Showing papers in "Menopause in 2010"

Associations of depression with the transition to menopause

Abstract: Objectives:The aims of this study were to identify the risk of depression in the transition to menopause in women with and without a history of depression and to consider that the changing hormonal milieu is one of multiple risk factors for perimenopausal depression.Method:A review of epidem

Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women: results from a pivotal phase 3 study.

Abstract: Objective: The aim of this study was to study the efficacy and safety of ospemifene, a new selective estrogen receptor modulator, in the treatment of vulvovaginal atrophy in postmenopausal women. Methods: A randomized, double-blind phase 3 study in which 826 postmenopausal women were randomized 1:1:1 to receive treatment with ospemifene 30 or 60 mg/day or placebo orally for 12 weeks was conducted. The primary inclusion criteria were having 5% or less superficial cells on the vaginal smear (maturation index), vaginal pH greater than 5.0, and at least one moderate or severe symptom of vulvovaginal atrophy. The four coprimary endpoints were the change from baseline to 12 weeks in the percentage of superficial and parabasal cells on the vaginal smear, change in vaginal pH, and change in severity of most bothersome symptom (vaginal dryness or dyspareunia) compared with placebo. All participants were given a nonhormonal vaginal lubricant for use as needed. Results: Ospemifene was statistically significantly superior to placebo in each of the coprimary endpoints at the 60-mg dose. Statistically significant results were achieved for all coprimary endpoints with the 30-mg dose except for dyspareunia. Ospemifene was well tolerated at both doses and demonstrated a favorable safety profile. Conclusions: Ospemifene was shown to be effective and well tolerated for the treatment of the symptoms of vaginal dryness and dyspareunia associated with vulvovaginal atrophy over and above the use of provided lubricants.

Obesity and reproductive hormone levels in the transition to menopause.

Abstract: Objective: The aim of this study was to estimate associations of obesity with reproductive hormone levels as women progress from premenopausal to postmenopausal status. Methods: This was a longitudinal study conducted in the population-based Penn Ovarian Aging Cohort (N = 436). At cohort enrollment, the women were premenopausal, ages 35 to 47 years, with equal numbers of African Americans and whites. Anthropometric measures, menopause status, and reproductive hormone measures were evaluated for 12 years. Associations of the anthropometric measures with estradiol, follicle-stimulating hormone, and inhibin B in the menopausal transition were estimated using generalized linear regression models for repeated measures. Results: Associations between obesity and hormone levels differed by menopause status as indicated by significant interactions between each hormone and menopausal stage. Premenopausal obese and overweight women had significantly lower estradiol levels compared with nonobese women, independent of age, race, and smoking (obese: 32.8 pg/mL [95% CI, 30.6-35.2] vs nonobese: 39.8 pg/mL [95% CI, 37.0-42.8], P < 0.001). The associations reversed postmenopause, with obese women having the highest estradiol levels (obese: 20.6 pg/mL [95% CI, 17.2-24.7] vs nonobese: 12.2 pg/mL [95% CI, 10.1-14.8], P < 0.001). Inhibin B levels were significantly lower in premenopausal obese compared with nonobese women but reversed in the late transition stage. Follicle-stimulating hormone levels were lowest in postmenopausal obese compared with nonobese women (P < 0.001). Measures of waist circumference (central adiposity) and waist-to-hip ratio paralleled the body mass index results. Conclusion: Obesity is an important factor in hormone dynamics independent of age, race, and smoking in midlife women, although the mechanisms remain unclear.

A randomized, placebo- and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women.

Abstract: Objectives: The primary objective of the Selective estrogen Menopause And Response to Therapy 3 (SMART-3) trial was to compare the efficacy and safety of two doses of bazedoxifene (BZA)/conjugated estrogens (CE) versus placebo for the treatment of moderate to severe vulvar/vaginal atrophy (VVA) associated with menopause. Methods: This was a phase 3, multicenter, double-blind, randomized, placebo-controlled, and active comparator―controlled study. Healthy postmenopausal women (n = 664; aged 40-65 y) were randomized to BZA 20 mg/CE 0.625 mg, BZA 20 mg/CE 0.45 mg, BZA 20 mg, or placebo once daily for 12 weeks. Changes in vaginal maturation, vaginal pH, and severity of the most bothersome symptom of VVA from baseline were assessed at screening and at weeks 4 and 12. Adverse events were recorded throughout the study. Results: BZA 20 mg/CE 0.625 or CE 0.45 mg significantly (P < 0.01) increased superficial cells and decreased parabasal cells compared with placebo. Vaginal pH and most bothersome symptom significantly improved with BZA 20 mg/CE 0.625 mg compared with placebo (P < 0.05). Improvements in vaginal dryness were also observed with both BZA/CE doses (P < 0.05). The incidence of treatment-related adverse events were similar across treatment groups. Conclusions: BZA/CE is effective in treating moderate to severe VVA and vaginal symptoms. These data further support the use of a tissue-selective estrogen complex containing BZA/CE as a new menopausal therapy for postmenopausal women.

