The Menopause Transition: Signs, Symptoms, and Management Options.

CONTEXT: Menopause, the permanent cessation of menses, reflects oocyte depletion and loss of gonadal steroids. It is preceded by a transition state, the perimenopause, which is characterized by the gradual loss of oocytes, altered responsiveness to gonadal steroid feedback, wide hormonal fluctuations, and irregular menstrual patterns. The goal of this mini-review is to discuss the basic pathophysiology of the menopausal transition and the hormonal and nonhormonal management of clinicopathology attributed to it. EVIDENCE ACQUISITION: A Medline search of epidemiologic, population-based studies, and studies of reproductive physiology was conducted. A total of 758 publications were screened. EVIDENCE SYNTHESIS: The reproductive hormonal milieu of the menopausal transition precipitates bothersome vasomotor symptoms, mood disruption, temporary cognitive dysfunction, genitourinary symptoms, and other disease processes that reduce the quality of life of affected women. The endocrine tumult of the menopause transition also exposes racial and socioeconomic disparities in the onset, severity, and frequency of symptoms. Hormone therapy (HT) treatment can be effective for perimenopausal symptoms but its use has been stymied by concerns about health risks observed in postmenopausal HT users who are older than 60 and/or women who have been postmenopausal for greater than 10 years. CONCLUSIONS: The menopause transition is a disruptive process that can last for over a decade and causes symptoms in a majority of women. It is important for clinicians to recognize early signs and symptoms of the transition and be prepared to offer treatment to mitigate these symptoms. Many safe and effective options, including HT, are available.

Higher symptom burden is associated with lower function in women taking adjuvant endocrine therapy for breast cancer.

OBJECTIVE: To explore the impact of symptoms on physical function in women on adjuvant endocrine therapy for breast cancer. METHODS: Eligible women were postmenopausal, had hormone receptor positive, stage I-IIIA breast cancer, completed surgery, chemotherapy, radiation, and on adjuvant endocrine therapy. At a routine follow-up visit, women (N = 107) completed standardized symptom measures: Brief Fatigue Inventory, Brief Pain Inventory, Menopause Specific Quality of Life Questionnaire, Functional Assessment of Cancer Therapy Neurotoxicity scales. Two performance measures assessed function: grip strength (Jamar dynamometer; n = 71) and timed get-up-and-go (TUG; n = 103). Analyses were performed with an overall symptom composite score. Correlations and multiple linear regression analyses were performed to test adverse effects on physical function. RESULTS: The mean age was 64 years (range 45-84), 81% white, 84% on an aromatase inhibitor, and on endocrine therapy for mean 35 months (range 1-130 months). Dominant hand grip strength was inversely correlated with symptom composite scores (r = -0.29, p = .02). Slower TUG was positively correlated with higher Charlson comorbidity level (r = 0.36, p < .001) and higher symptom composite scores (r = 0.24, p = .01). In multivariate analyses, weaker dominant and non-dominant hand grip strength were significantly associated with greater symptom composite scores (ß = -0.27, t = 2.43, p = .02 and ß = -0.36, t = 3.15, p = .003, respectively) and slower TUG was associated with higher symptom composite scores (ß = 0.18, t = 1.97, p = .05). CONCLUSIONS: Higher symptom burden is associated with worse physical function, as measured by hand grip strength and TUG. Further study to determine the impact of endocrine therapy and its side effects on function is warranted.

Vasomotor Symptoms Across the Menopause Transition: Differences Among Women.

Vasomotor symptoms (VMS) are the primary menopausal symptoms, occurring in up 80% of women and peaking around the final menstrual period. The average duration is 10 years, longer in women with an earlier onset. Compared with non-Hispanic white women, black and Hispanic women are more likely and Asian women are less likely to report VMS. Risk factors include greater body composition (in the early stage of menopausal transition), smoking, anxiety, depression, sensitivity to symptoms, premenstrual syndrome, lower education, and medical treatments, such as hysterectomy, oophorectomy, and breast cancer-related therapies. VMS patterns over time and within higher-risk subgroups are heterogeneous across women.

