Pomegranate effects on the health aspects of women during peri- and postmenopause: A systematic review and meta-analysis.

Pomegranate is widely used to preserve human health and help prevent many kinds of diseases. This study aims to review and assess the effects of pomegranate on women's health during and after menopause. PubMed, Web of science, Cochrane, Scopus, and Google Scholar were searched up to the end of 2022 with no language or study type restriction. All types of clinical research studies (randomized clinical trial [RCT], pre-post, case report, and case series) were included. The Cochrane RoB 2.0 tool was used for quality assessment of RCTs. A summary of intervention's effects for each study was provided by calculating standardized mean differences and accompanying 95% confidence interval using random effect model. Weighted mean differences and heterogeneity between studies were assessed using Hedges's method and Cochran's Q test, respectively. Pomegranate can significantly improve hot flashes severity and menopause symptoms and decrease FSH. It significantly improves high-density lipoprotein but not low-density lipoprotein, body mass index, and weight. Most of our results are inconclusive, and the small sample sizes and the lack of blinding and randomization have led to an increased risk of bias. Pomegranate can decrease menopause symptoms, but more well-designed studies, with bigger sample sizes are needed to establish its other clinical benefits for menopausal women.

Women in LOVe: Lacto-Ovo-Vegetarian Diet Rich in Omega-3 Improves Vasomotor Symptoms in Postmenopausal Women. An Exploratory Randomized Controlled Trial.

OBJECTIVES: In the postmenopausal period, most women suffer vasomotor symptoms (VMS). It is well-known that VMS can worsen the quality of life. Diet seems to play a relevant role in the development of VMS, but the effect of diet on VMS is mainly limited to observational studies, and analyses of nutritional supplements. The aim of this study was thus to determine the efficacy of a lactoovo- vegetarian (LOVe) diet rich in omega-3 fatty acids vs. a lacto-ovo-vegetarian diet rich in EVO (extra-virgin olive oil) in reducing VMS frequency in postmenopausal women. METHODS: A two-arms (lacto-ovo-vegetarian diet with EVO vs. lacto-ovo-vegetarian diet rich in omega-3) randomized-controlled trial with a follow-up period of 16 weeks. We considered as primary outcome the change in the Kupperman index (follow-up vs. baseline evaluation, reported as delta, D) and in its subscales. Secondary outcomes included changes in common anthropometric and biohumoral measurements. RESULTS: Among 54 women randomly assigned to a study group, 40 (mean age 55.1±5.4 years) completed the study and complied with their assigned diet. Women randomized to the omega-3 group (n=18) showed significant improvements, compared to the EVO group (n=22), in Kupperman index (Δ=-11.4±9.8 vs. -5.9±8.2; p=0.045), hot flashes (Δ=-3.3±3.4 vs. -1.3±2.6; p=0.04), and a marginally significant improvement in nervousness (Δ=-1.7±1.7 vs. -0.8±1.5; p=0.07). No significant differences were observed for the secondary outcomes. No relevant side effects were reported. CONCLUSION: After 16 weeks, a lacto-ovo-vegetarian diet rich in omega-3 reduced VMS frequency in postmenopausal women more than the lacto-ovo-vegetarian diet rich in EVO.

Evidence for Chemopreventive and Resilience Activity of Licorice: Glycyrrhiza Glabra and G. Inflata Extracts Modulate Estrogen Metabolism in ACI Rats.

