phytoestrogens and Atrophy

The aim of this overview was to evaluate the effectiveness of phytoestrogens on vaginal health and dyspareunia in peri- and post-menopausal women.. Three databases including MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials were from inception to August 2017.. Two systematic reviews and 11 RCTs were included in the overview. According to the findings, isoflavones increased the maturation value and attenuated the vaginal atrophy in the post-menopausal women. Topical isoflavones had beneficial effects on the vaginal atrophy. Similar efficacy was found in Pueraria mirifica and conjugated estrogen cream on dryness ( p = 0.277), soreness ( p = 0.124) and irritation ( p = 0.469), as well as discharge ( p = 0.225) and dyspareunia ( p = 0.089). However, the conjugated estrogen cream was more effective compared to Pueraria mirifica ( p > 0.005) regarding maturation index improvement. Comparison of fennel 5% vaginal cream and placebo gel showed significant difference in superficial cells ( p < 0.01), parabasal cells ( p < 0.01) and intermediate cells ( p < 0.01), whereas no difference was found between the oral fennel and placebo in terms of superficial, parabasal and intermediate cells as well as Maturation value. Administration of 80 mg red clover oil had a significant effect on superficial ( p < 0.005), intermediate ( p < 0.005) and parabasal and vaginal dryness ( p < 0.005) compared to the placebo. Flaxseed had also a trivial effect on maturation value. Genistein had a more prominent effect on the genital score. The severity of dyspareunia decreased by 27%.. Phytoestrogens have various effects based on administration route and type on the vaginal atrophy.

Topics: Atrophy; Dyspareunia; Female; Flax; Foeniculum; Gels; Humans; Isoflavones; Perimenopause; Phytoestrogens; Plant Preparations; Postmenopause; Pueraria; Trifolium; Vagina; Vaginal Creams, Foams, and Jellies

Concerns pertaining to the risk of estrogen exposure through HT have prompted an increase in the use of natural alternatives. Phytoestrogens may provide postmenopausal women with a practical alternative and many women have already begun to utilize phytoestrogen supplements. However, research regarding the efficacy of phytoestrogens as a hormone therapy alternative has been previously pessimistic or questionable at best. This review scrutinizes the most current research regarding the efficacy of three types of phytoestrogens, isoflavones, lignans and coumestans, and their specific effect on the reduction of climacteric symptoms, specifically vasomotor symptoms, vaginal atrophy, insomnia and osteoporosis. A discussion of the research pertaining to the relative safety of each phytoestrogen in terms of breast and endometrial health is also included. Overall, current research demonstrates that phytoestrogens are effective in reducing the intensity of hot flushes, and some phytoestrogen combinations result in a decreased frequency. Certain phytoestrogens have also been shown to decrease vaginal atrophy, improve sleep and cognition, and positively affect bone health. Even though initial research was generally unconvincing, the more recent evidence reviewed here is rather positive. In terms of safety and reports of adverse reactions, trials have not shown an increase in breast cancer risk or increase in endometrial hyperplasia following phytoestrogen use, but trials explicitly designed to find neoplasia have not been reported. Moreover, unlike hormone therapy, lignans may not increase clotting risk in postmenopausal women, thus supplements may serve as a treatment option for patients who have contraindications to hormone therapy. Phytoestrogens may provide a safe and partially effective alternative to HT. However, because research regarding phytoestrogens is relatively new, pharmaco-vigilence is still required, as these products are not yet FDA-approved. This article is part of a Special Issue entitled 'Phytoestrogens'.

Topics: Atrophy; Coumarins; Estrogen Receptor Modulators; Estrogen Replacement Therapy; Female; Hot Flashes; Humans; Phytoestrogens; Postmenopause; Vagina; Vasomotor System

Women frequently chose alternatives to hormone replacement therapy (HRT) for treatment of menopause even though medical indications for estrogens may be present. Prior breast cancer or fear of breast cancer is a major consideration. This review of alternatives to estrogen discusses the evidence linking breast cancer to HRTs and compares potential risks and benefits of HRT to nonHRT alternatives for relief of vasomotor symptoms, vaginal atrophy, neurocognitive changes and prevention of heart disease and osteoporosis. Practical guidelines are suggested for use of alternatives for each problem.

