Flushes In Postmenopausal Women Research Articles

Effect of 3α-dihydroprogesterone and 5α-dihydroprogesterone on DCIS cells and possible impact for postmenopausal women

Objective Progesterone metabolites 5α-dihydroprogesterone (5αP) and 3α-dihydroprogesterone (3αP) have opposite effects on proliferation, apoptosis and metastasis in the breast. Evidence regarding their influence on ductal carcinoma in situ (DCIS) lesions is lacking. Methods MCF10DCIS.com cells were cultured in a 3D culture system and treated with 5αP or 3αP. After 5 and 12 days of treatment, polymerase chain reaction (PCR) of proliferation, invasion/metastasis, anti-apoptotic or other markers was performed. Cells treated with the tumor-promoting 5αP were observed under the light and confocal microscopes to reveal possible morphological changes that could indicate a transition from an in situ to an invasive phenotype. As a control, the morphology of the MDA-MB-231 invasive cell line was examined. The invasive potential after exposure to 5αP was also assessed using a detachment assay. Results The PCR analysis of the chosen markers showed no statistically significant difference between naive cells and cells treated with 5αP or 3αP. DCIS spheroids retained their in situ morphology after treatment with 5αP. The detachment assay showed no increased potential for invasion after exposure to 5αP. Progesterone metabolites 5αP and 3αP do not facilitate or prohibit tumor promotion/invasion in MCF10DCIS.com cells, respectively. Conclusion As oral micronized progesterone has been proved effective for hot flushes in postmenopausal women, first in vitro data propose that progesterone-only therapy could possibly be considered for women after DCIS suffering from hot flushes.

Ultra-low-dose estradiol and dydrogesterone: a phase III study for vasomotor symptoms in China

Objective This study aimed to evaluate the efficacy and safety of ultra-low-dose estradiol plus dydrogesterone for vasomotor symptoms in postmenopausal women in China (trial registration CTR20160689). Methods A total of 332 patients were randomized to continuous combined estradiol 0.5 mg + dydrogesterone 2.5 mg or placebo for 12 weeks. The primary efficacy endpoint was change in the number of hot flushes per day from baseline to end of treatment. Secondary efficacy endpoints included change in the number of moderate-to-severe hot flushes per day, menopausal symptoms from baseline and quality of life. Results Between baseline and end of treatment, change in the mean number of hot flushes per day was −5.9 (95% confidence interval [CI] − 6.6, −5.2) with estradiol + dydrogesterone and −4.5 (95% CI −5.1, −3.8) with placebo, with a mean difference of −1.4 hot flushes per day (95% CI −2.2, −0.7; p < 0.001). Significant differences in favor of estradiol + dydrogesterone were also observed in several secondary efficacy endpoints. The study treatment was well tolerated. Conclusion Continuous combined estradiol 0.5 mg + dydrogesterone 2.5 mg reduced hot flushes in postmenopausal women in China. This ultra-low-dose regimen provides an additional option for women experiencing the vasomotor symptoms of menopause. These data are consistent with previous results in other populations.

Association of hot flushes with ghrelin and adipokines in early versus late postmenopausal women.

