phytoestrogens and Endometrial-Hyperplasia

The objective of this systematic review was to evaluate the influence of the use of phytoestrogens on variations in endometrial thickness in postmenopausal women. Randomized controlled trials were searched in the following electronic databases until March 2020: MEDLINE, Embase, Cochrane Library, Web of Science and LILACS. We used the terms 'phytoestrogens' and 'endometrium' or 'endometrial hyperplasia' to search for relevant trials. The data were analyzed using RevMan 5.3 software. A total of 10 studies involving 1476 patients were included. The difference in endometrial thickness was evaluated in 10 studies, with a total of 805 participants in the phytoestrogen group and 761 in the control group. Such a difference was not significant between groups after 3 months (standardized mean difference [SMD] 0.00, 95% confidence interval [CI] - 0.37 to 0.37;

Topics: Endometrial Hyperplasia; Endometrium; Female; Humans; Phytoestrogens

Phytoestrogens are widely used by postmenopausal women for the treatment of the climacteric syndrome. The risk of adverse effects of this treatment, however, is unknown.. Using a fixed-effects model, we performed a meta-analysis of side effects comparing phytoestrogen treatment with placebo or no treatment in randomized controlled trials.. We identified 174 randomized controlled trials. Side effects were reported in 92/174 randomized controlled trials with 9629 participants. The overall incidence of side effects in the phytoestrogen and control groups was 2019/5502 (36.7%) and 1824/4806 (38.0%), respectively (P=.2; incidence rate ratio [IRR] 1.01; 95% confidence interval [CI], 0.95-1.08). Comparing various side effect categories, we found significantly higher rates of gastrointestinal side effects among phytoestrogen users (P=.003; IRR 1.28; 95% CI, 1.08-1.50). Gynecological (IRR 0.94; 95% CI, 0.74-1.20), musculoskeletal (IRR 1.20; 95% CI, 0.94-1.53), neurological (IRR 0.91; 95% CI, 0.70-1.19), and unspecific side effects (IRR 0.95; 95% CI, 0.88-1.03) were not significantly different between groups. Within side effect categories, we found no significantly higher rates of side effects in women using phytoestrogens. Specifically, the rates of hormone-related side effects such as endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly different between groups.. Based on the available evidence, phytoestrogen supplements have a safe side-effect profile with moderately elevated rates of gastrointestinal side effects. Rates of vaginal bleeding, endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly increased among phytoestrogen users in the investigated studies.

Topics: Breast Neoplasms; Dietary Supplements; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Endometrial Hyperplasia; Endometrial Neoplasms; Estrogen Replacement Therapy; Female; Follow-Up Studies; Gastrointestinal Diseases; Humans; Incidence; Phytoestrogens; Plant Extracts; Postmenopause; Randomized Controlled Trials as Topic; Risk Assessment; Uterine Hemorrhage

This study aims to determine whether long-term isoflavone soy protein (ISP) supplementation affects endometrial thickness and rates of endometrial hyperplasia and cancer in postmenopausal women.. In this randomized, double-blind, placebo-controlled trial, 350 postmenopausal women aged 45 to 92 years were randomized to a total daily dose of 154 mg of ISP or a milk protein-matched placebo for a 3-year period. Women with a surgically absent uterus were excluded from the analysis (final study population, N = 224). The main outcome measures were as follows: mean change in endometrial thickness on transvaginal ultrasound from baseline until up to 36 months of follow-up and the incidence of endometrial sampling, endometrial hyperplasia, and endometrial cancer.. A total of 666 visits among 224 participants were evaluated. Treatment groups did not significantly differ on the mean baseline or on-trial changes in endometrial thickness. Of the 103 placebo-treated participants, 7 (6.8%) underwent endometrial biopsy; 6 (85.7%) of these biopsies were benign. One woman in the placebo group was diagnosed with complex endometrial hyperplasia with atypia and underwent hysterectomy. The pathology result from this surgical operation was stage IB endometrial cancer. Of the 121 participants in the soy group, 9 (7.4%) underwent endometrial biopsy. The results were benign in all nine cases (100%). Although the rate of hyperplasia/malignancy was higher in the placebo group (14.3% vs 0%), the difference was not statistically significant.. Three-year ISP supplementation has no effect on endometrial thickness or on the rates of endometrial hyperplasia and cancer in postmenopausal women.

