Amos Pines

Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health

MediClinic Panorama and Department of Obstetrics and Gynecology, Stellenbosch University, Cape Town, South Africa; * Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; † Queen Charlotte ’ s & Chelsea Hospital, and Chelsea and Westminster Hospital, London, UK; ‡ Department of Obstetrics and Gynecology, Pisa University Hospital, Pisa, Italy; * * Jones Institute, Eastern Virginia Medical School, Norfolk, VA, USA; † † Sydney Medical School, The University of Sydney, NSW, Australia; ‡ ‡ Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; * * * UF de Gyn e cologie, Universit e Paris Descartes, AP-HP, H o tel-Dieu, Paris, France; † † † Departments of Health Research & Policy (Epidemiology) and of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USA; ‡ ‡ ‡ Associate Dean for Clinical and Translational Research and Professor of Family Medicine-Las Vegas, University of Nevada School of Medicine, Las Vegas, NV, USA; * * * * Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA; † † † † Unit e de Gyn e cologie M e dicale, H o tel Dieu, Paris, France; ‡ ‡ ‡ ‡ Heart of England NHS Foundation Trust, Solihull Hospital, Birmingham, UK

Intensive home-care surveillance prevents hospitalization and improves morbidity rates among elderly patients with severe congestive heart failure

The purpose of this study was to examine the impact of intensive home-care surveillance on morbidity rates of elderly patients with severe congestive heart failure. Forty-two patients aged 78 +/- 8 years who had severe congestive heart failure (New York Heart Association functional classes III through IV, mean ejection fraction 27% +/- 6%), were examined at least once a week at home by internists from the district hospital and by a trained paramedical team. The year before entry to the home-care program was compared to the first year of home surveillance. The mean total hospitalization (hosp) rate was reduced from 3.2 +/- 1.5 hosp/yr to 1.2 +/- 1.6 hosp/yr and duration from 26 +/- 14 days/yr to 6 +/- 7 days/yr (p < 0.001 for both). Cardiovascular admissions decreased from 2.9 +/- 1.5 hosp/yr to 0.8 +/- 1.1 hosp/yr and duration from 23 +/- 13 days/yr to 4 +/- 4 days/yr (p < 0.001). The vital status (ability to perform daily activities, expressed in a 1 to 4 scale) was improved from 1.4 +/- 0.9 to 2.3 +/- 0.7 (p < 0.001). In conclusion, an intensive home-care program was associated with a marked decrease in the need for hospitalization and improved the functional status of elderly patients with severe congestive heart failure. Such a service might also have a cost-effective advantage and a major impact on health expenditure.

Myocardial ischemia during sexual activity in patients with coronary artery disease.

I t is generally agreed that oxygen requirements during sexual activity are moderate’.*; heart rate values during intercourse arc similar to those found in daily life’*; sexual activity in most patients with coronary artery disease (CAD) is associated with low risk of cardiac complications’; and coital death among patients with CAD is rare.’ There is, however, a paucity of relevant data on sexual activity in patients with CAD. The occurrence of silent ischemia during sexual intercourse in patients with coronary disease is among the issues that still require elucidation. This study utilized ambulatory elcctrocardiographic monitoring to detect the occurrence of ischemia during intercourse in patients with CAD. The relation between electrocardiographic findings on sexual activity and a near-maximal exercise test were compared. . . . The study group comprised 88 male CAD outpatients, mean age 52 years (range 36 to 66), who participated in our long-term cardiac rehabilitation program. Patients’ informed consent to undergo 24-hour ambulatory electrocardiographic monitoring, which included monitoring during sexual activity, was a prerequisite for admission into the study. The diagnosis of CAD was established by one or both of the following criteria: previous myocardial infarction (73 patients [83%]) and typical effort-induced angina (15 patients [17%]). Functional capacity (New York Heart Association classification) was established as class I for SO patients (57%), class II for 26 (30%), and class I11 for 12 (14%). All patients were in sinus rhythm and had been clinically stable for at least 4 months. None had anemia, respiratory disease, or chronic renal failure. Patients with cchocardiographic evidence of left ventricular hypertrophy or cardiomyopathy were excluded from the study, as were patients using digitalis, diuretics, or antiarrhythmic medication. Beta-blocking agents were discontinued 24 days before examination, and nitrates and calcium channel blockers were discontinued 224 hours before examination. Detailed individual case histories were recorded. All patients underwent thorough physical examination, a resting 12-lead electrocardiogram, a cycloergometric test: and 24-hour ambulatory electrocardiographic monitoring. The ergometric test was performed on a mcchanitally braked Monark bicycle ergometer, following our protocol described elsewhere.* All patients underwent a near-maximal test (85% of predicted maximal heart rate according to age) based on progressively increasing intermittent workloads at 5-minute intervals. The initial

Menopause-induced changes in Doppler-derived parameters of aortic flow in healthy women

Currently, estrogen replacement therapy is widely used as a specific treatment for hypoestrogenic associated conditions such as vasomotor instability, genitourinary atrophy and osteoporosis. These conditions affect a substantial number of postmenopausal women.1 The favorable effects of estrogen replacement therapy on cardiac morbidity and mortality in postmenopausal women have usually been attributed to an improved lipid profile. 2–4 It is now accepted that other mechanisms, such as the direct effect of estrogens on coronary vasculature and atherosclerotic plaque, may also have an important role in cardioprotection.3–5 Using Doppler echocardiography we recently demonstrated a significant increase in aortic flow velocity and acceleration after 10 weeks of hormone replacement therapy.6 These findings led us to investigate whether menopause and the related decrease in estrogen levels were associated with changes in Doppler-derived parameters of aortic flow.