Aerobic exercise for vasomotor menopausal symptoms: A cost-utility analysis based on the Active Women trial.

OBJECTIVE: To compare the cost-utility of two exercise interventions relative to a control group for vasomotor menopausal symptoms. DESIGN: Economic evaluation taking a UK National Health Service and Personal Social Services perspective and a societal perspective. SETTING: Primary care. POPULATION: Peri- and postmenopausal women who have not used hormone therapy in the past 3 months and experience ≥ 5 episodes of vasomotor symptoms daily. METHODS: An individual and a social support-based exercise intervention were evaluated. The former (Exercise-DVD), aimed to prompt exercise with purpose-designed DVD and written materials, whereas the latter (Exercise-Social support) with community exercise social support groups. Costs and outcomes associated with these interventions were compared to those of a control group, who could only have an exercise consultation. An incremental cost-utility analysis was undertaken using bootstrapping to account for the uncertainty around cost-effectiveness point-estimates. MAIN OUTCOME MEASURE: Cost per quality-adjusted life-year (QALY). RESULTS: Data for 261 women were available for analysis. Exercise-DVD was the most expensive and least effective intervention. Exercise-Social support was £52 (CIs: £18 to £86) and £18 (CIs: -£68 to £105) more expensive per woman than the control group at 6 and 12 months post-randomisation and led to 0.006 (CIs: -0.002 to 0.014) and 0.013 (CIs: -0.01 to 0.036) more QALYs, resulting in an incremental cost-effectiveness ratio of £8,940 and £1,413 per QALY gained respectively. Exercise-Social support had 80%-90% probability of being cost-effective in the UK context. A societal perspective of analysis and a complete-case analysis led to similar findings. CONCLUSIONS: Exercise-Social support resulted in a small gain in health-related quality of life at a marginal additional cost in a context where broader wellbeing and long-term gains associated with exercise and social participation were not captured. Community exercise social support groups are very likely to be cost-effective in the management of vasomotor menopausal symptoms.

Cerebral vasomotor reactivity assessment using Transcranial Doppler and MRI with apnea test.

Differently from previous studies that used Transcranial Doppler (TCD) and functional MRI (fMRI) for cerebral vasomotor reactivity (CVR) assessment in patients with carotid stenosis (CS), we assessed CVR using an identical stimulus, the Breath-Holding Test (BHT). We included 15 patients with CS and 7 age-matched controls to verify whether fMRI responded differently to BHT between groups and to calculate the agreement rate between tests. For TCD, impaired CVR was defined when the mean percentage increase on middle cerebral artery velocities was ≤31% on 3 consecutive 30-s apnea intercalated by 4-min normal breathing intervals. For fMRI, the percent variation on blood oxygen level-dependent (BOLD) signal intensity in the lentiform nucleus (LN) ipsilateral to the CS (or both LNs for controls) from baseline breathing to apnea was measured. The Euclidian differences between the series of each subject and the series of controls and patients classified it into normal or impaired CVR. We found different percent variations on BOLD-signal intensities between groups (P=0.032). The agreement was good in Controls (85.7%; κ=0.69) and overall (77.3%; κ=0.54). We conclude that BHT was feasible for CVR assessment on fMRI and elicited different BOLD responses in patients and controls, with a good overall agreement between the tests.

Validation of a new method for non-invasive assessment of vasomotor function.

