Duration Of Menopausal Hormone Therapy Research Articles

Counseling in menopausal women: How to address the benefits and risks of menopause hormone therapy. A FIGO position paper.

Menopause marks the end of menstrual cyclicity and, depending on individual vulnerability, has several consequences related to gonadal steroid deprivation, especially if it is premature. Menopause may be more burdensome for some women than for others. Individual factors, such as personal history, socioeconomic status, ethnicity, and current health conditions, affect symptomatology and, thereby, the menopausal experience. In addition, some menopausal symptoms, such as severe hot flashes, sleep disorders, and depression, are markers of future health risks. Counseling is a fundamental part of health care in the peri- and postmenopause periods. It must include an assessment of the patient's symptoms, needs, desires, and risk profile to address the benefits and risks of menopausal hormone therapy (MHT) on an individual basis and promote a healthy lifestyle. Indeed, healthcare practitioners can and must protect the health and lives of mid-life women by increasing awareness of menopausal symptoms and ensuring healthcare options, especially MHT. The type and duration of MHT should be tailored based on the patient's history, menopausal age, physical characteristics, and current health status so that the benefits always outweigh the risks. This FIGO position paper focuses on the benefits and risks of MHT on health domains, target organs, and systems, and on systemic and vaginal MHT regimens, to provide indications that can be used in the clinical practice for menopausal counseling. Moreover, it offers insights into what FIGO considers the mainstay for the healthcare management of women in peri- and postmenopause, worldwide.

Association Between Menopausal Hormone Therapy and Risk for Parkinson's Disease.

The relationship between menopausal hormone therapy (MHT) and risk of Parkinson's disease (PD) remains controversial. This nationwide population-based cohort study investigated the association between MHT and PD development. Data from the National Health Insurance System of South Korea from 2007 to 2020 were used. The MHT group included women who underwent MHT for the first time between 2011-2014, while the non-MHT group included women who visited a healthcare provider for menopause during the same period but never received hormonal therapy. We used propensity score matching (1 : 1) to adjust for potential confounders, and Cox regression models to assess the association between MHT and PD. We selected 303,260 female participants (n = 151,630 per MHT and non-MHT groups). The median age of the participants was 50 (48-54) years, and the follow-up period lasted 7.9 (6.9-8.9) years. Cox regression analysis revealed an increased risk of PD with MHT (hazard ratio [HR] 1.377, 95% confidence interval [CI] 1.184-1.602), particularly with tibolone (HR 1.554, 95% CI 1.297-1.861) and estrogen alone (HR 1.465, 95% CI 1.054-2.036). Tibolone and estrogen alone were linked to PD within three years; however, no association was observed after three years. In contrast, the use of combined estrogen-progesterone was linked to a higher risk of PD, which increased with the duration of MHT (HR 1.885, 95% CI 1.218-2.918 for over five years). This study demonstrated that the MHT is closely associated with the risk of PD in a regimen- and duration-specific manner.

The beneficial effects of menopausal hormone therapy on renal survival in postmenopausal Korean women from a nationwide health survey

Several studies have demonstrated the nephroprotective effects of estrogen on renal damage. In light of the inconsistent results of previous findings, this study aims to evaluate the in-depth role of menopausal hormone therapy (MHT) on the development of end stage renal disease (ESRD). 3,109,506 Korean adult women who had undergone a medical examination in 2009 (index year) were initially identified for inclusion in this study. We excluded subjects had not experienced menopause naturally, had data missing for at least one variable, and were diagnosed with ESRD within 1 year from the index year. MHT data was obtained from self-reporting questionnaires and the primary outcome was the development of ESRD from the index year until December 31, 2018. A final total of 1,460,311 subjects were included in this study. The participants were divided into four groups according to the duration of MHT; no history of MHT, MHT < 2 years, 2 ≤ MHT < 5 years, MHT ≥ 5 years. During the 9-year study period, a total of 4905 participants developed ESRD. The participants who had a history of MHT use were found to have a 30% reduced risk of developing ESRD. Results from the subgroup analyses were similar to that of the primary study. The findings in this study demonstrate the beneficial effects of MHT on the development of ESRD in postmenopausal women. Based on results, our study may offer suggestions for further studies to investigate the therapeutic options on kidney disease.