Age-related pelvic floor modifications and prolapse risk factors in postmenopausal women.

Abstract: Objective: Genital prolapse is frequent in postmenopausal women; it describes the loss of support to the pelvic organs, resulting in a herniation of these into the vaginal channel. This problem affects 50% of parous women, and at least 50% of all women develop a mild form of genital prolapse after pregnancy. Methods: An extensive literature review from 1990 to 2008 was performed on prolapse etiology and its risk factors; analyzing the data, we reviewed the genetic and biological aspects, age-related prolapse, biological tissue modifications, surgical problems, pelvic musculature modifications, and neuropathy. Results: Data suggested that aging, pelvic trauma, and surgery evoke tissue denervation and devascularization, anatomic alterations, and increased degradation of collagen; all of these may lead to a decrease in mechanical strength and predispose an individual to prolapse. It has been demonstrated that there is a reduction in protein content and estrogens in uterosacral ligaments, in the vagina, and in the parametrium of women with prolapse. This is a possible explanation for why many surgical procedures to correct prolapse fail and recurrences after surgical correction are frequent. Conclusions: Even if the etiology of pelvic prolapse is poorly defined and multifactorial, aging risk factors, such as biomechanical abnormalities in connective tissue composition, hormonal deficiency, and irregular tissue metabolism, are nonmodifiable and therefore largely stated in clinical practice. Regardless of future developments, based on the reported findings, prolapse therapy will be more influenced by genetics, biological pelvic changes, changes in tissue homeostasis, and topical hormones, rather than general pelvic corrective surgical anatomy.

The impact of smoking on antimüllerian hormone levels in women aged 38 to 50 years.

Abstract: Objective Smoking is associated with increased follicle-stimulating hormone levels and early menopause. Smoking may directly accelerate ovarian follicular depletion or may act indirectly by increasing the pituitary production of follicle-stimulating hormone. Antimullerian hormone (AMH), produced by ovarian follicles, is a more direct measure of ovarian reserve. The objective of our study was to determine the extent to which smoking influences ovarian reserve, as measured by AMH levels. Methods A community sample of 284 women aged 38 to 50 years completed a self-administered questionnaire including a detailed smoking history. Serum AMH levels were measured on day 2, 3, or 4 of the menstrual cycle. The association between AMH and smoking was analyzed using linear regression, adjusting for age and body mass index. Results Participants aged 38 to 42, 43 to 45, and 46 to 50 years had geometric mean AMH values of 6.7 pM (95% CI, 5.2-8.7 pM), 2.7 pM (95% CI, 1.9-3.8 pM), and 1.3 pM (95% CI, 1.0-1.7 pM), respectively. Current smokers, but not past smokers, had 44% lower AMH values than did the reference group (participants with neither active nor former or passive smoke exposure; P = 0.04). Passive smoking had no effect on AMH values when compared with the reference group (P = 0.55). The impact of smoking on AMH values was not dose dependent based on cigarettes per day (P = 0.08) or pack-years (P = 0.22). Finally, prenatal exposure to smoking (either maternal or paternal) had no impact on AMH levels (P = 0.47 and P = 0.89, respectively). Conclusions Active smoking, but not former smoking, is associated with decreased AMH values in late-reproductive-age and perimenopausal women, suggesting a possible direct effect of smoking on the depletion of the antral but not primordial follicles. The direct impact of active smoking on AMH levels in younger women requires further investigation.

Efficacy and tolerability of local estrogen therapy for urogenital atrophy.

Abstract: Objective:This study aimed to identify vaginal discomfort in the form of dryness, itching, burning, and dyspareunia, which remains an inadequately addressed clinical problem for many postmenopausal women, and to describe the age or menopause-related dysfunction of the female urethral tract,

Calcium/vitamin D supplementation and coronary artery calcification in the Women's Health Initiative.

Abstract: Objectives Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. The relationship between calcium plus vitamin D supplementation and coronary artery calcium (CAC) has not been previously assessed in a randomized trial setting. We compared coronary artery calcium scores among women randomized to calcium/vitamin D supplementation versus placebo following trial completion.