BACKGROUND: Reactive hyperaemia induces a slowing of pulse wave velocity (PWV) in conduit arteries of healthy subjects (flow-mediated slowing (FMS)). This could be an alternative method for assessing peripheral vasomotor function to the gold standard method of flow-mediated dilatation (FMD) a more expensive and technically demanding technique. We aimed to assess the reproducibility of FMS in healthy participants and to test its ability to detect differences in vasomotor function in patients with familial hypercholesterolaemia (FH) and post-lipoprotein apheresis (LA) treatment. METHODS: Altogether 25 healthy participants were studied on two occasions to assess reproducibility of FMS. In a case control study of 22 patients with FH and matched healthy controls, FMD and FMS were compared. An intervention study in 12 patients with FH looked at the impact of a single LA treatment on FMS assessed pre and post treatment. RESULTS: FMS demonstrated good reproducibility (coefficient of variation (CoV) 7.3%). Patients with FH had reduced FMS in comparison to matched healthy controls (FMS% FH -15.13 ± 5.04% vs controls -18.41 ± 5.15%, p = 0.023), with no difference in FMD% between the two groups. A single LA treatment significantly improved FMS (pre -18.81 ± 9.84 vs post -24.09 ± 7.61%, p = 0.016). CONCLUSIONS: FMS is a reproducible technique, which is able to detect differences in vasomotor function both in a condition associated with endothelial dysfunction and following an acute intervention known to improve endothelial function. This simple technique has potential for accessible assessment of vasomotor function in clinical studies.

Comparative efficacy and safety of estradiol transdermal preparations for the treatment of vasomotor symptoms in postmenopausal women: an indirect comparison meta-analysis.

OBJECTIVE: Divigel and Estrogel are estradiol gels for the treatment of postmenopausal women with moderate to severe vasomotor symptoms. They differ with respect to several factors including estradiol concentration and surface application, and cannot be compared solely on the basis of their estradiol dose. No randomized clinical trials have compared them head to head, but both have been compared with placebo. Therefore, the objective of this study was to conduct a systematic review and network meta-analysis of the two estradiol gels. METHODS: We performed a comprehensive systematic literature review. One publication reporting on one Divigel trial, three publications reporting on two Estrogel trials, and five publications reporting on other estradiol transdermal preparations were identified. Efficacy outcomes were change from baseline in daily hot flush frequency and change from baseline in daily hot flush severity. Safety outcomes were frequency of treatment-related adverse events (AEs) and frequency of treatment-emergent AEs leading to discontinuation. Bayesian indirect treatment comparison meta-analysis of trial-level data was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research, Academy of Managed Care Pharmacy, National Pharmaceutical Council (ISPOR-AMCP-NPC) Good Practice Questionnaire. All outcomes were compared with respect to doses of the considered preparations. RESULTS: For hot flush frequency, Divigel 0.25 mg was similar to Divigel 0.5 mg and to Estrogel 0.75 mg, and was statistically significantly superior to Estrogel 1.5 mg. The largest effect was observed with Divigel 1.0 mg (mean difference of 3.91 hot flushes/wk vs placebo), and was statistically significantly superior to all other interventions. The 1.5 mg Estrogel dose was associated with the smallest estimate of efficacy. For hot flush severity, Divigel 0.25 mg was similar to the efficacy of Divigel 0.5 mg, and for 0.25 mg and 0.5 mg of other estradiol gels, but was statistically inferior to Divigel 1.0 mg, Estrogel 0.75 mg, Estrogel 1.5 mg, and the 1.0 and 1.5 mg doses of all other estradiol gels. The estimated efficacy of Divigel 0.5 mg was similar to that of Estrogel 0.75 mg, Estrogel 1.5 mg, and the 0.25 and 0.5 mg doses of other transdermal estradiol preparations. Risks of treatment-related AEs for Divigel 0.25 mg, Divigel 0.5 mg, Estrogel 0.75 mg, and Estrogel 1.5 mg were similar and all were of a slightly higher risk than placebo. Among these, Divigel 1.0 mg, Estrogel 1.5 mg, and other gels 0.5 mg were statistically significantly less safe than placebo. However, for treatment-emergent AEs leading to discontinuation, none of the gels were associated with statistically significantly higher relative risks compared with placebo. In this study, statistically significant refers to the 95% credible intervals used in the Bayesian Network Analysis. CONCLUSIONS: Using network meta-analysis for indirect treatment comparison, we have shown that the efficacy of Divigel 0.25 mg, as measured by reduced hot flush frequency and severity, was similar to that of Divigel 0.5 mg and of Estrogel 0.75 and 1.5 mg. Overall, our analysis showed that Divigel 1.0 mg provided the best efficacy profile, but that this treatment was also associated with a higher risk of AEs. The network meta-analysis also showed that treatment with Estrogel 1.5 mg was associated with the smallest estimate of reduction in frequency of hot flushes.