Vasomotor flushing (hot flushes) is a common menopausal symptom experienced by most women going through the menopausal transition; flushing continues for a variable period in postmenopause. Primarily due to lack of ovarian estrogen, other biomarkers of hot flushes have not been clearly identified. We examined the relationship of hot flushes with ghrelin and adipokines. Baseline data from two clinical trials, the Women's Isoflavone Soy Health (WISH) trial and Early versus Late Intervention Trial of Estrogen (ELITE), were used in this post hoc cross-sectional study. Both WISH and ELITE had similar study designs, inclusion criteria, and data collection processes. Study participants were healthy postmenopausal women not taking estrogen-based hormone therapy, free of cardiovascular disease, or any other chronic diseases. Both trials used the same hot flush diary in which participants recorded the number of daily hot flushes by severity over a month on average. Serum concentrations of ghrelin, leptin, adiponectin, and resistin were assessed in stored fasting blood samples using highly specific radioimmunoassay. In this analysis, self-reported flushing experience was tested for an association with leptin, adiponectin, resistin, and ghrelin concentrations using logistic regression and mean comparisons. A total of 898 postmenopausal women from the ELITE and WISH trials contributed to this analysis. Mean (SD) age was 60.4 (7.0) years, body mass index (BMI) 27 (5.3) kg/m, 67% were white, and 47% were within 10 years of menopause. Reported flushing was significantly associated with younger age, lower education, lower BMI, being married, and more recent menopause. Adjusted for these factors other than BMI, women in the highest quartile of ghrelin had significantly greater likelihood of experiencing hot flushes (OR [95% CI] = 1.84 [1.21-2.85]) compared to women in the lowest quartile. The association was more pronounced among overweight or obese women (OR [95% CI] = 2.36 [1.28-4.35]) compared to those with normal BMI (1.24 [0.54, 2.86]; interaction P value = 0.46). The association between ghrelin and hot flushes was similar among early (within 10 y) and late (over 10 y) postmenopausal women. Blood levels of adiponectin and resistin were not associated with hot flushes. Higher concentrations of ghrelin were associated with greater likelihood of hot flushes in both early- and late-postmenopausal women. Leptin, adiponectin, and resistin levels were not associated with hot flushes in postmenopausal women.

Resistance training for hot flushes in postmenopausal women: A randomised controlled trial

ObjectivesTo investigate the effect of 15 weeks of resistance training on the frequency of moderate to severe hot flushes in postmenopausal women. Study designPostmenopausal women with at least 4 moderate or severe hot flushes or night sweats per day day were randomized to a 15-week resistance training intervention or unchanged physical activity. Participants did not exercise regularly at baseline and had not used any therapy for hot flushes two months prior to study entry. The resistance training was performed three times per week and the program contained 8 exercises performed with 8–12 repetitions in 2 sets. Loads were set individually from eight-repetition maximum-strength tests and increased progressively. Main outcome measuresThe primary outcome was change in mean moderate or severe hot flushes per day from baseline to week 15, assessed with symptom diaries. Secondary outcomes included change in hot flush score and time spent on physical activity. ResultsBetween November 19, 2013, and October 26, 2016, 65 women were enrolled; 58 completed the trial and were included in the analyses. The mean age was 55 and the mean number of moderate or severe hot flushes per day at baseline was 7.1; there were no baseline differences between groups. The frequency of hot flushes decreased more in the intervention group than in the control group (mean difference −2.7, 95% CI −4.2 to −1.3). The mean percentage change was -43.6% (−56.0 to −31.3) in the intervention group and −2.0% (−16.4–12.4) in the control group. ConclusionA 15-week resistance-training program decreased the frequency of moderate and severe hot flushes among postmenopausal women and could be an effective and safe treatment option to alleviate vasomotor symptoms.

Clinical Translational Studies of Kisspeptin and Neurokinin B.

Kisspeptin and neurokinin B (NKB) are hypothalamic neuropeptides that are vital for reproductive health. An absence of either kisspeptin or NKB signaling results in hypogonadotrophic hypogonadism and a failure to proceed through puberty. In recent years, several studies have demonstrated potential avenues for the clinical utility of medications that act through these pathways in the assessment and treatment of reproductive disorders. Kisspeptin acts to stimulate hypothalamic gonadotrophic-releasing hormone (GnRH) secretion from the hypothalamus. Kisspeptin induces gonadotrophin secretion in both healthy men and women, and in women with reproductive disorders such as hypothalamic amenorrhea (HA). Kisspeptin-based treatments hold promise for use during in vitro fertilization (IVF) treatment; a bolus of kisspeptin-54 induces an LH surge of 12 to 14 hours of duration sufficient to induce oocyte maturation, but with markedly reduced rates of the most significant complication of IVF treatment, ovarian hyperstimulation syndrome (OHSS). Kisspeptin could also be used chronically to restore reproductive health in patients with functional hypogonadism, such as those with HA. Furthermore, kisspeptin has potential as a diagnostic test of hypothalamic function; a "kisspeptin test" could be used in children with delayed puberty to identify the subset with genetically determined deficits in hypothalamic pathways (congenital hypogonadotrophic hypogonadism [CHH]). In addition to its role in hypothalamic GnRH pulse generation, NKB plays a critical role in the occurrence of one of the most troubling symptoms of the menopause, the "hot flush." Neurokinin-3 receptor (NK3R) antagonists are highly effective as treatments for hot flushes in postmenopausal women, with several compounds now in late-phase development. Furthermore, NK3R antagonism leads to a reduction in LH secretion by reducing GnRH pulsatility in the hypothalamus and has been shown to reduce androgen levels in women with polycystic ovary syndrome (PCOS) (in whom GnRH pulsatility is often increased). In summary, although further detailed evaluation in several clinical settings is ongoing, medications based on kisspeptin and NKB pathways have prodigious potential in the assessment and treatment of reproductive disorders.

