Postmenopausal Symptoms Research Articles

Estrogen-deficient skin: The role of topical therapy.

Menopause is a major turning point in a woman’s life that is characterized by declining ovarian function and decreased serum estrogen levels. The resulting hormonal changes particularly affect the skin, with postmenopausal symptoms such as loss of structural architecture and increased propensity to damage becoming rapidly noticeable. Interestingly, studies have shown that estrogen deprivation in postmenopausal conditions accelerates many skin changes, including dryness, atrophy, fine wrinkling, and poor wound healing. Thus, the effects of low estrogen on the skin are an important endogenous cause of aging skin in women, yet topical treatment strategies that target cutaneous symptoms are limited. The goal of this article is to provide an overview of the role of estrogen in the skin and changes associated with estrogen deficiency, as well as review alternatives to systemic estrogen therapy and describe the effects of these interventions on cutaneous aging in postmenopausal skin. Specifically, clinical studies that utilize topical estrogens and topical isoflavones, which are soy-derived compounds that interact with estrogen receptors, are discussed.

DEMO REVIEW - Menopause

The female reproductive system matures in a continuous, natural process from menarche to menopause as the finite numbers of oocytes produced during fetal development are gradually lost to ovulation and senescence. Menopause is defined as the permanent cessation of menses; by convention, the diagnosis of menopause is not made until the individual has had 12 months of amenorrhea. Menopause is thus characterized by the menstrual changes that reflect oocyte depletion and subsequent changes in ovarian hormone production. However, hormonal changes, rather than the cessation of menstruation itself, cause the manifestations that occur around the time of menopause. Therefore, a woman who has undergone a hysterectomy but who retains her ovaries can experience normal menopausal symptoms as oocyte depletion leads to changes in estrogen levels, even though cessation of menstruation occurred with surgery. This review covers definitions, natural menopause, menopausal transition and postmenopausal symptom management, and premature ovarian insufficiency. Figures show stages of reproductive aging, serum concentrations of hormones during menopausal transition and postmenopause, hormonal changes associated with reproductive aging, symptoms of menopausal transition and menopause, treatment algorithm(s), and Women’s Health Initiative findings: risks and benefits of estrogen alone and estrogen plus progestin by age group: 50 to 59, 60 to 69, and 70 to 79 years. Tables list target tissues, physical manifestations, and menopausal symptoms; selective estrogen receptor modulators used in postmenopausal women; differential diagnosis and evaluation of common menopausal symptoms; estrogen doses; progestogen dosing for endometrial protection; nonhormonal pharmaceutical hot flash therapies; and pharmacologic therapy for genitourinary atrophy. This review contains 6 highly rendered figures, 7 tables, and 119 references.

Hormone Replacement Therapy and Postmenopausal Cardiovascular Events: A Meta-Analysis

Context: Hormone replacement therapy (HRT) is widely used to control postmenopausal symptoms. This therapy is also used to prevent diseases such as osteoporosis and dementia. However, clinical trials suggest some negative effects regarding postmenopausal HRT. This study evaluates the effects of HRT on postmenopausal cardiovascular events. Evidence Acquisition: We collected data from 32 articles by using valid keywords and searching databases of PubMed, Medlib, ScienceDirect, EmBase, Scopus, Index Copernicus, SID, and Iranmedex. Analysis was performed by comparing three groups of postmenopausal women: combined hormone therapy (estrogen + progesterone), estrogen alone treated group, and placebo-receiving group (control group). Data were analyzed using the random effect model meta-analysis by using R software and Stata software Version 11.2. Results: Of the collected 32 studies between 1998 and 2016, there were 1277686 subjects with an average age of 60.6 years. The prevalence of myocardial infarction were (2.64%), coronary heart disease (1.7%), stroke (254%), cardiovascular death (1.54%), revascularization (3.26 %), and cerebrovascular disease (CVD) (2.78%) in the combined hormone therapy group. Also, in the estrogen-treated group were 2.95%, 3.41%, 2.49%, 2.8%, - , 3.14%, respectively. In the placebo-receiving group these events were 2.09%, 2.73%, 2.9%, 2.25%, 4.96%, and 11.92, respectively. The results showed that estrogen therapy could increase the incidence of stroke. Moreover, HRT could have positive effects on the serum lipid profile in postmenopausal women. Conclusion: Postmenopausal HRT appears to be non-effective on coronary artery disease, revascularization, myocardial infarction, and cardiac-related deaths; however, it could play a role in increasing the stroke rate.

