Primary prevention of coronary heart disease in women

The British Menopause Society Council is committed to provide up-to-date authoritative reviews to aid health professionals to inform and advise women about key issues in postreproductive health. Coronary heart disease (CHD) is a leading cause of death in women. Observational studies have consistently shown estrogen to help prevent CHD in postmenopausal women. The large randomized controlled Women's Health Initiative (WHI) trial did not confirm these observational findings. However, further analyses of the WHI study as well as the observational Nurses' Health Study have now found that the timing of onset of hormone replacement therapy (HRT) use is important and that estrogen may have a protective role in CHD in women aged 50-59 years. This consensus statement will examine the evidence regarding HRT and non-estrogen therapies (lipid lowering agents, aspirin, antihypertensives, antidiabetic medications, selective estrogen receptor modulators [SERMs]) as well as diet, lifestyle and smoking cessation in the primary prevention of CHD in women.     

Systemic lupus erythematosus and hormone replacement therapy

The indications for hormone replacement therapy (HRT) in postmenopausal women is the treatment of climacteric symptoms and the prevention of osteoporosis. Women with systemic lupus erythematosus (SLE) are more likely to have a premature menopause, osteoporosis and cardiovascular disease. HRT can induce SLE flares and cardiovascular or venous thromboembolic events. Therefore it should not be used in women with active disease or those with antiphospholipid (aPL) antibodies. In general, it should be used only for patients without active disease, a history of thrombosis or aPL antibodies. Non-oral administration of estrogen is recommended because of its lesser effect on coagulation. With regard to the progestogen, progesterone or pregnane derivatives are preferred. Otherwise, non-estrogen-based strategies should be used.     

Metabolic syndrome and the menopause

The metabolic syndrome consists of a combination of risk factors that include abdominal obesity, atherogenic dyslipidaemia, hypertension and insulin resistance. It increases the risk of cardiovascular disease and type 2 diabetes. The increased risk of cardiovascular disease is higher in women than in men. The first manifestation of metabolic syndrome may occur in pregnancy presenting as gestational diabetes or preeclampsia. Both conditions are associated with increased insulin resistance. Also metabolic syndrome is more common in polycystic ovarian syndrome. It has been suggested that there is a metabolic syndrome resulting from the menopause due to estrogen deficiency, as many of the risk factors are more prevalent in postmenopausal women. Also estrogen replacement improves insulin sensitivity and reduces the risk of diabetes. The key elements in managing the metabolic syndrome are weight reduction, increasing physical activity and diet modification. If blood pressure, lipid and glycaemic control are not achieved through these interventions then pharmacological therapy will be required.     

National Osteoporosis Society's Position statement on hormone replacement therapy in the prevention and treatment of osteoporosis

Hormone replacement therapy (HRT) has been shown to increase bone density, reduce the risk of fracture and can successfully relieve menopausal symptoms. From a time when HRT was the major therapeutic option for the management of osteoporosis, women and their clinicians now have a range of treatments available. Following the publication of the Women's Health Initiative (WHI) and the Million Women Study highlighting potential side-effects, such as breast cancer, heart disease and stroke, many doctors and women are now reluctant to use HRT. The National Osteoporosis Society felt that the role of HRT in the management of osteoporosis needed to be clarified. Using the Charity's expert clinical and scientific advisers, and through public consultation with members and key stakeholders, a Position Statement has been published. We conclude that HRT has a role to play in the management of osteoporosis in postmenopausal women below the age of 60 years. The key recommendations of the Position Statement are presented in this paper.     

Insulin resistance and management of the menopause: a clinical hypothesis in practice

Insulin resistance (IR) is associated with a number of metabolic abnormalities including glucose intolerance, dyslipidemia and central obesity (the metabolic syndrome), which predispose to cardiovascular disease, diabetes mellitus and some cancers. The incidence of many of these conditions increases after the menopause, a time when IR also increases. Medical intervention to help alleviate menopausal symptoms, frequently vasomotor in origin, usually involves hormone replacement therapy (HRT), but some women may only experience partial symptom relief. We have hypothesized that this may be due to concurrent IR. Our approach is therefore to manage menopausal symptoms in conjunction with the treatment of any concurrent IR, achieved through a combination of hormone replacement, dietary intervention and, if necessary, an insulin sensitizer. We suggest that this approach may not only improve symptom relief but may also reduce the risk of developing more serious health complaints in the future.     

