Severity of hot flushes is inversely associated with dietary intake of vitamin B6 and oily fish.

Objectives: This study investigated the links between the severity of vasomotor symptoms (VMS) and the dietary consumption of a variety of nutrients. Method: A cross-sectional analysis of the first-visit records of 262 women aged 40-65 years was conducted. The severity of their hot flushes (HF) and night sweats (NS) and their dietary consumption of nutrients were evaluated using the Menopausal Health-Related Quality of Life Questionnaire and the brief-type self-administered Diet History Questionnaire, respectively. The relationships between severity of HF/NS and dietary intake were analyzed separately for 43 major nutrients. We then evaluated different food items as sources of the nutrients. Results: After adjustment for age, body mass index, menopausal status, and background factors significantly related to VMS, only vitamin B6 (VB6) was significantly related to severity of HF (adjusted odds ratio per 10 µg/MJ in VB6 intake, 0.92; 95% confidence interval, 0.86-0.97). Moreover, a significant inverse relationship was found between the consumption of oily fish as a source of VB6 and the severity of HF. Conclusions: VB6 and oily fish intake is inversely associated with the severity of HF in middle-aged women. Therefore, increased intake of VB6 could help attenuate HF.

CYP2D6 genotype and endoxifen plasma concentration do not predict hot flash severity during tamoxifen therapy.

PURPOSE: Tamoxifen is frequently prescribed to prevent breast cancer recurrence. Tamoxifen is a prodrug and requires bioactivation by CYP2D6. Tamoxifen use is often limited by adverse effects including severe hot flashes. There is paucity of prospectively collected data in terms of CYP2D6 genotype and measured tamoxifen, 4-hydroxytamoxifen and endoxifen concentrations in relation to hot flash severity during tamoxifen therapy. METHODS: We conducted a longitudinal prospective study of breast cancer patients on tamoxifen (n = 410). At each visit, blood samples were collected, and patients completed a standardized hot flash survey (n = 1144) that reflected hot flash severity during the 7 days prior to the visit. Plasma concentrations of tamoxifen, 4-hydroxytamoxifen, and endoxifen were measured using liquid chromatography-tandem mass spectrometry and genotyping was carried out for CYP2D6. A linear mixed-effects regression analysis assessed the association of covariates in relation to the hot flash severity score (HFSS). RESULTS: Median age at first assessment was 50 years with 61.9% of patients considered peri-menopausal. Most patients (92.2%) experienced hot flash symptoms with 51.0% having low HFSS (0-4) and 7.32% experiencing HFSS > 25. Age was significantly associated with hot flash severity, with patients aged 45-59 more likely to have higher HFSS. Neither duration of tamoxifen therapy nor observed tamoxifen, endoxifen and 4-hydroxy tamoxifen plasma concentration predicted hot flash severity. Genetic variation in CYP2D6 or CYP3A4 was not predictive of hot flash severity. CONCLUSIONS: Hot flash severity during tamoxifen therapy can not be accounted for by CYP2D6 genotype or observed plasma concentration of tamoxifen, 4-hydroxytamoxifen, or endoxifen.

Temporal sequencing of brain activations during naturally occurring thermoregulatory events.

Thermoregulatory events are associated with activity in the constituents of the spinothalamic tract. Whereas studies have assessed activity within constituents of this pathway, in vivo functional magnetic resonance imaging (fMRI) studies have not determined if neuronal activity in the constituents of the tract is temporally ordered. Ordered activity would be expected in naturally occurring thermal events, such as menopausal hot flashes (HFs), which occur in physiological sequence. The origins of HFs may lie in brainstem structures where neuronal activity may occur earlier than in interoceptive centers, such as the insula and the prefrontal cortex. To study such time ordering, we conducted blood oxygen level-dependent-based fMRI in a group of postmenopausal women to measure neuronal activity in the brainstem, insula, and prefrontal cortex around the onset of an HF (detected using synchronously acquired skin conductance responses). Rise in brainstem activity occurred before the detectable onset of an HF. Activity in the insular and prefrontal trailed that in the brainstem, appearing following the onset of the HF. Additional activations associated with HF's were observed in the anterior cingulate cortex and the basal ganglia. Pre-HF brainstem responses may reflect the functional origins of internal thermoregulatory events. By comparison insular, prefrontal and striatal activity may be associated with the phenomenological correlates of HFs.