Esmirtazapine treatment of postmenopausal vasomotor symptoms: two randomized controlled trials

Objectives: Two identical 12-week, randomized, double-blind, placebo-controlled, multi-arm, parallel-group Phase III studies (Study P012, NCT00560833; Study P013, NCT00535288) evaluated the efficacy and safety of esmirtazapine, an investigational medicine, for the treatment of moderate to severe vasomotor symptoms (VMS) in postmenopausal women.Methods: Participants were randomized to placebo or esmirtazapine (2.25, 4.5, 9.0, or 18.0 mg). Co-primary efficacy endpoints (daily frequency and severity of moderate to severe VMS, both at weeks 4 and 12) were based on participative LogPad daily diaries. Adverse events (AEs) were recorded.Results: In Studies P012 and P013, 942 and 946 participants were randomized, respectively. Compared with placebo, esmirtazapine significantly reduced the mean daily frequency by 1.4–2.2 moderate to severe VMS at weeks 4 and 12 (both ≥4.5 mg) and mean daily severity by 0.06–0.08 symptoms at weeks 4 (≥4.5 mg) and 12 (9.0 mg P012; 18.0 mg P013 only). Esmirtazapine was generally well tolerated with a more favorable safety profile at lower doses. Somnolence and fatigue were the most frequently reported AEs.Conclusions: Esmirtazapine reduced the frequency and severity of moderate to severe VMS associated with menopause and was generally well tolerated in the study population.

Re: Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: .

Re: Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: .

Prospective and retrospective study of weekly intermittent hormone (estrogen and progesterone) replacement therapy in hysterectomised women

Background: Estrogen therapy in younger postmenopausal women is associated with a decisive reduction in morbidity and mortality, but estrogen use in this population is low because of risk of side effects. Weekly intermittent therapy is a more patient friendly approach with reduced pill burden increasing compliance and adherence as well as reducing side effects. Therefore, authors wanted to study the effect of weekly intermittent fixed dose estrogen and progesterone (ultra-low dose) supplements in hysterectomised surgically menopaused women.Methods: The present study was prospective and retrospective study. For retrospective study authors records of 100 hysterectomised women up to 45years of age with severe post-menopausal symptoms treated in authors Medicine Department of Hospital with once weekly MALA-D tablets were studied. For prospective study, all consecutive hysterectomised patients with severe post-menopausal symptoms attending medicine OPD were given once weekly MALA-D which contains ethinylestradiol 0.03mg and levonorgestrel 0.15mg tablets and followed up monthly with outcomes measured by Modified Kuppermann Index, visual analogue scale, and women’s health questionnaires.Results: Present retrospective study showed moderate degree of postmenopausal symptoms as indicated by Modified Kuppermann index of 19.57. Prospective study showed significant improvement in postmenopausal symptoms with weekly intermittent hormone replacement therapy as indicated by outcomes measured by Modified Kupperman index and Visual analogue scale. Women’s health questionnaire also showed statistically significant improvement in 6 out of 8 dimensions.Conclusions: Authors concluded that weekly estrogen progesterone hormone replacement therapy with mala-D tablet (ultra-low dose therapy) was 100% effective in relieving vasomotor symptoms and it is very effective in improving psychosomatic symptoms, urinary symptoms and quality of life with no obvious side effects and greater adherence.

Magnitude and factors influencing post menopausal symptoms – A Cross sectional study in Mysuru

Background Menopause is a critical period in a womanrsquos life that not only marks the end of reproductive ability but is also associated with multiple physical vasomotor psychological and sexual complaints. Women in the menopausal age group often suffer from multiple health issues which have their roots in socio-cultural domains. Thus there is a need to explore the bio-social factors associated with menopausal symptoms among women which can largely influence their well being.Objectives To assess the magnitude and factors influencing post menopausal symptoms in post menopausal women in urban slum of Mysore.Methodology This cross-sectional community-based study was conducted in the urban slum of Mysore for three months. A total of 118 postmenopausal women in the age group of 45ndash75 years residing in the field practice area JSS Medical College were selected by purposive sampling. Details regarding socio-demographic characteristics postmenopausal symptoms and factors associated with them were collected in a pretested structured pro forma by interview technique.Results Among 118 post-menopausal women included in the present study 41.5 were in the age group of 51 ndash 60 years. Overall prevalence of menopausal symptoms was 69.5. Joint and muscular pain was found to be commonest post menopausal symptom 94.9 followed by irritability 92.4 anxiety 89.8 depressive mood 88.1 physical and mental exhaustion 82.2. The association of post menopausal symptoms with literacy staying alone and consult doctor were found to be statistically significant.Conclusion There is a high burden of postmenopausal symptoms which have shown an increasing trend with advancement of age. This calls for establishment of specific health interventions for postmenopausal women in the health-care settings.nbsp

Zinc-containing Vaginal Moisturizer Gel Improves Postmenopausal Vulvovaginal Symptoms: A Pilot Study.