Homocysteine, menopause and cardiovascular disease

A high plasma concentration of total homocysteine (tHcy) and a deficiency of vitamins related to its metabolism, such as vitamin B12 and folate, have been associated with cardiovascular disease. Postmenopausal women have higher concentrations than age-matched premenopausal women, and plasma concentrations of homocysteine in postmenopausal women taking hormone replacement therapy are significantly lower than they are in those who do not take estrogen supplements. Because of the possible mixed effects of HRT on cardiovascular events, surrogate end-points must be evaluated with caution. While measuring homocysteine levels is relatively simple, evidence from well designed trials is awaited before population screening can be advocated. Also, the benefits of reducing homocysteine levels with folic acid and vitamin B6 and B12 supplements are highly debated.     

Women's perceptions of the effects of menopause and hormone replacement therapy on skin

Although women frequently associate skin issues with menopause and hormone replacement therapy (HRT), little work has been done to investigate a possible relationship. A questionnaire was given to women attending a specialist menopause clinic; 87 women responded. Skin problems generally were common, with over 64% of respondents reporting past problems. Around half felt that the menopause had resulted in skin changes; dry skin was the predominant complaint at this stage. However, use of HRT in the short term did not result in any conclusive trends in skin condition in the majority of users.     

Menopause and schizophrenia

We have come a long way from our understanding of the menopause as it was described in the 11th century by Trotula of Salerno, a female gynaecologist who said 'there are older women who give forth blood matter especially as menopause approaches them'. Yet very little is known about the impact menopause has on the mental health of women especially severe and enduring illnesses like schizophrenia. A lot of research has shown that estrogen acts as a protective factor due to its antidopaminergic properties, thus providing an explanation for the increase in risk of a new psychotic disorder during the menopause. This has further led to the hypothesis of hormone replacement therapy providing benefits in the management of these disorders in menopausal women. This review article highlights the importance of a clear understanding of this phase of life in patients suffering from or who present with a risk of developing schizophrenia.     

Management of premature menopause

There has been some confusion among women and health professionals since the publication of the Women's Health Initiative and Million Women studies about the management of premature ovarian failure (POF). Both studies were undertaken in women aged 50 and over, and cannot be extrapolated to their younger counterparts, who would normally be producing their endogenous estrogen, since they have functioning ovaries. Estrogen-based replacement therapy is the main stay of treatment for women with POF and is recommended at least until the average age of natural menopause (52 years in the UK). This view is endorsed by regulatory bodies such as the Committee on Safety of Medicines (now the Commission on Human Medicines) in the UK. No evidence shows that estrogen replacement increases the risk of breast cancer to a level greater than that found in normally menstruating women, and women with POF do not need to start mammographic screening early unless other risk factors are present, such as family history.     

Estrogen treatment affects brain functioning after menopause

Sex hormones have powerful neuromodulatory effects on functional brain organization and cognitive functioning. This paper reviews findings from studies investigating the influence of sex hormones in postmenopausal women with and without hormone therapy (HT). Functional brain organization was investigated using different behavioural tasks in postmenopausal women using either estrogen therapy or combined estrogen plus gestagen therapy and age- and IQ-matched postmenopausal women not taking HT. The results revealed HT-related modulations in specific aspects of functional brain organization including functional cerebral asymmetries and interhemispheric interaction. In contrast to younger women during the menstrual cycle, however, it seems that HT, and especially estrogen therapy, after menopause affects intrahemispheric processing rather than interhemispheric interaction. This might be explained by a faster and more pronounced age-related decline in intrahemispheric relative to interhemispheric functioning, which might be associated with higher sensitivity to HT. Taken together, the findings suggest that the female brain retains its plasticity even after reproductive age and remains susceptible to the effects of sex hormones throughout the lifetime, which might help to discover new clinical approaches in the hormonal treatment of neurological and psychiatric disorders.     

Mental health around and after the menopause

The menopause is a time in a woman's life when it is recognized that biological and social changes can impact upon mental wellbeing. Several studies have investigated the relationship between menopause and psychological symptoms, especially depression, with mixed results. In part, this is due to a considerable overlap between depressive symptoms and those due to declining estrogen levels, causing challenges in assessment. However it appears that vulnerable women are at a higher risk of succumbing to depression during menopausal transition. Antidepressants remain the mainstay of treating depressive symptoms, with little conclusive evidence for hormone replacement therapy. Memory problems during menopause are a common complaint, but there is no demonstrated link to subsequent dementia. This paper also reviews considerations of diagnosis and treatment of postmenopausal depression.     

