Influence of pattern of menopausal transition on the amount of trabecular bone loss. Results from a 6-year prospective longitudinal study

INTRODUCTION: Bone density is lower in postmenopausal than in premenopausal women. Recent findings have suggested that accelerated bone loss already begins before menopause. Despite numerous cross-sectional studies on menopause-related bone density, longitudinal data on perimenopausal bone density changes are scarce. This study sought to characterize the dynamics of changes leading to postmenopausal osteopenia and to possibly find the time point at which accelerated bone loss begins. METHODS: We prospectively followed 34 pre-, peri- and early postmenopausal women without prior external hormone use, measuring their lumbar spine trabecular bone density with quantitative computer tomography at 0, 2 and 6 years. The analysis of the changes over time was done in a tri-parted fashion, since menopausal status changed variably for individual subjects: we grouped the participants according to their currently valid menopausal classification for prospective (baseline classification), interim (2 years) and retrospective (6-year classification) analysis. RESULTS: Six different patterns of menopausal transition were identified in our sample. Bone loss in the groups not reaching postmenopause during 6 years of observation was >50% of the maximum bone loss observed during the study period. Invariably for all analyses, the perimenopausal phase with estrogen levels still adequate was associated with the greatest reduction of trabecular bone mineral density, reaching 6.3% loss annually in the lumbar spine. By comparison, the average rate of loss was slower in the early postmenopause; total bone loss differed by pattern of menopausal transition (one-way ANOVA p<0.05). CONCLUSION: The presented data for the first time show the perimenopausal course of trabecular bone loss (as measured by QCT of the lumbar spine). Acceleration of bone loss during perimenopause reached half-maximal values of the total bone loss measured around menopause, despite adequate serum estradiol levels.     

Influence of the menopausal transition on polysomnographic sleep characteristics: a longitudinal analysis

Study ObjectivesTo evaluate how change in menopausal status related to spectral analysis and polysomnographic measures of sleep characteristics.MethodsThe Study of Women’s Health Across the Nation (SWAN) Ancillary Sleep Study evaluated sleep characteristics of 159 women who were initially pre- or early perimenopausal and repeated the assessment about 3½ years later when 38 were pre- or early perimenopausal, 31 late perimenopausal, and 90 postmenopausal. Participants underwent in-home ambulatory polysomnography for two to three nights. Average EEG power in the delta and beta frequency bands was calculated during NREM and REM sleep, and sleep duration, wake after sleep onset (WASO), and apnea hypopnea index (AHI) were based on visually-scored sleep.ResultsThe women who transitioned to postmenopause had increased beta NREM EEG power at the second assessment, compared to women who remained pre-or early premenopausal; no other sleep measures varied by change in menopausal status. In multivariate models the associations remained; statistical controls for self-reported hot flashes did not explain findings. In secondary analysis, NREM beta power at the second assessment was greater among women who transitioned into the postmenopause after adjustments for initial NREM beta power.ConclusionsSleep duration and WASO did not vary by menopause transition group across assessments. Consistent with prior cross-sectional analysis, elevated beta EEG power in NREM sleep was apparent among women who transitioned to postmenopause, suggesting that independent of self-reported hot flashes, the menopausal transition is associated with physiological hyperarousal during sleep.     

Changes in serum cytokine concentrations during the menopausal transition

OBJECTIVE: The purpose of the present study was to clarify the changes in serum concentrations of 17 cytokines in healthy women during the menopausal transition by using a multiplexed cytokine assay and to clarify the associations of these cytokines with serum estradiol concentration. METHODS: Sixteen premenopausal, 54 perimenopausal and 52 postmenopausal women were enrolled in this study. Seventeen cytokines in serum samples were measured simultaneously using a Bio-Plex human cytokine 17-Plex assay. RESULTS: Serum IL-6 concentration showed a weak positive correlation with age (r=0.196, p<0.05). Postmenopausal women for whom less than 5 years had passed since menopause showed significant (p<0.05) increase in serum concentrations of IL-2, GM-CSF and G-CSF, while serum IL-4 concentration was significantly (p<0.05) increased in postmenopausal women for whom more than 5 years had passed since menopause. Serum estradiol concentration showed a significant negative correlation with serum IL-6 concentration and weak negative correlations with serum concentrations of IL-2, IL-8 and GM-CSF. CONCLUSION: We were able to simultaneously measure the levels of 17 cytokines using a highly sensitive cytokine assay, and we found that the changes in serum cytokine concentrations during the menopausal transition differed. We also found that serum IL-6 concentration during the menopausal transition was negatively correlated with serum estradiol concentration.     

Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis

OBJECTIVE: Loss of ovarian function and subsequent deficiency of endogenous estrogens is suggested to enhance cardiovascular disease risk and related death after menopause. The aim was to obtain valid estimates of the cardiovascular disease risk associated with postmenopausal status and early menopause. DESIGN: A literature search of observational studies was performed using PubMed and EMBASE (1966 to May 1, 2004). Eighteen studies on postmenopausal status and age at menopause in relation to cardiovascular disease were selected. Six studies investigated menopausal status, nine studies investigated menopausal age, and three studied both. General variance-based methods were used to pool relative risk estimates and corresponding 95% confidence intervals. Stratification was performed for study design, type of menopause, outcome, and adjustment for age and smoking. RESULTS: The pooled relative risk estimate for postmenopausal versus premenopausal status and cardiovascular disease was 1.36 (95% CI, 1.15-1.60). In the stratified analysis, the pooled effect was 0.96 (95% CI, 0.77-1.21) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 2.62 (95% CI, 2.05-3.35). For early menopause and cardiovascular disease, with the menopausal age category containing 50 years as a reference, the pooled relative risk estimate was 1.25 (95% CI, 1.15-1.35). In the stratified analysis, the pooled effect was 1.38 (95% CI, 1.21-1.58) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 4.55 (95% CI, 2.56-8.01). CONCLUSIONS: Overall, there was no convincing relationship between postmenopausal status and cardiovascular disease. However, there was a modest effect of early menopause on cardiovascular disease. The effect was more pronounced for women with an artificial menopause than for women with a natural menopause.     

Associations of endogenous sex hormones with the vasculature in menopausal women: the Study of Women's Health Across the Nation (SWAN)

OBJECTIVE: As associations between endogenous sex hormones and the vasculature are not well characterized, the objective was to examine the cross-sectional associations of menopausal status and endogenous sex hormones with vascular characteristics. DESIGN: Common carotid artery adventitial diameter and intima-media thickness were determined using B-mode ultrasonography among 483 middle-aged women enrolled in the Pittsburgh and Chicago sites of the Study of Women's Health Across the Nation. RESULTS: Sixty-two percent of women were pre- or early perimenopausal (<3 mo amenorrhea), 12% were late perimenopausal (3-12 mo amenorrhea), and 27% were postmenopausal (>or=12 mo amenorrhea). After adjustment for age, compared with pre-/early perimenopause, late perimenopause was associated with a 0.28-mm larger adventitial diameter (P=0.001), whereas postmenopause was associated with a 0.15-mm larger adventitial diameter (P=0.040). Adjustment for traditional cardiovascular risk factors slightly attenuated these associations, but the association with late perimenopause remained statistically significant (P=0.001). Each SD lower log estradiol value was associated with a 0.07-mm larger adventitial diameter after adjustment for traditional cardiovascular risk factors (P=0.023), whereas other endogenous hormones showed no associations. Intima-media thickness values were not significantly associated with menopausal status or endogenous sex hormones after adjustment for age. CONCLUSIONS: The menopausal transition and declining estrogen levels are associated with alterations of the peripheral vasculature, which may help to explain the increased risk of cardiovascular disease with postmenopause.     

Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition

OBJECTIVE: To compare age-adjusted and ethnic differences in prevalences of sleep difficulty at various stages of the menopausal transition and to determine the relative contribution of other factors, including vasomotor symptoms, sociodemographics, and psychological and physical health factors, to self-reported sleep difficulty in middle-aged women. DESIGN: A community-based survey of women's health and menopausal symptoms was conducted between November 1995 and October 1997 at each of the seven US sites participating in the Study of Women's Health Across the Nation. A multiethnic sample of 12,603 Caucasian, African American, Chinese, Japanese, and Hispanic women aged 40 to 55 years was categorized into six groups: premenopausal, early perimenopausal, late perimenopausal, naturally postmenopausal, surgically postmenopausal, and postmenopausal receiving hormone replacement therapy. The women were asked whether they had experienced difficulty sleeping in the past 2 weeks. RESULTS: Difficulty sleeping was reported by 38%. Age-adjusted rates were highest in the late perimenopausal (45.4%) and surgically postmenopausal (47.6%) groups. Among ethnic groups, rates ranged from 28% in Japanese women to 40% in Caucasian women. In the multivariate analysis, menopausal status was significantly associated with difficulty sleeping. Ethnicity, vasomotor and psychological symptoms, self-perceived health and health behaviors, arthritis, and education also were significantly associated with difficulty sleeping. CONCLUSIONS: These results suggest that stage of the menopausal transition, independent of other potential explanatory factors, is associated with self-reported sleep difficulty. Older age per se was not significantly associated with difficulty sleeping.     

Vasomotor symptoms are associated with depression in perimenopausal women seeking primary care

OBJECTIVE: To compare the relationship between vasomotor symptoms (hot flushes and night sweats) and depression in perimenopausal women with that in postmenopausal and older premenopausal women. DESIGN: Questionnaire data assessing current depressive symptoms (Center for Epidemiologic Studies Depression Scale), hot flushes, night sweats, menopausal status, depression history, hormonal therapy use, and demographic characteristics were collected from women aged 40 to 60 years seeking primary care. Multivariable logistic regression models were used to examine the relationship between vasomotor symptoms and depression. RESULTS: Depression (defined by a Center for Epidemiologic Studies Depression Scale score >/= 25) was observed in 14.9% of 141 perimenopausal women, 13.9% of 151 postmenopausal women, and 7.6% of 184 older premenopausal women. Recent vasomotor symptoms were reported by 53.9% of perimenopausal women, 43.7% of postmenopausal women, and 20.7% of older premenopausal women. Perimenopausal women with vasomotor symptoms were 4.39 times more likely to be depressed than those without vasomotor symptoms (95% CI, 1.40-13.83), an association that did not change after controlling for depression history. In contrast with perimenopausal women, postmenopausal and older premenopausal women with vasomotor symptoms did not have a significantly greater risk for depression than women of the same menopausal status without vasomotor symptoms (adjusted odds ratios, 1.28 and 1.77; 95% CI, 0.47-3.46 and 0.53-5.89, respectively). CONCLUSIONS: Hot flushes and night sweats are associated with depression in perimenopausal women. Further investigation is warranted to elucidate the mechanism by which hot flushes may be associated with depression in perimenopausal women and not in postmenopausal or older premenopausal women.     

Influence of menopause on high density lipoprotein-cholesterol and lipids

It has been generally accepted that high density lipoprotein cholesterol (HDL-C) level decreases with menopause in women. However, recent reports show different results. There is very little data concerning perimenopausal women. To verify these findings, lipids and lipoprotein(a) [Lp(a)] levels were compared among pre-, peri- and postmenopausal women of similar mean ages. Postmenopausal women had higher HDL-C levels than premenopausal women (p<0.001) and there was no difference between peri- and postmenopausal women. LDL-C level in perimenopausal women was lower than in postmenopausal women (p<0.001) and higher than in premenopausal women with borderline significance (p=.051). Total cholesterol levels showed stepwise elevation from premenopause to postmenopause. Perimenopausal women had lower Lp(a) levels than postmenopausal women (p<0.0005) and similar levels to premenopausal women. Lp(a) levels between 0.1 to 10.0 mg/dL were the most prevalent in pre- and perimenopausal women, and those between 10.1 to 20.0 mg/dL in postmenopausal women. In conclusion, menopause itself is associated with the elevation of HDL-C level, and the postmenopausal increase of coronary artery disease is not related to postmenopausal change of HDL-C level. Perimenopausal status, although transient, may favor Lp(a) and lipid profiles for delaying atherosclerosis.     

