ratio, 1.25; 95% CI, 0.99-1.58). CONCLUSIONS: Women with menopausal symptoms of night sweats have a significantly moderately increased risk of CHD, which cannot be totally explained by the levels of CVD risk factors.

Menstrual cycle characteristics and risk of coronary heart disease and type 2 diabetes.

In a prospective cohort study, we observed that women with a history of irregular cycles have a 28% increased coronary heart disease risk and tended to have a higher type 2 diabetes risk as compared with women who had a regular cycle length of 27 to 29 days. This association could not be explained by metabolic risk factors or altered hormone levels.

Vasomotor symptoms, estradiol levels and cardiovascular risk profile in women.

OBJECTIVES: We investigated whether menopausal vasomotor symptoms (VMS) are related to an adverse cardiovascular risk profile. Furthermore, we examined the association between estradiol levels and VMS, and whether an association between VMS and cardiovascular risk factors can be explained by estradiol levels. STUDY DESIGN: We used data from a Swedish population-based sample of 5857 women, aged 50-64 years. Data on VMS and potential confounders were collected by questionnaires. MAIN OUTCOME MEASURES: Body mass index (BMI), waist hip ratio (WHR), glucose, blood pressure, lipid profile and estradiol levels were measured. RESULTS: Symptoms of flushing/sweats were reported by 55% and sweats by 31% of all women. Estradiol concentrations were significantly lower in women with VMS. After multivariate adjustment, women with symptoms of sweats had a statistically significantly higher BMI, waist hip ratio, total cholesterol level, LDL level, triglycerides level, glucose level, systolic and diastolic blood pressure. These patterns did not change after correction for estradiol. The associations between flushing/sweats combined and cardiovascular risk factors were less pronounced. CONCLUSIONS: Women with VMS have a less favorable cardiovascular risk profile. Although estradiol levels were significantly lower among women with VMS, the increased cardiovascular risk profile cannot be explained by circulating estradiol levels.

Vasomotor symptoms are associated with a lower bone mineral density.

OBJECTIVE: The severity of vasomotor symptoms has been hypothesized to be linked to a lower bone mineral density (BMD). We examined whether women with vasomotor symptoms are different from women without symptoms with regard to BMD. METHODS: We used data from a population-based sample of 5,600 women, aged 46 to 57 years and free from bone diseases, who participated in the first cross-sectional part of the Eindhoven Perimenopausal Osteoporosis Study between 1994 and 1995. Questionnaires at baseline were used to collect data on vasomotor symptoms and potential confounders. At baseline, BMD of the lumbar spine was measured using dual energy x-ray absorptiometry. Linear regression analysis was used to analyze the data. RESULTS: Flushing was reported by 39% of all women, and night sweats, by 38% of all women. The average BMD was 1.01 +/- 0.14 g/cm and decreased with increasing frequency of flushing (P for trend < 0.0001) and night sweats (P for trend = 0.03). After multivariate adjustments for age, body mass index, menopause status, smoking, education, exercise, and hormone use, women with the highest frequency of symptoms had a 0.022 g/cm (95% CI, -0.03 to -0.01) lower BMD compared with asymptomatic women. Women who reported having the highest frequency of night sweats had a 0.011 g/cm (95% CI, -0.02 to -0.001) lower BMD compared with women with no symptoms of night sweats. CONCLUSIONS: Our findings show that vasomotor symptoms are associated with reduced bone density. It could be hypothesized that women with vasomotor symptoms might be more susceptible to the beneficial effects of estrogens, possibly by neutralizing the effect of estrogen fluctuations. Further research is needed to extend these findings to other estrogen-sensitive end organs.

Prevalence of symptoms in relation to androgen concentrations in women using estrogen plus progestogen and women using estrogen alone.

OBJECTIVE: Women using estrogen plus progestogen therapy sometimes report difficult to describe symptoms, eg, changes in libido, mood, and memory, that may be related to decreased androgens. To evaluate the prevalence of such symptoms and relate these symptoms to androgen levels in women using estrogen plus progestogen therapy, data from the Women's Health in the Lund Area Study were analyzed. DESIGN: A total of 2,816 women using estrogen plus progestogen therapy were asked to complete a questionnaire consisting of questions concerning sexual well-being and different aspects of quality of life. Serum concentrations of testosterone, androstendione, sex hormone-binding globulin, and estradiol were measured. RESULTS: A total of 2,048 questionnaires were eligible for evaluation. Almost 40% of the women reported decreased libido. Approximately 70% were satisfied with their current sex life. Eight percent reported that intercourse was unpleasant because of vaginal dryness. No evident associations were found between libido and serum hormone concentrations. The most positive effects of estrogen plus progestogen therapy concerning memory and urinary tract and vaginal complaints were found in women with the highest and/or moderate testosterone levels (P < 0.05). CONCLUSIONS: We found no strong association between symptoms related to sexual well-being or quality of life and androgen concentrations in this study. Estrogen plus progestogen therapy did not seem to affect symptoms that might be related to low levels of androgens in the group of climacteric women whom we studied.

Menopausal complaints are associated with cardiovascular risk factors.

It has been hypothesized that women with vasomotor symptoms differ from those without with respect to cardiovascular risk factors or responses to exogenous hormone therapy. We studied whether the presence and extent of menopausal complaints are associated with cardiovascular risk profile. Data were used from a population-based sample of 5523 women, aged 46 to 57 years, enrolled between 1994 and 1995. Data on menopausal complaints and potential confounders were collected by questionnaires. Total cholesterol, systolic and diastolic blood pressures, and body mass index were measured. Linear and logistic regression analyses were used to analyze the data. Night sweats were reported by 38% and flushing by 39% of women. After multivariate adjustment, women with complaints of flushing had a 0.27-mmol/L (95% CI: 0.15 to 0.39) higher cholesterol level, a 0.60-kg/m(2) (95% CI: 0.35 to 0.84) higher BMI, a 1.59-mm Hg (95% CI: 0.52 to 2.67) higher systolic blood pressure, and a 1.09-mm Hg (95% CI: 0.48 to 1.69) higher diastolic blood pressure compared with asymptomatic women. Flushing was also associated with hypercholesterolemia (odds ratio: 1.52; 95% CI: 1.25 to 1.84) and hypertension (OR: 1.20; 95% CI: 1.07 to 1.34). Results were similar for complaints of night sweating. The findings support the view that menopausal complaints are associated with a less favorable cardiovascular risk profile. These findings substantiate the view that differences in the presence of menopausal symptoms as a reason for using hormone therapy could explain discrepant findings between observational research and trials.