Search

Untreated menopause may have serious health implications, but treatments can have dangerous side effects. We evaluate menopausal symptoms as well as available treatments -the routes of administration and their effect on blood coagulation. Menopausal females may experience hot flushes, vulva- and vaginal atrophy and osteoporosis. Many treatments are available to relieve these symptoms such as Conjugated Equine Estrogen and bioidentical hormones. The routes of administration include oral and transdermal. Hormones that are administered orally undergo a hepatic first pass metabolism. The by-products have a lower efficacy and possibly enhanced side effects. Furthermore, hormone treatments influence the coagulation cascade through coagulation factors or their regulators. Increased coagulation poses a risk for venous thromboembolism. Currently a definite conclusion on whether the side effects from hormone treatments exceed the risk of untreated menopause cannot be made. However, a more individualised approach to hormone treatments may be the most feasible solution to this dilemma.

The aim of this study was to quantify changes in serum total estradiol (E2) and estrone (E1) concentrations with initiation of low-dose oral estradiol treatment and evaluate whether changes in concentrations mediate the effect of treatment in reducing vasomotor symptom (VMS) frequency.We analyzed baseline and week 8 (W8) data from 171 perimenopausal and postmenopausal women with VMS enrolled in low-dose 17β estradiol ( n = 72) and placebo ( n = 99) groups of a randomized clinical trial.From baseline to W8, women in the low-dose estradiol group had a fourfold increase in E2, resulting in a W8 E2 of 23 pg/mL, and a fivefold increase in E1, resulting in a W8 E1 of 110.7 pg/mL. In contrast, E2 and E1 among women in the placebo group were unchanged from baseline to W8. Changes in E2 and E1 from baseline to W8 met criteria for mediating the effect of low-dose estradiol treatment on VMS frequency. With change in estrogen concentration added to treatment assignment in a regression model predicting W8 VMS frequency, the effect of treatment with low-dose estradiol versus placebo was attenuated, with change in E2 representing a 44.1% reduction ( P = 0.03) and change in E1 representing a 69.5% reduction ( P = 0.02) in total intervention effect.Among perimenopausal and postmenopausal women with VMS, treatment with low-dose oral estradiol versus placebo results in four- to fivefold increases in serum E2 and E1. The increases in serum E2 and E1 with low-dose oral estradiol treatment seem to mediate in part the effect of treatment in reducing VMS frequency.

This guidance document by the British Menopause Society provides an overview of the management of women experiencing estrogen deficiency symptoms and arthralgia following a breast cancer diagnosis. It is now recommended breast cancer patients are referred to health care professionals with an expertise in menopause for management of such symptoms, which in turn often involves liaison with patients’ breast cancer teams.1 However, as many women initially present to primary health care professionals for advice, this statement is aimed to support the latter in such consultations by providing information about symptom aetiology, current management strategies and controversies and identifying useful practice points. This is an updated version of the 2018 consensus statement prepared by Miss Jo Marsden Consultant Breast Surgeon, King’s College Hospital, London, (retired), Mr Mike Marsh, Consultant Gynae-endocrinologist, King’s College Hospital, London, Dr Anne Rigg, Consultant Medical Oncologist, Guy’s and St Thomas' Hospital, London.

Treatment for cervical cancer can cause cessation of ovarian function in young patients. Physician counselling practices related to premature menopause and hormonal therapy (HT) for young cervical cancer patients is not well known. The primary objective of this study was to assess the frequency of HT counselling and usage among young cervical cancer patients. The secondary objective was to assess clinical and demographic factors associated with HT use.This retrospective review included adult women younger than age 50 years who received treatment for cervical cancer between 2007 and 2017. Patient and disease characteristics, disease outcome, and documentation of HT and bone health counselling were collected from electronic records. Descriptive statistical analysis was performed for the primary objective, and independent t tests and χIn this study, 67 premenopausal women with cervical cancer (stages I-III) lost ovarian function from cancer treatment, of whom 52% had received counselling on HT from their oncologists. Thirty-nine percent of patients were using HT at the time of their last review. Younger women were more likely than older women to receive HT counselling (mean age 37.3 ± 6.6 y vs. 42.4 ± 6.0 y; P = 0.001). Counselling frequency and usage of HT were not affected by cancer stage, body mass index, or smoking status.Young asymptomatic patients should receive HT if not contraindicated, yet half of qualified cervical cancer patients in this study received counselling on premature menopause and HT. Structured counselling on HT should be implemented as an integral part of cervical cancer care.

Women with preexisting cardiovascular disease (CVD) or vascular risk factors commonly experience bothersome symptoms of menopause, including vasomotor symptoms (VMS) and genitourinary syndrome of menopause (GSM). Due to confusion surrounding the safety of menopausal hormone therapy (HT) in symptomatic women with CVD, evidence-based guidelines should be followed regarding identifying candidates for treatment and HT decision making. This review summarizes best practices in the evaluation and treatment of VMS and GSM in women with preexisting CVD, based on international expert consensus guidelines and/or expert opinion when data are scarce. For women with preexisting CVD or vascular risk factors who are candidates for HT, guidelines often address the appropriate formulation, dose, and route of delivery. For women who are not candidates for HT, non-hormonal options are reviewed, and their safety and efficacy in treating VMS and GSM are discussed. Due to increased knowledge of the role that pregnancy-related complications play in maternal risk for future CVD, these conditions are considered when addressing the use of systemic HT. Women at increased risk for future CVD without the use of HT, such as women with premature or early menopause, are also discussed, as well as the safely profile of HT in these special populations. With worldwide rates of CVD increasing among women in midlife, it is important for clinicians to have clear guidelines for identifying candidates for hormonal and nonhormonal treatments for symptom management to safeguard the health and quality of life of these patients through the menopause transition and post-menopause.