Cerebral vasomotor reactivity assessment using Transcranial Doppler and MRI with apnea test

Differently from previous studies that used Transcranial Doppler (TCD) and functional MRI (fMRI) for cerebral vasomotor reactivity (CVR) assessment in patients with carotid stenosis (CS), we assessed CVR using an identical stimulus, the Breath-Holding Test (BHT). We included 15 patients with CS and 7 age-matched controls to verify whether fMRI responded differently to BHT between groups and to calculate the agreement rate between tests. For TCD, impaired CVR was defined when the mean percentage increase on middle cerebral artery velocities was ≤31% on 3 consecutive 30-s apnea intercalated by 4-min normal breathing intervals. For fMRI, the percent variation on blood oxygen level-dependent (BOLD) signal intensity in the lentiform nucleus (LN) ipsilateral to the CS (or both LNs for controls) from baseline breathing to apnea was measured. The Euclidian differences between the series of each subject and the series of controls and patients classified it into normal or impaired CVR. We found different percent variations on BOLD-signal intensities between groups (P=0.032). The agreement was good in Controls (85.7%; κ=0.69) and overall (77.3%; κ=0.54). We conclude that BHT was feasible for CVR assessment on fMRI and elicited different BOLD responses in patients and controls, with a good overall agreement between the tests.

Socioeconomic disadvantage and neural development from infancy through early childhood.

BACKGROUND: Early social experiences are believed to shape neurodevelopment, with potentially lifelong consequences. Yet minimal evidence exists regarding the role of the social environment on children's neural functioning, a core domain of neurodevelopment. METHODS: We analysed data from 36 443 participants in the United States Collaborative Perinatal Project, a socioeconomically diverse pregnancy cohort conducted between 1959 and 1974. Study outcomes included: physician (neurologist or paediatrician)-rated neurological abnormality neonatally and thereafter at 4 months and 1 and 7 years; indicators of neurological hard signs and soft signs; and indicators of autonomic nervous system function. RESULTS: Children born to socioeconomically disadvantaged parents were more likely to exhibit neurological abnormalities at 4 months [odds ratio (OR) = 1.20; 95% confidence interval (CI) = 1.06, 1.37], 1 year (OR = 1.35; CI = 1.17, 1.56), and 7 years (OR = 1.67; CI = 1.48, 1.89), and more likely to exhibit neurological hard signs (OR = 1.39; CI = 1.10, 1.76), soft signs (OR = 1.26; CI = 1.09, 1.45) and autonomic nervous system dysfunctions at 7 years. Pregnancy and delivery complications, themselves associated with socioeconomic disadvantage, did not account for the higher risks of neurological abnormalities among disadvantaged children. CONCLUSIONS: Parental socioeconomic disadvantage was, independently from pregnancy and delivery complications, associated with abnormal child neural development during the first 7 years of life. These findings reinforce the importance of the early environment for neurodevelopment generally, and expand knowledge regarding the domains of neurodevelopment affected by environmental conditions. Further work is needed to determine the mechanisms linking socioeconomic disadvantage with children's neural functioning, the timing of such mechanisms and their potential reversibility.

IMS study of climate, altitude, temperature and vasomotor symptoms in the United Arab Emirates.