Menopausal symptoms are associated with subclinical atherosclerosis in healthy recently postmenopausal women.

OBJECTIVES: To determine whether menopausal symptoms are associated with changes in arterial structure and function in healthy, recently postmenopausal women. METHODS: One hundred and ten postmenopausal women aged 45-55 years were included in the present cross-sectional study. Menopausal symptoms were recorded by the Greene Climacteric Scale. Anthropometric measures, blood pressure, serum lipids, glucose, insulin, sex and thyroid hormones were determined in each individual. Arterial structure, function and stiffness were assessed by intima-media thickness (IMT), flow-mediated dilation and pulse-wave velocity, respectively. RESULTS: Women with moderate to severe hot flushes had increased IMT compared to women with no or mild hot flushes (IMT in women with no hot flushes 0.61±0.08 mm, IMT in women with mild hot flushes 0.62±0.11 mm, IMT in women with moderate to severe hot flushes 0.67±0.11 mm; p = 0.034). This difference was independent of cardiovascular risk factors like age, menopausal age, smoking, blood pressure, adiposity, lipid levels, insulin resistance or hormone levels. No association was detected between psychological or psychosomatic symptoms and arterial indices. Furthermore, menopausal symptoms were not associated with serum sex steroids or thyroid hormone levels. CONCLUSIONS: Carotid IMT, a surrogate marker of subclinical atherosclerosis and cardiovascular risk, was found to be increased in women with vasomotor symptoms as compared to asymptomatic women. This association was independent of cardiovascular risk factors or endogenous hormone levels. It remains to be elucidated whether the presence of menopausal symptoms is an additional cardiovascular risk factor requiring preventive intervention.

Hot flashes and subclinical cardiovascular disease: findings from the Study of Women's Health Across the Nation Heart Study.

BACKGROUND: Although evidence suggests adverse vascular changes among women with hot flashes, it is unknown whether hot flashes are associated with subclinical cardiovascular disease. The aim of this study was to examine relations between menopausal hot flashes and indices of subclinical cardiovascular disease. We hypothesized that women with hot flashes would show reduced flow-mediated dilation and greater coronary artery and aortic calcification compared with women without hot flashes. METHODS AND RESULTS: The Study of Women's Health Across the Nation Heart Study (2001 to 2003) is an ancillary study to the Study of Women's Health Across the Nation, a community-based cohort study. Participants were 492 women (35% black, 65% white) 45 to 58 years of age who were free of clinical cardiovascular disease and had a uterus and at least 1 ovary. Measures included a brachial artery ultrasound to assess flow-mediated dilation, electron beam tomography to assess coronary artery and aortic calcification, reported hot flashes (any/none, previous 2 weeks), and a blood sample for measurement of estradiol concentrations. Cross-sectional associations were evaluated with linear regression and partial proportional odds models. Hot flashes were associated with significantly lower flow-mediated dilation (beta=-1.01; SE, 0.41; P=0.01) and greater coronary artery (odds ratio, 1.48; 95% confidence interval, 1.04 to 2.12) and aortic (odds ratio, 1.55; 95% confidence interval, 1.10 to 2.19) calcification in age- and race-adjusted models. Significant associations between hot flashes and flow-mediated dilation (beta=-0.97; SE, 0.44; P=0.03) and aortic calcification (odds ratio, 1.63; 95% confidence interval, 1.07 to 2.49) remained in models adjusted for cardiovascular disease risk factors and estradiol. CONCLUSIONS: Women with hot flashes had reduced flow-mediated dilation and greater aortic calcification. Hot flashes may mark adverse underlying vascular changes among midlife women.

Exploratory study evaluating the association of polymorphisms of angiogenesis genes with hot flashes.