Objetivo: analisar a literatura acerca dos efeitos da terapia de reposição hormonal (TRH) no humor de mulheres em climatério/menopausa. Metodologia: Revisão sistemática realizada nas bases de dados Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS),Biomedical Literature from Medical Literature Analy-sis and Retrieval System Online(PubMed) eMedical Literature Analysis and Retrievel System Online(MEDLINE) com os descritores: ((((menopause) OR (postmenopause)) AND (Hormone Replacement Therapy)) OR (Estrogen Replacement Therapy)) AND (mood disorder). Resultados: Os estudos divergiram quanto ao uso da TRH, visto que, uns relataram prevenção e melhora dos transtornos de humor nos períodos de climatério, menopausa e pós menopausa e outros evidenciaram que seu uso induzia a desenvolver ansiedade, depressão, estresse e transtornos de sono. Conclusão: Apesar de terem sido realizados estudos sobre o efeito da TRH no humor em mulheres nos períodos de climatério, menopausa e pós-menopausa, ainda não foram encontradas evidências científicas consistentes que comprovem seus benefícios, sendo evidenciado em alguns estudos que o uso de hormônios nessas mulheres predispõe ao desenvolvimento de ansiedade e transtornos depressivos.&nbsp

Endocrine complications are a common late effect after childhood cancer. Our study assessed the prevalence and predictors of premature ovarian insufficiency (POI) and prospects of pregnancy in young female survivors. This nationwide study combined registry and survey data for female childhood cancer survivors aged 19 to 40 years, identified through the National Quality Registry for Childhood Cancer in Sweden. Of 1989 approached young women, 1333 (67%) participated by completing a survey. Median age at diagnosis 1981 to 2017 was 6 (range 0-17) and at study 28 (19-40) years. There were two indicators of POI, induced puberty reported in 5.3% and estrogen replacement therapy (ERT) in 9.3% at assessment. In separate logistic regression analyses (P

The use of exogenous estrogen and progesterone/progestin medications spans the reproductive and postreproductive lives of millions of women providing control over pregnancy timing, management of premenopausal and postmenopausal symptoms, and prevention of disease, including endometrial and ovarian cancer. These same hormones can also increase the risk of breast cancer in some settings and their use in breast cancer survivors may increase the risk of breast cancer recurrence. Given both the benefits and risks of these exogenous hormones, a detailed understanding of the available scientific evidence is imperative to help counsel individuals in their use across various settings.

Women spend approximately one-third of their lives with menopause, which occurs around 50 years of age. It is now appreciated that several important metabolic and cardiovascular disease risks emerge during the menopausal transition. Many important conditions occur 10-15 years after menopause, including weight gain and obesity, metabolic syndrome, diabetes, osteoporosis, arthritis, cardiovascular disease, dementia, and cancer; therefore, the occurrence of menopause heralds an important opportunity to institute preventative strategies. These strategies will lead to improved quality of life and decreased mortality. Various strategies are presented for treating symptoms of menopause and diseases that are asymptomatic. Among several strategies is the use of hormone therapy, which has efficacy for symptoms and osteoporosis, and can improve metabolic and cardiovascular health. When instituted early, which is key, in younger postmenopausal women (under 60 years) oestrogen has been found to consistently decrease mortality with a favourable risk-benefit profile in low-risk women. Prospective data show that long-term therapy might not be required for this benefit.

Prescribing hormone replacement therapy (HRT) requires consideration of the selection of its two components, the estrogen and the progestogen. In terms of the estrogen, the decision is mainly whether to use estradiol (E2) or conjugated equine estrogens (CEE). These are the components needed to efficiently treat climacteric symptoms or/and prevent osteoporosis, currently the only labeled indications. There is still controversy regarding the adequate dosages comparing E2 and CEE; however, the consensus is that the differences in the efficacy of E2 and CEE are not a real issue. Therefore, other criteria have to be used. The first reason to add the progestogen is to avoid the development of endometrial cancer (i.e. to achieve 'endometrial safety'). Any available 'fixed-combined' HRT preparation has to be tested for sufficient endometrial efficacy, because the first question the health authorities ask before product registration relates to endometrial safety. We can generally rely on the endometrial safety of these fixed-combined products. However, it could be that we want to use 'free' combinations, which are necessary if we use transdermal E2 (patches, gel, spray), but also to individualize schedules, for example when treating bleeding problems. The question here is how to attain knowledge about the endometrial efficacy of the different progestogens and how to monitor therapy. We will try to answer these two questions from a 'clinical pharmacology' point of view, as a discipline which preferably considers pharmacological properties, but also relating to clinical practice, to achieve individualized therapy with optimal efficacy, best tolerability and minimal risks.

After participating in this activity, learners should be better able to:• Outline the clinical recommendations for menopausal hormone treatment related to cognitive concerns• Debate and discuss the various research pieces on the use of menopausal hormone therapy cognitive decline, dysfunction, and dementia.Menopause has been associated with subjective cognitive dysfunction and elevated rates of depression. While menopausal hormone therapy (MHT) is Food and Drug Administration-approved for the treatment of vasomotor symptoms related to menopause, a potential role for MHT in treating and preventing cognitive decline, dysfunction, and dementia has remained unclear and a topic of continued interest and debate across decades of research. Increasing numbers of patients are seeking help for subjective cognitive decline, and those with poorer mental health are substantially more likely to perceive themselves to be at high risk of developing dementia; thus, mental health professionals are likely to encounter such patients and may be asked to provide advice concerning MHT, cognition, and indications for MHT use. Here, we synthesize the neurobiological effects of MHT, make recommendations for its use in current clinical practice in the contexts of cognitive dysfunction associated with major depressive disorder, cognitive decline, and Alzheimer's disease, and discuss the frontiers being explored by ongoing research on this topic. We conclude that MHT to improve cognitive functioning has only a few scenarios where it would be recommended and that particular caution may be warranted for carriers of the APOE ε4 allele.

Cognitive and mood changes are frequently mentioned as complaints before, during and after menopausal transition. There is substantial biological evidence for such associations to occur, as there are many mechanisms through which estrogens can affect the brain, by regulating metabolism, increasing cerebral blood flow and dendritic outgrowth, by acting on nerve growth factors through co-localisation of receptors, via neurotransmitters synthesis and turn-over and many more. However, the evidence for objective and longer term changes in cognitive function and mental health over the menopausal transition and beyond is less clear. While hormone treatment including estrogens could potentially reverse these psychological issues, the evidence of long-term benefit is also inconclusive. However, for women with severe menopausal complaints, and particularly for those who undergo early menopause, including women with Premature Ovarian Insufficiency, personalised hormone treatment at least up to the natural age of menopause around 50 should be considered, which is probably safe up to 10 years of treatment, unless contraindicated. This paper reviews the evidence for changes in psychological health related to menopausal transition and hormone treatments.

Age at menopause has been shown to have an impact on bone and heart health, with younger menopause age consistently associated with a higher risk of cardiovascular disease, osteoporosis, and fracture. These risks are particularly high increased among women who encountering menopause at an early age, including women with premature ovarian insufficiency (POI) and early menopause, due to a prolonged period of oestrogen deprivation. Several interventions are suggested to optimise the bone and cardiovascular health of women with menopause including lifestyle modification, dietary supplements, hormonal, and non-hormonal therapies. Hormone therapy (HT) is indicated for women with POI. For women with early menopause, there is a paucity of evidence for the management of bone and cardiovascular health. For women beyond the average age of menopause, HT is not indicated solely for bone protection and cardiovascular health. In this group, screening for bone and heart disease, as well as primary and secondary prevention, should be undertaken in line with national and international guidelines.