OBJECTIVE: To examine the relationships between temperature, season (summer versus winter), lifestyle, health, mood, beliefs, and experience of hot flushes and night sweats (HFNS), amongst mid-aged women living in the United Arab Emirates (UAE). METHODS: The UAE climate is hyper-arid, being a hot desert climate, with warm winters and hot summers. A total of 372 peri- and postmenopausal women, aged from 45 to 55 years, from urban UAE regions were included. Data were collected during both summer and winter months. Participants completed questionnaires eliciting information about sociodemographics, HFNS (prevalence, frequency and problem-rating), health and lifestyle (body mass index (BMI), diet, exercise), mood (Women's Health Questionnaire) and menopause attributions and beliefs (Menopause Representations Questionnaire). RESULTS: HFNS were currently being experienced by 46.5% of women, with an average weekly frequency of five and problem-rating of 5.7/10. Seasonal variation in temperature was not associated with prevalence, frequency or problem-rating. Hot flush prevalence was associated with poor health, life satisfaction, mood, employment, lower BMI and diet. Higher frequency was associated with higher BMI and more years since the last period. HFNS were more problematic mainly for women who reported lower life satisfaction and held more negative beliefs about the menopause. CONCLUSIONS: In this UAE study, temperature and seasonal temperature variation did not appear to influence HFNS-reporting, but health, life satisfaction, BMI, beliefs and lifestyle factors partially explained women's experiences of menopausal symptoms. A qualitative study might provide further information about the meanings of HFNS and menopause amongst UAE women.

An International Menopause Society study of climate, altitude, temperature (IMS-CAT) and vasomotor symptoms in urban Indian regions.

OBJECTIVE: To examine the relationships between climate (season, temperature, humidity), lifestyle, health, mood and beliefs and experience of hot flushes and night sweats amongst mid-aged women living in eight urban Indian centers. METHODS: A total of 717 peri- and postmenopausal women, aged 45-55 years, from urban centers in different regions of India were included. Data were collected during both summer and winter months. Participants completed questionnaires eliciting information about sociodemographics, hot flushes (prevalence, frequency and problem-rating), health and lifestyle (body mass index, diet, exercise, alcohol use), mood (Women's Health Questionnaire) and attributions and beliefs (Menopause Representations Questionnaire). RESULTS: The prevalence of vasomotor symptoms was low, with 34% of the sample reporting hot flushes and/or night sweats. Seasonal variation in temperature was not associated with hot flush prevalence, frequency or problem rating. Hot flush prevalence was mainly associated with higher anxiety and intake of spicy foods, frequency with (older) age and (more) frequent exercise, while hot flushes were more problematic for women who reported poorer general health and more negative beliefs about menopause. CONCLUSIONS: In this study of Indian women, seasonal temperature variation did not appear to influence hot flush reporting. Health, mood, beliefs and lifestyle factors appear to explain some, but not all, of the variance in experience of menopausal symptoms.

[Consensus conference of the Mexican Association for the Study of Climateric on veralipride prescription for patients with vasomotor symptoms]. / Consenso de la Asociación Mexicana para el Estudio del Climaterio para la indicación de veraliprida a pacientes con síntomas vasomotores.

Vasomotor symptoms are one of the main reasons for climateric women to consult a physician. Hormone therapy is the first treatment choice, but it is not indicated to all patients. Veralipride is an option for those who cannot or will not try hormone treatment. The Mexican Association for the Study of Climateric (AMEC) assembled an interdisciplinary group of medical experts so that they revised the medical literature on the subject and reached a consensus on veralipride indication, doses, counterindications and safety. The recommendations of the consensus conference on veralipride are: (1) Physicians must be familiar with its indication, side effects, pharmacokinetics and dosage. (2) Patients must be informed on other therapeutical options. (3) Patients' mental and neurological state must be evaluated, in particular to identify movement disorders, extrapyramidal symptoms (tremor or dystonia), anxiety and depression that can be mistaken for climateric symptoms. (4) Any adverse effect associated with the drug must be reported. (5) A random multicenter trial must be carried out in order to identify the frequency and severity of side effects, and (6) Written information on possible health risks when using the drug must be provided.