Gender,the Marital Life Course,and Cardiovascular Disease in Late Midlife

Drawing on 5 waves of the Health and Retirement Study, we examine the influence of the marital life course on the prevalence and incidence of cardiovascular disease among 9,434 middle‐aged individuals. Results show that compared to continuously married persons, both men and women with a marital loss have significantly higher prevalence of cardiovascular disease at baseline. Men and women, however, differ in the effects of marital loss on the incidence of cardiovascular disease over the course of the study. Women with a marital loss have a higher risk of cardiovascular disease in late midlife compared to continuously married women, whereas marital loss is not associated with men’s risk of cardiovascular disease. Emotional distress and socioeconomic status account for the higher risk of cardiovascular disease among divorced women.     

Treating cardiovascular disease in women

Cardiovascular disease (CVD) is the most common cause of death in women but some of the challenges of management differ from those in men. This article addresses the gender-specific issues of cardiovascular management, with emphasis on ischaemic heart disease and modification of coronary risk factors. Women with ischaemic heart disease present later than men, and are therefore older and more likely to suffer from co-morbidities such as diabetes and hypertension. Proven CVD risk factors in women can be divided into those that are modifiable and those that are non-modifiable. The former include diabetes, dyslipidaemia, hypertension, smoking, obesity, sedentary lifestyle and poor nutrition; the latter include family history of heart disease and older age at presentation. It is this difference in age and general health that explains much of the variability in response to treatment. Pharmacotherapy, percutaneous intervention, surgical revascularization, and cardiac rehabilitation and disease prevention are discussed.     

The future of the new selective estrogen receptor modulators

Selective estrogen receptor modulators (SERMs) are compounds that display mixed estrogen agonist/antagonist activity. Currently, four SERMs are licensed for clinical use: tamoxifen, toremifene, clomifene and raloxifene. The STAR and RUTH trials have provided useful data about the potential role of SERMs in the primary prevention of breast cancer and cardiovascular disease in postmenopausal women. New-generation SERMs, such as bazedoxifene, arzoxifene, lasofoxifene and ospemifene, are currently being evaluated. The aim is to find a SERM that conserves the skeleton and prevents breast cancer without increasing the risk of endometrial cancer and venous thromboembolism, and without inducing hot flushes. Technological advances in the study of estrogen receptor activation will provide key information for drug development.     

Not Such Strange Bedfellows After All

Abstract

The irritable bowel syndrome (IBS) is best defined as abdominal pain of greater than three months duration, with or without a change in bowel habits. Barium studies, sedimentation rate, and the lactose tolerance test are usually within normal limits. The underlying physiology includes a predominance of 3 cycles/minute basal electrical rhythm (BER). The abdominal pain is poorly localized and usually intermittent, without a clear relationship to medication. Differential diagnosis should include inflammatory bowel disease, infectious colitis or gastroenteritis, lactose intolerance, gallbladder disease, peptic ulcer disease, pelvic inflammatory disease, ovarian cysts and tumors, and endometriosis. A sedimentation rate is an important part of the diagnostic workup which may or may not include barium studies. Anticholinergics have been shown to alter the abnormal BER of irritable bowel syndrome and have proven to be of use in treating this syndrome. Dietary counseling should include advising the patient to eat slowly and at regular hours, and heat applied to the abdomen in the form of a hot water bag has been useful. “Overprogrammed” individuals with irritable bowel syndrome should be advised to modify their activities as this type of stress may give rise to the symptoms.

“Effect of Estrogen/Progestin Potency on Lipid/Lipoprotein Cholesterol,” PATRICIA WAHL, CAROLYN WALDEN, ROBERT KNOPP, JOANNE HOOVER, ROBERT WALLACE, GERARDO HEISS, and BASH RIFKIND. We studied 374 women taking oral contraceptives, 284 women taking estrogen preparations after menopause, and 1086 women taking no hormones, to determine the relation of plasma lipids and lipoprotein cholesterol concentrations to various types of estrogen/progestin formulations. Premenopausal women using oral contraceptives containing a relatively low dose of estrogen combined with a medium or high dose of progestin (Norlestrin, Ovral, or Demulen) had a 24 per cent higher median concentration of low-density-lipoprotein cholesterol than did those not using hormones (P < 0.05). Women using oral contraceptives that are high in estrogen and low in progestin (Envoid or Oracon) had significantly higher concentrations of high-density-lipoprotein cholesterol than did nonusers; those using Ovral, a low-estrogen and high-progestin formulation, had significantly lower levels of high-density-lipoprotein cholesterol. In postmenopausal women the use of estrogen was associated with concentrations of low-density-lipoprotein cholesterol that were 11 to 19 per cent below the levels in postmenopausal women who did not use hormones. The effects of estrogen-progestin balance on low-density and high-density lipoproteins may underlie the increased incidence of stroke and myocardial infarction in women of childbearing age who take oral contraceptives. (New England Journal of Medicine 1983;308:862–7.)     

