Salt sensitivity and hypertension after menopause: role of nitric oxide and angiotensin II

Hypertension is a major risk factor for cardiovascular disease and renal disease. After menopause, the incidence of hypertension increases in women to levels that equal or exceed that in men, suggesting a protective role of female sex hormones. Salt sensitivity of blood pressure is associated with an increased risk for development of hypertension and cardiovascular disease. We and others have demonstrated that after menopause, the prevalence of salt sensitivity increases, suggesting that female sex hormones influence renal sodium handling and blood pressure regulation. A homeostatic balance between the counteracting effects of nitric oxide (NO) and angiotensin (Ang) II on pressure natriuresis, renal hemodynamics, tubular sodium reabsorption, and oxidative stress plays an important role in modulating salt sensitivity as well as hypertensive end-organ injury. Estrogens modulate the activity and expression of NO and Ang II. We infer that after menopause, estrogen deficiency promotes an unbalance between NO and Ang II, resulting in disturbed renal sodium handling, oxidative stress, and hypertension, particularly in genetically prone women. A better understanding of the mechanisms underlying the development of postmenopausal hypertension and associated cardiovascular and renal diseases should provide insights into preventive and therapeutic strategies.     

Role of Inflammation and Infection in Vascular Disease

Relationship of infection, inflammation, and atherosclerosis has been a subject of intensive investigation in recent years. Potential mechanisms whereby chronic infections may play a role in atherogenesis are myriad. Chlamydia pneumoniae (Cp) infection in early life may accelerate atherosclerosis, leading to cardiovascular complications. Other infections, simultaneously occurring with Cp, may result in a synergistic effect to promote atherosclerosis. Chronic Helicobacter pylori infection is known to increase the pH level of the gastric juice and to decrease ascorbic acid levels, both of which will lead to a reduced folate absorption. Low folate hampers the methionine synthase reaction. This leads to an increased concentration of homocysteine in the blood, resulting in damage of endothelial cells. Cytomegalovirus (CMV) infection is associated with accelerated atherosclerosis following cardiac transplantation; several studies have found that patients with a previous CMV infection had a high independent risk of restenosis after coronary angiography. Inflammatory markers are independent predictors of cardiovascular and cerebrovascular events. Large population-based studies such as the study from the MONICA (MONItoring trends and determinants in CArdiovascular disease) Augsberg Center in Germany, the Atherosclerosis Risk in Communities Study, the Women’s Health Study, the Honolulu Heart Study, have also suggested the relation between the levels of CRP and risk of coronary disease. Over the past decade also another marker of inflammation has been studied; fibrinogen has been identified as an independent risk factor for CAD in several large prospective studies. All these studies suggested a new, possible role of markers of infection and inflammation beyond traditional cardiovascular risk factors, in the development and progression of atherosclerosis. However, the clinical and therapeutic implications of these results remain to be evaluated. Although antibiotic treatment of infections in CAD patients had no impact on mortality in large prospective trials, promising data is coming from smaller studies and further studies are needed to investigate the possibility to submit this category of high-risk patients to therapeutical approaches of primary prevention.     