ObjectivesAlthough vaginal estrogen is highly effective in alleviating genitourinary symptoms of menopause (GSM), some women are reluctant to use hormonal treatment. Our aim was to evaluate the effect of a zinc-containing vaginal moisturizer gel on GSM.MethodsWomen with GSM were enrolled. Patients were asked to use the vaginal gel daily for 2 weeks. Vaginal Health Index (VHI) was calculated. Visual analogue scale (VAS) was obtained on vaginal pain, dryness, burning, itching, dyspareunia and dysuria before and 2 weeks after the completion of treatment. Vaginal cytology was obtained. Vulvovaginal symptom questionnaire (VSQ-21) was used to assess subjective symptoms.ResultsThirty-seven women with GSM participated in the study. The VHI improved significantly (mean ± standard deviation, 13 ± 4 before vs. 17 ± 4 after treatment, P < 0.01). The patient reported VAS combined score was significantly lower after the treatment (18 ± 14 before vs. 7 ± 12 after treatment, P < 0.01). The largest improvement occurred in vaginal dryness. The maturation value did not change significantly. There were no signs of inflammation on vaginal cytology. VSQ-21 combined scores also improved significantly (7.9 ± 5.5 before vs. 2.7 ± 3.6 after the intervention, P < 0.01). Side effects were rare and minor.ConclusionsNovel zinc-containing vaginal moisturizer gel significantly improves postmenopausal vulvovaginal symptoms without serious side effects.

Position statement by Experts of the Polish Menopause and Andropause Society, and the Polish Society of Aesthetic and Reconstructive Gynaecology on the medicinal product Intrarosa®.

A set of menopause-related symptoms affecting the external genitalia and lower urinary tract is discussed in contemporary scientific literature under the name of urogenital atrophy (UGA) or vulvovaginal atrophy (VVA) [1]. In 2014, a team of experts from two scientific associations – The North American Menopause Society (NAMS) and The International Society for the Study of Women’s Sexual Health (ISSWSH) – proposed a new terminology for postmenopausal atrophic symptoms, replacing the terms VVA and UGA with the term genitourinary syndrome of menopause (GSM) [2]. The change was motivated by the belief that this set of symptoms requires a more holistic therapeutic approach falling outside the scope of interest of gynaecologists and urologists only. The signs and symptoms of GSM are summarised in the Table 1. Table 1 Genitourinary syndrome of menopause (GSM) –symptoms and signs

Knowledge and perception of postmenopausal symptoms among postmenopausal women presented at the gynecological clinic of a tertiary health institution in Abakaliki

Introduction: As life expectancy increases, most women spend a larger part of their lives in the postmenopausal state. This period is associated with other medical comorbidities which affect the quality of life. Knowledge and perception of postmenopausal symptoms could help them cope with such a situation. Aim: To determine the knowledge and perception of postmenopausal symptoms among postmenopausal women presented to the gynecological clinic of Alex Ekwueme Federal University Teaching Hospital, Abakaliki. Materials and Methods: This was a cross-sectional study carried out at the Gynecological clinic of Alex Ekwueme Federal University Teaching Hospital, Abakaliki. Around 408 women were administered structured questionnaires. The information obtained was analyzed using SPSS version 20. Results: Majority (50%) of the respondents were 50–54 years age group and the least (6.9%) were 55–59 years. The commonest menopausal symptom reported was hot flushes by 300 (73.5%) respondents. Tiredness and vaginal dryness were reported by 188 (46.1%) and 180 (44.1%) respondents, respectively. The knowledge of hormone replacement therapy was low (7.8%). The study showed that 356 (87.3%) women have no knowledge of hormone replacement therapy. Conclusion: There is a need for educating women in the clinics regarding menopause and hormone replacement therapy which would further enable women to make informed choices about their health postmenopause.

Oestrogenic activity of mimosine on MCF-7 breast cancer cell line through the ERα-mediated pathway.