Topics: Aged; Antidepressive Agents; Atrophy; Bone Density; Bone Resorption; Breast Neoplasms; Calcitonin; Calcium; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Contraindications; Diphosphonates; Double-Blind Method; Estrogen Replacement Therapy; Estrogens; Estrogens, Non-Steroidal; Female; Fractures, Bone; Hot Flashes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isoflavones; Life Style; Menopause; Mental Disorders; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic; Risk; Safety; Selective Estrogen Receptor Modulators; Urothelium; Vagina

The estrogenic efficacy of topical vaginal application of Pueraria mirifica extract (PM) on the restoration of vaginal atrophy, and the presence of any systemic side effects, were investigated in postmenopausal cynomolgus macaques. Twelve postmenopausal cynomolgus macaques, with complete cessation of menstruation for at least 5 years before start of this experiment, were divided into three groups. They received a topical vaginal application daily of 0.1 or 1% (w/w) PM cream or a conjugated equine estrogen (CEE) cream (a mixture of estrone, equilin, 17β-dihydroequilin, 17α-estradiol and 17α-dihydroequilin at 0.625 mg total estrogen/g cream) for 28 days. Estrogenic efficacy was assessed weekly by vaginal cytology assay and vaginal pH measurement, whilst the plasma luteinizing hormone (LH) and sex skin coloration levels were determined at the end of each treatment period to evaluate the systemic side effects. PM significantly increased the proportion of superficial cells in a dose-dependent manner, with a similar efficacy between 1% (w/w) PM and CEE. Together with increased vaginal maturation, PM decreased the vaginal pH to acidic levels, as observed in the CEE group. PM induced no detected systemic side effects, whilst CEE decreased the plasma LH level and increased the reddish color of the sex skin during the posttreatment period. Topical vaginal treatment with PM stimulated the maturation of the vaginal epithelium without causing systemic side effects in postmenopausal monkeys. The implication is that PM could be a safer alternative to treat vaginal atrophy in postmenopausal women.

Topics: Administration, Topical; Animals; Atrophy; Female; Macaca fascicularis; Monkey Diseases; Phytoestrogens; Phytotherapy; Plant Extracts; Plants, Medicinal; Postmenopause; Pueraria; Vagina; Vaginal Diseases

Evaluate the effects of vaginal administration of isoflavones derived from Glycine max (L.) Merr. as a treatment option for vaginal atrophy, on the morphology and expression of estrogen receptors in vaginal epithelium of postmenopausal women.. The double-blind, randomized, placebo-controlled, clinical trial. Sixty women were treated for 12 weeks with isoflavone vaginal gel 4% (1g/day) and a placebo gel. After 4 and 12 weeks, the vaginal atrophy symptoms were classified at none, mild, moderate and severe and the vaginal cytology were taken to determine the maturation value. Vaginal pH was measured at the beginning and end of therapy. Microbiopsies in vaginal fornix were performed before the treatment and after 12 weeks of treatment.. Isoflavone vaginal gel was effective for relief of vaginal dryness and dyspareunia symptons and an increase in the intermediate and superficial cells was noted. The vaginal pH in the isoflavone group was 7.1 at baseline and 5.4 after 12 weeks, whereas in the placebo group there was no significant change. A significant increase in thickness after treatment was detected in the Isoflavone Group. The percentage of estrogen receptor positive cells in vaginal epithelium for the Isoflavone Group ranged from 58.5% at the beginning of treatment to 82.6% after 12 weeks. These results were superior to placebo gel.. Glycine max (L.) Merr. at 4% vaginal gel on a daily basis in postmenopausal women led to improvements in vaginal atrophy symptoms, maturation values, vaginal pH, morphology and expression of estrogen receptors in vaginal epithelium. Isoflavones proved good treatment options for relief of vulvovaginal atrophy.