PURPOSE: Hot flashes are a common symptom and an important cause of decreased quality of life in women with breast cancer. Hot flashes involve vasodilatation and flushing, however, their complex etiology is not fully understood. We evaluated the association between germline polymorphisms in genes important to angiogenesis and subjective reporting of hot flashes. EXPERIMENTAL DESIGN: We recruited 1,244 subjects; 520 were breast cancer cases, 715 were documented healthy controls, and nine were of unknown status. Subjects were asked to provide a blood specimen and complete a questionnaire which included whether they had recently or had ever experienced hot flashes. We evaluated candidate polymorphisms in the following genes: hypoxia inducible factor-1 alpha (HIF1alpha), vascular endothelial growth factor (VEGF), VEGF-receptor 2 (VEGFR-2), endothelial nitric oxide synthase (eNOS), neuropilin-1 (NRP-1), and NRP-2. Testing for an association between polymorphisms and a history of current flashes or ever having hot flashes was performed. RESULTS: 441 premenopausal and 533 postmenopausal, Caucasian women were evaluable for hot flash analysis. For premenopausal women the eNOS-786 CT and TT genotypes were significantly associated with a greater likelihood of a subject reporting current hot flashes than the CC genotype (P = 0.03). After adjusting for clinical variables, the genotype association was no longer significant (P = 0.08). For postmenopausal women, the HIF1alpha 1744 CT and TT genotypes were significantly associated with a greater likelihood of a subject reporting current hot flashes (P = 0.05) and this remained significant after consideration of established clinical variables (P = 0.04). CONCLUSION: Hot flashes may be regulated by genes that control angiogenesis.

Evidence for a role of hot flushes in vascular function in recently postmenopausal women.

OBJECTIVE: Observational studies indicate that postmenopausal hormone therapy (HT) prevents cardiovascular disease, but randomized clinical trials have not confirmed this effect. Hot flushes were more likely to be present in women starting HT in observational studies, whereas these symptoms were mild or absent among women attending randomized clinical trials. We hypothesized that vascular function may differ in women with and without vasomotor hot flushes. METHODS: One hundred forty-three recently postmenopausal women showing a broad range of variation in hot flushes were studied with radial artery tonometry. Pulse wave analyses were assessed at baseline and after nitroglycerin and salbutamol challenges. Wilcoxon signed rank test was used for paired comparisons after challenges with nitroglycerin and salbutamol. RESULTS: Neither baseline arterial stiffness nor endothelial function differed between women without or with mild, moderate, or severe hot flushes. However, after nitroglycerin challenge, the time to the onset of the reflected wave (dependent on pulse wave velocity) was 9.5% longer (P=.014), and the time to the first systolic peak (dependent on the rapid phase of ventricular ejection) was 13.9% longer (P=.025) in women with severe hot flushes as compared with asymptomatic women. CONCLUSION: Women with severe vasomotor hot flushes show greater vascular responsiveness to nitroglycerin than women without hot flushes. This may partially explain the conflicting data between observational and randomized HT studies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00668603 LEVEL OF EVIDENCE: II.

Self-awareness and the evaluation of hot flash severity: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: The purpose of this study was to test the association of two dimensions of self-awareness with hot flash (HF) severity. METHODS: A subset of women from the Seattle Midlife Women's Health Study (N = 232) provided data for these analyses. Structural equation modeling was used to evaluate two dimensions of self-awareness (Internal States Awareness [ISA] and Self-Reflectiveness [SR]), and secondary factors of perceived stress, anxiety, and attitudes toward menopause as continuous with earlier life, health perceptions, and menopausal stage with respect to HF severity. The measurement and structural models were tested with a maximum likelihood missing values estimator and displayed good model fit. RESULTS: Women with greater ISA reported greater HF severity (ß = 0.17, P < 0.05). In addition, women in later menopausal transition stages reported greater HF severity and those with attitudes of continuity toward menopause reported less severe HFs (ß = 0.20, P < 0.01, ß = -0.30, P < 0.001, respectively). SR was not related to HF severity. Women with higher levels of SR reported greater perceived stress levels (ß = .51, P < 0.001), and those with greater perceived stress reported greater anxiety levels (ß = 0.63, P < 0.001) and attitudes of continuity toward menopause as less continuous with earlier life (ß = -0.30, P < 0.001). CONCLUSIONS: ISA (balanced self-awareness) was associated with greater HF severity, suggesting that enhanced balanced self-awareness may promote women's ability to evaluate their symptom experience. A multidimensional construct of self-awareness, perceived stress, anxiety, and attitude toward menopause are all plausible targets for future intervention studies of symptom management.