New trends in current menopausal hormone therapy

The article presents the results of recent studies on the effectiveness, safety and duration of menopausal hormone therapy (MHT). The main cardio-metabolic risk factors for cardiovascular diseases are formed in women precisely during the transition to menopause and are clearly associated with the appearance of vegetative menopausal symptoms and the development of endothelial dysfunction, which is a predictor of future serious health problems, especially cardiovascular diseases. The results of a number of epidemiological studies have shown that in women with severe climacteric manifestations, especially with hot flashes, the overall risk of developing cardiovascular diseases is increased. The need for early initiation of MHT is an indisputable truth and is not disputed by anyone, but the formed tendency to discontinue treatment in 56 years raises many questions among patients and their doctors. However, recent guidelines from the International Menopause Society state that there is no reason to arbitrarily limit the duration of MHT. This paper presents current evidence on the indications and benefits of low and ultra-low doses of MHT. In view of the high efficacy and safety of low doses of MHT, they seem to be the most acceptable starting doses of oral MHT for most women. In addition, women with early menopause should also receive higher doses of estrogens, as they are more physiological for them. The choice in favor of starting MHT in a postmenopausal woman with a low or ultra-low dose in each case should be selected individually.

Effect of Half-dose and Standard-dose Conjugated Equine Estrogens Combined with Natural Progesterone or Dydrogesterone on Components of Metabolic Syndrome in Healthy Postmenopausal Women: A Randomized Controlled Trial.

Background:Menopausal hormone therapy (MHT) has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration of MHT. The aim of the study was to evaluate the effect of standard-dose 0.625 mg conjugated equine estrogen (CEE) and half-dose 0.3 mg CEE daily with different progestogens in a continuous sequential regimen on postmenopausal metabolic parameters in generally healthy postmenopausal women.Methods:A prospective, open-label, randomized controlled clinical trial was conducted between February 2014 and December 2015. Totally 123 Chinese postmenopausal women with climacteric symptoms were included in this study and were randomly assigned to three groups: Group A received CEE 0.3 mg/micronized progesterone (MP) 100 mg daily; Group B received CEE 0.625 mg/MP 100 mg daily; and Group C received CEE 0.625 mg/dydrogesterone 10 mg daily. Drugs were given in a continuous sequential pattern. The duration of treatment was 12 months. Clinical, anthropometrical, and metabolic variables were measured. Data were analyzed according to intention-to-treat analysis, using Student's t-test and analysis of variance.Results:A total of 107 participants completed the 12-month follow-up and were included in the data analysis. At 12 months of treatment, high-density lipoprotein cholesterol and apolipoprotein A significantly increased, and low-density lipoprotein cholesterol, fasting glucose, and glycosylated hemoglobin significantly decreased in Groups B and C, compared with baseline (all P < 0.05). Among the three groups, only Group C showed significantly increased triglycerides compared with baseline (1.61 ± 0.80 mmol/L vs. 1.21 ± 0.52 mmol/L, P = 0.026). Each group showed a neutral effect on total cholesterol, lipoprotein A, apolipoprotein B, and fasting insulin levels. No cardiovascular and venous thromboembolic events occurred in the three groups.Conclusions:Among Chinese postmenopausal women, half-dose CEE was not sufficient to induce a favorable lipid and carbohydrate profile compared with standard-dose CEE. Adding natural MP may counterbalance the TG-increasing effect of CEE.Trial Registration:ClinicalTrials.gov, NCT01698164; https://clinicaltrials.gov/ct2/show/NCT01698164?term=NCT01698164&rank=1.

The Benefit of Menopausal Hormone Therapy on Bone Density and Microarchitecture Persists After its Withdrawal.