A review of estrogen receptor α gene (ESR1) polymorphisms, mood, and cognition

Abstract: OBJECTIVE—There are significant individual differences in the extent to which mood and cognition change as a function of reproductive stage, menstrual phase, postpartum, and hormone therapy. This review explores the extent to which variations or polymorphisms in the estrogen receptor α gene (ESR1) predict cognitive and mood outcomes. METHODS—A literature search was conducted from 1995 to November 2009 through PubMed, EMBASE, and PsychINFO. Twenty-five manuscripts were reviewed that summarize investigations of ESR1 in mental health. RESULTS—Among studies investigating ESR1 in relation to cognition, 11 of 14 case-control studies reported an association between ESR1 polymorphisms and risk for developing dementia. Three of four prospective cohort studies reported an association between ESR1 polymorphisms and significant cognitive decline. There are inconsistencies between case-control and cohort studies regarding whether specific ESR1 alleles increase or decrease the risk for cognitive dysfunction. The relationships between ESR1 and cognitive impairment tend to be specific to or driven by women and restricted to risk for Alzheimer’s disease rather than other dementia causes. Three of five studies examining ESR1 polymorphisms in relation to anxiety or depressive symptoms found significant associations. Significant associations have also been reported between ESR1 polymorphisms and childhood-onset mood disorder and premenstrual dysphoric disorder. CONCLUSIONS—A strong relationship between ESR1 variants and cognitive outcomes is evident and preliminary evidence suggests a role of the ESR1 gene in certain mood outcomes. Insights into the discordant results will come from future studies that include haplotype analyses, analyses within specific ethnic/racial populations, and gender-stratified analyses.

Soy isoflavones versus placebo in the treatment of climacteric vasomotor symptoms: systematic review and meta-analysis.

Abstract: Objective The incidence of vasomotor crises during the climacterium varies in women across different populations, and phytoestrogen consumption seems to play an important role in this problem. The aim of this study was to determine whether intervention with soy (dietary, extract, or concentrate), as compared with placebo, reduces the incidence of hot flashes in climacteric women. Methods Only published, randomized, placebo-controlled clinical trials were selected, with a 12-week duration of intervention, having selected postmenopausal women affected with hot flashes attributed to the climacterium (without cancer background). The intervention to be evaluated was soy, as "soy dietary supplement," "soy extract," or "isoflavone concentrate" (genistein or daidzein). The results were expressed as the number of hot flashes, average score of vasomotor symptoms, or average percent reduction in hot flashes within a time unit (day, week, or month). Results Nineteen studies were analyzed. The minimum heterogeneity was observed in the "isoflavone concentrate" group. In the "extract" and "dietary supplement" groups, heterogeneity reached an intermediate level, I(2) = 42% and 59.73%, respectively. The overall result showed a standardized mean difference of -0.39 (95% CI, -0.53 to -0.25) in favor of soy as well as -0.45 (95% CI, -0.64 to -0.25), -0.51 (95% CI, -0.79 to -0.22), and -0.20 (95% CI, -0.46 to -0.06) for the "concentrate," "extract," and "dietary supplement" subgroups, respectively. Conclusions Although the overall combined results and the results by subgroups (according to the type of supplement used) showed a significant tendency in favor of soy, it is still difficult to establish conclusive results given the high heterogeneity found in the studies.

Metabolic syndrome and bone metabolism: the Camargo Cohort study.

Abstract: Objectives: The aims of this study were to compare in participants with and without metabolic syndrome (1) bone mineral density (BMD), (2) prevalent vertebral and nonvertebral fractures, and (3) calciotropic hormones and bone turnover markers and to examine the association of each component of metabolic syndrome with bone parameters. Methods: A cross-sectional study (495 men and 1,013 women) from the Camargo Cohort Study was conducted. A multivariable regression approach was used to analyze the relationship between the components of metabolic syndrome and bone parameters. Results: Women with metabolic syndrome had higher age-adjusted BMD at all localizations (P < 0.0001) than did women without metabolic syndrome. Adjusting for body mass index canceled out this difference at the spine and femoral neck, although borderline significance persisted at the total hip. Moreover, in regression analyses, waist circumference (P < 0.0001) and hypertension (P between 0.002 and <0.0001) highly correlated with BMD at the three sites. However, no significant differences in BMD were found in men between those with and without metabolic syndrome. No differences in the prevalence of vertebral or nonvertebral fractures between participants with metabolic syndrome and controls were found for either sex. 25-Hydroxyvitamin D was significantly lower (P < 0.0001) and parathyroid hormone was significantly higher (P < 0.0001) in women with metabolic syndrome than in women without metabolic syndrome, whereas no differences were seen in men. Propeptide of type I collagen and C-terminal telopeptide of type I collagen were significantly lower in participants with metabolic syndrome than in controls in either sex. Conclusions: Women with metabolic syndrome show higher BMD than controls do, mainly driven by their higher body weight. Bone remodeling in these women is lower. Despite the greater bone mass and lower bone turnover, fracture prevalence is not reduced, suggesting worse bone quality and/or higher tendency to fall. No differences in BMD or fractures were seen in men, suggesting that the impact of metabolic syndrome on bone is sex dependent.