Physical activity and hormone-replacement therapy: interactive effects on cognition?

The purpose of this study was to examine the interactive effects of hormone-replacement therapy (HRT) and physical activity (PA) on the cognitive performance of older women. Postmenopausal women (n = 101) were recruited to complete a PA questionnaire, provide demographic information, and perform the digit-symbol substitution task (DSST) and the trail-making tests (TMT). Regression analyses were conducted for participants with complete data for each cognitive test (DSST n = 62; TMT n = 69). For both tasks, results indicated that PA and education were positively related and age was negatively related to cognitive performance. The interaction of HRT with PA did not add to the predicted variance of either measure of cognitive performance. This was true even after limiting the HRT users to women using unopposed estrogen. It is concluded that the beneficial relationship between PA and these two measures of cognitive performance in postmenopausal women exists irrespective of HRT use.     

Thyroid dysfunction in perimenopausal and postmenopausal women

Thyroid dysfunction is common, especially among women over the age of 50. In caring for peri- and post-menopausal women, it is important to recognize the changing clinical manifestations of thyroid disease with age. Postmenopausal women are at increased risk of both osteoporosis and cardiovascular disease, and untreated thyroid disease may exacerbate these risks. Screening for thyroid dysfunction in asymptomatic individuals is controversial, but aggressive case-finding should be pursued, especially in older women. Women with overt thyroid dysfunction should be treated. Therapy for women with subclinical thyroid dysfunction is more controversial, although women with levels of thyroid stimulating hormone (TSH) > or =10 mU/L should be treated, and treatment may be considered in symptomatic women with subclinical hypothyroidism and TSH values <10 mU/L, and in women with subclinical hyperthyroidism who have TSH values consistently <0.1 mU/L. In women who are treated with thyroxine, careful dose titration and monitoring are required in order to prevent the adverse consequences of iatrogenic subclinical hyperthyroidism or hypothyroidism. Finally, caution is required in diagnosing and treating thyroid dysfunction in women who are taking oral estrogens or selective estrogen receptor modulators.     

Heart disease risk perception in college men and women

The authors sought to assess the perception of risks for coronary heart disease (CHD) in college men and women. They surveyed 470 undergraduates from 2 major 4-year institutions who completed a questionnaire that measured perceived risks for heart disease. Sixty-eight percent of the respondents rated their risks as lower or much lower than those of their peers, indicating a clear optimistic bias. The research also revealed that the students who exercised regularly rated their risk of coronary disease lower than those who did not do so. In addition, women perceived a number of risk markers to be more potent or causative factors than men did. A significant number of participants did not comprehend commonly understood causal relationships associated with heart disease risk. The findings in this preliminary investigation suggest that college men and women do not accurately perceive their risks for developing heart disease.     

Heart Disease Risk Perception in College Men and Women

Abstract

The authors sought to assess the perception of risks for coronary heart disease (CHD) in college men and women. They surveyed 470 undergraduates from 2 major 4-year institutions who completed a questionnaire that measured perceived risks for heart disease. Sixty-eight percent of the respondents rated their risks as lower or much lower than those of their peers, indicating a clear optimistic bias. The research also revealed that the students who exercised regularly rated their risk of coronary disease lower than those who did not do so. In addition, women perceived a number of risk markers to be more potent or causative factors than men did. A significant number of participants did not comprehend commonly understood causal relationships associated with heart disease risk. The findings in this preliminary investigation suggest that college men and women do not accurately perceive their risks for developing heart disease.     

Gender differences in cardiovascular disease prevention

Risk factors are generally shared between men and women with the major differences being hormonal. Nine modifiable risk factors account for over 90% of the risk of a coronary event in men and women--smoking, hypertension, hyperlipidaemia, diabetes, abdominal obesity, lack of exercise, alcohol excess, reduced intake of fruit and vegetables, and psychosocial issues. Approximately half the decline in deaths from coronary heart disease (CHD), between 1980 and 2000, can be attributed to a reduction in the major risk factors and the other half to the use of evidence-based management. As educational efforts to increase awareness of cardiovascular disease (not cancer) to be the leading cause of death and disability in women are also associated with preventative action, it is important that health-care professionals educate themselves about CHD in women and communicate with women themselves, so that women can come forward for advice and evaluation.