Women are increasingly using botanical dietary supplements (BDS) to reduce menopausal hot flashes. Although licorice (Glycyrrhiza sp.) is one of the frequently used ingredients in BDS, the exact plant species is often not identified. We previously showed that in breast epithelial cells (MCF-10A), Glycyrrhiza glabra (GG) and G. inflata (GI), and their compounds differentially modulated P450 1A1 and P450 1B1 gene expression, which are responsible for estrogen detoxification and genotoxicity, respectively. GG and isoliquiritigenin (LigC) increased CYP1A1, whereas GI and its marker compound, licochalcone A (LicA), decreased CYP1A1 and CYP1B1 The objective of this study was to determine the distribution of the bioactive licorice compounds, the metabolism of LicA, and whether GG, GI, and/or pure LicA modulate NAD(P)H quinone oxidoreductase (NQO1) in an ACI rat model. In addition, the effect of licorice extracts and compounds on biomarkers of estrogen chemoprevention (CYP1A1) as well as carcinogenesis (CYP1B1) was studied. LicA was extensively glucuronidated and formed GSH adducts; however, free LicA as well as LigC were bioavailable in target tissues after oral intake of licorice extracts. GG, GI, and LicA caused induction of NQO1 activity in the liver. In mammary tissue, GI increased CYP1A1 and decreased CYP1B1, whereas GG only increased CYP1A1 LigC may have contributed to the upregulation of CYP1A1 after GG and GI administration. In contrast, LicA was responsible for GI-mediated downregulation of CYP1B1 These studies highlight the polypharmacologic nature of botanicals and the importance of standardization of licorice BDS to specific Glycyrrhiza species and to multiple constituents.

N-3 Polyunsatured Fatty Acids in Menopausal Transition: A Systematic Review of Depressive and Cognitive Disorders with Accompanying Vasomotor Symptoms.

Depression is one of the most important health problems worldwide. Women are 2.5 times more likely to experience major depression than men. Evidence suggests that some women might experience an increased risk for developing depression during "windows of vulnerability", i.e., when exposed to intense hormone fluctuations, such as the menopause transition. Indeed, this period is associated with different symptoms, including vasomotor, depressive, and cognitive symptoms, which have all been shown to worsen as women approach menopause. Even though hormonal therapy represents the most effective treatment, side effects have been reported by several studies. Therefore, an increased number of women might prefer the use of alternative medicine for treating menopausal symptoms. N-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) are included among these alternative treatments. We here provide a review of studies investigating the effects of n-3 LCPUFAs on hot flashes and depressive and cognitive disorders in menopausal women. The reported results are scattered and heterogeneous. In conclusion, a beneficial role of n-3 LCPUFAs in hot flashes, and depressive and cognitive symptoms related to menopausal transition is still far from conclusive.

Effects of a phyto complex on well-being of climacteric women.

AIM: The aim of this study was to assess the effects of a phyto complex on menopausal symptoms. MATERIAL AND METHODS: A total of 151 women aged 42-67 years were enrolled. They were in spontaneous or surgical menopause by at least 12 months, reporting symptoms referable to the climacteric syndrome. Two validated and standardized tests were given to the whole sample at the entrance of the study (T0) and after 6 months of treatment (T6): the Greene Climacteric Scale (GCS) and the Beck Depression Inventory (BDI). Interim evaluations were carried out at 1-3 months (T1 and T3) on five symptoms selected from the GCS. The phyto complex was given to each enrolled woman, from the T0 to T6 time-points, for a total of 180 days. RESULTS: At the T0 time-point, the average scores were: GCS, 28.98 (standard deviation [SD] ± 10.71); BDI, 14.48 (SD ± 6.5). At the T1 time-point, five parameters of the GCS were assessed with a reduction of 36.25% in symptoms (5.69, SD ± 3.53). At the T6 time-point the assessment was completed: average GCS results were 11.54 (SD ± 8.01) with a 60.17% improvement; and average BDI results were 6.11 (SD ± 4.6) with a 58.91% improvement in the depressive symptoms. CONCLUSIONS: The phyto complex under consideration is an effective tool to counter, in a quick and long-lasting manner, the most common and nagging symptoms of the climacteric syndrome, such as hot flushes, insomnia and depression.

Effects of a dietary intervention and weight change on vasomotor symptoms in the Women's Health Initiative.