Objective Inequity of access and choice to different hormone replacement therapy (HRT) products across the UK has been suggested (Hillman, 2020). While, the cause is not entirely understood, potential contributors include conflicting national guidance, economic deprivation and a local formulary approach. With a diverse and growing population of women reaching and living well beyond the menopause, the impact of this inequity is becoming more pronounced, and challenges the goal of providing personalised care. The study objective is to establish a consensus that supports a greater equity of access and choice of HRT and provision of individualised care. Study Design Modified Delphi study designed by UK HCPs with expertise in menopause care. This group identified 40 consensus statements over four key topics, related to access and choice of different HRT products. An online 4-point Likert scale questionnaire, sent to UK HCPs, was used to assess agreement, with a consensus threshold set at 75%. Main Outcome Measures 150 HCP responses between June and September 2021 Results A total of 137 responses were received. Analysis identified 37/40 statements attaining very high agreement (≥ 90%) and 3/40 statements attaining high agreement (< 90% and ≥75%). Nine recommendations were developed with the intent to inform potential improvements to menopause care in the UK. Conclusions The high levels of agreement displayed suggest a desire to change the way menopause care is delivered in the UK. Implementation of the suggested recommendations has the potential to improve equity of access to licensed treatment options, compliant with the NICE recommendation for personalisation of care.

This study aimed to investigate Chinese physicians' perception and attitudes toward menopausal hormone therapy (MHT).This nationwide online survey was conducted in China. Physicians registered in the WeChat groups of the Gynecological Endocrinology Committee of China's Maternal and Child Health Care Association received a message invitation to complete this anonymous online survey from April 2020 to July 2020. Physicians' knowledge of and attitudes toward MHT were surveyed.In total, 4672 questionnaires were submitted; only completed questionnaires could be submitted. The message was sent to 6021 doctors, so the response rate was 77.6%. Overall, 77.9-92.9% of physicians knew the common indications and contraindications to MHT. Additionally, 90.6%, 85.4%, 80.7% and 37.5% of physicians thought that MHT would increase the risk of venous thrombosis, breast cancer, endometrial cancer and weight gain, respectively. In total, 58.1% of the physicians mistakenly believed that a sex hormone test was one of the necessary examinations to reassess MHT prescription during follow-up visits. We found that 68.5% of physicians would consider using MHT themselves or recommend MHT to their partners in the future, and 11.4% were currently using MHT.Most Chinese physicians have basic knowledge of MHT. Their misunderstandings about MHT mainly centered on the risks of endometrial cancer, weight gain and the necessary examinations during follow-up visits. These misunderstandings need to be clarified in future professional training programs.

The skin is an endocrine organ and a major target of hormones such as estrogens, androgens and cortisol. Besides vasomotor symptoms (VMS), skin and hair symptoms often receive less attention than other menopausal symptoms despite having a significant negative effect on quality of life. Skin and mucosal menopausal symptoms include dryness and pruritus, thinning and atrophy, wrinkles and sagging, poor wound healing and reduced vascularity, whereas skin premalignant and malignant lesions and skin aging signs are almost exclusively caused by environmental factors, especially solar radiation. Hair menopausal symptoms include reduced hair growth and density on the scalp (diffuse effluvium due to follicular rarefication and/or androgenetic alopecia of female pattern), altered hair quality and structure, and increased unwanted hair growth on facial areas. Hormone replacement therapy (HRT) is not indicated for skin and hair symptoms alone due to the risk–benefit balance, but wider potential benefits of HRT (beyond estrogen’s effect on VMS, bone, breast, heart and blood vessels) to include skin, hair and mucosal benefits should be discussed with women so that they will be able to make the best possible informed decisions on how to prevent or manage their menopausal symptoms. post-print 1529 KB

Hormone therapy (HT) has been used in postmenopausal women for decades in clinical practice. With further analysis and newer studies, the benefits and risks of HT have been repeatedly verified and discussed. HT is recommended for the treatment of vasomotor symptoms (VMS), genitourinary syndrome of menopause (GSM) and the prevention of osteoporosis. However, the precise association between HT and the risks of cardiovascular diseases, venous thromboembolism, neurodegenerative diseases, breast cancer, and endometrial cancer remains controversial. Therefore, determining how to take advantage of and control the risks of HT by adjusting the initiation time, regimen, and duration is crucial. Recent studies have indicated that HT is not related to the risk of all-cause, cardiovascular, or breast cancer mortality although it might increase the incidence of some chronic diseases. For symptomatic postmenopausal women under the age of 60 without contraindications, early initiation of HT is safe and probably has a mortality benefit over the long term. Initiating HT close to menopause at the lowest effective dose is more likely to have maximal benefits and the lowest risks. Transdermal and vaginal HT may have a lower risk, but recent evidence suggests additional clinical benefits of oral HT formulations in relieving VMS and preventing osteoporosis. The pooled cohort risk equation for atherosclerotic cardiovascular disease (ASCVD) and the free app named Menopro can be used to perform individual risk assessments. In addition, Chinese herbal medicines have benefits in alleviating hot flashes, depression, and menopausal symptoms, although further data are needed to strongly support their efficacy. Acupuncture and electroacupuncture have definite efficacy in the treatment of postmenopausal symptoms with few adverse effects, so they are a reasonable option as an alternative therapy for high-risk women. This review discusses the history of, guidelines on, and strategies for HT in order to make suggestions based on the most up-to-date evidence for the management of postmenopausal women.

This update will address 3 areas specifically that are essential to improving cardiovascular outcomes for women.The current literature has been reviewed and three important areas of cardiovascular care in women are highlighted. First is that even though women and men share many traditional risk factors for ischemic heart disease, several of these risk factors affect women disproportionately when it comes to CVD risk and events. There are also unique sex-specific risk factors for women and risk factors that are more common in women than in men. Adverse outcomes of pregnancy and hypertensive disorders of pregnancy are associated with an increased long-term risk of CVD and events. At menopause, cardiovascular risks increase, and lipids become unfavorable. Second is that diagnostic testing for ischemic heart disease presents different specificities and sensitivities between men and women and testing should be determined according to what is best and safest for women. Third is that currently, menopause hormone therapy is approved by the U.S. Food and Drug Administration for the treatment of vasomotor and genitourinary symptoms, prevention of osteoporosis, and estrogen replacement in the setting of surgical menopause, hypogonadism, or premature ovarian insufficiency. It is not recommended for the primary or secondary prevention of CVD and not recommended for women with high atherosclerotic CVD risk.Cardiovascular disease (CVD) remains the most common cause of death in women in the United States despite tremendous improvements in cardiovascular care for men and women. The prevention of CVD in women with early detection and implementation of preventive therapies before atherosclerotic CVD develops is critical to improving outcomes for women.