Prospects of and limitations to the clinical applications of genistein.

Genistein is an isoflavone derived from soy-rich products, which is known to exhibit several beneficial biological effects, such as anti-tumor activity, improvement of glucose metabolism, and reduction of the frequency of peri-menopausal hot flashes, and thus has potential for clinical application. Certain limitations and side effects, such as low bioavailability, biological estrogenic activity, and detrimental effects on thyroid function, have restricted its clinical applications to some extent. Recently, it has been reported that fermentation, use of micromicelles, and modification of its chemical structure can enhance the bioavailability of genistein. Moreover, the modification of its molecular structure may also eliminate its biological estrogenic activity and adverse effects on thyroid function. In this review, we summarize the clinical application prospects and limitations of genistein, as well as the plausible solutions to overcome its low bioavailability, phytoestrogenic activity, and adverse effects on thyroid function.

Acupuncture for the relief of hot flashes in breast cancer patients: A systematic review and meta-analysis of randomized controlled trials and observational studies.

OBJECTIVE: To critically assess the effectiveness and safety of acupuncture for treating hot flashes (HFs) among breast cancer (BC) patients, and to get much more highly compelling evidence then to guide clinical practice. METHODS: Comprehensive systematic literature searches were carried out for identifying randomized controlled trials and observational studies (OSs) published before January 2015. The meta-analysis (MA) was performed by Review Manager 5 software if data could be merged routinely, if not descriptions would be given. RESULTS: A total of 18 studies were eligible ultimately. With respect to HFs frequency, the MA during treatment showed a significant difference (MD = -1.78, 95% confidence intervals [95% CIs]: -3.42--0.14), but no statistical differences were observed when posttreatment or follow-up period. While electroacupuncture versus applied relaxation, they both helped to promote HFs markedly but did not reveal statistically significance between them. Referring to Kupperman's index, all the treatment brought out great assistance when compared with baseline conditions, and there was significant difference between real acupuncture sham acupuncture (posttreatment: MD = -4.40, 95% CI: -6.77--2.03; follow-up: MD = -4.30, 95% CI: -6.52--2.08). In terms of OS, 7 prospective single arm studies focused on exploring the efficacy of traditional acupuncture, and all revealed moderate or great benefit for BC patients suffering from HFs. CONCLUSIONS: Acupuncture still appeared to be an efficacious therapeutic strategy, especially for the less/no side effects. Because of its widespread acceptance and encouraging effectiveness for improving HFs, much more high-quality studies are in need urgently.

Improvement effects of a mixed extract of flowers of Pueraria thomsonii Benth. and peels of Citrus unshiu Markovich on postmenopausal symptoms of ovariectomized mice.

BACKGROUND: Menopausal hot flushes occur frequently in postmenopausal women. In the present study, we investigated a regulatory effect of a mixed extract of flowers of Pueraria thomsonii Benth. and peels of Citrus unshiu Markovich (PCE17), an extract of flowers of Pueraria thomsonii Benth. (PE), an extract of peels of Citrus unshiu Markovich (CE), a mixture of tectorigenin 7-O-xylosylglucoside, tectoridin, and tectorigenin (Tec, the active compounds of PE), and hesperidin (Hes, an active compound of CE) on menopausal hot flushes. METHODS: We examined the anti-hot flushes properties of PCE17, PE, CE, Tec, or Hes using a mouse model of ovariectomy-induced hot flushes. RESULTS: The ovariectomy-induced rise in the tail skin temperature was significantly prevented by PCE17, PE, CE, Tec, or Hes. PCE17, PE, CE, Tec, or Hes significantly enhanced 5-HT levels and attenuated RANKL levels in the hypothalamus of ovariectomized (OVX) mice. Treatment with PCE17, PE, CE, Tec, or Hes significantly enhanced the levels of estrogen receptor (ER)-ß, 5-HT1A, 5-HT2A, and tryptophan hydroxylase mRNA expression in the hypothalamus of OVX mice. PCE17, PE, or CE decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, but did not increase estrogen levels in the serum of OVX mice. Tec or Hes decreased FSH or LH levels and increased estrogen levels. Treatment with PCE17, PE, CE, or Tec ameliorated vaginal atrophy in OVX mice. Finally, PCE17, PE, CE, Tec, or Hes significantly increased norepinephrine and dopamine levels in the hypothalamus of OVX mice. CONCLUSION: Thus, these results imply that PCE17 has protective effects against hot flushes.