OBJECTIVE: The aim of this study was to determine whether a dietary intervention designed to reduce fat intake and increase intake of fruit, vegetables, and whole grains, and weight loss, reduces vasomotor symptoms (VMS; ie, hot flashes or night sweats) in postmenopausal women. METHODS: We included 17,473 postmenopausal US women, ages 50 to 79 years, at baseline who participated in the Women's Health Initiative Dietary Modification trial and were not taking menopausal hormone therapy. Logistic regression was used to evaluate associations. RESULTS: In multivariate-adjusted analyses, with simultaneous adjustment for the intervention and weight change, assignment to the dietary intervention versus the control arm was significantly (odds ratio [OR], 1.14; 95% CI, 1.01-1.28) related to a higher likelihood of symptom elimination among women with VMS at baseline. In addition, women with symptoms at baseline who lost 10 lb or more (OR, 1.23; 95% CI, 1.05-1.46) or lost 10% or more of their baseline body weight (OR, 1.56; 95% CI, 1.21-2.02) between baseline and year 1 were significantly more likely to eliminate VMS compared with those who maintained weight. Upon examining the joint effect of the dietary modification and weight loss, compared with women in the control arm who maintained weight, women who lost substantial weight (≥ 10%) as a part of the intervention (OR, 1.89; 95% CI, 1.39-2.57) but not as part of the control arm (OR, 1.40; 95% CI, 0.92-2.13) were significantly more likely to end VMS, although these two groups did not differ significantly from each other. Large weight loss (>22 lb), but not dietary changes, was related to the elimination of moderate/severe VMS. CONCLUSIONS: Weight loss as part of a healthy dietary modification may help eliminate VMS among postmenopausal women.

The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women.

OBJECTIVE: To evaluate the effect of red clover isoflavone supplementation over vasomotor and overall menopausal symptoms in postmenopausal women. METHODS: One hundred and nine postmenopausal women aged 40 or more were assigned to randomly receive either two daily capsules of the active compound (80 mg red clover isoflavones, Group A) or placebo of equal appearance (Group B) for a 90-day period. After a washout period of 7 days, medication was crossed over and taken for 90 days more. Daily hot flush and night sweat frequency and overall menopausal symptom intensity (Kupperman Index) were measured at baseline, 90, 97 and 187 days. RESULTS: Daily hot flush/night sweat frequency and Kupperman Index values were similar in both studied groups at baseline. All indices significantly decreased after red clover phase in Group A, corresponding, respectively to a 73.5%, 72.2% and 75.4% average decrement. These decrements were significantly higher than those observed for Group B after placebo phase (8.2%, 0.9% and 6.7% respectively). In Group A, after washout and placebo phases all values significantly increased. In Group B, all indices remained similar after placebo and washout phases, however significantly dropping after red clover treatment. These values were also significantly lower than those observed in Group A after placebo phase. No side effects were encountered after treatment with the active compound or placebo. CONCLUSION: Red clover isoflavone supplementation was more effective than placebo in reducing daily vasomotor frequency and overall menopausal intensity in postmenopausal women.

Vasomotor symptoms, adoption of a low-fat dietary pattern, and risk of invasive breast cancer: a secondary analysis of the Women's Health Initiative randomized controlled dietary modification trial.

PURPOSE: To assess whether the effect of a low-fat dietary pattern on breast cancer incidence varied by report of baseline vasomotor symptoms. METHODS: Postmenopausal women age 50 to 79 years enrolled onto the Women's Health Initiative (WHI) Dietary Modification trial from 1993 to 1998 were randomly assigned to a low-fat dietary intervention (n = 19,541) or comparison (n = 29,294). Presence of vasomotor symptoms at baseline was ascertained from a 34-item self-report symptom inventory. Women were queried semi-annually for a new diagnosis of breast cancer. Each case report was verified by medical record and pathology report review by centrally trained WHI physician adjudicators. RESULTS: Among participants who reported hot flashes (HFs) at baseline (n = 3,375), those assigned to the low-fat diet had a breast cancer rate of 0.27 compared with their counterparts in the control group who had a rate of 0.41 (hazard ratio [HR] = 0.65; 95% CI, 0.42 to 1.01). Among women reporting no HFs (n = 45,160), the breast cancer rate was 0.42 in those assigned to the low-fat diet compared with 0.46 in the control group (HR = 0.93; 95% CI, 0.84 to 1.03; P for interaction = .12 by HF status). Furthermore, the dietary benefits observed seemed to be specific to estrogen receptor (ER) -positive/progesterone receptor (PR) -positive tumors (ER positive/PR positive v other, P for risk = .03). Although women with and without HFs differed with regard to breast cancer risk factors, the effect of the diet intervention on breast cancer incidence by HF status was consistent across risk factor strata. CONCLUSION: The results of this trial, which are hypothesis generating, suggest that HFs may identify a subgroup of postmenopausal women whose risk of invasive breast cancer might be reduced with the adoption of a low-fat eating pattern.