OBJECTIVE: Oral postmenopausal hormone therapy (HT) has been shown to be associated with venous thromboembolism (VTE), but whether this association is modified by VTE-associated genetic susceptibility is unknown. We examined interactions between oral HT use and a genetic risk score (GRS) of VTE. METHOD: Eligible women were postmenopausal women who had data on oral HT use, VTE incidence between 1990 and 2012, and genetic data in the Nurses’ Health Study. We built a GRS aggregating 16 VTE-related genetic variants. We used Cox regression to estimate associations of HT use with incident VTE and assessed interactions between HT use and VTE GRS. We also estimated incidence of VTE between age 50 and 79 years for groups of women defined by HT use and VTE GRS. RESULTS: We identified 432 incident VTE cases. Current HT users were at higher risk of VTE than never users (HR: 1.9, 95% CI: 1.5–2.6), with slightly higher risk for estrogen plus progestin HT than estrogen only (HR: 2.4 versus 1.9). The GRS was associated with VTE risk (HR comparing 4(th) quartile to 1(st): 2.0, 95% CI: 1.2–3.4). We did not observe significant multiplicative interactions between HT use and GRS. The estimated VTE risk difference (per 10,000 person-years) comparing 50-year-old current HT users to never users was 22.5 for women in the highest GRS quartile and 9.8 for women in the lowest GRS quartile. CONCLUSION: The VTE GRS might inform clinical guidance regarding the balance of risks and benefits of HT use, especially among younger women.

Effects of sex hormones on stroke outcome is not fully understood. A deleterious consequence of cerebral ischemia is upregulation of vasoconstrictor receptors in cerebral arteries that exacerbate stroke injury. Here, we tested the hypothesis that female sex hormones alter vasocontractile responses after experimental stroke in vivo or following organ culture in vitro, a model of vasocontractile receptor upregulation. Female rats with intact ovaries and ovariectomized females treated with 17β-estradiol, progesterone or placebo were subjected to transient, unilateral middle cerebral artery occlusion followed reperfusion (I/R). The maximum contractile response, measured my wire myography, in response to the endothelin B (ETB) receptor agonist sarafotoxin 6c was increased in female arteries after I/R, but the maximum response was significantly lower in arteries from ovariectomized females. Maximum contraction mediated by the serotonin agonist 5-carboxamidotryptamine (5-CT) was diminished after I/R, with arteries from ovariectomized females showing a greater decrease in maximum contractile response. Contraction elicited by angiotensin II was similar in all arteries. Neither estrogen nor progesterone treatment of ovariectomized females affected I/R-induced changes in ETB and 5-CT induced vasocontraction. These findings suggest sex hormones do not directly influence vasocontractile alterations that occur after ischemic stroke; however, loss of ovarian function does impact this process.

Objective To evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy (HT) use and endometriosis affect this association. Methods We conducted a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC). Women with (n = 5350) and without ovarian cancer (n = 7544) who never used HT or exclusively used either estrogen-only therapy (ET) or estrogen+progestin therapy (EPT) were included. Risk of invasive epithelial ovarian cancer adjusted for duration of ET and EPT use and stratified on history of endometriosis was determined using odds ratios (ORs) with 95% confidence intervals (CIs). Results Overall and among women without endometriosis, there was a positive association between ovarian cancer risk and hysterectomy (OR = 1.19, 95% CI 1.09-1.31 and OR = 1.20, 95% CI 1.09-1.32, respectively), but no association upon adjusting for duration of ET and EPT use (OR = 1.04, 95% CI 0.94-1.16 and OR = 1.06, 95% CI 0.95-1.18, respectively). Among women with a history of endometriosis, there was a slight inverse association between hysterectomy and ovarian cancer risk (OR = 0.93, 95% CI 0.69-1.26), but this association became stronger and statistically significant after adjusting for duration of ET and EPT use (OR = 0.69, 95% CI 0.48-0.99). Conclusions The hysterectomy-ovarian cancer association is complex and cannot be understood without considering duration of ET and EPT use and history of endometriosis. Failure to take these exposures into account in prior studies casts doubt on their conclusions. Overall, hysterectomy is not risk-reducing for ovarian cancer, however the inverse association among women with endometriosis warrants further investigation.

Objectives To analyze and compare the experience of climacteric symptoms and their associations with sociodemographic and health-related characteristics in two cohorts of Finnish women aged 52–56 years, born ten years apart and not now or previously on menopausal hormone therapy (MHT). Study design Nationwide population-based time-trend study with a large number of participants (n = 1986 + 1988). Main outcome measures The experience of climacteric symptoms was assessed by 12 commonly used menopause-related symptoms. Results Women aged 52–56 experienced more moderate or severe symptoms and fewer mild symptoms in 2010 than in 2000. Being unemployed or inactive was associated with more severe symptoms (P = 0.007), but employment status had no effect on the relative odds estimates. Conclusions The influence of the birth cohort and time-period effects as well as work-related factors on the experience of climacteric symptoms in women not now or previously on MHT needs further research, particularly since the change in the experience of symptoms found in this study occurred within only ten years.

Objective This study aimed to investigate the relationship between menopausal hormone therapy (MHT) and endometriosis recurrence in women who underwent hysterectomy with bilateral salpingo-oophorectomy to treat endometriosis. Method This retrospective cohort study included 330 women who underwent definitive surgery to treat endometriosis during 1996-2012. Follow-up data until December 2018 were analyzed. Patients were grouped as MHT non-users (non-MHT, n = 43), estrogen-only therapy (ET, n = 230), estrogen-progestogen therapy (EPT, n = 39) and tibolone (n = 18). Results The mean age at surgery was 41.5 ± 5.3 years. The overall median follow-up duration was 6.0 years (interquartile range [IQR]: 3.0-10.4), and the median duration of MHT use was 66.0 months (IQR: 36.0-116.3). The overall recurrence rate was 3.0% (95% confidence interval: 1.5-5.5) and there was no significant difference in recurrence among the study groups. Disease recurrence resolved after MHT discontinuation, or change in MHT type and/or dose. Conclusions No significant association between MHT use and endometriosis recurrence was found in this study. The endometriosis recurrence rate was non-significantly different between ET and EPT. Recurrent endometriosis can be successfully treated without invasive measures. No study patients had malignant transformation after a median follow-up of 6 years. Our findings suggest that any of the three evaluated MHT regimens can be used in surgically menopausal Thai women with underlying endometriosis.