Menopausal hormone therapy (MHT) favorably affects bone mineral density (BMD). Whether MHT also affects bone microarchitecture, as assessed by trabecular bone score (TBS), has never been evaluated. Our objective was to assess the effect of MHT on TBS and BMD before and after its withdrawal. This was a cross-sectional study. This study included the general community. Data were collected from the OsteoLaus cohort (1500 women aged 50-80 years). After exclusion of women with bone-modulating treatments, 1279 women were categorized according to MHT status into current (CU), past (PU), and never (NU) users. Spine TBS and BMD at lumbar spine, femoral neck, and total hip were assessed by dual X-ray absorptiometry. Age- and body mass index-adjusted analysis showed higher TBS values in CU vs PU or NU (1.31 ± 0.01, 1.29 ± 0.01, and 1.27 ± 0.01, respectively; P < .001). All BMD values were significantly higher in CU vs PU or NU. Compared to NU, PU exhibited higher lumbar spine (0.94 ± 0.01 vs 0.91 ± 0.01 g/cm2; P = .017) and total hip (0.86 ± 0.01 vs 0.84 ± 0.01 g/cm2; P = .026) BMD and a trend for higher TBS (P = .066). The 10-year loss of TBS and BMD at lumbar spine and total hip was significantly lower for both CU and PU vs NU. MHT duration had no effect on bone parameters. In PU, the residual effect on TBS and BMD was significantly more prominent in early discontinuers (<2 years). MHT is associated with bone microarchitecture preservation, as assessed by TBS. The effect of MHT on TBS and BMD persists at least 2 years after withdrawal.

Relationship between menopausal hormone therapy and mortality after breast cancer The MARIEplus study, a prospective case cohort.

Cohort studies of breast cancer (BC) patients, but not of disease-free women at inclusion, have found menopausal hormone therapy (MHT) to be associated with decreased BC specific mortality (BCM). Here, the German population-based MARIEplus BC cohort was analyzed to further elucidate associations of prediagnostic MHT with BCM (and modification by tumor characteristics), recurrence, and secondarily with other cause and overall mortality. Enrolled 2002-2005, incident invasive BC cases (N = 3,321) were followed up for a median of 6.1 years. Cox proportional hazards models adjusted for tumor characteristics, mammography and lifestyle were applied. Compared with never users of MHT, current users at date of diagnosis had significantly lower BCM (Hazard ratio (HR) 0.72, 95% CI 0.53-0.97) and risk of recurrence (HR 0.61, 95% CI 0.46-0.82). The MHT related reduced BCM was confined to patients with low grade tumors (HR 0.44, 95% CI 0.28-0.70; phet = 0.01) and not modified by estrogen receptor or nodal status. BCM decreased with MHT duration in current and increased in past users (phet = 0.015). Mortality due to causes other than BC and overall mortality were also reduced in current MHT users (HR 0.51, 95% CI 0.32-0.81, HR 0.66, 95% CI 0.52-0.86, respectively). Favorable tumor characteristics and mammographic surveillance could not fully explain associations of current MHT use with BCM and recurrence risk. Thus, the study contributes to the evidence that prediagnostic MHT does not have a negative impact on prognosis after BC. The restriction of a reduced BCM to low grade tumors should be confirmed in independent studies.

Abstract POSTER-CTRL-1212: The impact of social isolation on ovarian cancer risk and survival