Topics: Aged; Aged, 80 and over; Biopsy; Dietary Supplements; Double-Blind Method; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Isoflavones; Middle Aged; Phytoestrogens; Placebos; Postmenopause; Risk Factors; Soybean Proteins; Ultrasonography

Endometrial hyperplasia without cytological atypia is commonly treated with progestins, but other treatment regimes may be available with equivalent efficacy and low side effects.. A randomized double-blind, placebo and progesterone-controlled clinical trial to evaluate the effects of genistein aglycone in reducing endometrial hyperplasia.. A group of 56 premenopausal women with non-atypical endometrial hyperplasia were enrolled and received: genistein aglycone (n=19; 54 mg/day); norethisterone acetate (n=19; 10 mg/day on days 16-25 of the menstrual cycle) or placebo (n=18) for 6 months.. Hysteroscopy was performed with biopsies and symptomology assessed at baseline, 3 and 6 months of administration. The effect on estrogen (ER) and progesterone receptors (PR) expression in uterine biopsies were assessed after 3 and 6 months. For each treatment follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), sex hormone-binding globulin (SHBG) and progesterone (PG) levels were also evaluated.. After 6 months, 42% of genistein aglycone-administered subjects had a significant improvement of symptoms (histologically confirmed in the 29%) compared to 47% of norethisterone acetate subjects (histologically confirmed in the 31%), but only 12% in the placebo group with 19% exhibiting worsening symptoms and increased endometrial thickness. No significant differences were noted for hormone levels for any treatment, but immunohistochemical analysis revealed significantly reduced staining for ER-alpha and PR and enhanced ER-beta1 staining in genistein-administered subjects associated with a complete regression of bleeding.. These results suggest that genistein aglycone might be useful for the management of endometrial hyperplasia without atypia in women that cannot be treated with progestin.

Topics: Adult; Contraceptives, Oral, Synthetic; Double-Blind Method; Endometrial Hyperplasia; Endometrium; Female; Genistein; Humans; Middle Aged; Norethindrone; Norethindrone Acetate; Phytoestrogens; Phytotherapy; Plant Extracts; Premenopause; Receptors, Estrogen; Receptors, Progesterone; Uterine Hemorrhage

Tissue-selective estrogen complex (TSEC), which combines a selective estrogen receptor modulator (SERM) with one or more estrogens, is a novel approach to menopausal therapy. It has been demonstrated that the phytoestrogen genistein (GEN) exhibits mixed estrogen receptor agonist and antagonist activity, suggesting that GEN may have potential for use as a natural SERM. We evaluated, for the first time, the effects of GEN, conjugated estrogens (CE), and their pairing effects as a TSEC treatment on estrogen-induced endometrial hyperplasia and metabolic dysfunction in ovariectomized (OVX) mice fed a high-fat diet. CE replacement prevented fat accumulation in the adipose tissue and liver, improved glucose homeostasis, and induced endometrial hyperplasia in OVX mice. GEN at 100 mg/kg showed CE mimetic effects in preventing ovariectomy-induced metabolic dysfunctions without endometrial stimulation. Combination treatments with CE and GEN prevented metabolic dysfunctions more strongly than CE alone, but at both low and high doses, GEN did not reverse CE-induced endometrial hyperplasia. In addition, we found that in a TSEC regimen, a typical SERM raloxifene maintains the metabolic benefits of CE while simultaneously protecting the endometrium in OVX mice. These findings indicate that GEN acts as an estrogen agonist in metabolic regulation, but has no SERM function in the uteri of OVX mice.

Topics: Adiposity; Animals; Diet, High-Fat; Dietary Supplements; Endometrial Hyperplasia; Endometrium; Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Female; Genistein; Glucose Intolerance; Liver; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Ovariectomy; Overweight; Phytoestrogens; Raloxifene Hydrochloride; Random Allocation; Selective Estrogen Receptor Modulators

Resveratrol (Res), a polyphenol that is abundant in many medicinal plants and is a selective oestrogen receptor modulator, exhibits multiple biological activities. In the present study, we determined whether Res prevents oestrogen deficiency-induced osteopenia and whether Res administration decreases pathological changes in the endometrium and lumen of the uterus compared with oestradiol replacement therapy (ERT). A total of sixty 3-4-month-old female Wistar rats were randomly divided into a sham-operated group (Sham) and five ovariectomy (OVX) subgroups, i.e. OVX rats as a control group (OVX); OVX rats receiving oestradiol valerate (ERT, 0·8 mg/kg); and OVX rats receiving Res 20, 40 and 80 mg/kg. Daily oral administration was initiated at week 2 after OVX for 12 weeks. A dose-response difference was observed in the effects of Res on bone mineral density (BMD) and trabecular microarchitecture. Only at the highest dose, bone loss was almost equivalent to that observed in the ERT group. The dose-response effects of Res on the biochemical parameters (alkaline phosphatase, IL-6, TNF-α and transforming growth factor-β1 concentrations in the serum as well as urinary Ca and P excretion) and the expressions of receptor activator of nuclear factor κB ligand (RANKL) and the RANKL:osteoprotegerin protein ratio in the femur were also observed. Furthermore, the thickening of the endometrium and the infiltration of lymphocytes were prevented in all the three Res-treated groups compared with the ERT group. In conclusion, Res treatment not only improves BMD and trabecular microarchitecture but also does not affect the uterus and Res might be a potential remedy for the treatment of postmenopausal osteoporosis.