Role of inflammation and infection in vascular disease

Relationship of infection, inflammation, and atherosclerosis has been a subject of intensive investigation in recent years. Potential mechanisms whereby chronic infections may play a role in atherogenesis are myriad. Chlamydia pneumoniae (Cp) infection in early life may accelerate atherosclerosis, leading to cardiovascular complications. Other infections, simultaneously occurring with Cp, may result in a synergistic effect to promote atherosclerosis. Chronic Helicobacter pylori infection is known to increase the pH level of the gastric juice and to decrease ascorbic acid levels, both of which will lead to a reduced folate absorption. Low folate hampers the methionine synthase reaction. This leads to an increased concentration of homocysteine in the blood, resulting in damage of endothelial cells. Cytomegalovirus (CMV) infection is associated with accelerated atherosclerosis following cardiac transplantation; several studies have found that patients with a previous CMV infection had a high independent risk of restenosis after coronary angiography. Inflammatory markers are independent predictors of cardiovascular and cerebrovascular events. Large population-based studies such as the study from the MONICA (MONItoring trends and determinants in Cardiovascular disease) Augsberg Center in Germany, the Atherosclerosis Risk in Communities Study, the Women's Health Study, the Honolulu Heart Study, have also suggested the relation between the levels of CRP and risk of coronary disease. Over the past decade also another marker of inflammation has been studied; fibrinogen has been identified as an independent risk factor for CAD in several large prospective studies. All these studies suggested a new, possible role of markers of infection and inflammation beyond traditional cardiovascular risk factors, in the development and progression of atherosclerosis. However, the clinical and therapeutic implications of these results remain to be evaluated. Although antibiotic treatment of infections in CAD patients had no impact on mortality in large prospective trials, promising data is coming from smaller studies and further studies are needed to investigate the possibility to submit this category of high-risk patients to therapeutical approaches of primary prevention.     

Current Treatment Options: Headache Related to Menopause—Diagnosis and Management

Purpose of review

Menopause is a life-changing event in numerous ways. Many women with migraine hold hope that the transition to the climacteric state will coincide with a cessation or improvement of migraine. This assumption is based mainly on common lay perceptions as well as assertions from many in the healthcare community. Unfortunately, evidence suggests this is far from the rule. Many women turn to a general practitioner or a headache specialist for prognosis and management. A natural instinct is to manipulate the offending agent, but in some cases, this approach backfires, or the concern for adverse events outweighs the desire for a therapeutic trial, and other strategies must be pursued. Our aim was to review the frequency and type of headache syndromes associated with menopause, to review the evidence for specific treatments for headache associated with menopause, and to provide management recommendations and prognostic guidance.

Recent findings

We reviewed both clinic- and population-based studies assessing headache associated with menopause. Headache in menopause is less common than headache at earlier ages but can present a unique challenge. Migraine phenotype predominates, but presentations can vary or be due to secondary causes. Other headache types, such as tension-type headache (TTH) and cluster headache (CH) may also be linked to or altered by hormonal changes. There is a lack of well-defined diagnostic criteria for headache syndromes associated with menopause. Women with surgical menopause often experience a worse course of disease status than those with natural menopause. Hormonal replacement therapy (HRT) often results in worsening of migraine and carries potential for increased cardiovascular and ischemic stroke risk. Estrogen replacement therapy (ERT) in patients with migraine with aura (MA) may increase the risk of ischemic stroke; however, the effect is likely dose-dependent. Some medications used in the prophylaxis of migraine may be useful in ameliorating the vasomotor and mood effects of menopause, including venlafaxine, escitalopram, paroxetine, and gabapentin. Other non-medication strategies such as acupuncture, vitamin E, black cohosh, aerobic exercise, and yoga may also be helpful in reducing headache and/or vasomotor symptoms associated with menopause.

Summary

The frequency and type of headache associated with menopause is variable, though migraine and TTH are most common. Women may experience a worsening, an improvement, or no change in headache during the menopausal transition. Treatment may be limited by vascular risks or other medical and psychiatric factors. We recommend using medications with dual benefit for migraine and vasomotor symptoms including venlafaxine, escitalopram, paroxetine, and gabapentin, as well as non-medication strategies such as acupuncture, vitamin E, black cohosh, aerobic exercise, and yoga.If HRT is pursued, continuous (rather than cyclical) physiological doses should be used, transdermal route of administration is recommended, and the patient should be counseled on the potential for increased risk of adverse events (AEs). Concomitant use of a progestogen decreases the risk of endometrial hyperplasia with ERT. Biological mechanisms are incompletely understood, and there is a lack of consensus on how to define and classify headache in menopause. Further research to focus on pathophysiology and nuanced management is desired.

     

高血压对女性性功能的影响

女性性功能障碍(FSD)是一种与年龄相关的进展性疾病,可能影响多达半数的成年妇女,长期以来,FSD未得到重视.高血压是一种常见病、多发病.高血压及抗高血压药物与FSD有密切关系,其中高血压引起的动脉粥样硬化和内皮功能障碍、抗高血压药物对女性性功能的影响尤为显著,现就高血压对女性性功能的影响机制及研究进展作一综述.     