Summary of the National Institute on Aging-sponsored conference on depressive symptoms and cognitive complaints in the menopausal transition.

Abstract: This NIA-sponsored workshop was aimed at understanding the impact of the menopausal transition on mood symptoms and cognitive disorders during the menopausal transition and identifying research priorities for further investigation. Longitudinal studies provide insights into the frequency of these problems in representative samples of midlife women. The majority of women do not experience serious depressive symptoms during the transition, but a subgroup of women is at increased risk. Slight changes in memory function and processing speed are evident during the transition, and physiological factors associated with hot flashes may contribute to memory problems. Clinical trial evidence indicates that estradiol therapy can be effective in treating perimenopausal depression. There is some limited evidence of a cognitive benefit with estrogen alone therapy in younger postmenopausal women, and stronger evidence that certain forms of combination hormone therapy produce modest deficits in verbal memory in younger and older women. Identifying a cognitively neutral or beneficial combination therapy for the treatment of menopausal symptoms in naturally menopausal women is an important goal for future research. Pharmacological challenge studies bridge the basic science and clinical literatures to provide insights into the extent to which changes in endogenous and exogenous hormones and other neurotransmitter systems contribute to cognitive and mood problems. Routine evaluation of depressive symptoms in perimenopausal women is warranted by the literature. Quick and valid screening tools for assessing depression in the clinic are available on-line and free of charge.

Effects of acupuncture on hot flashes in perimenopausal and postmenopausal women--a multicenter randomized clinical trial.

Abstract: Objective:The aim of this study was to evaluate the effectiveness of acupuncture plus usual care for relief of hot flashes and menopause-related symptoms compared with usual care alone in perimenopausal or postmenopausal women.Methods:A multicenter, randomized, controlled trial was conducted

Role of androgens in women's sexual dysfunction

Abstract: Objective: Although suspected, androgen deficit in women with sexual dysfunction has never been established. Given that serum testosterone levels are of limited value, we sought to compare total androgen activity in women with and without hypoactive sexual desire disorder (HSDD). Intracellular production in target tissues is the major source of testosterone in older women and can now be measured. Androgen metabolites, specifically androsterone glucuronide (ADT-G), reflect intracellular and ovarian sources of testosterone. Thus, we predicted significantly lowered levels of metabolites in women with sexual dysfunction. Methods: A detailed assessment of the sexual function of women without depression, without serious relationship discord, or receiving medications affecting sexual function included 121 women with HSDD and 124 sexually healthy community controls. Sexual function was assessed using structured interviews, validated questionnaires, and steroid analysisYmass spectrometry levels of ADT-G, testosterone, and precursor hormones. Results: No group differences in serum levels of testosterone or ADT-G were found. Significantly lower levels of two precursor hormones, dehydroepiandrosterone sulfate and androstene-3A,17A-diol, were found in women with sexual dysfunction (P = 0.006 and P = 0.020, respectively). The variability of metabolite and precursor levels was substantial for all women. Conclusions: Significantly lower levels of the two precursor steroids dehydroepiandrosterone sulfate and androstene-3A,17A-diol but not the major androgen metabolite ADT-G were found in women with HSDD. Although the significance of the former awaits further study, androgen deficiency in women with HSDD was not confirmed. Given the unknown long-term effects of testosterone supplementation, women receiving testosterone therapy should be informed that a deficit of testosterone activity in women with HSDD has not been identified.

The prevalence of depression symptoms and influencing factors among perimenopausal and postmenopausal women.