Changes in physical symptoms during the menopause transition

This article analyzes physical symptoms experienced by mid-age Australian women in different stages of the menopause transition. A total of 8,623 women, aged 45 to 50 years in 1996, who participated the mid-age cohort of the Australian Longitudinal Study on Women’s Health, completed Survey 1 in 1996 and Survey 2 in 1998. Women were assignedto 1 of6menopause groups according totheir menopausal status at Surveys 1 and 2, and compared on symptoms experienced at Surveys 1 and 2, adjusted for lifestyle, behavioral and demographic factors. At Survey 1, the most commonly reported symptoms were headaches, back pain, stiff joints, tiredness, and difficulty sleeping. Perimenopausal women were more likely than premenopausal or postmenopausal women to report these symptoms. Hot flushes and night sweats were more common among postmenopausal women. Compared with those who remained premenopausal, women who were in the early stages of menopause or perimenopausal were more likely to report tiredness, stiff joints, difficulty sleeping, and hot flushes at Survey 2. Women who remained perimenopausal were also more likely to report back pain and leaking urine. Compared with premenopausal women, odds ratios for night sweats increased for women in consecutive stages of the menopause transition and remained high in the postmenopausal women. The Women’s Health Australia project, which was conceived and developedby groups ofinterdisciplinary researchers at the Universities of Newcastle and Queensland, is funded by the Commonwealth DepartmentofHealth and Aged Care. The supportofEli Lilly for partofthe analysis costs for this article is gratefully acknowledged. Finally, we would like to thank all the participants for their valuable contribution to this project.     

The menopause transition: an update

The menopausal transition is an area of active clinical investigation and epidemiological research. Recent results from several worldwide cohorts of women are beginning to provide a paradigm by which to explain the epidemiological and clinical manifestations of the ovarian process of follicle attrition. Genetic research has also provided some insight into differential ovarian ageing and disease/risk susceptibility in populations of women. Atresia of follicles occurs throughout reproductive life in women. The ever-shrinking follicle pool does not appear to result in any overt disruption of cycles for most women until they are in their forties. Subtle hormonal changes precede overt cycle disruption in mid-life. Obvious failures of ovulation or folliculogenesis lead to menstrual disturbances, and these provide the first clinical indication that the menopause transition is underway. A variety of hormonal patterns have been identified and an overall physiological progression appears to exist. The likelihood that reproductive hormone patterns influence symptomatology is high, although the analysis of the nature of such relationships is under way. For most women, effective lifestyle changes or hormonal therapy is available for symptoms associated with the menopause transition. This review will cover the existing body of knowledge, particularly regarding the clinical management of women who present with symptomatology during their menopausal transitions.     

Cognitive function across the life course and the menopausal transition in a British birth cohort