Hormone replacement therapy and peripheral vascular disease in women

Women have been shown to have a lower incidence of vascular disease when compared to men. However, the incidence of vascular disease increases as women progress through menopause and reaches an incidence similar to that of men later in life. Women with peripheral vascular disease often have a delay in diagnosis, a higher incidence of asymptomatic disease, and poorer outcome after interventions. The differences in outcome have been attributed to a number of factors such as anatomic and hormonal differences. It is thought that estrogen deficiency is at least partially responsible for the increased risk of developing vascular disease after menopause, and thus hormone replacement therapy has been considered as a method to prevent progression of vascular disease. Conclusions drawn from a number of recent studies have resulted in a divergent view of hormone replacement therapy (HRT). This article explores the risk of peripheral vascular disease in women and the current state of research on hormone replacement therapy. The aims of this review are to present current perspectives on gender differences in the pathogenesis and outcomes of peripheral arterial disease (PAD). The effect of estrogen on atherogenesis, the role it plays in modulating the vascular endothelium, and the current evidence of the effects of HRT on vascular pathology is discussed. The most recent HRT clinical trials and present evidence for the benefits and risks of postmenopausal hormone replacement therapy are summarized. The effect of these issues on treatment practices is explained and suggestions are made for future directions of HRT and PAD research.     

Menopause and postmenopausal hormone use and risk of incident kidney stones

Menopause is associated with increased urinary calcium excretion, which could increase the risk for the development of calcium-containing kidney stones. However, it is unknown whether menopause and postmenopausal hormone (PMH) use are independent risk factors for incident kidney stone disease in women. Data from 91,731 female Nurses' Health Study participants who provided information on diet, menopause status, and kidney stone disease were used to examine the independent association between menopause and PMH use and risk of incident kidney stones. No association was found between menopause and incident kidney stones in age-adjusted (relative risk [RR], 1.07; 95% CI, 0.85 to 1.34) or multivariate models (RR, 1.12; 95% CI, 0.89 to 1.41). However, when the association between the type of menopause and risk of incident kidney stones was examined, surgical menopause was associated with an increased risk in both the age-adjusted (RR, 1.37; 95% CI, 1.05 to 1.77) and multivariate models (RR, 1.39; 95% CI, 1.07 to 1.81), whereas natural menopause was not. Compared with never-use, past or current PMH use (including duration of PMH use) was not associated with incident kidney stones among postmenopausal women. In conclusion, no association was found between menopause and PMH use and incident kidney stones. Surgical menopause, however, may be associated with an increased risk.     

Worry and risk perception of breast cancer in a prevention trial of low dose tamoxifen in midlife postmenopausal hormone users

ObjectiveThere is increasing interest in combining postmenopausal hormone therapy (HT) and SERMs in midlife women. We previously showed that refusal to participate in a prevention trial of low dose tamoxifen in HT users was associated with higher worry about breast cancer. Given this counterintuitive finding, we studied which factors influenced worry and risk perception of breast cancer.MethodsWe assessed the relationships of breast cancer worry and risk perception with age, age at menopause, Gail risk, education, adherence to mammographic screening, BMI, smoking, physical activity, alcohol use, anxiety and depression in 457 midlife HT users who were eligible to participate in the trial.ResultsWomen with menopause <48 years were more worried about breast cancer than women with menopause >52 years (OR = 5.0, 95% CI, 1.2–21.1). Worry was also associated with high absolute risk perception and former smoking. Factors associated with higher risk perception were age>60 years, at-risk life style, worry about breast cancer and depression.ConclusionsThe inverse association between early menopause and worry about breast cancer is in contrast with the known protective effect of early menopause on breast cancer risk and seems to reflect a feeling of aging and disease vulnerability. Our findings indicate that worry about cancer has an affective construct which is independent of breast cancer biology but is engaged in health decision making. Increasing breast cancer risk awareness in subjects high in worry without a plan of emotional coping may therefore be counterproductive because of avoidant attitudes.     