Abstract: Objective This study was conducted for the purpose of determining the prevalence of depression in perimenopausal and postmenopausal women and the factors that influence the development of depression. Methods A community-based sample of 685 women aged 45 to 59 years who were living in Malatya was recruited in this cross-sectional study. An information form that included questions on descriptive characteristics and lifestyle variables of cases, the Menopause-Specific Quality of Life Questionnaire, and the Beck Depression Inventory were administered to each woman in the sample. The data were collected through personal interviews with women at their home between February and May 2008. Results The mean age of the respondents was 50.66 (4.15) years. The prevalence of depression symptoms among the perimenopausal and postmenopausal women was 41.8%. Of all women, 23.2% were premenopausal and 56.9% were postmenopausal. The logistic regression analysis revealed that depression symptom development was 1.8 times higher in the perimenopausal-postmenopausal period than in the premenopausal period, 3.6 times higher among those with an event history affecting life in a negative way than among those without, and 2.0 times higher among those with a body mass index of 25 kg/m or higher than among those with a body mass index of less than 25 kg/m. Conclusions There is a high level of prevalence of depression symptoms in perimenopausal and postmenopausal women.

Hot flashes and cardiac vagal control: a link to cardiovascular risk?

Abstract: Objective The understanding of the physiology of hot flashes is incomplete. The autonomic nervous system has been hypothesized to play a role in hot flashes but has received limited empirical attention. Furthermore, emerging research has linked hot flashes to cardiovascular risk. Reduced high-frequency heart rate variability (HF-HRV), an index of vagal control of heart rate, has been associated with cardiovascular events. We hypothesized that decreases in HF-HRV would occur during hot flashes relative to periods before and after hot flashes. Methods Thirty perimenopausal and postmenopausal women aged 40 to 60 years reporting four or more hot flashes per day underwent laboratory hot flash provocation testing, with electrocardiogram and measurement of sternal skin conductance. Hot flashes were reported and identified from sternal skin conductance. HF-HRV was estimated using spectral analysis of the heart rate time series. The 5-minute interval during the hot flash period was compared with that during two nonflash periods before and after the hot flash via mixed-effects models. Results HRV was significantly decreased during hot flashes relative to periods before (b = 0.18, SE = 0.05; P = 0.0001) and after (b = 0.16, SE = 0.05; P = 0.002) physiologically measured hot flashes, controlling for age, race, education, task condition, menopause status, task, hypertension status, diabetes status, physical activity, body mass index, smoking, and anxiety. Findings were unchanged when considering self-reported hot flashes. Conclusions Significant decreases in cardiac vagal control occurred during hot flashes, which may help shed light on the physiology of hot flashes. The autonomic nervous system may deserve greater attention in understanding the mechanisms linking hot flashes to cardiovascular risk.

Black cohosh and suspected hepatotoxicity: inconsistencies, confounding variables, and prospective use of a diagnostic causality algorithm. A critical review.

Abstract: Objective:The data of 69 cases of initially suspected black cohosh (BC)-induced liver disease were reviewed and analyzed to clarify whether BC hepatotoxicity really exists as a disease entity in these cases comparable to toxic liver disease being caused by various drugs and dietary supplemen

Daily vasomotor symptoms, sleep problems, and mood: using daily data to evaluate the domino hypothesis in middle-aged women.

Abstract: Objective:The aim of this study was to investigate the relationships among daily reports of vasomotor symptoms (hot flashes and/or sweats), same-day sleep problems, and next-day mood reports in middle-aged women.Methods:Fifty-five healthy middle-aged women were recruited to keep daily record

Burden associated with chronic sleep maintenance insomnia characterized by nighttime awakenings among women with menopausal symptoms.

Abstract: Objective:The aim of this study was to quantify the burden associated with chronic sleep maintenance insomnia characterized by nighttime awakenings (CINA) among women with menopausal symptoms.Methods:Data were obtained from the 2006 US National Health and Wellness Survey, an annual cross-sec

Self-reported sleep difficulty during the menopausal transition: results from a prospective cohort study.

Abstract: Objective: The aim of this study was to examine the relationship between menopausal transition status and self-reported sleep difficulty.

Endometrial safety: a key hurdle for selective estrogen receptor modulators in development.

Abstract: Selective estrogen receptor modulators (SERMs) have the ability to provide mixed functional estrogen receptor (ER) agonist or antagonist activity, depending on the target tissue. Tamoxifen, the first SERM available for clinical use, is regarded as a highly effective agent for the prevention and treatment of breast cancer. However, tamoxifen exhibits ER agonist activity in the uterus and is associated with an increased risk of endometrial hyperplasia and malignancy. Endometrial safety has been an important consideration in the clinical development of SERMs, with improved benefit-risk profiles. Raloxifene, which is currently approved for the prevention and treatment of postmenopausal osteoporosis and for the prevention of breast cancer, seems to have neutral effects on the uterus. Promising results have been observed with the targeted development of newer and more tissue-specific SERMs, many of which are under investigation for postmenopausal osteoporosis. Of the newer SERMs in development, lasofoxifene has been shown to reduce fracture risk and decrease the incidence of breast cancer but has been associated with an increased incidence of vaginal bleeding, endometrial thickening, and endometrial polyps. Lasofoxifene and ospemifene have shown beneficial effects on the vaginal epithelium. Phase 3 clinical data have shown that bazedoxifene is effective in preventing and treating postmenopausal osteoporosis, without adverse effects on the endometrium or breast. Arzoxifene has been evaluated in phase 3 trials for postmenopausal osteoporosis and has been studied for the treatment of uterine malignancies but is no longer in clinical development. Further investigation of newer SERMs is warranted to more clearly define the endometrial safety of these agents.