Topics: Atrophy; Double-Blind Method; Dyspareunia; Epithelium; Female; Glycine max; Humans; Hydrogen-Ion Concentration; Isoflavones; Male; Middle Aged; Phytoestrogens; Phytotherapy; Plant Extracts; Postmenopause; Receptors, Estrogen; Vagina; Vaginal Creams, Foams, and Jellies; Vaginal Diseases

The quality of life in postmenopause is seriously affected by the symptoms related to vaginal atrophy. To evaluate in a 3-month, prospective, randomized, double blind, study whether vaginal suppositories containing genistein might improve genital symptoms, colposcopical and cytologic findings or modify DNA cytometric features in postmenopausal women affected by vaginal atrophy, in comparison with vaginal suppositories containing hyaluronic acid (HA).. A total of 62 postmenopausal women were randomly assigned to receive intravaginally 97 μg of genistein (group A, n = 31) or 5 mg of HA (group B, n = 31) daily for 15 days continuously/month for 3 months. Vaginal and cervical smear, colposcopy, vaginal biopsy were performed before and at the end of the study. Maturation value (MV) was calculated. Flow cytometric analysis of DNA ploidy (DI) and S-phase fraction (SPF) were performed.. After 90 days of study, a significant improvement was obtained in genital symptoms, colposcopy scores and MV (p < 0.001) in both groups; the improvement obtained by genistein was more effective especially regarding genital score (p value between groups 0.001). No significant change was found in SPF value and DI.. Both treatments improved genital symptoms, colposcopical features and MV, although genistein was more effective on genital score. Both treatments did not significantly influence flow cytometry parameters, although genistein showed slight decrease in DI, with a normalization of the aneuploid content present in some cases that could represent an additional application of intravaginal phytoestrogen therapy, providing an alternative therapy of vaginal atrophy in postmenopausal patients. The results of this investigation should be considered preliminary and need to be verified in larger, prospective studies.

Topics: Aged; Atrophy; Biopsy; Colposcopy; DNA; Double-Blind Method; Epithelium; Female; Flow Cytometry; Genistein; Humans; Hyaluronic Acid; Middle Aged; Phytoestrogens; Ploidies; Postmenopause; Suppositories; Vagina; Vaginal Smears; Vaginitis

Menopause is often associated with vaginal atrophy and related symptoms, such as vaginal dryness, burning, itching, and dyspareunia, decrease in libido and in general a decrease in the quality of life. The common treatment up to the 1990's has been the oral hormone replacement therapy (HRT), but this treatment has been consequently re-considered due to its adverse effects. Topical estrogenic products have been subsequently developed to minimize the systemic adverse effects of the oral HRT, but they are still considered at risk in case of prolonged use. As an alternative, two clinical trials were performed to investigate the effects of a medical device in the form of a gel, containing hyaluronic acid, liposomes, phytoestrogens from Humulus lupulus extract, and Vitamin E, with the aim of testing its safety and efficacy in post-menopausal women with urogenital atrophy. The first pilot study confirmed in 10 women the good safety profile, both locally and systemically, of the device applied on the external genitals at the dose of 1-2 g/day for 30 days. The second study was carried out, according to a multicenter, open, non-controlled design, in 100 post-menopausal women assigned to the vaginal application of 2.5 g of gel/day for 1 week followed by two applications/week for 11 weeks. The primary end-point was the evaluation of vaginal dryness assessed by a Visual Analogue Scale both by the investigator and the subject. Secondary endpoints were the evaluation of all other symptoms and signs associated with atrophic vaginitis (itching, burning, dyspareunia, vaginal inflammation/oedema and rash assessed by a 4-point scale and presence of vaginal abrasions and disepithelialisation), and the recording of adverse events during the study. At the end of the treatment, an overall judgment on the efficacy and safety of the device was made by the investigator and a judgment on the acceptability of the treatment was made by the subjects. The results showed a marked effect of the tested product on the vaginal dryness and on all other symptoms and signs with statistically significant reductions since the first week of treatment. No treatment-related adverse events were complained by the subjects and the treatment course showed a high level of acceptability by the subjects. This device could be considered an effective and safe alternative treatment of genital atrophy in post-menopausal women, especially when HRT is not recommended.