Health symptoms during midlife in relation to menopausal transition: British prospective cohort study.

OBJECTIVE: To characterise symptoms experienced by women during the transition into natural menopause, to classify women into distinct symptom profiles or trajectories, and to relate these profiles to sociodemographic factors and health behaviours. DESIGN: Nationally representative cohort study. SETTING: England, Scotland, and Wales. PARTICIPANTS: 695 women followed-up since birth in 1946 and annually from age 47 to 54 who experienced natural menopause and reported on 20 common health symptoms. MAIN OUTCOME MEASURE: Longitudinal profiles for reported bothersome symptoms. RESULTS: Of 20 individual symptoms, 18 formed into four stable symptom groups: psychological, somatic, vasomotor, and sexual discomfort. Using latent class analyses, all except the somatic group of symptoms showed a clear relation with the timing of menopause for some women. A small proportion of women (10%, n=63) had a severe psychological symptom profile that peaked at or in the year after menopause. For vasomotor symptoms, 14% of women (n=83) had the early severe profile that also peaked around early postmenopause and then declined noticeably; 11% (n=67) had the late severe profile of bothersome symptoms that increased rapidly in perimenopause and remained high for four years or more after menopause. Women were less likely to have a profile for severe vasomotor symptoms if they were from a non-manual social class (odds ratio 0.79, 95% confidence interval 0.57 to 1.01) or had degree level qualifications (0.37, 0.18 to 0.77). The 14% of women (n=85) who had the late severe profile for sexual discomfort showed a similar increase in symptoms until menopause, with symptoms persisting after menopause. Married women were more likely to have the late severe or late moderate profile than women of other marital status (2.40, 1.30 to 4.41). Four profiles each were identified for somatic symptoms (mild, moderate, severe, and very severe), although these did not vary by chronological age or age at menopause. CONCLUSION: Profiles for psychological, vasomotor, and sexual discomfort symptoms relative to age at menopause could help health professionals to tailor their advice for women with natural menopause.

Cerebrovascular reacivity assessment in patients with carotid artery disease: a combined TCD and NIRS study.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) are two noninvasive diagnostic tools that have been shown to evaluate cerebral vasomotor reactivity by measuring changes in mean cerebral blood flow velocities (MCBFV) of proximal intracranial arteries and absolute brain-tissue oxygen-saturation (TOS) in microcirculation, respectively, during hemodynamic challenge. We evaluated the potential correlation between TCD and NIRS measurements of vasomotor reactivity (VMR) in patients with carotid artery disease (CARAD). METHODS: Consecutive patients (n = 24) with CARAD underwent simultaneously TCD and NIRS examinations during voluntary breath-holding (BH). MCBFV and TOS values were recorded at baseline (BAS) and at the end of BH, while BH duration (DBH) was documented. VMR was quantified by means of TCD-BHI (Breath-holding Index: [MCBFV(BH) - MCBFV(BAS)]× 100/MCBFV(BAS)/DBH) and NIRS-BHI ([TOS(BH) - TOS(BAS)]× 100/ TOS(BAS)/DBH). RESULTS: TCD-BHI correlated positively with NIRS-BHI in the affected side (r = .538, P = .007). A stronger correlation between TCD-BHI and NIRS-BHI was documented in the nonaffected side (r = .768, P< .001). After adjusting for demographic characteristics, stroke risk factors and symptomatic status NIRS-BHI was linearly and independently associated with TCD-BHI both in the affected (ß:+ .813, P = .001) and unaffected (ß:+ .823, P < .001) side. CONCLUSIONS: Circulatory assessment of VMR in proximal cerebral vessels by TCD correlates positively to functional measurements of VMR in microcirculation by NIRS in CARAD patients.