Menopausal symptom experience before and after stopping estrogen therapy in the Women's Health Initiative randomized, placebo-controlled trial.

Abstract: Objective The aim of this study was to assess vasomotor and other menopausal symptoms before starting estrogens or placebo, 1 year later, again at trial closure, and after stopping estrogens or placebo. The role of baseline symptoms and age was examined, as was the frequency and determinants of hormone use and symptom management strategies after discontinuing conjugated equine estrogens (CEE) or placebo. Methods Intent-to-treat analyses of 10,739 postmenopausal women before and 1 year after randomization to CEE or placebo at 40 clinical centers and a cohort analysis of participants (n = 3,496) who continued taking assigned study pills up to trial closure and completed symptom surveys shortly before (mean, 7.4 +/- 1.1 y from baseline) and after (mean, 306 +/- 55 d after trial closure) stopping pills were performed. Generalized linear regression modeled vasomotor symptoms, vaginal dryness, breast tenderness, pain/stiffness, and mood swings as a function of treatment assignment and baseline symptoms, before and after stopping study pills. Results Approximately one third of participants reported at least one moderate to severe symptom at baseline. Fewer symptoms were reported with increasing age, except joint pain/stiffness, which was similar among age groups. At 1 year, hot flashes, night sweats, and vaginal dryness were reduced by CEE, whereas breast tenderness was increased. Breast tenderness was also significantly higher in the CEE group at trial closure. After stopping, vasomotor symptoms were reported by significantly more women who had reported symptoms at baseline, compared with those who had not, and by significantly more participants assigned to CEE (9.8%) versus placebo (3.2%); however, among women with no moderate or severe symptoms at baseline, more than five times as many reported hot flashes after stopping CEE (7.2%) versus placebo (1.5%). Conclusions CEE significantly reduced vasomotor symptoms and vaginal dryness in women with baseline symptoms but increased breast tenderness. The likelihood of experiencing symptoms was significantly higher after stopping CEE than placebo regardless of baseline symptom status. These potential effects should be considered before initiating CEE to relieve menopausal symptoms.

History of hot flashes and aortic calcification among postmenopausal women.

Abstract: Objective: Menopausal hot flashes are considered largely a quality-of-life issue. However, emerging research also links hot flashes to cardiovascular risk. In some investigations, this risk is particularly apparent among women using hormone therapy. The aim of this study was to determine whether a longer history of reported hot flashes over the study period was associated with greater aortic and coronary artery calcification. Interactions with hormone therapy use were examined in an exploratory fashion. Methods: Participants included 302 women participating in the Healthy Women Study, a longitudinal study of cardiovascular risk during perimenopause and postmenopause, which was initiated in 1983. Hot flashes (any/none) were assessed when women were 1, 2, 5, and 8 years postmenopausal. Electron beam tomography measures of coronary artery calcification and aortic calcification were completed in 1997-2004. Associations between the number of visits with report of hot flashes, divided by the number of visits attended, and aortic or coronary artery calcification (transformed) were examined in linear regression models. Interactions by hormone therapy use were evaluated. Results: Among women using hormone therapy, a longer history of reported hot flashes was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors (b = 2.87, SE = 1.21, P < 0.05). There were no significant associations between history of hot flashes and coronary artery calcification. Conclusions: Among postmenopausal women using hormone therapy, a longer history of reported hot flashes measured prospectively was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors. Hot flashes may signal adverse cardiovascular changes among certain postmenopausal women.

Premature menopause is associated with increased risk of cerebral infarction in Japanese women.