Changing use of hormone therapy among minority women since the Women's Health Initiative.

OBJECTIVE: There has been a significant shift in the use of hormone therapy (HT) among nonminority women since the publication of results of the Women's Health Initiative (WHI). Little is known about how the WHI results affected minority populations. This survey measured patterns of HT use among inner city women after publication of the WHI results, identified factors involved in the decision to continue or discontinue HT, and characterized the symptom burden and the experience of women who attempted to discontinue HT. DESIGN: We conducted a cross-sectional survey of 101 English- and Spanish-speaking women in an inner city general internal medicine clinic from August 2003 to April 2004. All women had been taking HT at the time of the publication of the WHI results. The survey included questions on patient-reported experience with HT, symptoms of menopause, and use of alternative treatments. RESULTS: Overall, 101 of 142 (71%) eligible women agreed to participate. The mean age of participants was 60 years; 43% were African American and 46% were Hispanic. The mean duration of HT use was 9.6 years. Three quarters (74%) had heard about the WHI findings, and 87% had attempted to stop taking HT after their publication. The most common reason for attempting to stop HT was concern about an increased risk of cancer or a general increase in risk to health. Of those who stopped HT, the vast majority (85%) reported vasomotor symptoms, and 26% restarted HT, mostly to treat those symptoms. CONCLUSIONS: Nearly all minority women in this small sample attempted to stop HT use after the results of the WHI were published. Restarting HT for treatment of symptoms was common.

Minimal decrease in hot flashes desired by postmenopausal women in family practice.

OBJECTIVE: To determine the minimal important difference in the frequency and severity of hot flashes that postmenopausal women desire from a nonhormonal agent. DESIGN: Women recorded their number of hot flashes daily, along with their degree of severity, using a diary for 1 week and completed the Menopause-Specific Quality of Life Questionnaire. Women were asked to report the percentage reduction in hot flashes that they would find clinically important. Distribution-based estimates were used to estimate the minimal important difference. RESULTS: Approximately 69% of the postmenopausal women who reported their hot flashes as moderate to severe responded that they wanted a nonhormonal agent that provided at least a 50% mean reduction in the frequency of hot flashes (95% CI, 32% to 66%). Median hot flash reduction for all respondents was 50%. CONCLUSIONS: The minimal clinically important difference in hot flashes is approximately 50%. This estimate can provide the basis to calculate sample size in clinical trials of anti-hot flash agents and in selecting possible candidates for investigation.

Development and preliminary validation of the Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ).

OBJECTIVE: The Menopause Symptoms Treatment Satisfaction Questionnaire, an eight-item questionnaire with a 4-week recall period, was developed to assess women's satisfaction with treatment for symptoms associated with menopause. We describe the development and initial testing of the scale. DESIGN: Following standard instrument-development procedures, focus groups were conducted with menopausal women experiencing hot flushes to generate potential constructs. Multiple items were drafted to address each construct. An iterative process of cognitive testing, item revision, and item reduction was followed to identify the most appropriate items and optimal response scales. The psychometric validation of the questionnaire used data collected through a multicenter, randomized, double-blind, placebo-controlled study including 543 postmenopausal women. Psychometric analyses were conducted to explore potential item reduction and to address questionnaire scaling and scoring. Internal consistency reliability, construct validity, and discriminant validity of the new scale were also examined. RESULTS: The questionnaire includes items addressing the control of daytime and nighttime hot flushes; effects of treatment on sleep, mood, libido, and cognition; medication tolerability; and overall satisfaction. Correlation analyses indicated that the items are related to each other without being overly redundant and that the item set is best described using a one-factor model. The subsequent scale score demonstrated sound internal consistency reliability, strong construct validity, and good discriminant validity. CONCLUSIONS: The results of the development and initial validation are favorable. It is expected that the questionnaire will prove to be a worthwhile tool for assessing women's satisfaction with treatment for menopausal symptoms.