Pulsed wave Doppler ultrasonography for the assessment of peripheral vasomotor response in an elderly population.

PURPOSE: To assess sympathetic vasomotor activity and its changes with age, using pulsed wave Doppler ultrasound. METHODS: We recruited 20 young adults (24-37 years old) and 20 older individuals (60-81 years old). Pulsed wave Doppler ultrasound was applied over the right radial artery to measure blood flow at rest and after a voluntary inspiratory cough eliciting sympathetic activation. The maximal (Vmax), minimal (Vmin), time-averaged (TAMaxV) blood flow velocity, and the pulsatility index (PI) were calculated and compared between groups. RESULTS: At rest, PI was similar in both groups but Vmax and TAMaxV were higher in the older group (p < 0.05). Vmax, Vmin, and TAMaxV decreased, and PI increased after inspiratory cough in both groups (p ≤ 0.001), but this increase was lower in the older group (p < 0.001). TAMaxV after coughing was higher in the older group (p < 0.05). Heart rate did not differ significantly within or between groups. CONCLUSIONS: The older group exhibited reduced vasomotor reactivity of the radial artery after sympathetic stimulus. Peripheral vasomotor response should be interpreted with caution in elderly populations.

Self-reported anxiety, depressive, and vasomotor symptoms: a study of perimenopausal women presenting to a specialized midlife assessment center.

OBJECTIVE: The aim of this study was to examine the association of vasomotor symptoms (VMS) with anxiety and/or depressive symptoms in perimenopausal women. METHODS: A retrospective chart review of 487 women 40 to 64 years old seen during October 2004 to December 2006 in the Women's Midlife Assessment Program at the University of California, Davis, was performed. Of these, 395 women were included in the analysis: 58 (15%) were premenopausal, 199 (50%) were perimenopausal, and 138 (35%) were postmenopausal. VMS bothersomeness was represented by converting Likert-scale ratings for hot flashes and night sweats to scores and adding them into an overall score. Multiple logistic regression models were used to quantify the association of self-reported anxiety and/or depressive symptoms with VMS bothersomeness. RESULTS: Thirty-one (53%) premenopausal, 131 (66%) perimenopausal, and 69 (50%) postmenopausal women reported anxiety and/or depressive symptoms. Perimenopausal and postmenopausal women reporting anxiety and/or depressive symptoms had significantly higher VMS bothersomeness scores (2.2 +/- 1.7 and 2.2 +/- 1.9, respectively) than did women who did not report these symptoms (1.7 +/- 1.7 and 1.6 +/- 1.7, respectively; both P values < 0.05). Women experiencing more bothersome VMS were significantly more likely to report anxiety and/or depressive symptoms (odds ratio, 1.5; P < 0.01). Perimenopausal women were significantly more likely to report anxiety and/or depressive symptoms than were postmenopausal women (odds ratio, 1.9; P < 0.01). Both associations remained significant after restricting the analyses to women not taking hormone therapy or psychotropics. CONCLUSIONS: VMS bothersomeness was associated with self-reported anxiety and/or depressive symptoms, showing the importance of screening for anxiety and mood changes during perimenopause.

Measurements of sweat response and skin vasomotor reflex for assessment of autonomic dysfunction in patients with diabetes.