Abstract: Objective : Few epidemiological studies have examined the relationship between age at menopause and stroke incidence, and none have done so in Japanese women. Here, we investigated the relationship between age at menopause and stroke incidence in a large group of Japanese women. Methods : The study participants were 4,790 postmenopausal women aged 36 to 89 years enrolled in the Jichi Medical School Cohort Study, a population-based prospective study. Baseline data were obtained by questionnaire and health checkups between April 1992 and July 1995 in 12 rural areas in Japan. The incidence of all strokes and stroke subtypes was monitored. Results : Mean (SD) participant age was 61.0 (6.7) years, and mean (SD) age at menopause was 48.3 (4.8) years. A total of 185 strokes were observed during a mean follow-up of 10.8 years. On adjustment for age, systolic blood pressure, total cholesterol, body mass index, smoking habits, and alcohol drinking habits, hazard ratios (95% CIs) of stroke for women who underwent menopause before age 40 years, at 40 to 44 years, at 45 to 49 years, and at 55 years or after relative to those who underwent menopause at age 50 to 54 years were 1.56 (0.78-3.12), 1.59 (1.00-2.51), 1.28 (0.92-1.78), and 0.83 (0.38-1.81), respectively. However, hazard ratios (95% CI) of cerebral infarction for women who underwent menopause before age 40 years, at 40 to 44 years, at 45 to 49 years, and at 55 years or after relative to those who underwent menopause at age 50 to 54 years were 2.57 (1.20-5.49), 1.49 (0.80-2.78), 1.06 (0.67-1.68), and 1.08 (0.43-2.74), respectively. Conclusions : Our data suggest that Japanese women who undergo menopause before age 40 years are at an increased risk of cerebral infarction. Premature menopause should be considered an indicator of the need for more aggressive medical intervention aimed at the prevention of cerebral infarction.

Vaginal symptoms in postmenopausal women: self-reported severity, natural history, and risk factors.

Abstract: Objective: This study aimed to examine factors other than estrogen deficiency influencing the development and persistence of vaginal dryness, itching, and painful sexual intercourse after menopause. Methods: We analyzed data from a 2-year, population-based cohort of 1,017 postmenopausal women aged 55 to 75 years. Vaginal symptoms were assessed by interviewer-administered questionnaire, and vaginal swabs were performed to assess vaginal pH and microbial flora at baseline, 12 months, and 24 months. Generalized estimating equations were used to identify characteristics associated with symptoms. Results: Half of the women (n = 471) reported problematic vaginal dryness, a third (n = 316) reported itching, and 40% of sexually active women (n = 166) reported painful intercourse at baseline. Of women not taking estrogen, half of those reporting baseline symptoms were symptomatic after 24 months. Vaginal dryness was associated with younger age (odds ratio [OR], 0.81; 95% CI, 0.69-0.94, per 5-y increase), nonwhite race (ie, African American, Hispanic, Asian or Pacific Islander, or American Indian [OR, 1.53; 95% CI, 1.04-2.27]), diabetes (OR, 1.51; 95% CI, 1.07-2.12), lower 36-item Short-Form Health Survey physical functioning scores (OR, 0.90; 95% CI, 0.85-0.97, per 10-point increase), lower body mass index (OR, 0.81; 95% CI, 0.71-0.93, per 5 kg/m 2 increase), recent sexual activity (OR, 1.14; 95% CI, 1.08-1.21), and vaginal colonization with enterococci (OR, 1.25; 95% CI, 1.04-1.51). Vaginal itching was also associated with lower physical functioning scores (OR, 0.86; 95% CI, 0.80-0.92, per 10-point increase). Risk factors for painful intercourse included younger age (OR, 0.72; 95% CI, 0.56-0.93, per 5-y increase), diabetes (OR, 3.48; 95% CI, 1.93-6.27), lower body mass index (OR, 0.76; 95% CI, 0.61-0.95, per 5 kg/m 2 increase), and higher vaginal pH (OR, 1.10; 95% CI, 1.00-1.21, per 0.5 units). Conclusions: Vaginal symptoms affect a large proportion of postmenopausal women, particularly those with diabetes and those with lower body mass index, but may resolve for up to half of women without estrogen therapy.

Early menopausal hormone use influences brain regions used for visual working memory.