Precision of MRI-based body composition measurements of postmenopausal women.

ObjectivesTo determine precision of magnetic resonance imaging (MRI) based fat and muscle quantification in a group of postmenopausal women. Furthermore, to extend the method to individual muscles relevant to upper-body exercise.Materials and methodsThis was a sub-study to a randomized control trial investigating effects of resistance training to decrease hot flushes in postmenopausal women. Thirty-six women were included, mean age 56 ± 6 years. Each subject was scanned twice with a 3.0T MR-scanner using a whole-body Dixon protocol. Water and fat images were calculated using a 6-peak lipid model including R2*-correction. Body composition analyses were performed to measure visceral and subcutaneous fat volumes, lean volumes and muscle fat infiltration (MFI) of the muscle groups’ thigh muscles, lower leg muscles, and abdominal muscles, as well as the three individual muscles pectoralis, latissimus, and rhomboideus. Analysis was performed using a multi-atlas, calibrated water-fat separated quantification method. Liver-fat was measured as average proton density fat-fraction (PDFF) of three regions-of-interest. Precision was determined with Bland-Altman analysis, repeatability, and coefficient of variation.ResultsAll of the 36 included women were successfully scanned and analysed. The coefficient of variation was 1.1% to 1.5% for abdominal fat compartments (visceral and subcutaneous), 0.8% to 1.9% for volumes of muscle groups (thigh, lower leg, and abdomen), and 2.3% to 7.0% for individual muscle volumes (pectoralis, latissimus, and rhomboideus). Limits of agreement for MFI was within ± 2.06% for muscle groups and within ± 5.13% for individual muscles. The limits of agreement for liver PDFF was within ± 1.9%.ConclusionWhole-body Dixon MRI could characterize a range of different fat and muscle compartments with high precision, including individual muscles, in the study-group of postmenopausal women. The inclusion of individual muscles, calculated from the same scan, enables analysis for specific intervention programs and studies.

REPLENISH trial: TX-001HR (17β-estradiol and progesterone combination) significantly improved moderate to severe hot flushes in postmenopausal women

REPLENISH trial: TX-001HR (17β-estradiol and progesterone combination) significantly improved moderate to severe hot flushes in postmenopausal women

REPLENISH Trial: Combination Capsule of Estradiol/Progesterone (TX-001HR) for Treating Hot Flushes [5M