OBJECTIVE: Despite biological plausibility, relationships between menopause and cognitive function are inconsistent. We investigated whether menopause status and menopause age were associated with general cognitive ability, verbal memory, and visual search speed and concentration in a large cohort of women while considering vasomotor and psychological symptoms, previous childhood and adult measures of cognitive function, lifetime socioeconomic circumstances, educational attainment, lifestyle factors, and chronic diseases. DESIGN: A nationally representative British cohort of 1261 women born in March 1946 and all aged 53 years at cognitive testing, with prospective information on previous cognitive function, menopausal characteristics, and potential confounders. RESULTS: There was only weak evidence of the effect of natural menopause on cognitive function and no evidence of any effects of hormone therapy use or hysterectomy status. There was a trend across the phases of the natural menopausal transition (pre-, peri-, and postmenopause) for the National Adult Reading Test (P = 0.005) and search speed and concentration (P = 0.042), with postmenopausal women having the lowest cognitive function, but there was no trend in verbal memory. Variation in vasomotor and psychological symptoms did not explain these trends. In postmenopausal women, there was a positive trend across menopause age for verbal memory (P = 0.004) and a weak positive trend for the National Adult Reading Test (P = 0.052), with women who reached menopause later having higher cognitive function. Previous cognitive function generally explained the associations, which were further weakened by adjusting for socioeconomic and educational confounders. One exception was the association between the natural menopause transition and search speed and concentration, which remained after adjustment for these factors. CONCLUSION: Menopause adversely affects cognitive function, but this effect may be largely explained by premenopausal cognitive function. These findings suggest that common environmental or genetic factors, operating through long-term or lifelong hormonal mechanisms, may influence the timing of natural menopause and lifetime cognitive function.     

Systematic review of progesterone use by midlife and menopausal women

Progesterone treatment for menopausal symptoms is still controversial. Progesterone levels fall during menopause transition, therefore some menopausal women may benefit from progesterone therapy. A systematic review was conducted of studies published from 2001 reporting on progesterone use to treat symptoms associated with menopause or postmenopausal women. Fourteen data bases were searched using the search terms progesterone, menopause, aged, female and human; exclusions were breast cancer, animal and contraception. Thirteen studies were selected for inclusion (11 clinical trials, 1 cohort study and 1 qualitative study), evaluating progesterone effects on menopausal symptoms, bone, sleep, skin, cognition, plasma lipids and plaque progression. Most studies were of low methodological quality (GRADE low or very low). Progesterone improved vasomotor symptoms and sleep quality, with minimal risk. Large studies designed to identify confounders, such as hormone levels, menopausal status and metabolism are required to understand the place of progesterone in clinical practice.     

Postmenopausal status according to years since menopause as an independent risk factor for the metabolic syndrome

OBJECTIVE: Features of the metabolic syndrome such as abdominal adiposity, insulin resistance, and dyslipidemia develop with the transition from pre- to postmenopausal status in women. We investigated the effects of postmenopausal status on the prevalence of the metabolic syndrome according to years since menopause. DESIGN: We studied 1,002 women, 618 premenopausal and 384 postmenopausal, who participated in annual health examinations at Anam Hospital in Seoul, Korea. RESULTS: Using multivariate logistic regression analysis, we determined that postmenopausal status was an independent risk factor for the metabolic syndrome. Moreover, after controlling for age and body mass index, postmenopausal women had an increased risk of the metabolic syndrome (odds ratio, 2.93; 95% CI, 1.62-5.33) and the abnormalities of its individual components. The risk for the metabolic syndrome increased up to 14 years since menopause, then decreased. For its individual components, postmenopausal women with 5 to 9 years since menopause had the highest risk of high blood pressure; postmenopausal women with less than 5 years since menopause had an increased risk of abdominal obesity and high glucose. With 10 to 14 years since menopause, postmenopausal women had an increased risk of high triglycerides. CONCLUSIONS: Postmenopausal status is an independent risk factor for the metabolic syndrome and all of its individual components. The risk for the metabolic syndrome increased up to 14 years since menopause. In addition, postmenopausal status has effects during different periods since menopause for each of these components.     

Attribution of menopause symptoms in human immunodeficiency virus-infected or at-risk drug-using women