Hormone replacement therapy and cardioprotection: basic concepts and clinical considerations

A large body of epidemiological evidence shows that estrogen use after the menopause reduces the incidence of cardiovascular disease up to 50%. The use of progestin as co-medication in HRT appears not to attenuate the cardioprotective effects of estrogen. Menopause-related changes in metabolic cardiovascular risk factors are identifiable, as are HRT-related changes in these factors. Estrogens may act in a gender-specific way on vascular endothelial cells and other components of the vessel wall enhancing the synthesis and release of NO and other vasodilators and by inhibiting the synthesis and release of vasoconstricting agents, thus favoring vasodilation. Angiographic studies demonstrated in postmenopausal women with ischemic heart disease a reduction in coronary stenosis by estrogen monotherapy. Several studies, including the PEPI-trial, failed to demonstrate any major effect of HRT on blood pressure. The information on HRT and cardioprotection which is available so far is very promising and merits recommending HRT not only in healthy women but also in women with cardiovascular disease as well as in women with increased risk for this disease.

Comparison of Left Ventricular Function Using Isometric Exercise Doppler Echocardiography in Competitive Runners and Weightlifters Versus Sedentary Individuals

It is unclear whether cardiovascular responses to heavy isometric exercise are changed by intensive training. We evaluated the effects of this type of exercise on left ventricular (LV) function in athletes engaged in static and dynamic sport, compared with sedentary persons, and looked for peculiarities in static athletes responses that might reflect adaptive mechanisms to their specific activity. The study population comprised 45 men (age 24 +/- 5 years): 29 dynamic and 16 static athletes (runners and weightlifters, respectively). The control group consisted of 20 age and gender-matched healthy sedentary persons. All performed 50% of maximal voluntary contraction on a whole-body isometric exercise device for 2 minutes. Echocardiographic calculations were determined at rest and exercise. Upon exercise, stroke volume, cardiac output, end-diastolic volume, and ejection fraction increased significantly in athletes, while end-systolic volume and systemic vascular resistance decreased. In sedentary persons, stroke volume and resistance remained unchanged, cardiac output and LV volumes increased, and ejection fraction decreased from 67 +/- 5% to 60 +/- 5% (p <0.01 compared with rest; p <0.0001 compared with athletes). Whereas peak flow velocity decreased from 103 +/- 10 to 81 +/- 6 cm/s in sedentary persons, it increased from 112 +/- 9 to 126 +/- 8 cm/s in the static group and from 120 +/-3 to 126 +/- 9 cm/s in the dynamic athletes (p <0.0001 compared with the sedentary group). Mean acceleration decreased in the sedentary group, remained unchanged among the dynamic athletes, and increased among the static athletes. We conclude that cardiovascular responses to heavy isometric exercise are modified by intensive training. Athletes, taken as a group, react differently and adapt better than sedentary individuals. Moreover, among them, those involved in static sport show an improved cardiovascular adaptation to this type of exercise.

Does hormone replacement therapy inhibit coronary artery calcification

Objective To determine the association between the use of hormone replacement therapy (HRT) and coronary calcium, in psotmenopausal women who had no history of coronary artery disease by double helical computed tomography (CT). Methods We used CT to compare the prevalence and extent of coronary clacium in 41 postmenopausal women who were on HRT from the first year of menopause and 37 age-matched controls who had never used HRT. Results Both groups had a similar rate of smoking, hypertension, a positive family history, and hypercholesterolemia. Coronary calcification was observed in 28.2% of the 78 women studied. The prevalence of coronary calcium was significantly lower among HRT users; six of the 41 (14.6%), compared with 16 of the 37 nonusers (43.2%) (P < .01). The recorded risk factors had no effect on the prevalence of coronary calcium. Stepwise logistic regression analysis, including age, coronary risk factors, and HRT use as independent variables, yielded HRT as the only variable determining the presence of coronary calcium (odds ratio = 0.2;95% confidence interval 0.06, 0.63; P = .006). Conclusion The lower incidence of coronary calcium in the HRT users suggests that HRT is associated with decreased prevalence of the coronary aclcification.