Symptoms of treatment-induced menopause negatively affect quality of life and adherence to endocrine therapy of breast cancer (BC) survivors. Nevertheless, the use of systemic hormone replacement therapy (HRT) to mitigate these symptoms may be associated with an increased risk of disease recurrence in these patients. This systematic review and meta-analysis aimed to assess the safety of systemic HRT on risk of disease recurrence in BC survivors. A systematic search of PubMed up to April 20, 2021 was conducted to identify randomized controlled trials (RCTs) that investigated the risk of disease recurrence with the use of HRT in BC survivors. A random-effect model was applied to calculate the risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). A subgroup analysis was performed to estimate the risk of recurrence according to hormone receptor status. Four RCTs were included in the meta-analysis (n = 4050 patients). Overall, 2022 patients were randomized to receive HRT (estrogen/progestogen combination or tibolone) and 2023 to the control group with placebo or no HRT. HRT significantly increased the risk of BC recurrence compared to placebo (HR 1.46, 95% CI 1.12–1.91, p = 0.006). At the subgroup analysis, the risk of BC recurrence with the use of HRT was significantly increased in patients with hormone receptor-positive disease (HR 1.8, 95% CI 1.15–2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.19, 95% CI 0.80–1.77, p = 0.390). Use of HRT was associated with a detrimental prognostic effect in BC survivors, particularly in those with hormone receptor-positive disease. Alternative interventions to mitigate menopause-related symptoms should be proposed.

Objective Initiation of and compliance with menopausal hormonal therapy (MHT) have been dropping due to the 2002 Women's Health Initiative (WHI) publication. We evaluated the change in practice of MHT for surgical menopause after implementing the 2013 'Global Consensus Statement on MHT' to our institutional guideline. Methods A retrospective study was conducted in surgically menopausal women newly registering at the Siriraj Menopause Clinic in a university hospital, Thailand, from 1995 to 2013. The patients were categorized into four groups according to periods of MHT initiation: 1995-1998 (control), 2000-2003 (WHI affected), 2005-2008 (post WHI) and 2010-2013 (Global Consensus Statement affected). Their 3-year compliance with MHT was compared using forward stepwise regression analysis. Results There were 288, 156, 107 and 104 cases in the 1995-1998, 2000-2003, 2005-2008 and 2010-2013 groups. Their mean age at surgery was 42.8 ± 4.7 years. After the first, second and third years, overall compliance was 82.4%, 70.9% and 61.2%, respectively. The 3-year compliance drastically dropped in the 2000-2003 group, and then improved to control level in the 2010-2013 group (51.9% vs. 77.9%, p = 0.035). Conclusion The initiation of MHT continuously dropped during 2000-2013; however, compliance with MHT initiated during 2010-2013 improved after implementing the 2013 'Global Consensus Statement on MHT' to our institutional guideline. Each institute should have a strategy to encourage the initiation of and compliance with MHT for surgical menopause to achieve long-term health benefits.

OBJECTIVES To evaluate whether change in menopausal symptoms is related to modification of 24-hour urinary cortisol. METHODS Sixty-nine postmenopausal women were treated for their menopausal symptoms with either estrogen progestin therapy (0.3 mg conjugate equine estrogens and 1.5 mg medroxyprogesterone acetate; n = 25), phytoestrogens (75 mg isoflavones, twice daily; n = 21) or acupuncture (once a week; n = 23). Baseline and treatment-induced changes of total and subscale scores (vasomotor, depression, anxiety, somatization, sexuality) of the Greene's Climacteric Scale and of 24-hour urinary cortisol were evaluated. RESULTS At baseline, 24-hour urinary cortisol was related to Greene's Climacteric Scale score (P

To evaluate the association between female reproductive factors and the incidence of exudative age-related macular degeneration (AMD).A total of 1,297,388 postmenopausal women over 50 years of age who participated in both national health screening and cancer screening in 2009 were identified using the Korea National Health Insurance System database. Data on female reproductive factors were collected using a self-administered questionnaire. Patients were followed up until 2018, and the incident cases of exudative AMD were identified. The hazard ratios and 95% confidence intervals for exudative AMD were estimated using the multivariable-adjusted Cox proportional hazard model.During a mean follow-up of 7.27 years, 4,086 patients were newly diagnosed with exudative AMD. The hazard ratio (95% confidence intervals) for exudative AMD was 1.14 (1.01-1.31) for a reproductive period ≥40 years compared with a reproductive period30 years, 1.72 (1.48-2.00) for patients with ≥5 years of hormone replacement therapy, and 1.29 (1.09-1.52) for those with 2 to 5 years of hormone replacement therapy compared with those who never underwent hormone replacement therapy.Female reproductive factors were associated with the risk of exudative AMD. Greater lifetime exposure to endogenous and exogenous estrogen was associated with a higher incidence of exudative AMD.

Objectives To summarise the available data regarding the effect of hormone replacement therapy (HRT) on cognition and mood in women. Background Complaints of impaired cognition and mood are common in the peri-menopausal and menopausal period. There is debate as to whether HRT can ameliorate this phenomenon. Design A literature search of studies using electronic databases was conducted. Both randomised control trials and observational studies were included. Patients Perimenopausal and menopausal women. Results Due to the heterogenicity of results it is challenging to draw firm conclusions. The preparations used in many of the studies are older regimes no longer routinely used clinically. The notion of a ‘critical window’ for HRT is compelling, suggesting HRT has a positive impact on cognition when administered in the peri-menopausal or early postmenopausal period but may have negative effects on cognition in the older, postmenopausal woman. The evidence would seem to suggest importance of hormonal replacement in woman undergoing a surgical menopause, especially when young. It remains unclear for how long they ought to continue HRT though until at least the natural age of the menopause seems reasonable. Evidence for a positive effect of HRT on mood is more convincing, though possibly more efficacious in the younger age group. The effect of HRT on anxiety is less clear. Conclusions Further study, particularly focusing on the more contemporaneous HRT preparations, is warranted before evidence-based conclusions can be drawn.

Objectives Two-thirds of individuals living with Alzheimer’s disease are women. Declining estrogen levels influence mood and cognition. Cumulative lifetime estrogen exposure (CLEE) correlates with cognition later in life. We examined the relationship of CLEE to depression and cognition in older women with major depression compared to non-depressed women. Design Older women (age ≥60 years) with depression were compared to non-depressed women using a lifetime estrogen exposure questionnaire. CLEE was defined as combined durations of reproductive span (age of menopause minus age of menarche) and any post-menopausal hormone replacement therapy use. Higher vs lower CLEE groups were based on a median of 474 months of estrogen exposure. Setting University hospital outpatient research program Participants 135 women ≥60 years; 64 depressed and 71 non-depressed Measurments Participants completed a comprehensive cognitive test battery. General linear models were used to examine the association between cognitive domain scores and CLEE in depressed and non-depressed women, controlling for age, education, and ethnicity. Results Depressed and non-depressed groups had significantly different levels of CLEE, measured in months: mean 495.7 (SD 108.6) vs 456.4 (SD 66.0) months, F(1,130) = 5.01, p = .03. Within the non-depressed participants, higher CLEE was associated with improved delayed recall (F(1,59) = 5.94, p = .02, effect size = .61), while no such relationship was observed in the depressed group. Conclusion Higher CLEE was associated with improvement in delayed recall among non-depressed, but not among depressed participants. This suggests a protective role of estrogen on memory in non-depressed older postmenopausal women. Further research should examine the role of the CLEE in antidepressant response and cognitive decline.