Topics: Administration, Intravaginal; Administration, Topical; Aged; Antioxidants; Atrophy; Elasticity; Endpoint Determination; Equipment and Supplies; Estrogen Replacement Therapy; Female; Gels; Humans; Humulus; Hyaluronic Acid; Liposomes; Lubrication; Middle Aged; Phytoestrogens; Pilot Projects; Postmenopause; Vaginal Diseases; Vitamin E

A traditional asiatic phytoestrogen-rich diet is associated with a lower incidence of estrogen-dependent cancers and clinical consequences of postmenopausal estrogen deficiency. First Wilcox in 1990, showed an increase of the vaginal cell maturation with phytoestrogens on postmenopausal women, but this has not been confirmed in some subsequent studies.. In this study, we analyzed the effects of a 6-month soy-rich diet on the vaginal epithelium of asymptomatic postmenopausal women in a randomized clinical trial. 187 women were recruited for the study and divided into three groups: a phytoestrogen rich diet group; a hormonal replacement group, and a control group. A vaginal sample for hormonal cytology was taken before and at the end of the study, and sent unnamed to a cytologist.. The karyopycnotic index (KI) increased significantly in the diet group and in the HRT group but not in the control group. The maturation value (MV) had an identical trend to the KI.. We conclude that a soy rich diet is efficacious in increasing the maturation indices of vaginal cells. This effect could be a useful marker of the efficacy of a dietary intervention with phytoestrogen rich foods, and should be considered during preventive interventions against menopausal effects and vaginal atrophy.

Topics: Adult; Atrophy; Diet; Double-Blind Method; Epithelium; Female; Hormone Replacement Therapy; Humans; Isoflavones; Middle Aged; Phytoestrogens; Phytotherapy; Plant Preparations; Postmenopause; Soybean Proteins; Treatment Outcome; Vagina; Vaginal Diseases

Topics: Atrophy; Female Urogenital Diseases; Humans; Phytoestrogens; Urogenital System; Urologic Diseases

The growth and development of prostate gland is governed by testosterone. Testosterone helps in maintaining the adipose tissue stores of the body. It is well documented that with advancing age there has been a gradual decline in testosterone levels. Our aim was to study the protective role of daidzein on flutamide-induced androgen deprivation on matrix degrading genes, lipid profile and oxidative stress in Wistar rats. Sub-chronic (60 days) flutamide (30 mg/kg b.wt) administration resulted in marked increase in expressions of matrix degrading genes [matrix metalloproteases 9 and urokinase plasminogen activation receptor]. Additionally, it increased the levels of low density lipoproteins, total cholesterol, triglycerides, and lowered the levels of high density lipoproteins and endogenous antioxidant levels. Oral administration of daidzein (20 and 60 mg/kg b.wt) restituted the levels to normal. Daidzein administration resulted in amelioration of the prostate atrophy, degeneracy and invasiveness induced by flutamide. Our findings suggest that the daidzein may be given as dietary supplement to patients who are on androgen deprivation therapy, to minimize the adverse effects related to it and also retarding susceptibility of patients to cardiovascular diseases.

Topics: Androgen Antagonists; Animals; Atrophy; Catalase; Cholesterol; Flutamide; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Isoflavones; Lipid Metabolism; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Male; Matrix Metalloproteinase 9; Orchiectomy; Oxidative Stress; Phytoestrogens; Prostate; Rats; Rats, Wistar; Receptors, Urokinase Plasminogen Activator; Triglycerides

Despite the health risks for postmenopausal women, the indications and ideal candidates for hormone replacement therapy remain unclear. The present study used ovariectomized rats to examine the safety and effects of the Chinese herbal formula Menoprogen (MPG), which is prescribed for menopausal syndrome. Daily oral MPG (1000 mg/kg body weight) for 2 weeks significantly recovered uterine and adrenal gland atrophy and restored serum estradiol, estrone and progesterone levels that were decreased in rats by bilateral ovariectomy. However, yeast two-hybrid and nuclear receptor cofactor assays showed that MPG did not bind estrogen receptors alpha (ERalpha) and beta, and immunohistochemical staining revealed that unlike 17beta-estradiol, MPG did not stimulate the protein expression of ERalpha, progesterone receptor, c-jun and c-fos in the uterus. No side effects of MPG were confirmed in vivo. These findings suggest that MPG would be useful for treating women with premenopausal and postmenopausal syndromes.