INTRODUCTION: Many FDA-approved hormone therapies (HTs) combining estrogens and progestins are currently available in the US for treating menopausal symptoms. The use of FDA-approved HT has recently declined, while that of custom-compounded hormone therapy (CHT) with estradiol and progesterone has increased. Current reports suggest that up to 3 million women 40 years and older are using CHT (30 million prescriptions/year). Compounded BHT may be associated with endometrial cancer. No single product combining natural 17β-estradiol and progesterone has been approved yet by the FDA. METHODS: REPLENISH (NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial (∼100 US sites) that evaluated the safety and efficacy of TX-001HR (a 17β-estradiol‒natural progesterone combination capsule) for treating moderate to severe hot flushes in postmenopausal women with an intact uterus. Of the total 1,847 women enrolled, 767 were randomly assigned to one of four TX-001HR daily doses (estradiol 1.0 mg/progesterone 100 mg, 0.5 mg/100 mg, 0.5 mg/50 mg, or 0.25 mg/50 mg) or placebo for 12 months (vasomotor symptom substudy); the remaining 1,080 women were randomly assigned between the active treatments. The four co-primary efficacy endpoints were the mean change from baseline to weeks 4 and 12 in frequency and severity of moderate to severe vasomotor symptoms for active treatments vs placebo. The primary safety endpoint was the incidence of endometrial hyperplasia at 12 months. RESULTS: TX-001HR 1.0 mg/100 mg or 0.5 mg/100 mg met all 4 co-primary endpoints, with significant improvements from baseline in frequency and severity of moderate to severe hot flushes at weeks 4 (all, P&lt; 0.05) and 12 (all, P&lt; 0.001) compared with placebo. Women treated with TX-001HR 0.5 mg/50 mg had significant improvements in hot flush frequency and severity at week 12 (both, P&lt; 0.05) vs placebo, while those taking 0.25 mg/50 mg had significant improvements in frequency, but not in severity, at weeks 4 and 12 (both, P≤ 0.001). The incidence of endometrial hyperplasia or malignancy was 0% (by consensus read) with all four TX-001HR doses and placebo after 12 months of therapy. A high incidence of amenorrhea was achieved with all TX-001HR doses. CONCLUSION: TX-001HR 1.0 mg/100 mg or 0.5 mg/100 mg effectively treated menopause-related moderate to severe hot flushes and had a safe endometrial safety profile. If approved, TX-001HR – the first combination HT product containing naturally occurring 17β-estradiol and progesterone – may provide an alternative option for the estimated 3 million of women currently using unregulated, unapproved, compounded bio-identical in the US.

Resistance training for hot flushes in postmenopausal women: Randomized controlled trial protocol

ObjectivesHot flushes and night sweats affect 75% of all women after menopause and is a common reason for decreased quality of life in mid-aged women. Hormone therapy is effective in ameliorating symptoms but cannot be used by all women due to contraindications and side effects. Engagement in regular exercise is associated with fewer hot flushes in observational studies, but aerobic exercise has not proven effective in randomized controlled trials. It remains to be determined whether resistance training is effective in reducing hot flushes and improves quality of life in symptomatic postmenopausal women. The aim of this study is to investigate the effect of standardized resistance training on hot flushes and other health parameters in postmenopausal women. Study designThis is an open, parallel-group, randomized controlled intervention study conducted in Linköping, Sweden. Sixty symptomatic and sedentary postmenopausal women with a mean of at least four moderate to severe hot flushes per day or 28 per week will be randomized to an exercise intervention or unchanged physical activity (control group). The intervention consists of 15 weeks of standardized resistance training performed three times a week under supervision of a physiotherapist. Main outcome measuresThe primary outcome is hot flush frequency assessed by self-reported hot flush diaries, and the difference in change from baseline to week 15 will be compared between the intervention group and the control group. ConclusionThe intention is that this trial will contribute to the evidence base regarding effective treatment for hot flushes.

A prospective study of DT56a (Femarelle®) for the treatment of menopause symptoms

ABSTRACTBackground DT56a (Femarelle®) is a natural medication that contains a variety of phytoestrogens derived from tofu. Treatment with DT56a affects bones, vascular tissues and the nervous system in a manner similar to that of estrogen but DT56a acts as an estrogen antagonist in breast and uterine tissues.Aim The objective of this study was to analyze the efficacy of DT56a in the reduction of menopause symptoms in Spanish women who participated in the Post Marketing Menopausal Symptoms International Survey (POMMSIS).Patients and methods A total of 631 Spanish menopausal or perimenopausal women with vasomotor symptoms who took DT56a for 4 weeks participated in this study. This study was an observational, questionnaire-based investigation that consisted of a baseline questionnaire, a hot flushes daily diary and a feedback questionnaire.Results A statistically significant (p < 0.01) reduction in the number and intensity of hot flushes was experienced after 2 and 4 weeks of DT56a treatment. After 4 weeks of treatment with DT56a, 80.7% of the patients reported that their hot flushes were ‘better’ or ‘much better’. The severity of hot flushes was also reduced by 38% in all study participants and by 36% in women who had experienced more than seven hot flushes per day initially, before treatment.Conclusion Treatment with DT56a resulted in a significant reduction in the number and intensity of hot flushes in postmenopausal women, especially in those with frequent symptoms, and these effects were observed within the first month of treatment.