Effects of ethyl-eicosapentaenoic acid omega-3 fatty acid supplementation on hot flashes and quality of life among middle-aged women: a double-blind, placebo-controlled, randomized clinical trial.

OBJECTIVE: To compare the effects of enriched ethyl-eicosapentaenoic acid (E-EPA) omega-3 fatty acid supplementation with those of placebo on hot flashes (HFs) and quality of life among middle-aged women. METHODS: Women were considered for participation if they were between 40 and 55 years of age and had moderate to severe psychological distress. A total of 120 women were randomly assigned to E-EPA or placebo for 8 weeks. Only women with HFs were included in this analysis (E-EPA, n = 45; placebo, n = 46). Outcomes were changes from baseline to week 8 postintervention regarding hot flash (HF) frequency (number of HFs per day), intensity and score (frequency x intensity), and Menopause-specific Quality of Life questionnaire scores. RESULTS: At baseline, the average number of HFs was 2.8 per day. After 8 weeks, HF frequency and score decreased significantly in the E-EPA group compared with the placebo group. There was no difference in the change in HF intensity between groups. Frequency of HFs declined by a mean of 1.58 per day (95% CI, -2.18 to -0.98) in the E-EPA group and by 0.50 per day (95% CI, -1.20 to 0.20) in the placebo group. The odds of being a responder among those taking E-EPA were about three times greater than among those taking placebo (odds ratio, 2.70; 95% CI, 1.03-7.03; P = 0.04). Menopause-Specific Quality of Life scores improved significantly over time in both groups but no significant differences were noted between them. CONCLUSIONS: Supplementation with E-EPA omega-3 fatty acid reduced HF frequency and improved the HF score relative to placebo. These results need to be confirmed by a clinical trial specifically designed to evaluate HFs in more symptomatic women.

Pilot evaluation of flaxseed for the management of hot flashes.

The objective of this study was to evaluate, in a phase 2 pilot study, tolerability and the effect of 6 weeks of flaxseed therapy on hot flash scores in women not wishing to receive estrogen therapy. Eligibility included 14 hot flashes per week for at least 1 month. In the baseline week, participants took no study medication and documented the characteristics of their hot flashes. Thereafter, crushed flaxseed was administered at 40 g daily. Participants provided weekly toxicity reports and health-related quality of life information. The primary end point was a change in hot flash score prospectively reported in a daily hot flash diary. Thirty women were enrolled between June 17 and November 8, 2005. The mean decrease in hot flash scores after flaxseed therapy was 57% (median decrease 62%). The mean reduction in daily hot flash frequency was 50% (median reduction 50%), from 7.3 hot flashes to 3.6. Fourteen of the 28 participants (50%) experienced mild or moderate abdominal distention. Eight participants (29%) experienced mild diarrhea, one experienced flatulence, and six (21%) withdrew because of toxicities. This study suggests that dietary therapy decreases hot flash activity in women not taking estrogen therapy. This reduction is greater than what would be expected with placebo.

Dietary factors and vasomotor symptoms in breast cancer survivors: the WHEL Study.

OBJECTIVE: Vasomotor symptoms (VMS)(hot flashes, night sweats) are associated with natural or surgically or chemotherapy-induced menopause, the latter occurring frequently in women treated for breast cancer. To manage VMS, some women seek alternatives to menopausal hormone therapy, such as supplements or modified food choices. The objective of the present analyses was to assess associations of VMS occurrence and change in severity of VMS over 12 months with dietary intakes of fiber, fat, and selected soy-containing foods, and use of phytoestrogen or vitamin E supplements in women with recent early stage breast cancer, adjusting for covariates. DESIGN: Using multivariate logistic regression, data were analyzed from 2,198 women with early-stage breast cancer who enrolled 2 to 48 months after diagnosis in the Women's Healthy Eating and Living randomized, controlled trial of a high-vegetable, high-fiber, reduced-fat diet. RESULTS: Being peri- or postmenopausal, using tamoxifen, having low social support or depressive symptoms, and using vitamin E or phytoestrogen supplements were significantly associated cross-sectionally with reporting moderate/severe VMS at enrollment. Increased symptom severity after 12 months was significantly associated with higher body mass index, tamoxifen use, and smoking. Decreased symptom severity at 12 months was significantly associated with high dietary fiber intake; no decrease was observed in women who were peri- or postmenopausal, using tamoxifen, or had low fat intake or low social support. CONCLUSIONS: High dietary fiber intakes, premenopausal, and high social support were related to decreased severity of VMS 1 year after study enrollment in women recently treated for breast cancer.