Hormone replacement therapy has been a conventional treatment for postmenopausal symptoms in women. However, it has potential risks of breast and endometrial cancers. The aim of this study was to evaluate the oestrogenicity of a plant-based compound, mimosine, in MCF-7 cells by in silico model. Cell viability and proliferation, ERα-SRC1 coactivator activity and expression of specific ERα-dependent marker TFF1 and PGR genes were evaluated. Binding modes of 17β-oestradiol and mimosine at the ERα ligand binding domain were compared using docking and molecular dynamics simulation experiments followed by binding interaction free energy calculation with molecular mechanics/Poisson-Boltzmann surface area. Mimosine showed increased cellular viability (64,450 cells/ml) at 0.1μM with significant cell proliferation (120.5%) compared to 17β-oestradiol (135.2%). ER antagonist tamoxifen significantly reduced proliferative activity mediated by mimosine (49.9%). Mimosine at 1μM showed the highest ERα binding activity through increased SRC1 recruitment at 186.9%. It expressed TFF1 (11.1-fold at 0.1μM) and PGR (13.9-fold at 0.01μM) genes. ERα-mimosine binding energy was -49.9kJ/mol, and it interacted with Thr347, Gly521 and His524 of ERα-LBD. The results suggested that mimosine has oestrogenic activity.

Menopause

The female reproductive system matures in a continuous, natural process from menarche to menopause as the finite numbers of oocytes produced during fetal development are gradually lost to ovulation and senescence. Menopause is defined as the permanent cessation of menses; by convention, the diagnosis of menopause is not made until the individual has had 12 months of amenorrhea. Menopause is thus characterized by the menstrual changes that reflect oocyte depletion and subsequent changes in ovarian hormone production. However, hormonal changes, rather than the cessation of menstruation itself, cause the manifestations that occur around the time of menopause. Therefore, a woman who has undergone a hysterectomy but who retains her ovaries can experience normal menopausal symptoms as oocyte depletion leads to changes in estrogen levels, even though cessation of menstruation occurred with surgery. This review covers definitions, natural menopause, menopausal transition and postmenopausal symptom management, and premature ovarian insufficiency. Figures show stages of reproductive aging, serum concentrations of hormones during menopausal transition and postmenopause, hormonal changes associated with reproductive aging, symptoms of menopausal transition and menopause, treatment algorithm(s), and Women’s Health Initiative findings: risks and benefits of estrogen alone and estrogen plus progestin by age group: 50 to 59, 60 to 69, and 70 to 79 years. Tables list target tissues, physical manifestations, and menopausal symptoms; selective estrogen receptor modulators used in postmenopausal women; differential diagnosis and evaluation of common menopausal symptoms; estrogen doses; progestogen dosing for endometrial protection; nonhormonal pharmaceutical hot flash therapies; and pharmacologic therapy for genitourinary atrophy. This review contains 6 highly rendered figures, 7 tables, and 119 references.

The inclusion complexation of daidzein with β-cyclodextrin and 2,6-dimethyl-β-cyclodextrin: a theoretical and experimental study

Daidzein is an isoflavone of the group of phytoestrogens extracted from soybeans and other legumes. As its structure is relatively similar to that of the hormone estrogen, daidzein is able to bind with estrogen receptors leading to a reduced postmenopausal women symptom. A common problem of the compounds of this group is the rather low water solubility with the consequence of limited pharmaceutical applications. Inclusion complexation between daidzein and two β-CDs (β-CD and DM-β-CD) was investigated by theoretical and experimental techniques. Based on multiple MD simulations in combination with different binding-free energy calculations, the most preferential mode of daidzein binding to cyclodextrins is the insertion of the chromone ring fitting well into the hydrophobic cavity. All four methods of binding-free energy calculations (MM/PBSA, MM/GBSA, QM/PBSA, and QM/GBSA) predict the binding affinity of the daidzein/DM-β-CD complex significantly higher than the daidzein/β-CD. Following the same trend, the experimental results also indicated the enhancement of solubility and stability of the daidzein/DM-β-CD complex. Moreover, it was found that the complexation process was favorably enthalpy driven.

Nonprescription Treatments are an Option for Many Women with Postmenopausal Vulvovaginal Symptoms.

According to this study: Active treatment with either vaginal estradiol tablets or vaginal moisturizer provided no additional benefit over placebo in women with postmenopausal vulvovaginal symptoms.Many women can be treated with a nonprescription vaginal lubricating gel.

Insights from outside BJOG

Insights from outside BJOG

The number of treatment options for female intimate health issues is increasing

Although sexual dysfunction and post-menopausal symptoms were issues that were previously overlooked, many women are now confiding in the health professionals they present to about their experiences of these common problems. Rosalind Fazzi summarises the main conditions women are facing and explores the expanding pool of surgical interventions and non-surgical procedures available for

Absolute oral bioavailability and disposition kinetics of puerarin in female rats