Glucosamine-induced endoplasmic reticulum dysfunction is associated with accelerated atherosclerosis in a hyperglycemic mouse model

Diabetes is a major independent risk factor for cardiovascular disease and stroke; however, the molecular and cellular mechanisms by which diabetes contributes to the development of vascular disease are not fully understood. Our previous studies demonstrated that endoplasmic reticulum (ER) stress-inducing agents, including homocysteine, promote lipid accumulation and activate inflammatory pathways-the hallmark features of atherosclerosis. We hypothesize that the accumulation of intracellular glucosamine observed in diabetes may also promote atherogenesis via a mechanism that involves ER stress. In support of this theory, we demonstrate that glucosamine can induce ER stress in cell types relevant to the development of atherosclerosis, including human aortic smooth muscle cells, monocytes, and hepatocytes. Furthermore, we show that glucosamine-induced ER stress dysregulates lipid metabolism, leading to the accumulation of cholesterol in cultured cells. To examine the relevance of the ER stress pathway in vivo, we used a streptozotocin-induced hyperglycemic apolipoprotein E-deficient mouse model of atherosclerosis. Using molecular biological and histological techniques, we show that hyperglycemia is associated with tissue-specific ER stress, hepatic steatosis, and accelerated atherosclerosis. This novel mechanism may not only explain how diabetes and hyperglycemia promote atherosclerosis, but also provide a potential new target for therapeutic intervention.     

Potential clinical impact of reporting breast arterial calcifications on screening mammograms in women without known coronary artery disease

Cardiovascular disease remains a leading cause of death in women. 10-year likelihood for a cardiovascular event is determined by the American College of Cardiology Atherosclerotic Cardiovascular disease risk score calculator (ASVCD); however, this does not encompass risk factors unique to women. Breast arterial calcifications (BAC) detected on screening mammography may serve as a proxy for coronary atherosclerosis (CAC) in women. Our purpose was to investigate the correlation between BAC and CAC on imaging in women without a diagnosis of atherosclerosis to determine the potential clinical impact. Retrospective review was performed on a cohort of females evaluated by internists at our institution in 2019. Study patients had a screening mammogram within 1 year of a noncardiac chest CT. Clinical data were collected to determine ASCVD risk score. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of BAC in detecting CAC were determined. 222 women met inclusion criteria, ranging from 41 to 77 years of age, among which 25% (56/222) had BAC. 84% (47/56) of women with BAC had CAC on CT, yielding a sensitivity, specificity, PPV, and NPV of 51%, 93%, 84%, and 72%, respectively. Of the 47 patients who had both BAC and CAC, 66% had an unknown or low-to-borderline ASCVD score. Women with BACs have a high specificity for CAC. The reporting of BACs should prompt clinicians to risk stratify women for atherosclerotic disease. These women may otherwise be undetected by conventional risk calculators.     

Vitamin D and its analogues: do they protect against cardiovascular disease in patients with kidney disease?