Abstract: Objective—Cognitive benefit of postmenopausal hormone use is controversial; however, timing treatment close to menopause may increase the likelihood of preserving cognitive function. We examined effects of early-initiation hormone use on visual working memory, hypothesizing that longterm hormone use is associated with greater brain activation during visual working memory. Methods—This is a cross-sectional comparison of long-term early hormone users – current (n=13) and past (n=24, 2.1±1.0 years off hormones) – to never-users (n=18), using a visual memory task and functional MRI. We evaluated 55 women over age 60 at the University of Michigan’s General Clinical Research Center. Hormone users had completed at least ten continuous years of conjugated equine estrogens with or without medroxyprogesterone acetate, began within two years of menopause. Women were excluded for illness, medication, intermittent estrogen use, phytoestrogen use, recent smoking, and MRI contraindications. The primary outcome was functional MRI-detected brain activity during the visual memory task. Results—Compared to never-users, both hormone-user groups had increased activation in the frontal and parietal cortices, insula, hippocampus, and cingulate; combined hormone-users also had increased activation in the putamen and raphe (corrected p<0.05 or uncorrected p<0.001 with a priori hypothesis). Across the entire sample, medial temporal cortex (p<0.000 right; p<0.018 left) and right hippocampus (p<0.000) positively correlated with task performance.

The influence of menopause status and postmenopausal use of hormone therapy on presentation of major depression in women.

Abstract: Objective: The purpose of this study was to determine whether there are differences in depression characteristics among premenopausal, perimenopausal, and postmenopausal women with major depressive disorder. This study also evaluated these differences between postmenopausal women with major depressive disorder who are taking and not taking hormone therapy.

Augmentation of venlafaxine and selective serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer patients with hot flashes: a randomized, double-blind, placebo-controlled trial.

Abstract: Objective Hot flashes are a major quality-of-life issue for breast cancer survivors, interrupting sleep, reducing quality of life, and diminishing treatment adherence to adjuvant endocrine therapies. Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) are used widely but are only partially effective for hot flashes. Alternative strategies are needed. We hypothesized that augmentation of SSRI/SNRI therapy with hypnotic agents would optimize hot flash therapy by improving sleep and quality of life. Methods Women with breast cancer or at high risk for developing the disease who had hot flashes in association with nocturnal awakenings were randomized to double-blinded treatment with zolpidem 10 mg or placebo for 5 weeks. SSRI/SNRI nonusers (81%) started venlafaxine XR 75 mg/day concurrently, whereas SSRI/SNRI users continued that therapy. We compared the proportion of responders, defined as study completers with improved subjective sleep quality (Pittsburgh Sleep Quality Index) and/or objectively assessed wake time after sleep onset on actigraphy, between groups. Results Of 53 women (aged 51 ± 8 y) randomized to zolpidem augmentation (n = 25) or placebo augmentation (n = 28), 38 completed the protocol (57% on placebo, 88% on zolpidem). More women augmented with zolpidem than placebo were responders on the sleep outcome (40% vs 14%; P = 0.035). Quality of life improved more with zolpidem than with placebo (P = 0.01). Treatment effects on hot flashes and mood did not differ between groups. Conclusions Augmentation of SSRI/SNRI with zolpidem improves sleep and quality of life in breast cancer survivors with hot flashes and associated sleep disturbance. Adding a hypnotic agent to an SSRI/SNRI helps women to sleep through nighttime hot flashes. Treatments targeting sleep may be an important supplemental strategy to optimize well-being.

Effects of age at first pregnancy and breast-feeding on the development of postmenopausal osteoporosis.

Abstract: OBJECTIVE Although pregnancy and breast-feeding require adequate calcium mobilization, it is not known if these affect the acquisition of a healthy peak bone mass (PBM) and, hence, postmenopausal osteoporosis (OPS). The objective of this study was to analyze previous pregnancies and/or breast-feeding and their association with OPS. METHODS After obtaining institutional review board approval, postmenopausal women (>49 y) presenting for a dual-energy x-ray absorptiometry bone density scan were invited to participate. Risk factors for OPS, including previous fractures, pregnancy information, and dual-energy x-ray absorptiometry results, were collected. OPS was defined as a T score of -2.5 or lower. RESULTS Data were obtained from 619 women. Of these, 49.8% were smokers, 27.2% used a bisphosphonate, 64.1% used hormone therapy, and 5.5% had used steroids. Based on PBM, ages at first pregnancy were dichotomized to younger than 27 years and 27 years or older. Women with a history of breast-feeding had a lower prevalence of OPS (7.6%) versus women who had never breast-fed (18.7%; P < 0.001). Women with a first pregnancy when they were 27 years or older and a history of breast-feeding had the lowest prevalence of OPS (4.6%) versus women with a first pregnancy when they were younger than 27 years and no history of breast-feeding (16.3%; P = 0.001). CONCLUSIONS Breast-feeding seems to significantly decrease the incidence of postmenopausal OPS. Women whose first pregnancy occurs after PBM (≥27 y of age) and who have a history of breast-feeding had the lowest prevalence of OPS. Thus, an association between OPS and both breast-feeding and age of pregnancy seems to be present.