Topics: Animals; Antioxidants; Biomarkers; Bone Density; Bone Density Conservation Agents; Dietary Supplements; Disease Models, Animal; Endometrial Hyperplasia; Endometrium; Estrogen Replacement Therapy; Female; Femur; Humans; Osteoporosis, Postmenopausal; Osteoprotegerin; Phytoestrogens; Random Allocation; RANK Ligand; Rats; Rats, Wistar; Resveratrol; Stilbenes; Time Factors

Many women suffering from menopausal symptoms choose to use dietary supplements made from plants for the relief of their symptoms. These herbal preparations can have phyto-oestrogenic properties. Although probably regarded as 'safe', such preparations can cause adverse drug reactions.. We describe four patient reports to the Netherlands Pharmacovigilance Centre Lareb. All of these patients suffered from postmenopausal bleeding and used hop- and soy-containing dietary supplements. The reports were all from the same gynaecologist.. Postmenopausal bleeding has many possible causes. The use of dietary supplements containing ingredients with phyto-oestrogenic properties, such as hop and soy, may give rise to proliferation of the endometrium. The four reports to Lareb illustrate the association between the use of these supplements and postmenopausal bleeding. Such products are available as over-the-counter preparations and consumers often mistakenly believe that they do not cause adverse drug reactions. During the diagnostic phase, it is important to be aware that the use of a dietary supplement or an herbal drug having phyto-oestrogenic properties may be a possible cause of postmenopausal bleeding.

Topics: Dietary Supplements; Endometrial Hyperplasia; Female; Humans; Humulus; Isoflavones; Middle Aged; Phytoestrogens; Postmenopause; Soy Foods; Uterine Hemorrhage

Recently, growing multiple uses of silymarin (SIL) as a complementary and alternative medicine, for alcohol-induced liver disease, acute and chronic viral hepatitis, as well as some other nonhepatic indications have been reported. Therefore, more attention should be paid for the hormonal side effects of SIL. Since the available data on the possible estrogenic effects of SIL is rather rare, this study aimed to further elucidate the different estrogenic effects and antiosteoporotic activity of SIL in ovariectomized (OVX) rats. OVX rats were treated chronically (12 weeks) with ethinylestradiol (EE) or SIL. Uterine and body weight were measured in all animals. Biochemical markers of bone formation (total alkaline phosphatase (ALP), calcium, phosphorus and osteocalcin), endocrinological analysis (estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)) and serum total cholesterol and total lipids were estimated. Formalin fixed femora and uteri specimens were used for histopathological examination. In addition, the binding property of SIL to the two estrogen receptors (ER) subtypes was tested by molecular docking. EE (strong) and SIL (mild) stimulated uterine weight (increased uterus hyperplastic endometrial glands) but EE only prevented body weight gain following OVX. Treatment of OVX rats with both EE and SIL resulted in protection of trabecula thickness, decreased serum levels of ALP and increased serum levels of both calcium and phosphorus. In contrast to EE, SIL did not decrease OVX induced serum osteocalcin. EE not SIL decreased serum cholesterol, total lipids, LH and FSH and increased serum E2. Both EE and SIL increased serum PTH. The docking study revealed a high affinity of SIL towards ERbeta. In conclusion, findings derived in the present study presented an overview of SIL many estrogenic effects in OVX rats. SIL significantly prevents the bone loss in rats induced by OVX with mild proliferative effects in uterus. The observed effects may be due to additive beneficial effect of SIL on bone either due to direct interaction with ERbeta or increasing bone formation parameters including calcium, phosphorus, osteocalcin and PTH.

Topics: Alkaline Phosphatase; Animals; Biomarkers; Bone and Bones; Bone Density Conservation Agents; Calcium; Endometrial Hyperplasia; Estradiol; Estrogen Receptor beta; Ethinyl Estradiol; Female; Hormones; Lipids; Organ Size; Osteocalcin; Osteoporosis; Ovariectomy; Phosphorus; Phytoestrogens; Phytotherapy; Plant Extracts; Rats; Selective Estrogen Receptor Modulators; Silybum marianum; Silymarin; Uterus; Weight Gain

(1) Short-term clinical trials have shown that soy phytoestrogens have a slight preventive effect on hot flushes. However, this finding is based on a low level of evidence. (2) A double-blind placebo-controlled trial involving about 300 women and lasting 5 years showed that phytoestrogens were associated with an increase in the incidence of endometrial hyperplasia (3.8% versus 0%). (3) In practice, the risk-benefit ratio of phytoestrogens has not been adequately assessed. Their effect on the endometrium, and the many unknowns concerning the risk of thromboembolism and breast cancer, may offset the modest effect of phytoestrogens on hot flushes.

Topics: Clinical Trials as Topic; Cost-Benefit Analysis; Endometrial Hyperplasia; Female; Hot Flashes; Humans; Isoflavones; Phytoestrogens; Postmenopause; Treatment Outcome

Topics: Endometrial Hyperplasia; Female; Glycine max; Humans; Isoflavones; Phytoestrogens