BACKGROUND: Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease, and despite recent advances in hypertension control, anemia management, and dialysis adequacy, mortality remains high. Improved understanding of nontraditional risk factors, including those present at early phases in CKD, may lead to novel therapeutic strategies. CKD has been demonstrated to be an independent risk factor for cardiovascular disease in the general population, but data are lacking as to the associated potential abnormalities that occur in association with reduced glomerular filtration rate (GFR), which may contribute to this increased risk. Data are accumulating regarding the role of abnormalities of calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) in cardiovascular disease. Vitamin D deficiency is present even in the early stages of CKD. Vitamin D plays a central role in calcium-phosphorus homeostasis, regulation of PTH, and formation and maintenance of bone. However, until recently, vitamin D has not been considered to have a biologic role in CKD beyond mineral regulation, or has been considered as a negative factor contributing to soft tissue and cardiovascular calcification. In light of recent observational studies showing an association of vitamin D therapy and survival benefit in hemodialysis patients, the effects of vitamin D on cardiovascular system have become a heavily debated issue. METHODS: A Medline search was performed to identify relevant literature describing the role of vitamin D in the pathogenesis of cardiovascular disease. Both the experimental and clinical literatures in English were reviewed. RESULTS: The accumulating published data demonstrate both associative relationships and mechanisms for biologic plausibility. The following three potential mechanisms may be important for the protective effects of vitamin D against cardiovascular disease mortality: vitamin D can inhibit various aspects of inflammation, which have been established as a key pathogenic mechanism in atherosclerosis; vitamin D exerts an antiproliferative effect on myocardial cell hypertrophy and proliferation, which underlies the pathogenesis of congestive heart failure; and vitamin D acts as a negative endocrine regulator for the renin-angiotensin system, which itself plays an important independent role in hypertension and cardiovascular health. CONCLUSION: Vitamin D deficiency might be an underestimated nonclassical risk factor for cardiovascular disease in CKD. Based on a review of the evidence, from both basic science and clinical studies, this article supports the possible protective role of vitamin D beyond its effect on mineral metabolism, and suggests the need for ongoing evaluation of the role of vitamin D in cardiovascular health in the CKD population.     

Osteoporosis and breast cancer

Osteoporosis affects one in three women after the menopause and the incidence of osteoporotic fractures increases steadily throughout life. Breast cancer is the most common cancer in women, both before and after the menopause. In younger women, recovery from breast cancer has been achieved using aggressive chemotherapy and radiotherapy that can adversely affect bone tissue or induce premature menopause. In postmenopausal women, breast cancer and osteoporosis are common, and although both are dependent on estrogens this leads to conflicting implications for the diagnosis and treatment: estrogens reduce the risk of fractures but increase the risk of breast cancer. Estrogen supplementation is, therefore, contraindicated in patients with a history of breast cancer. Selective estrogen response modifiers (SERMs) hold great promise, as they decrease both the fracture risk via an estrogen-agonist effect on bone and the breast cancer risk via an estrogen-antagonist effect on the breast tissue. SERMs can be used after successful treatment for breast cancer. Bisphosphonates, which are potent bone resorption inhibitors, are widely used both in cancer patients and in the prevention and treatment of spinal and peripheral osteoporotic fractures. Contraindications are exceedingly rare, and the satisfactory safety profile of these agents can be expected to improve further with newly developed modes of administration. Whether the bisphosphonates currently used to treat osteoporosis (alendronate and risendronate) have beneficial effects on skeletal events related to cancer progression remains to be determined, however. In sum, selection of the optimal treatment for osteoporosis in a patient with breast cancer involves assessment of the risk/benefit ratio of each treatment option, based on patient age, other risk factors for osteoporosis, and the stage of breast cancer progression.     

Magnitude and determinants of premenopausal bone loss

Bone loss prior to menopause may contribute to a woman's risk for fracture due to osteoporosis later in life. Most, but not all, longitudinal and cross-sectional studies suggest that bone mass decreases prior to menopause. This bone loss may be prevented by calcium supplementation. Heredity, exercise and menstrual status also have an impact on bone mass. Prevention of bone loss prior to menopause will allow women to enter menopause with a greater bone mass reducing their risk of subsequent fracture.     

Lipoprotein(a) and its role in occlusive vascular disease.

An increased serum level of lipoprotein(a) (LP(a)) is acknowledged as an independent risk factor for occlusive vascular disease, especially atherosclerosis. Recently, a considerable amount of data has been produced on the structure and functional relationships between Lp(a) and the primary cellular interactions of atherosclerosis. In this review we discuss the structure and function of Lp(a) with specific reference to its role in the proposed mechanisms of atherosclerosis.     

Association of cardiovascular risk factors with pattern of lower limb atherosclerosis in 2659 patients undergoing angioplasty.