AIMS: Some physical or arousal stimuli induce a rise in sweat secretion (sympathetic sweat response or SSwR) and a reduction in skin blood flow (skin vasomotor reflex or SkVR) to the palm. We recorded SSwRs and SkVRs in diabetic patients and assessed the usefulness of these parameters for evaluating autonomic dysfunction in diabetes. METHODS: We studied 42 diabetic patients (58+/-12 years) and 42 normal control subjects (59+/-11 years). Focal sweat secretion and skin blood flow were measured on the palm by a sudorometer and a Doppler flowmeter, respectively. SSwRs and SkVRs to deep inspiration, mental arithmetic, and isotonic exercise were recorded. SSwR amplitude was measured from baseline to peak, and SkVR amplitude (reduction rate) was calculated as: (blood flow reduction/basal blood flow)x100%. We also conducted head-up tilt tests and R-R interval variation tests (coefficient of variation of R-R intervals or CV(R-R)). RESULTS: The SSwR or SkVR amplitudes in the diabetic group were significantly lower than those in the control group for any stimulus. CV(R-R) in the diabetic group was significantly less than that in the control group. The diabetic group showed a significantly greater reduction in systolic blood pressure during head-up tilt compared with the control group. In the diabetic group, there were significant correlations in SSwR or SkVR amplitudes versus blood pressure falls during the head-up tilt test, and CV(R-R) values. CONCLUSION: We believe that SSwR and SkVR are useful indexes for the evaluation of autonomic involvement in diabetic patients.

A quantitative analysis of the menopause experience of Indian women living in Sydney.

AIMS: To examine the experience of menopause in Indian women (aged 45-65 years) in Sydney, and the relationship between sociodemographic factors and menopausal symptoms, and also to explore the cultural context. METHODS: Two hundred and three women were interviewed about their menopausal experiences in the preceding week using the 29-item Menopause-Specific Quality of Life questionnaire. RESULTS: The mean age of menopause for Indian women was found to be earlier than in other groups in the published literature, at 48.21 years. While there were higher scores for physical symptoms than for other symptoms, and there were significant differences between perimenopausal women and the others, it was found that the prevalence of classical menopausal symptoms was lower in Indian women than that found in Caucasians. However, physical and several psychological symptoms were found to be more prevalent than the usual vasomotor symptoms. Unemployed women and women with a tertiary level of education were found to experience a significantly higher score for all symptoms in our sample. CONCLUSIONS: Lower scores of menopause symptoms indicate that Indian women have fewer complaints of symptoms and a positive attitude towards menopause. Somatic symptoms are multifactorial in nature and could be because of health problems associated with ageing, midlife crises and cultural influences. Further detailed studies could examine the important relationship between cultural lifestyle factors and climacteric symptoms.

Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review.

Many women experience vasomotor symptoms at or around the time of menopause. Hot flushes and night sweats are considered primary menopausal symptoms that may also be associated with sleep and mood disturbances, as well as decreased cognitive function. All of these symptoms may lead to social impairment and work-related difficulties that significantly decrease overall quality of life. Hot flushes have shown a great deal of variability in their frequency and severity in women. In some women, hot flushes persist for several months; in others, they may last for more than 10 years. Traditionally vasomotor symptoms were reported to begin 5 to 10 years prior to the cessation of the final menstrual cycle, corresponding with the initial decline in circulating gonadal hormones; however, night sweats in particular most often begin in perimenopause. The pathogenesis of hot flushes has not yet been fully elucidated, but the circuitry involving estrogen and neurotransmitters, norepinephrine and serotonin specifically, are hypothesized to play a major role in the altered homeostatic thermoregulatory mechanisms underlying these events. Menopause-associated vasomotor symptoms are associated with significant direct and indirect costs. Overall costs of traditional pharmacotherapy or complementary and alternative medicine modalities, including over-the-counter treatments and dietary supplements, for managing menopause-related vasomotor symptoms are substantial and include initial and follow-up physician visits and telephone calls. Additional costs include laboratory testing, management of adverse events, loss of productivity at work, and personal and miscellaneous costs. Pharmacoeconomic analyses, including those that consider risks identified by the Women's Health Initiative, generally support the cost-effectiveness of hormonal therapy for menopause-associated vasomotor symptoms, which have been the mainstay for the management of these symptoms for more than 50 years. However, because many women now want to avoid hormone therapy, there is a need for additional targeted therapies, validated by results from controlled clinical trials that are safe, efficacious, cost-effective, and well tolerated by symptomatic menopausal women.