OBJECTIVE: To examine the relationship of human immunodeficiency virus (HIV) and attribution of menopausal symptoms. DESIGN: Peri- and postmenopausal women participating in a prospective study of HIV-infected and at-risk midlife women (the Ms. Study) were interviewed to determine whether they experienced hot flashes and/or vaginal dryness and to what they attributed these symptoms. RESULTS: Of 278 women, 70% were perimenopausal; 54% were HIV-infected; and 52% had used crack, cocaine, heroin, and/or methadone within the past 5 years. Hot flashes were reported by 189 women and vaginal dryness was reported by 101 women. Overall, 69.8% attributed hot flashes to menopause and 28.7% attributed vaginal dryness to menopause. In bivariate analyses, age 45 years and older was associated with attributing hot flashes and vaginal dryness to menopause, and postmenopausal status and at least 12 years of education were associated with attributing vaginal dryness to menopause, but HIV status was not associated with attribution to menopause. In multivariate analysis, significant interactions between age and menopause status were found for both attribution of hot flashes (P=0.019) and vaginal dryness (P=0.029). Among perimenopausal women, older age was independently associated with attribution to menopause for hot flashes (adjusted odds ratio=1.2, 95% CI: 1.1-1.4, P=0.001) and vaginal dryness (adjusted odds ratio=1.3, 95% CI: 1.1-1.6, P=0.011). None of the tested factors were independently associated with attribution to menopause among postmenopausal women. CONCLUSION: Tailored health education programs may be beneficial in increasing the knowledge about menopause among HIV-infected and drug-using women, particularly those who are perimenopausal.     

Determinants of self rated menopause status

This study, based on a population survey, examines the self ratings of progress through the menopausal transition of women in natural menopause, women using hormone therapy and women who have undergone hysterectomy. The latter two groups are usually excluded from discussions of menopausal transition, since the accepted menstrually defined criteria do not apply to them. Hysterectomised women do not differ in their self rating profile from non-hysterectomised women, after hormone therapy status is taken into account. This is surprising, since they may have been expected to see themselves as in the main postmenopausal. Use of hormone therapy is tantamount to self perception as at least perimenopausal. Among women in natural menopause there is 29% disagreement between self ratings and menstrually defined categories. On the basis of these observations it is hypothesised that experience of symptoms associated with menopause is important in determining self ratings. The good fit of logistic regression predictions of self ratings from hysterectomy status, hormone therapy status and experience of hot flushes is consistent with this hypothesis. This research indicates that it is important to take women's subjective evaluations into account in assessing progress through the menopausal transition.     

The demography of menopause

Menopause marks a time of dramatic hormonal and often social change for women. Both risk factors and health needs are likely to change as women pass through menopause. This paper examines the demographic characteristics of the world population of menopausal and post-menopausal women, and also examines the implications of menopause for mortality risks. The numbers of women involved are large. Using age 50 as a proxy for menopause, about 25 million women pass through menopause each year, and we estimate that in 1990 there were 467 million post-menopausal women in the world, with an average age of about 60 years. By 2030, the world population of menopausal and postmenopausal women is projected to increase to 1.2 billion, with 47 million new entrants each year. The mortality implications of menopause are also substantial. Ratios of female to male mortality risks from all causes and from all major cause groups except neoplasms decline to low levels around menopause or shortly thereafter, and then rise again to near unity. This pattern is taken as evidence that the female reproductive period is broadly protective of health, but that this protection disappears after menopause. The main protective effect is through reduced risk of cardiovascular disease mortality, partially offset by increased risks of cancer mortality, particularly of the breast and endometrium.     

Assignment to menopausal status and estimation of age at menopause for women with missing or invalid data--a probabilistic approach with weighting factors in a large-scale epidemiological study.

OBJECTIVE: Gynaecologic surgeries and hormone medication increasingly interfere with the concept of determining menopausal status based on self-reported data about the last menstrual period-an approach frequently applied in epidemiological studies. This analysis compared different approaches of menopausal status determination, including a probabilistic approach that was developed to reduce misclassification of menopausal status. METHODS: Interview and questionnaire data relating to hormone status from about 16,000 German women were used to determine menopausal status using different approaches: menses based, age based, self-assessment based, and a probabilistic approach. RESULTS: Applying strict menses-based criteria, 29.1% of the women were found to be with undetermined menopausal status. The probabilistic approach was applied to determine menopausal status and age at menopause for these women. The proposed approach uses the current age of the women with undetermined menopausal status, and the relative age-dependent frequencies of pre- or postmenopausal status among those with natural menopausal status to calculate weighting factors, which represent the probabilities of being pre- and postmenopausal of each woman previously undetermined. Correspondingly, the missing age at menopause was estimated with the same probabilistic approach. Applying various approaches to determine menopausal status, the ratio of pre- to postmenopausal women differed considerably, ranging from 1.03 to 1.61. In addition, considerable differences were observed with respect to the number of missing values for both menopausal status and age at menopause. CONCLUSION: The probabilistic approach allowed to estimate menopausal status and age at menopause with the advantage that all available information from the entire study population and from the individual is used.     