The objective of this study was to assess the effect of menopausal hormone therapy (HT) on blood pressure control in postmenopausal women with hypertension.The Women's Health Initiative HT clinical trials were double-blinded, randomized, placebo-controlled studies of women aged 50 to 79 years testing the effects of HT (conjugated equine estrogens [CEE, 0.625 mg/d] or CEE + medroxyprogesterone acetate [MPA; 2.5 mg/d]) on risks for coronary heart disease and invasive breast cancer, the primary outcomes for efficacy and safety, respectively. This secondary analysis of the Women's Health Initiative HT trials examined a subsample of 9,332 women with hypertension (reported ever taking pills to treat hypertension or were taking antihypertensive medication) at baseline. Blood pressure was measured at baseline and up to 10 annual follow-up visits during the planned study phase. Antihypertensive medications were inventoried at baseline and years 1, 3, 6, and 9 during the study, and self-reported during extended follow-up: 2009-2010 and 2012-2013, which occurred median of 13 and 16 years after randomization, respectively. The intervention effect was estimated through year 6. Cumulative follow-up included all visits.Compared with placebo, CEE-alone had significantly ( P = 0.02) higher systolic blood pressure (SBP) by mean (95% confidene interval [CI]) = 0.9 (0.2-1.5) mm Hg during the intervention phase. For cumulative follow-up, the CEE arm was associated with increased SBP by mean (95% CI) = 0.8 (0.1-1.4) mm Hg ( P = 0.02). Furthermore, CEE + MPA relative to placebo was associated with increased SBP by mean (95% CI) = 1.8 (1.2-2.5) mm Hg during the intervention phase ( P0.001). For cumulative follow-up, the CEE + MPA arm was associated with increased SBP by mean (95% CI) = 1.6 (1.0-2.3) mm Hg ( P0.001). The mean number of antihypertensive medications taken at each follow-up visit did not differ between randomization groups during the intervention or long-term extended follow-up of 16 years.There was a small but statistically significant increase in SBP in both CEE-alone and CEE + MPA arms compared with placebo during both the intervention and cumulative follow-up phases among postmenopausal women with hypertension at baseline. However, this increase in SBP was not associated with an increased antihypertensive medication use over time among women randomized to HT compared with placebo.

Some women experience bothersome symptoms around the time of menopause that may have a negative impact on their quality of life and prompt them to seek treatments. Menopausal hormone therapy was historically the treatment of choice. However, medical contraindications and personal preference for nonhormonal therapy have prompted the evaluation of a range of nonhormonal pharmacologic and non-pharmacologic therapies. This review provides an update focusing on the latest evidence-based approach for the management of bothersome symptoms of menopause.

Objective Oral but not transdermal menopausal hormone therapy (MHT) increases the risk of venous thromboembolism. There is no evidence regarding the risk of the serious complication pulmonary embolism (PE). The aim was to investigate the risk of PE in women using MHT depending on administration route, type of progestin and treatment duration. Method The population-based case-control study covered 1,771,253 women aged 40-69 years, during 2006-2015. Diagnoses of PE (n = 13,974) and drug dispensations were received from national validated registers. Results Current MHT users had a higher risk of PE than non-users (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.05-1.26). First ever users had the highest risk (OR 2.07, 95% CI 1.23-3.50). Transdermal administration was not associated with increased risk of PE. The OR was slightly but non-significantly higher with estrogen combined with medroxyprogesterone acetate than with norethisterone acetate. Discussion The risk of PE was significantly increased in users of oral but not transdermal MHT, with the highest risk in first ever users of oral estrogen combined with medroxyprogesterone acetate. The risk was considerably lower in women with recurrent treatment, probably because of the healthy user effect. Conclusion PE was most common close to initiation of oral treatment. Transdermal MHT did not increase the risk of PE.

Midlife women commonly experience changes in their cognitive function as they transition through menopause and express concern about whether these changes represent the initial stages of a more serious cognitive disorder. Health-care practitioners play an important role in counseling women on cognitive changes at midlife and normalizing women's experience. The aim of this commissioned International Menopause Society White Paper on cognition is to provide practitioners with an overview of data informing the clinical care of menopausal women and a framework for clinical counseling and decision-making. Among the topics presented are the specific cognitive changes occurring in menopause, the duration of such changes and their severity. The role of estrogen and menopause symptoms is reviewed. We present talking points for clinical counseling on the effects of hormone therapy on cognition and dementia risk in women, including discussion of absolute risk. Lastly, a brief review of modifiable risk factors for age-related cognitive decline and dementia is presented, with guidance for counseling patients on optimizing their brain health at midlife and beyond.

OBJECTIVES: Although menopausal hormone therapy (MHT) remains the most effective treatment for vasomotor symptoms of menopause, its association with the development of arterial hypertension remains unclear. We sought to explore associations between different formulations of MHT and incident hypertension among menopausal women in a prospective cohort study. METHODS: We used the Etude Epidemiologique de femmes de la Mutuelle Generale de l'Education (E3N) cohort, a French prospective population-based study initiated in 1990 on 98,995 women. Out of these, 49,905 menopausal women with complete information on the use of MHT, and without prevalent hypertension at inclusion were included. RESULTS: The mean age of the population at baseline was 54.2 ±â€Š4.3 years, and 32,183 (64.5%) reported ever using MHT. Among these women, 10,173 cases of incident hypertension were identified over an average follow-up time of 10.6 years. Compared with women who never used MHT, those who ever used it had an increased risk of incident hypertension (adjusted HR 1.07, 95% CI 1.02-1.12) after adjustment for body mass index and other potential confounders. Oral but not transdermal estrogen use was associated with an increased risk of hypertension (adjusted HR = 1.09; 95% CI: 1.04-1.14 and HR = 1.03; 95% CI: 0.99-1.07, respectively). However, the HRs associated with oral and transdermal estrogens did not differ significantly (P-homogeneity = 0.09). Regarding the role of concomitant progestogens, pregnane and norpregnane derivatives were significantly associated with hypertension risk (HR = 1.12; 95% CI: 1.06-1.19 and HR = 1.06; 95% CI: 1.01-1.13, respectively). CONCLUSIONS: MHT was associated with a modest but significant increased risk of incident hypertension, especially when using oral estrogen in combination with a progestogen such as pregnane and norpregnane derivatives. Surveillance of blood pressure should be added to the medical surveillance of MHT users.Video Summary:http://links.lww.com/MENO/A802.