Abstract Introduction: In ovarian cancer mouse models, social isolation has been associated with increased circulating markers of angiogenesis, cell migration, and impaired immune response, as well as increasing tumor burden and aggressiveness. In ovarian cancer patients, social isolation has been associated with increased circulating levels of inflammatory and pro-angiogenic factors. However, social isolation has not been investigated in relation to ovarian cancer risk or survival in humans; we addressed these questions in the Nurses’ Health Study (NHS), a longitudinal cohort of 121,701 US-based nurses. Methods: The Berkman-Syme social network index (BSSNI), a validated measure of social isolation, was assessed every four years in the NHS, starting in 1992. The BSSNI is based on marital status, close friends and relatives, as well as attendance at religious services and other group activities. Women were categorized into four groups: socially isolated, moderately isolated, moderately integrated, and socially integrated. We assessed risk of ovarian cancer associated with the BSSNI and its component parts using Cox proportional hazards models, adjusted for age, duration of oral contraceptive use, family history of ovarian cancer, parity, menopause status, duration of menopausal hormone therapy (by type), and tubal ligation. We further investigated whether the timing of social isolation impacted the results, by evaluating social isolation measured 0-4, 4-8, and 8-12 years prior to cancer diagnosis. In addition, we used Cox proportional hazards models to evaluate whether pre-diagnosis social isolation affected ovarian cancer survival, adjusting as described above plus stage and histology. Results: In follow-up from 1992-2010, we identified 494 epithelial ovarian cancer cases among 53,839 women who completed the BSSNI. In our main analysis, socially isolated women had no increased ovarian cancer risk compared to socially integrated women (relative risk [RR]: 0.93; 95% confidence interval [CI]: 0.65-1.34), although case numbers were small (N=38). However, moderate isolation was associated with increased ovarian cancer risk (RR: 1.27; 95% CI: 1.00-1.61). When we assessed the components of the BSSNI, widowed women were at increased ovarian cancer risk (RR: 1.40; 95% CI: 1.12-1.75) compared to married women; none of the other BSSNI components were associated with ovarian cancer risk. In the analysis evaluating the role of timing of isolation, socially isolated women in the 8-12 years prior to diagnosis had increased ovarian cancer risk compared to socially integrated women (RR: 1.54; 95% CI: 1.02-2.33). Among the 494 ovarian cancer cases in this analysis, 313 women died due to ovarian cancer during follow-up. Neither the BSSNI nor its components were statistically significantly associated with ovarian cancer-specific survival; however, several of the associations were suggestive. For example, social isolation was not associated with survival (RR: 1.13; 95% CI: 0.41-3.13), but moderate isolation was suggestively associated (RR: 1.61; 95% CI: 0.87-3.00). Additionally, being widowed was associated with a 71% increased risk of ovarian cancer death (95% CI: 0.99-2.96). Conclusion: These data add to a growing body of evidence that psychosocial stress is important for ovarian cancer risk and progression. Our data suggest that the timing of social isolation is key, which may have implications for the biology of stress. Future studies should confirm these results and evaluate additional sources of psychosocial stress. Citation Format: Elizabeth M. Poole, Laura Kubzansky, Olivia I. Okereke, Shelley S. Tworoger. The impact of social isolation on ovarian cancer risk and survival [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-CTRL-1212.

An epidemiological model for prediction of endometrial cancer risk in Europe.

Endometrial cancer (EC) is the fourth most frequent cancer in women in Europe, and as its incidence is increasing, prevention strategies gain further pertinence. Risk prediction models can be a useful tool for identifying women likely to benefit from targeted prevention measures. On the basis of data from 201,811 women (mostly aged 30-65 years) including 855 incident EC cases from eight countries in the European Prospective Investigation into Cancer and Nutrition cohort, a model to predict EC was developed. A step-wise model selection process was used to select confirmed predictive epidemiologic risk factors. Piece-wise constant hazard rates in 5-year age-intervals were estimated in a cause-specific competing risks model, five-fold-cross-validation was applied for internal validation. Risk factors included in the risk prediction model were body-mass index (BMI), menopausal status, age at menarche and at menopause, oral contraceptive use, overall and by different BMI categories and overall duration of use, parity, age at first full-term pregnancy, duration of menopausal hormone therapy and smoking status (specific for pre, peri- and post-menopausal women). These variables improved the discriminating capacity to predict risk over 5 years from 71% for a model based on age alone to 77% (overall C statistic), and the model was well-calibrated (ratio of expected to observed cases = 0.99). Our model could be used for the identification of women at increased risk of EC in Western Europe. To achieve an EC-risk model with general validity, a large-scale cohort-consortium approach would be needed to assess and adjust for population variation.