Endometrial safety assessment of a specific and standardized soy extract according to international guidelines.

OBJECTIVE: To assess the effects of an oral soy isoflavone extract (Phytosoya) on endometrium (evaluated by biopsy and ultrasonography) in postmenopausal women treated for 12 months. DESIGN: A total of 395 postmenopausal women were included in this international prospective, open-label study. The women were treated for 12 months with a specific standardized soy isoflavone extract (total of 70 mg/d). Endometrial biopsy and transvaginal ultrasonography were performed before and after 12 months of treatment according to European guidelines. RESULTS: A total of 301 assessable biopsy specimens were obtained from women treated for 12 months; the results were 99.67% atrophic/inactive endometrium and 0.33% proliferative endometrium. No case of hyperplasia or carcinoma was diagnosed, demonstrating the endometrial safety of this extract (point estimate: 0.0; upper limit of 95% CI: 0.012). Endometrial thickness did not show any increase after 12 months of treatment (2.2 mm at inclusion and 2.12 mm at the end of the study). Only eight women reported some kind of bleeding as an adverse event during the study. CONCLUSIONS: These results of endometrial biopsy and endometrial thickness suggest that daily administration of 70 mg of a specific and standardized isoflavone extract for 12 months does not stimulate the endometrium.

Raloxifene improves the ovariectomy-induced impairment in endothelium-dependent vasodilation.

OBJECTIVE: To examine the effect of raloxifene on the endothelial dysfunction caused by surgical menopause. DESIGN: Ten premenopausal women who underwent gynecological surgery with ovariectomy were divided into two groups. Five participants used raloxifene (60 mg/d) for 7 days staring 1 week after the surgery, and the other five participants did not use raloxifene. We examined the changes in flow-mediated dilatation (FMD) of the brachial artery using ultrasonography. Vasodilation in response to nitroglycerin was also studied. We also measured the brachial-ankle pulse wave velocity to examine the change in arterial stiffness in these participants before and after surgical menopause. RESULTS: In both the raloxifene and control groups, a significant decrease in FMD was observed 1 week after the surgery. Although no further changes in FMD were observed in the control group at 2 weeks after surgery, FMD was significantly increased in the raloxifene group. No remarkable changes in nitroglycerin or brachial-ankle pulse wave velocity were observed after surgery in either group. CONCLUSIONS: Raloxifene rapidly restored FMD that was impaired after surgical menopause. Therefore, raloxifene may be effective for ameliorating and maintaining endothelial function in premenopausal women who undergo ovariectomy.

Hot flashes and estrogen therapy do not influence cognition in early menopausal women.

OBJECTIVE: To examine how menopausal symptoms and estrogen therapy (ET)-induced symptom relief affect cognition in early menopause. DESIGN: There were two components. Part 1 was a cross-sectional study of 37 healthy, recently postmenopausal women with diverse menopausal symptoms. Women were categorized as having low (n=20) or high symptoms (n=17) based on a validated symptom questionnaire. Women completed mood and sleep questionnaires and underwent cognitive testing, which included verbal memory, visual memory, emotional memory, and verbal fluency. Thirty-two of these women went on to part 2 of the study. Fourteen were randomly assigned to receive ET and 18 to receive placebo for 8 weeks. Before treatment and at 4 and 8 weeks, women completed the same measures as in part 1 of the study. RESULTS: High symptom women had more negative mood (P=0.01) and lower quality sleep (P<0.001) than low symptom women. Despite suffering from more menopausal symptoms, worse mood, and poorer sleep, women in the high symptom group performed the same on cognitive testing as women in the low symptom group. Women receiving ET had greater improvements in menopausal symptoms and sleep compared with those receiving the placebo (P

Efficacy of citalopram on climacteric symptoms.