The heart of the WHI study: time for hormone therapy policies to be revised

In 2002, immediately after the first publication of the Women’s Health Initiative (WHI) results, attitudes to hormone therapy (HT) changed dramatically. Many millions of women in the USA and around the world stopped taking hormones because the WHI investigators and the media presentation of the data told them that HT is dangerous. The message that came out of the NIH-sponsored project was very clear: HT should not be prescribed for prevention of chronic diseases of old age (i.e. coronary artery disease and osteoporosis), but may still be considered on a short-term basis for women who have severe menopause-related symptoms. The resulting fear of increased risks of coronary artery disease and breast cancer in hormone users left many women suffering from sudden adverse changes in their quality of life following cessation of HT. Being captured by their own message, the WHI investigators failed to address during 2002–2006 an important issue that was already evident at the preliminary analyses – that age and years from menopause have major roles in the determination of benefits and risks of HT. It should not have been surprising that the WHI study did not reduce the incidence of coronary artery disease in women with a mean age of 63 years at enrolment, who are not the women usually seeking HT for the relief of menopausal symptoms. The problems have arisen because of inappropriate extrapolation and generalization of these results from mainly older women to those with symptoms around the time of menopause. Detailed evaluation of the WHI data and subgroup analyses showed that the initial conclusions drawn by the WHI investigators were in part misleading. It became apparent that, in the early postmenopausal period, coronary artery disease is no threat to hormone users. In fact, the data suggested a cardioprotective effect of estrogen-alone therapy in the younger age group (less than 60 years at recruitment to the study). Moreover, the most recent article, on coronary artery calcification, which reflects calcified atheroma and total plaque burden, showed that, 8.7 years after randomization, estrogen-alone users, who were 80% or more compliant, had 61% less atherosclerotic plaques in women whose mean age was 55 years at baseline, as compared to a placebo group (p1⁄4 0.004). Relative to placebo, for women in the WHI study below 60 years of age, conjugated estrogens alone reduced the following major adverse events per 10 000 treated women annually; coronary artery disease by 11, strokes by two, diabetes cases by 14, fractures by 56, breast cancer diagnoses by eight and deaths by ten. The only significant risk is an increase of four deep vein thromboses/pulmonary emboli, seen mostly in women with risk factors for thromboembolism in the early years of use. Data from the WHI study for combined HT need to be released to allow a similar analysis of these risks and benefits in younger postmenopausal women. This amazing shift in the interpretation of the WHI results should have been addressed by the WHI investigators, but, to date, generally they have preferred to remain silent. The WHI trial was stopped prematurely because an unvalidated global index, a measure balancing some of the risks and benefits of hormone use (quality of life was not included), exceeded a predetermined safety margin. The new analyses should have led to earlier assessment of the global index for the 50–59-year age group, which did show less morbidity in the treatment group versus the

Pronounced reduction of aortic flow velocity and acceleration during heavy isometric exercise in coronary artery disease

Doppler-derived parameters of aortic flow were examined during heavy isometric exercise in 48 men with coronary artery disease (CAD) and in 48 gender- and age-matched healthy controls. The aim was to determine which parameters best separated the groups and to look for a possible relation between exercise-induced Doppler patterns and the extent of CAD. Isometric exercise was performed with a 2-hand bar dynamometer, and the subjects were required to perform 50% of maximal voluntary contraction for 2 minutes. Examination was performed with a pulsed Doppler transducer positioned at the suprasternal notch. Resting peak flow velocity, acceleration time, stroke volume index and cardiac index did not show significant differences between the groups. However, mean acceleration and stroke work were significantly lower in patients with CAD. In this group, exercise peak flow velocity decreased from 98 +/- 13 to 55 +/- 12 cm/s, flow velocity integral from 14 +/- 3 to 7 +/- 3 cm, mean acceleration from 11 +/- 0.9 to 4.7 +/- 1 m/s/s, and stroke volume index from 41 +/- 6 to 23 +/- 4 ml/m2 (p less than 0.001 for all). Cardiac index decreased from 2.7 +/- 0.4 to 2 +/- 0.2 liters/min/m2 (p less than 0.05). Acceleration time increased from 82 +/- 6 to 116 +/- 7 ms. In most of the indexes, the directional changes induced by isometric exercise were similar in patients with CAD and in normal control subjects. The differences compared with the rest values were significantly greater in the CAD group, and especially in patients presenting with 3-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Depressed mood through women's reproductive cycle: correlation to mood at menopause

Objectives Depressive symptoms are frequent through the different stages of a womans reproductive cycle. The aim of this study was to evaluate a possible correlation of depressive mood before menstruation, during pregnancy, after delivery and around the menopause. Methods The sample consisted of 110 women (mean age 52 years, standard deviation 4 years) who rated their mood at present and retrospectively at different stages of the reproductive cycle. Mood was rated using a visual analogue scale. Results A significant statistical association was found between the present mood and mood at the premenstrual period, but not with mood at pregnancy or after delivery. These findings were independent of age, menopausal status or use of hormone replacement therapy. Conclusions The statistical association between depressed mood around menopause and before menstruation supports the assumption that there is a common etiology, which could be attributed to hormonal or psychological factors, or both.