OBJECTIVES: Aim of this study is to correlate distribution pattern of lower limb atherosclerosis with cardiovascular risk factor profile of patients with peripheral arterial occlusive disease (PAD). PATIENTS AND METHODS: Analysis is based on a consecutive series of 2659 patients (1583 men, 1076 women, 70+/-11 years) with chronic PAD of atherosclerotic origin undergoing primary endovascular treatment of lower extremity arteries. Pattern of atherosclerosis was grouped into iliac (n=1166), femoropopliteal (n=2151) and infrageniculate (n=888) disease defined according to target lesions treated. A multivariable multinomial logistic regression analysis was performed to assess relation with age, gender and classical cardiovascular risk factors (diabetes mellitus, arterial hypertension, hypercholesterolemia, cigarette smoking) using femoropopliteal disease as reference. RESULTS: Iliac disease was associated with younger age (RRR 0.95 per year of age, 95%-CI 0.94-0.96, p<0.001), male gender (RRR 1.32, 95%-CI 1.09-1.59, p=0.004) and cigarette smoking (RRR 2.02, 95%-CI 1.68-2.42, p<0.001). Infrageniculate disease was associated with higher age (RRR 1.02, 95%-CI 1.01-1.02, p<0.001), male gender (RRR 1.23, 95%-CI 1.06-1.41, p=0.005) and diabetes mellitus (RRR 1.68, 95%-CI 1.47-1.92, p<0.001). Hypercholesterolemia was less prevalent in patients with lesions below the knee (RRR 0.82, 95%-CI 0.71-0.94, p=0.006), whereas no distinct pattern was apparent related to arterial hypertension. CONCLUSION: Clinical phenotype of peripheral atherosclerosis varies with prevalence of cardiovascular risk factors suggesting differences in mechanisms involved in iliac as compared with infrageniculate lesions. Identification of molecular mechanism might have influence on future therapeutic strategies in PAD patients.     

Low Bone Mineral Density in the Hip as a Marker of Advanced Atherosclerosis in Elderly Women

Previous studies indicate that low bone mineral density (BMD) in the hip is a useful predictor of cardiovascular mortality among the elderly. The objective of this study was to investigate whether low hip BMD is directly associated with the severity of atherosclerosis. The per-protocol population consisted of 963 women aged 60-85 years. Study variables were aortic calcification (AC) graded on lateral lumbar radiographs, BMD at various anatomic sites (distal radius, lumbar spine, proximal femur) measured by DXA, information on various risk factors, and medical history. After adjustment for age, BMD at the proximal femur, but not at the radius or spine BMD, showed statistically significant association with the severity of AC (r = –0.12–17, P < 0.001). Age, years since menopause, BMI, level of education, current and previous smoking, and weekly fitness activity were significant common risk factors (all P < 0.05) with contrasting influence on AC and hip BMD. In a multiple regression model, AC contributed significantly and independently to the variation in hip BMD ( = –0.10, P = 0.004). Impaired blood flow represented by 40 women with documented history of intermittent claudication was not an independent contributor and did not alter the association between AC and hip BMD. However, AC and demineralization in the hip was particularly severe in women with intermittent claudication accompanied by a higher prevalence of coronary heart disease compared with age-matched controls (all P < 0.001). In conclusion, severe osteoporosis in the hip may indicate advanced atherosclerosis and thereby an increased risk for not only hip fractures but also for coronary heart disease. The results further emphasize that osteoporosis in the hip and peripheral vascular disease are linked by common risk factors and pathomechanisms.     

Inflammation in end-stage renal disease: sources,consequences, and therapy

Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Although traditional risk factors are common in ESRD patients, they alone may not be sufficient to account for the high prevalence of CVD in this condition. Recent evidence demonstrates that chronic inflammation, a nontraditional risk factor which is commonly observed in ESRD patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. The causes of inflammation in ESRD are multifactorial and, while it may reflect underlying CVD, an acute-phase reaction may also be a direct cause of vascular injury by several pathogenetic mechanisms. Available data suggest that proinflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. Thus it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. Recent evidence has demonstrated strong associations between inflammation and both increased oxidative stress and endothelial dysfunction in ESRD patients. As there is not yet any recognized, or even proposed, treatment for ESRD patients with chronic inflammation, it would be of obvious interest to study the long-term effect of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status as well as outcome in these patients.     