Internet-delivered applied relaxation for vasomotor symptoms in postmenopausal women: Lessons from a failed trial

Internet-delivered therapies have a short history and promising results have been shown for several health problems, particularly for psychiatric conditions. This study was a first attempt to evaluate whether Internet-delivered applied relaxation for hot flushes in postmenopausal women may be useful. Due to a high drop-out rate the study was prematurely terminated after inclusion of approximately two thirds of calculated women. The Internet-delivered applied relaxation must probably be modified for such populations and settings before it can be used further. This article will discuss the benefits and pitfalls to learn in order to meet the challenges of future studies.Clinical Trial Registration Number: NCT01245907.

Evaluation of gabapentin in management of hot flushes in postmenopausal women.

This study was conducted to assess the efficacy of gabapentin in controlling hot flushes in postmenopausal women. Fifty postmenopausal patients with hot flushes were randomized in two groups, one receiving gabapentin 900 mg daily along with calcium and another group receiving calcium alone. Frequency, duration and severity of hot flushes were noted and a composite score was calculated. There was around an 80% reduction in composite score in the gabapentin group at 3 and 6 months; significantly more than the placebo group. Gabapentin has a two-fold better response than placebo in reducing hot flushes with the relief starting from the first month and maximum effect at 3 months.

Folic acid supplementation: The new dawn for postmenopausal women with hot flushes

Hot flushes, experienced by 75% of menopausal women, are associated with estrogen deprivation. Estrogen was shown to ameliorate hot flushes by interacting with monoamine neurotransmitters in the brain; reducing noradrenaline and increasing serotonin. Hormone replacement therapy(HRT), the first treatment option, causes concerns over possible increased risks particularly breast cancer. Folic acid is involved in the biosynthesis of serotonin and nordrenaline, which is responsible for its effects on mood and cognition, and degrees of folate inadequacy, not severe enough to produce megaloblastic anaemia, were found to be associated with depression and cognitive malfunctioning. Also, increased age was observed to relate to reduced serum and cerebrospinal fluid folic acid levels. There is emerging evidence that folic acid supplementation ameliorates hot fl ushes by the same mechanism as estrogen. To explore this hypothesis, a multi-centre, double-blind, placebo-controlled randomized is being set up to compare the effect of 5 mg folic acid vs placebo in reducing the frequency and severity of hot fl ushes in postmenopausal women, and on the blood level of serotonin and noradrenaline. If folic acid supplementation is demonstrated to be effective, this will be a turning point in the clinical practice since it represents a cheap, safe and well-tolerated alternative to HRT.

KISSPEPTIN SYSTEM: A Multi-Homeostatic System

The last decades have witnessed an upsurge of neuropeptides research. These substances regulate or influence various functions in the body like appetite, water intake, learning and memory, adaptive responses to environmental stress, thermoregulation and fever, social behaviour, and sleep. Kisspeptin (formerly known as metastin) is a protein that is encoded by the KISS1 gene in the Anteroventral periventricular nucleus (AVPV) and Arcuate nucleus (ARC) nuclei of the hypothalamus which was originally discovered in 1996 by Lee and Welch while conducting oncology research at the Pennsylvania State University College of Medicine. It couple to G-protein receptor ligand for (GPR54) G-protein receptor 54 (Messager et al, 2005). It is found to play many important physiological roles which include: initiation of puberty, anti-oxidative effect, regulation of prolactin release, glucose homeostasis, role in nutrition status and fertility, role in pregnancy, increases sensitivity of chemoreceptors on type 2 carotid bodies, anti-metastatic effect, hot flushes in post-menopausal women. Kisspeptins are so named because the arginine–phenylalanine residues are present at the amino terminal “ArgPhe-NH2”; all of the kisspeptin fragments have a C-terminal decapeptide that is critical for biological activity (Clements et al, 2001; Kotani et al, 2001).