BackgroundPueraria candollei var. mirifica is a medicinal plant that is promoted as a “Champion Product” by the Government of Thailand. This plant has been reported to relieve postmenopausal symptoms, prevent and reverse bone loss, inhibit the growth of breast cancer, and alleviate cardiovascular diseases in preclinical and clinical studies. However, there is little information on the oral bioavailability and tissue distribution of puerarin with respect to its pharmacodynamic activities. Therefore, the aim of this study was to determine the pharmacokinetics of puerarin, including absorption, distribution, metabolism, and elimination, in rats. Moreover, this is the first study to examine the tissue distribution of puerarin in the hippocampus, femur, tibia, and mammary gland.MethodsAdult female rats were administered puerarin at 1 mg/kg intravenously or 5 and 10 mg/kg orally. Blood, tissue, urine, and feces were collected and analyzed by liquid chromatography–tandem mass spectrometry.ResultsPuerarin reached a maximum concentration in the blood of 140–230 μg/L within 1 h of oral dosing, and had an absolute oral bioavailability of approximately 7%. Following intravenous administration, puerarin was widely distributed in several tissues, including the hippocampus, heart, lung, stomach, liver, mammary gland, kidney, spleen, femur, and tibia. Approximately 50% of the intravenous dose was excreted as glucuronide metabolites via the urinary route.ConclusionsThe absolute oral bioavailability of puerarin was approximately 7% at doses of 5 and 10 mg/kg. Puerarin was widely distributed to several organs related to the diseases of aging, including the hippocampus, femur, tibia, and mammary gland. Glucuronides were the major metabolites of puerarin and were mainly excreted in the urine. These results are useful for the development of puerarin and Pueraria candollei var. mirifica as phytopharmaceutical products.

Vasomotor symptom characteristics: are they risk factors for incident diabetes?

Vasomotor symptoms (VMS), encompassing hot flashes and night sweats, may be associated with diabetes, but evidence is limited. We sought to estimate these associations. Among 150,007 postmenopausal Women's Health Initiative participants from 1993 to 2014, we prospectively examined associations of incident diabetes with VMS characteristics at enrollment: any VMS, severity (mild/ moderate/severe), type (hot flashes/night sweats), timing (early [premenopausal or perimenopausal]/late [postmenopausal]), and duration. Cox proportional-hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Mean duration of follow-up was 13.1 years. VMS prevalence was 33%. Reporting any VMS was associated with 18% increased diabetes risk (95% CI 1.14, 1.22), which increased with severity (mild: HR 1.13, 95% CI 1.08, 1.17; moderate: HR 1.29, 95% CI 1.22, 1.36; severe: HR 1.48, 95% CI 1.34, 1.62) and duration (4% per 5 years, 95% CI 1.03, 1.05), independent of obesity. Diabetes risk was more pronounced for women reporting any night sweats (night sweats only: HR 1.20, 95% CI 1.13, 1.26; night sweats and hot flashes: HR 1.22, 95% CI 1.17, 1.27) than only hot flashes (HR 1.08, 95% CI 1.02, 1.15) and was restricted to late VMS (late: HR 1.12, 95% CI 1.07, 1.18; early and late: HR 1.16, 95% CI 1.11, 1.22; early: HR 0.99, 95% CI 0.95, 1.04). VMS are associated with elevated diabetes risk, particularly for women reporting night sweats and postmenopausal symptoms. The menopause transition may be an optimal window for clinicians to discuss long-term cardiovascular/metabolic risk with patients and leverage the bother of existing symptoms for behavior change to improve VMS and reduce diabetes risk.

Estrogenic effects of phytoestrogens derived from Flemingia strobilifera in MCF-7 cells and immature rats.

Phytoestrogen (PE) has received considerable attention due to the physiological significance of its estrogenicity. Flemingia strobilifera (FS) has been used as a folk medicine in Asia for the treatment of inflammation, cancer, and infection; however, the estrogenic effects and chemical components of FS have not yet been reported. We aimed to uncover the estrogenic properties and PEs derived from FS using phytochemical and pharmacological evaluation. PEs from FS extract (FSE) were analyzed by NMR, HPLC, and MS. To evaluate estrogenic activity, FSE and its compounds were evaluated by in vitro and in vivo assays, including human estrogen receptor alpha (hERα) binding, estrogen response element (ERE)-luciferase reporter assays, and uterotrophic assays. FSE and its compounds 1-5 showed binding affinities for hERα and activated ERE transcription in MCF-7 cells. Additionally, FSE and compounds 1-5 induced MCF-7 cell proliferation and trefoil factor 1 (pS2) expression. In immature female rats, significant increases in uterine weight and pS2 gene were observed in FSE-treated groups. We identified estrogenic activities of FSE and its bioactive compounds, suggesting their possible roles as PEs via ERs. PEs derived from FSE are promising candidates for ER-targeted therapy for post-menopausal symptoms.

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

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