Breast cancer risk in older women: results from the NIH-AARP Diet and Health Study.

Divergent risk factors exist for premenopausal and postmenopausal breast cancers, but it is unclear whether differences by age exist among postmenopausal women. We examined relationships among 190,872 postmenopausal women, ages 50-71 years recruited during 1995-1996 for the NIH-AARP Diet and Health Study, in whom 7,384 incident invasive breast carcinomas were identified through 2006. Multivariable Cox regression hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for breast cancer risk factors by age (50-59, 60-69, ≥70 years). The only factor showing significant statistical heterogeneity by age (p(het) = 0.001) was menopausal hormone therapy duration, but trends were apparent across all ages and the strongest association prevailed among women 60-69 years. Although other risk factors did not show statistically significant heterogeneity by age, we did observe attenuated relations for parity and late age at first birth among older women [e.g., HR for age at first birth ≥30 vs. 20-24 = 1.62 (95% CI 1.23-2.14) for women 50-59 years vs. 1.12 (0.96-1.31) for ≥70 years]. In contrast, risk estimates associated with alcohol consumption and BMI tended to be slightly stronger among the oldest subjects [e.g., HR for BMI ≥35 vs. 18.5-24.9 = 1.24 (95% CI 0.97-1.58) for 50-59 years vs. 1.46 (1.26-1.70) for ≥70 years]. These differences were somewhat more pronounced for estrogen receptor positive and ductal cancers, tumors predominating among older women. Breast cancer family history, physical activity, and previous breast biopsies did not show divergent associations by age. Although breast cancer risk factor differences among older women were not large, they may merit further consideration with respect to individualized risk prediction.

Global Consensus Statement on menopausal hormone therapy

MediClinic Panorama and Department of Obstetrics and Gynecology, Stellenbosch University, Cape Town, South Africa; * Department of Surgery, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, OH, USA; † Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR; ‡ Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; * * Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA; † † University of Geneva, Switzerland; ‡ ‡ Reader Emeritus, University of Oxford, UK

Re: Louwman WJ et al. On the rising trends of incidence and prognosis for breast cancer patients diagnosed 1975–2004: a long-term population-based study in southeastern Netherlands. Cancer Causes Control 19:97–106

The authors state that a lack of decline in breast cancer incidence within the time period of 1975-2005 in the Eindhoven cancer registry is linked to "a different history in HRT use" in European countries in terms of a lower prevalence and shorter duration of use of menopausal hormones [ 1 ]. We doubt this explanation. At least in Germany, population-based nationally representative data suggest that 80% of current users (age: 40-79 years) of menopausal hormones have been using these therapies for more than 3 years in 2003/ 2004. Among current users of menopausal hormone therapy (MHT) aged 60 years and older, 96.4% had used MHT for more than 3 years [2]. These figures appear to be broadly consistent with a population-based cross-sectional survey conducted in 1997/1998 in one area of the north east of Germany; among women aged 40 and older, 25.1% used MHT for 3-5 years, 22.0% for 61 0 years, and 6.6% for more than 1 0 years [3] . In a further regional population-based study conducted in 2000, a project evolving from one German MONICA center, long-term use of MHT exceeding 10 years, as high as 43%, was self-reported by women aged 50_74 years [4]. Surveys conducted within the framework of the European Prospective Investigation into Cancer and Nutrition 1993-1997 [5] show substantial variation in both prevalence of use (maximum of 55% for long-term use in one German center, different from the study regions mentioned above) and duration of MHT (maximum of 10 years and more in 26% of the Danish cohort) across centers. Further studies from Sweden, Norway, and the UK also suggest substantial though different magnitudes of use of long-term MHT [6-8]. Thus, we doubt that use of MHT in European populations before the publication of results from the Women's Health Initiative trials is substantially different from the pattern of use high prevalence and long-term use in the United States (US). In Germany, use of MHT appeared to have at least equalled both prevalence and duration of use compared to that of the US.