BACKGROUND Menopausal symptoms can be very distressing and considerably affect a woman’s personal and social life. It is becoming more and more evident that leaving bothersome symptoms untreated in midlife may lead to altered quality of life, reduced work productivity and, possibly, overall impaired health. Hormone therapy (HT) for the relief of menopausal symptoms has been the object of much controversy over the past two decades. At the beginning of the century, a shadow was cast on the use of HT owing to the concern for cardiovascular and cerebrovascular risks, and breast cancer, arising following publication of a large randomized placebo-controlled trial. Findings of a subanalysis of the trial data and extended follow-up studies, along with other more modern clinical trials and observational studies, have provided new evidence on the effects of HT. OBJECTIVE AND RATIONALE The goal of the following paper is to appraise the most significant clinical literature on the effects of hormones in postmenopausal women, and to report the benefits and risks of HT for the relief of menopausal symptoms. SEARCH METHODS A Pubmed search of clinical trials was performed using the following terms: estrogens, progestogens, bazedoxifene, tibolone, selective estrogen receptor modulators, tissue-selective estrogen complex, androgens, and menopause. OUTCOMES HT is an effective treatment for bothersome menopausal vasomotor symptoms, genitourinary syndrome, and prevention of osteoporotic fractures. Women should be made aware that there is a small increased risk of stroke that tends to persist over the years as well as breast cancer risk with long-term estrogen–progestin use. However, healthy women who begin HT soon after menopause will probably earn more benefit than harm from the treatment. HT can improve bothersome symptoms, all the while conferring offset benefits such as cardiovascular risk reduction, an increase in bone mineral density and a reduction in bone fracture risk. Moreover, a decrease in colorectal cancer risk is obtainable in women treated with estrogen–progestin therapy, and an overall but nonsignificant reduction in mortality has been observed in women treated with conjugated equine estrogens alone or combined with estrogen–progestin therapy. Where possible, transdermal routes of HT administration should be preferred as they have the least impact on coagulation. With combined treatment, natural progesterone should be favored as it is devoid of the antiapoptotic properties of other progestogens on breast cells. When beginning HT, low doses should be used and increased gradually until effective control of symptoms is achieved. Unless contraindications develop, patients may choose to continue HT as long as the benefits outweigh the risks. Regular reassessment of the woman’s health status is mandatory. Women with premature menopause who begin HT before 50 years of age seem to have the most significant advantage in terms of longevity. WIDER IMPLICATIONS In women with bothersome menopausal symptoms, HT should be considered one of the mainstays of treatment. Clinical practitioners should tailor HT based on patient history, physical characteristics, and current health status so that benefits outweigh the risks.

Menopausal hormone therapy (MHT) has been used for prevention and treatment of postmenopausal osteoporosis for several decades. However, public concerns were raised over the safety of MHT after the initial report was published in 2002 by the Women's Health Initiative. We conducted a historical review on this subject, primarily focusing on level I evidence from randomized controlled trials, systematic reviews and meta-analyses, and summarized high-quality evidence on the efficacy and safety of MHT in management of postmenopausal osteoporosis. Clinical issues were also discussed on MHT initiation, identification of treatment candidates and treatment duration, as well as discontinuation of MHT.

Objective Hormone therapy (HT) is used by menopausal women to treat vasomotor symptoms. Venous thromboembolism (VTE) is an important risk of HT use, and more knowledge on the comparative safety of different estrogenic compounds is useful for women who use HT for these symptoms. The objective was to compare the risk of VTE among users of oral conjugated equine estrogen (CEE), oral estradiol (E2), and transdermal E2, in a cohort of women veterans. Methods This retrospective cohort study included all women veterans aged 40 to 89 years, using CEE or E2, without prior VTE, between 2003 and 2011. All incident VTE events were adjudicated. Time-to-event analyses using a time-varying HT exposure evaluated the relative VTE risk between estrogen subtypes, with adjustment for age, race, and body mass index, with stratification for prevalent versus incident use of HT. Results Among 51,571 users of HT (74.5% CEE, 12.6% oral, and 12.9% transdermal E2 at cohort entry), with a mean age of 54.0 years, the incidence of VTE was 1.9/1,000 person-years. Compared with CEE use, in the multivariable regression model, there was no difference in the risk of incident VTE associated with oral E2 use (hazard ratio 0.96, 95% CI 0.64-1.46) or with transdermal E2 use (hazard ratio 0.95, 95% CI 0.60-1.49). Results were unchanged when restricting to incident users of HT. Conclusions Among women veterans, the risk of VTE was similar in users of oral CEE, oral E2, and transdermal E2. These findings do not confirm the previously observed greater safety of transdermal and oral E2 over CEE.

ObjectiveTo explore the views of members of the British Menopause Society on the management of women with unscheduled bleeding on hormone replacement therapy.Study designAn electronic cross-sectional questionnaire survey.Main outcome measuresInvestigations, treatment options and preferences for the management of women with unscheduled bleeding on hormone replacement therapy.ResultsA total of 91/178 (51%) clinicians investigate patients with unscheduled bleeding within three to six months of starting sequential hormone replacement therapy (seq-HRT) versus 83/178 (47%) for continuous combined hormone replacement therapy (con-HRT). A total of 52/178 (29%) versus 54/178 (30%) would investigate unscheduled bleeding continuing beyond six months while 18/178 (10%) versus 26/178 (15%) would investigate within three months. Assessment is requested as urgent by 88/176 (50%) clinicians, routine by 47/176 (27%) and a two-week-wait-suspected cancer referral by 41/176 (23%). A total of 97/178 (55%) clinicians would continue seq-HRT and refer versus 117/178 (66%) for con-HRT. A total of 46/178 (26%) clinicians would change the progestogen preparation in women with unscheduled bleeding on seq-HRT. For women on con-HRT, 12/178 (7%) clinicians would change to seq-HRT and 8/178 (5%) to the Mirena IUS. The Mirena IUS is the preferred progestogen for 81/178 (45%) of clinicians when prescribing hormone replacement therapy.ConclusionsThere is a varied approach in the practise amongst British Menopause Society members to managing women with unscheduled bleeding on hormone replacement therapy. Further research is needed to determine the optimal assessment pathways for women with unscheduled bleeding on hormone replacement therapy.