Topics: Adrenal Glands; Animals; Atrophy; Drugs, Chinese Herbal; Estradiol; Estrone; Female; Gonadal Steroid Hormones; Menopause; Ovariectomy; Phytoestrogens; Phytotherapy; Plants, Medicinal; Progesterone; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Rats; Rats, Wistar; Receptors, Estrogen; Receptors, Progesterone; Uterus; Yeasts

Genistein is a phytoestrogen that occurs naturally in the diet, especially in soy-based foods. There is widespread interest in phytoestrogens as chemopreventive agents for a variety of diseases and cancers based on epidemiologic evidence. Although soy and its constituents, such as genistein, have been consumed at high levels in several Asian populations without apparent adverse effects, concern has been raised about potential adverse effects due to estrogenic and other activities. The subchronic and chronic safety of genistein were evaluated in the beagle dog including a 4-week study and a 52-week safety study with a 13 week interim sacrifice and a 4 week recovery period. In both studies at doses of 50, 150 and 500 mg/kg/day, genistein was well tolerated. In the 4 week study, except for an increase in uterine weights in female dogs at 500 mg/kg/day, there were no other treatment related findings. In the 52-week study, the primary effects of genistein were observed on the reproductive tract, which included for male dogs: reduced size and/or weight of the testes, epididymus and prostate of 2/2 dogs after 13 weeks of treatment and in 1/4 dogs after 52 weeks of treatment at 500 mg/kg/day. The histological changes observed in the affected dogs at 500 mg/kg/day indicated atrophy of the testes and prostate gland and absent spermatozoa in the epididymus. At the mid-dose of 150 mg/kg/day, although there was a reduction to a lesser extent in testes weight after 13, but not 52 weeks, there were no histopathological changes. In female dogs, the reproductive tract effects included increased uterine weight at 500 mg/kg/day after 13 weeks of treatment, but not after 52 weeks of treatment. There was also a small decrease in ovarian weights at 150 and 500 mg/kg/day after 13 weeks and at 500 mg/kg/day after 52 weeks of treatment. There were no histopathological correlates to the changes in organ weights in female dogs. In the 4-week recovery group dogs, no changes were observed in dogs previously treated for 52 weeks with 500 mg/kg/day of genistein. It is concluded that the administration of genistein to dogs for a period of 4-52 weeks was well tolerated and did not result in systemic toxicity. Effects of genistein on the reproductive tract at very high doses were functional in nature and are of a type that would be expected in view of the relatively weak estrogenic activity of genistein and were considered not adverse effects. In the 4-week study, the no observed adverse

Topics: Animals; Atrophy; Blood Cell Count; Blood Chemical Analysis; Body Weight; Capsules; Diet; Dogs; Dose-Response Relationship, Drug; Female; Genistein; Genitalia, Male; Male; No-Observed-Adverse-Effect Level; Organ Size; Phytoestrogens; Testicular Diseases; Tissue Distribution

Naturally occurring estrogen-like molecules in plants (phytoestrogens), present via soy, in animal diets can alter morphology and physiology in rodents. Phytoestrogens have the ability to bind estrogen receptors and exert many of the biological responses evoked by physiological estrogens. This study characterized the effects of dietary phytoestrogens on the expression of body and prostate weight, circulating testosterone and estradiol levels, puberty onset, vaginal cyclicity, and volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in Long-Evans rats. Using different experimental protocols, animals were fed either a phytoestrogen-rich (Phyto-600) or a phytoestrogen-free (Phyto-free) diet. Animals fed the Phyto-600 diet displayed significantly decreased body weights (in males and females), prostate weights and delayed puberty in females compared to that of animals fed the Phyto-free diet. Circulating testosterone or estradiol levels in males or estrous cyclicity were not altered by the diets. The volume of the SDN-POA was significantly altered by a change in diet at 80 days of age where one-half of the males or females fed the Phyto-600 diet (from birth) were switched to the Phyto-free diet until 120 days of age. Males initially fed a Phyto-600 diet but changed to a Phyto-free diet had significantly smaller SDN-POA volumes compared to males fed the Phyto-600 diet (long-term). These data suggest that consumption of phytoestrogens via a soy diet, significantly: (1) decreases body and prostate weight, (2) delays puberty onset, and (3) alters SDN-POA volumes during adulthood.

Topics: Aging; Animals; Atrophy; Body Weight; Cell Size; Estrogens; Estrogens, Non-Steroidal; Female; Food, Formulated; Genitalia; Glycine max; Isoflavones; Male; Neurons; Organ Size; Phytoestrogens; Plant Preparations; Preoptic Area; Prostate; Rats; Rats, Long-Evans; Reproduction; Sex Characteristics; Testosterone