An empirically validated responder definition for the reduction of moderate to severe hot flushes in postmenopausal women

The aim of this study was to derive an empirically validated definition of treatment responders for the reduction of moderate to severe hot flushes in postmenopausal women. This study used prospective blinded data analysis from a placebo-controlled study to investigate the efficacy of a treatment of moderate to severe hot flushes in postmenopausal women. Seven hundred ten postmenopausal women with at least 50 moderate to severe hot flushes per week participated in the study. The participants recorded the number of moderate to severe hot flushes each day in a diary. They also assessed their satisfaction with treatment on a Clinical Global Impression-improvement rating scale. Changes in the weekly number of moderate to severe hot flushes were compared with participants' self-assessments to derive an empirically validated minimal clinically important difference. This anchor-based value was compared with the conventional half-SD rule for minimal clinically important difference in participant-reported outcomes. Anchor- and distribution-based minimal clinically important differences between "no change/worse" and "minimally improved" were an absolute reduction of 19.1 and 18.6 in the weekly number of moderate to severe hot flushes, respectively. In addition, the threshold between "minimally improved" compared with "much improved or better" was determined, based on the anchor method, as an absolute reduction of 40.3 in the weekly number of moderate to severe hot flushes. A responder was defined as having at least an improvement of 19.1 hot flushes per week at week 4 and an improvement of 40.3 hot flushes per week at week 12.

Knowledge and attitude of primary care doctors towards management of postmenopausal symptoms

BackgroundAccording to the current recommendations, women with post-menopausal symptoms should be managed. Knowledge and perception of primary care physicians towards management of postmenopausal symptoms are deficient. AimThe aim of the present study was to explore knowledge and attitude of primary care doctors towards management of postmenopausal symptoms. MethodsThis study is a cross-sectional survey that was conducted from October to December 2010 in the five health regions in Kuwait. Two centers were selected randomly from each health region. All physicians who were currently working in the selected centers were asked to participate in the study. Out of 209 physicians, 142 agreed to participate and completed a self-administered questionnaire. ResultsThe study revealed that 82.4% of physicians had moderate knowledge about treatment options for postmenopausal symptoms, 88.0% discussed postmenopausal symptoms with their patients, and 45.1% of them either described or referred their patients for hormonal replacement therapy (HRT). The correct answers regarding 10 statements related to the Women Health Initiative finding were ranging from 2.8% to 78.9% which indicated low level of knowledge. Regarding the effectiveness of hormonal replacement therapy in postmenopausal women, the majority of the physicians agreed correctly that HRT is effective in prevention of osteoporosis (87.3%), treatment of vasomotor symptoms (83.7%), and treatment of vulvo-vaginal symptoms (82.4%). There was a variation among physicians opinion about the effectiveness of certain treatment options for managing hot flushes in postmenopausal women. ConclusionThe results suggest that there is a lack of primary care physicians knowledge and confidence in recognizing signs and symptoms of menopause and in identifying and prescribing appropriate management.

Soy extracts versus hormone therapy for reduction of menopausal hot flushes

The aim of this study was to make an indirect comparison of the results from meta-analyses that evaluated the severity of hot flushes in postmenopausal women exposed to hormone therapy (HT) or soy extracts. A systematic review and meta-analysis of HT and soy extracts related to the reduction of hot flushes in postmenopausal women versus the same control (placebo) were conducted. In addition, the combination of the overall results obtained from these two meta-analyses (indirect comparison) was adjusted to the common control (placebo). The indirect standardized mean difference (SMD) obtained from the combination of both individual meta-analyses was calculated by using the following equation: SMD(indirect SOY vs HT) = SMD(soy) - SMD(HT), with a total indirect variance (var) equivalent to the following equation: var(total) = var(soy) + var(HT). These calculations yielded a point estimate of -0.84 (95% CI, -1.33 to -0.35) for the indirect SMD favorable to HT. HT and soy interventions showed a significant difference in efficacy for the reduction of hot flushes in postmenopausal women when each treatment was compared with placebo. However, using indirect comparison, there is a statistically significant difference between HT and soy extracts in their effects on hot flushes.