Background Oral postmenopausal hormone therapy (HT) increases the risk of venous thrombosis (VT). We postulated that activated protein C (APC) resistance induced by HT is one of the mechanisms causing VT, and also assessed the role of one of the main determinants of APC resistance, i.e., tissue factor pathway inhibitor (TFPI). Methods We performed a nested case-control study embedded within two Women's Health Initiative (WHI) hormone trials. Women were randomized to hormone therapy or placebo. Biomarkers were measured at baseline and after one-year, in 217 cases and 817 controls. Results Increased APC resistance and decreased TFPI at baseline were associated with VT (OR ranging from 1.20 to 2.06). However, women with such prothrombotic profile at baseline did not have further increased risk of VT when randomized to HT compared with placebo. While there was no change in APC resistance or TFPI in placebo group after one-year, HT group showed prothrombotic changes in the biomarkers, i.e., an increase in APC resistance (mean(sd):0.39 (0.54)) and decrease in TFPI (-0.21(0.50): free TFPI, -0.24(0.22): TFPI activity and -0.22(0.20): total TFPI). However, HT induced prothrombotic change in biomarkers did not increase risk of VT. Conclusion Women with prothrombotic levels of APC resistance and TFPI at baseline were not at increased risk of VT when randomized to HT compared with placebo. This suggests that testing for these biomarkers prior to starting HT is not required. HT led to prothrombotic change in these biomarkers after one year, but this did not relate to increased risk of VT.

Frailty is a multidimensional clinical syndrome that increases the risk of adverse health outcomes. Previous studies have reported a close link between menopause and frailty. Combined estrogen–progestin therapy (or estrogen-only therapy in women who have undergone a hysterectomy) is currently approved as a menopausal hormone therapy (MHT) to treat menopausal symptoms. Despite increasing evidence of the importance of sex hormones in the development of frailty, very few studies have investigated the association between MHT and frailty. A cross-sectional evaluation was conducted using population-based survey data known as the Korea National Health and Nutrition Examination Survey (KNHANES IV-V, 2008–2012). The KNHANES data provided variables that were used to construct a 51-item frailty index (FI). The number of study population, only including postmenopausal women, was 7823 women, and their mean age was 62.51 years (range 32–80 years). Approximately 40% of them had graduated from middle school or higher, 45% lived in metropolitan statistical areas, and 5% were recipients of the national Medical Aid. The mean age at menopause was 48.66 years (range 30–62 years). Overall, the mean FI value was 0.15, and the prevalence of MHT was 13.23%. Findings from multiple regression analysis using the inverse probability of treatment weighting showed that a treatment duration of more than 2 years and up to 5 years, age at first treatment between 50 and 59 years, and MHT initiation 3 to 6 years after menopause were all negatively associated with frailty (p < 0.05). Further studies are needed to confirm these findings using prospective data.

In the Women's Health Initiative (WHI) randomized trial with 10,739 postmenopausal women with prior hysterectomy, conjugated equine estrogen (CEE) alone significantly reduced breast cancer incidence and breast cancer mortality. In contrast, epidemiological studies in a meta-analysis from the Collaborative Group on Hormonal Factors in Breast Cancer (Collaborative Group) with 108,647 breast cancers and the Million Women's Study cohort significantly associated estrogen-alone therapy with higher breast cancer incidence and breast cancer mortality. The Collaborative Group included a meta-analysis of five smaller randomized trials and the WHI randomized trial; however, findings were restricted to the Collaborative Group appendix. Our objective is to facilitate understanding of these discordant results.Data sources supporting our review findings include the randomized WHI CEE-alone trial and the meta-analysis of five smaller randomized trials evaluating estrogen alone. We summarize the smaller randomized trials' details of breast cancer relevance and place the findings in clinical context. We review findings of the WHI randomized trial evaluating CEE alone in the context of issues raised by Collaborative Group and the Million Women Study authors. We trace the evolution of the time-from-menopause, "window of opportunity" concept and augment the Collaborative Group meta-analysis by including the most recent WHI findings.Consideration of the smaller randomized trials evaluating estrogen alone with breast cancer signals that the WHI findings of lower breast cancer incidence and lower breast cancer mortality with CEE-alone use are not a "stand-alone" outcome or due to the play of chance. The serial reports of consistent favorable breast cancer findings through 20 years of cumulative follow-up suggest CEE-alone use initiates changes that persist. After full consideration of risks and benefits, randomized trial evidence provides reassurance for postmenopausal women with prior hysterectomy who are close to menopause considering estrogen alone for climacteric symptom management.

The aim of this study was to examine the effect of either conjugated equine estrogen or transdermal estradiol on vitamin D metabolism in postmenopausal women.Twenty-five women from the Kronos Early Estrogen Prevention Study who were randomized to conjugated equine estrogen 0.45 mg/d and 20 women who were treated with transdermal estradiol 50 mg/d (patch replaced weekly) were analyzed in the present study. All participants received micronized progesterone for 12 days per month.There was no significant treatment effect on serum total 25-hydroxyvitamin D over 48 months in either study group, and there were no significant differences between treatment arms. In contrast, at 12 months, directly measured free 25-hydroxyvitamin D was significantly higher in the transdermal estradiol group than in the conjugated equine estrogen group. Directly measured free 25-hydroxyvitamin D subsequently increased significantly from 12 to 48 months in both treatment arms. Calculated free 25-hydroxyvitamin D was also significantly higher in the transdermal estradiol group at 36 months. Vitamin D-binding protein decreased significantly in both treatment groups from 12 to 48 months, but at 48 months, least square mean values were no different based on treatment assignment.Directly measured free 25-hydroxyvitamin D levels, but not serum total 25-hydroxyvitamin D levels, are different within the first 12 months of estrogen replacement depending on the preparation. However, this difference is transient, in that there were no differences at 36 or 48 months. These findings suggest that there may be a short-term benefit to prescribing transdermal estradiol for women who are either vitamin D deficient or vitamin D insufficient.

Menopause is a period during which women undergo dramatic hormonal changes. These changes lead to physical and mental discomfort, are greatly afflictive, and critically affect women’s lives. However, the current safe and effective management measures for women undergoing menopause are insufficient. Several probiotic functions of lactic acid bacteria (LAB) have been recognized, including alleviation of lactose intolerance, protection of digestive tract health, activation of the immune system, protection against infections, improvement of nutrient uptake, and improvement of the microbiota. In this review, we highlight the currently available knowledge of the potential protective effects of LAB on preventing or mitigating menopausal symptoms, particularly in terms of maintaining balance in the vaginal microbiota, reducing bone loss, and regulating the nervous system and lipid metabolism. Given the increasing number of women entering menopause and the emphasis on the management of menopausal symptoms, LAB are likely to soon become an indispensable part of clinical/daily care for menopausal women. Herein, we do not intend to provide a comprehensive analysis of each menopausal disorder or to specifically judge the reliability and safety of complementary therapies; rather, we aim to highlight the potential roles of LAB in individualized treatment strategies for the clinical management of menopause.