Plasma lipoproteins in soy-treated postmenopausal women: a double-blind, placebo-controlled trial.

BACKGROUND AND AIM: Postmenopausal modification of the lipid profile plays a major role in the risk of ischemic heart disease. Lifestyle counseling and estrogen replacement therapy have all been proposed as first-line measures, but there is no agreement on the best way to treat climacteric dyslipidemia. Soybean-based diet seems particularly attractive in this context, given its cholesterol lowering potential, its hypothetical anticancerous effects and possible modification of climacteric symptoms. METHODS AND RESULTS: We evaluated the effect of 60 g isolated soy protein (ISP) daily on the lipid profile of 104 postmenopausal women (53.3 +/- 3.3 years) in a double-blind, parallel, placebo-controlled (caseinate) trial, as part of a broader assessment of the effect of ISP on climacteric symptomatology. Serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apo A-I, apo B and lipoprotein (a) were determined before and after a 12-week diet modification. Seventy-seven women completed the trial. Both soy and placebo determined a significant reduction in total cholesterol (-0.42 +/- 0.79 and -0.40 +/- 0.57 mmol/L) and LDL-cholesterol (-0.35 +/- 0.72 and -0.31 +/- 0.54 mmol/L), but only soy had a significant lowering effect on apo B and the LDL-cholesterol/HDL-cholesterol ratio (-6% and -8% from baseline respectively); lipoprotein (a) plasma levels were not significantly changed by either treatment. Forty-four women were dyslipidemic at baseline; those with increased LDL concentrations showed a somewhat greater improvement in their lipoprotein profile (LDL-cholesterol and apo B reduction) with soy rather than placebo. No further information emerged when the subjects were divided into three apo E phenotypes. CONCLUSIONS: We conclude that diet supplementation with 60 g ISP is slightly better than caseinate in favorably modifying the lipoprotein metabolism of postmenopausal women; this effect is more evident in hypercholesterolemic subjects.

The effect of dietary soy supplementation on hot flushes.

OBJECTIVE: To assess the effect of daily dietary supplementation of soy protein isolate powder on hot flushes in postmenopausal women. METHODS: We carried out a double-blind, parallel, multicenter, randomized placebo-controlled trial of 104 postmenopausal women. Fifty-one patients (age range 48-61 years) took 60 g of products containing 40 g of isolated soy protein [corrected] daily and 53 patients (age range 45-62 years) took 60 g of placebo (casein) daily. The study lasted 12 weeks. Using analysis of covariance, we analyzed changes from baseline in mean number of moderate to severe hot flushes (including night sweats) during treatment. RESULTS: Soy was significantly superior to placebo (P < .01 in reducing the mean number of hot flushes per 24 hours after 4, 8, and 12 weeks of treatment. In particular, women taking soy had a 26% reduction in the mean number of hot flushes by week 3 and a 33% reduction by week 4 (P < .001 by the Wilcoxon exact test). By the end of the 12th week, patients taking soy had a 45% reduction in their daily hot flushes versus a 30% reduction obtained with the placebo (P < .01). The overall rates of adverse effects were similar for soy and casein-placebo. Twenty-five patients dropped out of the study: 11 in the soy group and 14 in the placebo group. Gastrointestinal side effects were the most common cause of premature withdrawal from the study (seven patients in each group). CONCLUSION: Soy protein isolate added daily to the diet substantially reduced the frequency of hot flushes in climacteric women.