EMAS position statement: Managing the menopause in the context of coronary heart disease

Introduction

Cardiovascular disease (CVD) including coronary heart disease (CHD) and stroke is the most common cause of female death. Premenopausal CHD is very rare but when women enter the menopause the incidence of CHD increases markedly. CHD presents 10 years later in women than in men. The reason is still unclear but the protective effects of estrogens have been suggested.

Aims

To formulate a position statement on the management of menopause women in the context of coronary heart disease.

Materials and methods

Literature review and consensus of expert opinion.

Results and conclusions

Based on long term randomized placebo-controlled studies hormone therapy (HT) is not recommended for the primary or secondary prevention of CHD in postmenopausal women. In most countries the only indication for HT is the treatment of menopausal symptoms. Women with known CHD or with many coronary risk factors seeking HT because of troublesome climacteric symptoms should be evaluated for their individual baseline risk of developing breast cancer, venous thromboembolism and CHD recurrence. The same applies to non hormone therapy-based treatments where long term clinical studies are lacking. Risks should be weighed against expected benefit from symptom relief and improved quality of life. The lowest effective estrogen dose should be used during the shortest possible time. Transdermal administration is preferred if risk factors for VTE exist. Different progestogens might differ in their cardiovascular effects. Observational studies suggest that micronized progesterone or dydrogesterone may have a better risk profile than other progestogens with regard to thrombotic risk.     

Sexual functioning throughout menopause: the perceptions of women in a British cohort

OBJECTIVE: Previous studies on menopausal transition and sexual functioning have mixed findings. Most are cross-sectional, exclude hormone therapy users and hysterectomized women, and are unable to separate the effects of age from menopause or account for psychosocial, vasomotor, and somatic factors. We examine relationships between women's reports of a change in sex life and difficulties with intercourse and their experience of menopausal transition, use of hormone therapy, and hysterectomy. DESIGN: A British cohort study with 1,525 women were followed since their birth in 1946 and annually from age 47 to 54 years. The outcome measures were self-reported change in sex life and difficulties with sexual intercourse over 8 consecutive years. RESULTS: Compared with women who remained premenopausal, peri- and postmenopausal women reported a decline in sex life (mean difference [95% CI]: perimenopausal, -0.1 [-0.2 to -0.03]; became postmenopausal, -0.1 [-0.2 to -0.1]) and were more likely to report difficulties with intercourse (perimenopausal, 0.6 [0.1 to 1.1]; postmenopausal, 1.0 [0.5 to 1.5]) beyond the effects of aging and other psychosomatic factors. Women reported difficulties with intercourse more often if they had been on hormone therapy for more than a year (0.5 [0.03 to 1.0]) or if they had undergone a hysterectomy (0.6 [0.1 to 1.1]); no differences were found for change in sex life. For both outcomes, vaginal dryness was the major risk factor. Married women were also more likely to report adverse outcomes. Somatic symptoms and hot flushes/cold sweats were associated with difficulties with intercourse, whereas psychological symptoms, stressful lives, increasing age, and smoking were associated with a decline in sex life. CONCLUSIONS: Menopausal transition status had an independent effect on the reported change in sex life and difficulties with intercourse. The results support health professionals in their development of management strategies that (a) consider treatments directly for vaginal dryness, (b) identify somatic symptoms for difficulties with intercourse, (c) investigate psychological factors for a reported decline in sex life, and (d) for both outcomes, consider the potential role of intimate partners.