The effects of micronutrient supplementation on vasomotor symptoms in postmenopausal women

ABSTRACTObjective Estrogen is the most effective treatment for vasomotor symptoms. Given its potential risks, herbal preparations and nutritional supplements have been developed as alternative remedies. The main aim of this double-blind, randomized, placebo-controlled trial was to assess any impact of a nutritional supplement containing 12 vitamins and nine minerals on the frequency and severity of hot flushes in postmenopausal women over a 3-month period.Subjects and methods Ninety-one postmenopausal women were randomized to either the placebo (n = 45) or the treatment arm (n = 46). Seventy out of the 91 women completed the study (36 from the treatment group and 34 from the placebo group). At baseline and the 14-week post-intervention assessments, study participants completed questionnaires on the frequency and severity of hot flushes and night sweats, the Profile of Mood State questionnaire, the World Health Organization Quality of Life Questionnaire, the National Adult Reading Test and the Rey Auditory-Verbal Learning Test. Between assessments, the women also completed hot flush diaries.Results There was a significant decrease (p < 0.01) in the number (±standard error of the mean) of hot flushes experienced per week for treatment (pre 31.3 ± 4.7; post 23.1 ± 4.8) and placebo groups (pre 28.1 ± 4.7; post 17.3 ± 4.0). A significant decrease (p < 0.001) in the number of night sweats experienced per week was also observed in the treatment (pre 6.1 ± 1.0; post 4.2 ± 0.7) and placebo groups (pre 5.9 ± 0.7; post 3.7 ± 0.7).Conclusions This study demonstrates a significant placebo effect on hot flushes and night sweats, as consistent with other studies. The micronutrient supplement containing 21 vitamins and minerals was not superior over placebo in effects on hot flushes and night sweat experiences.

Soy extract phytoestrogens with high dose of isoflavones for menopausal symptoms

The aim of the present study was to assess the efficacy and safety of a standardized compound based on an extract of soy phytoestrogens, with high doses of isoflavones in the management of menopausal hot flushes. A total of 180 women aged 40-65 years with a minimum of five moderate-to-severe hot flushes in the last 7 days at baseline and absence of menstruation for at least 6 months participated in a 12-week prospective, randomized, double-blind, placebo-controlled multicenter trial. After a 2-week run-in period, women received one tablet a day of 80 mg isoflavones (corresponding to 60 mg of genistein) or a matching placebo. The mean daily number of moderate-to-severe hot flushes decreased in both study groups, but the reduction was greater in the isoflavones arm at 6 (36.2%) and 12 weeks (41.2%) than in the placebo arm (24.0% at 6 weeks, 29.3% at 12 weeks), with a difference of 1.1 (95% CI [-2.0 to -0.06]) (P = 0.038) at 6 weeks and 1.1 (95% CI [-2.05 to -0.15]) (P = 0.023) at 12 weeks. Similar findings were obtained for hot flushes of any intensity. The Kupperman index decreased in both study groups. Relief of hot flushes was greater when time to menopause was >or=12 months and in cases of BMI >or=27 kg/m(2). In daily practice conditions, high doses of isoflavones, particularly genistein, can be used for the management of hot flushes in postmenopausal women not treated with hormone replacement therapy due to their superior efficacy to placebo and very good safety profile.

Folic acid supplementation cures hot flushes in postmenopausal women

Over the past four decades, it was found that folic acid supplementation produced an antidepressant-like effect mediated by interaction with the brain noradrenergic receptors (inhibitory effect) and serotonergic receptors (stimulatory effect). Hot flushes occur in postmenopausal women because of disturbances in the thermoregulatory centre, most likely as a result of estrogen deficiency-related increase in central noradrenergic activity and reduced serotonergic activity. Therefore, we hypothesize that folic acid supplementation may ameliorate hot flushes by the same mechanism as estrogen replacement, i.e., by interacting with monoamine neurotransmitters in the brain; namely norepinephrine and serotonin. This article discusses the hypothesis and presents supportive preliminary data.