OBJECTIVE: The aim of this study was to evaluate the efficacy of citalopram for climacteric symptoms and to assess the combined effect of citalopram and hormone therapy (HT) on climacteric symptoms in women inadequately responsive to HT alone. DESIGN: The study included 100 postmenopausal women who were allocated into one of four groups: (1) citalopram, (2) placebo, (3) citalopram+HT, or (4) placebo+HT. The women who were unable or unwilling to take HT were randomly placed in groups 1 and 2. The women who were inadequately responsive to HT were randomly placed in groups 3 and 4. The initial dose of citalopram was 10 mg/day in groups 1 and 3. After 1 week, the dose was increased to 20 mg/day. After starting the medication, follow-up visits took place during the fourth and eighth weeks of treatment. During the first and eighth weeks, women completed two questionnaires: a modified Kupperman index and the Menopause-Specific Quality of Life Questionnaire. RESULTS: Mean hot flash scores significantly improved in all groups (P<0.05). The reduction rates were 37% in group 1, 13% in group 2, 50% in group 3, and 14% in group 4. Psychosocial complaints and mean values on the Kupperman index significantly decreased in all groups (P<0.05). Physical well-being significantly improved in groups 1, 3, and 4 (P<0.05). The decrease in all scores was significantly greater in groups 1 and 3 compared to groups 2 and 4 (P<0.01). CONCLUSION: Citalopram is an effective alternative treatment option for patients who do not want to take HT for the alleviation of climacteric symptoms. Adjuvant treatment with a selective serotonin reuptake inhibitor increases the effectiveness of HT for the treatment of climacteric symptoms in women who had responded inadequately to HT.

Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 1-year randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate in a 12-month, prospective, randomized, double-blind, placebo-controlled study whether pure administration of the phytoestrogen genistein (54 mg/d) might reduce the number and severity of hot flushes in postmenopausal women with no adverse effect on the endometrium. DESIGN: A total of 389 participants met the main study criteria and were randomly assigned to receive the phytoestrogen genistein (n=198) or placebo (n=191). About 40% of participants in both groups did not suffer from hot flushes, and the evaluation was performed in a subgroup of 247 participants (genistein, n=125; placebo, n=122). Reductions from baseline in the frequency and severity of hot flushes were the principal criteria of efficacy. Endometrial thickness was evaluated by ultrasonography. The maturation value was also used to determine hormonal action on the vaginal cells. RESULTS: There were no significant differences in age, time since menopause, body mass index, and vasomotor symptoms between groups at baseline (4.4 +/- 0.33 hot flushes per day in the genistein group and 4.2 +/- 0.35 hot flushes per day in the control group). The effect was already evident in the first month and reached its peak after 12 months of genistein therapy (-56.4% reduction in the mean number of hot flushes). Furthermore, there was a significant difference between the two groups at each evaluation time (1, 3, 6, and 12 months). No significant difference was found in mean endometrial thickness and maturation value score between the two groups, either at baseline or after 12 months. CONCLUSIONS: The phytoestrogen genistein has been shown to be effective on vasomotor symptoms without an adverse effect on endometrium.

Acupuncture for postmenopausal hot flashes.

OBJECTIVE: To determine whether individually tailored acupuncture is an effective treatment option for reducing postmenopausal hot flashes and improving quality of life. METHODS: In a randomized, placebo-controlled pilot study, 29 postmenopausal participants averaging at least seven moderate to severe hot flashes per 24h, with a baseline estradiol concentration of less than 50 pg/mL and a normal TSH level, were randomized to receive 7 weeks (nine treatment sessions) of either active acupuncture or placebo acupuncture (placebo needles that did not penetrate the skin at sham acupuncture points). Participants recorded hot flashes in logs that were reported daily. Global indices of the severity and frequency of hot flashes were derived from the participants' daily logs. RESULTS: Participants receiving the active treatment had a greater reduction in hot flash severity (24.5+/-30.7%) compared to those receiving placebo (4.4+/-17.1%, P=0.042). Within group repeated measures analyses of variance revealed a significant reduction in hot flash severity in the active (P=0.042), but not in the placebo treatment group (P=0.15). Although there was no significant group difference in the reduction of hot flash frequency between the active (42.4+/-32.2%) and placebo groups (32.0+/-26.5%; P>or=0.352), within group repeated measures analyses of variance revealed that the reduction was statistically significant in both groups (P