Fractures Before Menopause: A Red Flag for Physicians

There is substantial interest in the early identification of women at risk for osteoporotic fractures, so that preventive measures may be instituted early. We examined whether women with a history of fractures before menopause were at an increased risk of fractures after menopause. We obtained information about any lifetime fractures of the hip, arm, spine, wrist, leg, ankle, foot and finger from 9086 ambulatory white women ages 65 years and older participating in the Study of Osteoporotic Fractures. We also measured bone mineral density and recorded history of falls, maternal fracture history, drug use, diet, functional status, and other characteristics commonly associated with osteoporotic fractures. We used proportional hazards models to estimate the effects of fractures that occurred before menopause on the risk of fractures after menopause, in particular those that occurred during the 12 years of study follow-up. The risk of fractures of all types during the study period was greater among women with a premenopausal fracture of any type compared with women without a premenopausal fracture (hazard ratio (HR), 1.33; 95% confidence interval (CI), 1.14–1.56; p<0.001). Adjustment for possible confounders, including bone mineral density, had only a modest effect (HR, 1.25; 95% CI, 1.03–1.50; p<0.02). An increased risk of fracture among women with a premenopausal fracture was also seen after stratification by estrogen use, propensity to fall and maternal fracture history. Premenopausal fractures are therefore a risk factor for subsequent fractures independent of other risk factors for osteoporotic fractures, such as bone mineral density. A fracture history, including fractures before menopause, should be obtained when making decisions about preventive treatments. Received: 17 April 2000 / Accepted: 14 June 2000     

Prämature Atherosklerose

Coronary heart disease (CAD) is the leading cause of death in men and women. However, men develop heart disease about 10 years earlier, which reduces their average life expectancy by about 6 years. The cause is the high incidence of premature atherosclerosis in men. In fairly young and middle-aged men with the same blood pressure or cholesterol levels as women cardiovascular risk is double that in women the same age, or the same as in women 10 years older but with the same risk factor profile otherwise. This means that like age, male sex is a cardiovascular risk factor that noone can do anything about. The sex difference does not even out until after the age of 75 years and cannot be explained on the basis of the different sex hormones. The data currently available do not allow any definitive explanation for the premature atherosclerosis seen in men. In parallel with CAD, men also suffer more frequently and earlier in life than women from peripheral arterial disease and aortic aneurysms.     

The menopause and urinary incontinence

The objective was to study the possible role of the menopause in adult female urinary incontinence (UI) etiology, using a cross-sectional population study comprising a random sample of adult females and self-reported data based on postal questionnaires.The study group comprised 915 women who reported continued menstruation and 636 women who had stopped menstruation after the age of 39; in total, 1551 women aged 40–59 years, from the Municipality of Aarhus, Denmark. Ooophorectomized or hysterectomized women not reporting menstruation were excluded.The main outcome measures were the period prevalence in 1987 of episodes of stress and urge urinary incontinence; prevalence of menopause and exposure to childbirth, gynecologic surgery, cystitis and obesity as indicated by body mass index more than 29; prevalence relative risks, as indicated by odds ratio of UI conditional on menopause and other prevalence risk indicators.The 1987 period prevalences of stress and urge urinary incontinence were 15.9% and 8.7%, respectively. Forty-one percent had ceased to menstruate. Irrespective of the UI risk indicators mentioned, UI prevalence was significantly raised from 1 year before until 1 year after the year of final menstruation. The findings suggest perimenopausal processes rather than the menopause in general to be responsible for an increased risk of developing UI. The elevation of UI prevalence in the perimenopause may reflect the adjustment of the female continence mechanism to function with a lower estrogen level than previously. Perimenopausal processes seem to contribute much less than surgical operations, for example, to the amount of UI in middle-aged women. This may affect assessment of the relevance of estrogen supplementation of menopausal UI patients aged 40–59.