Menopausal Hormone Therapy Use Research Articles

Endocrinological aspects of gout

Gout is the most common inflammatory joint disease, and its incidence increases with age and the presence of certain diseases, primarily obesity and chronic kidney disease, as well as while taking certain medications. Treatment of a patient with gout requires the interaction of a rheumatologist, cardiologist and endocrinologist, and even better, a well-trained therapist who is able to independently supervise gout-related diseases without the involvement of specialized specialists. This review was written to highlight current data on the most common endocrinopathies in gout for practitioners. The data presented indicate the existence of a relationship between gout and various endocrine diseases. The most important aspect is the presence of metabolic syndrome in most patients with gout, the treatment of which also requires taking into account the effect of prescribed drugs on purine metabolism. On the other hand, effects on certain endocrinological diseases can lead to improved purine metabolism. It has been shown that weight loss, including through bariatric means, is accompanied by a decrease in uric acid levels and may be accompanied by a decrease in the need for urate-lowering therapy. Most glucose-lowering drugs affect purine metabolism, and the presence of concomitant gout may determine the specific choice of antidiabetic therapy. Menopause is characterized by an increase in uric acid levels and the incidence of gout. At the same time, the use of menopausal hormone therapy may be accompanied by both a decrease in uric acid levels and the risk of developing gout. Despite the fact that an increase in testosterone levels in men is positively correlated with uric acid levels, its deficiency is accompanied not by a decrease, but by an increase in uric acid levels.

Female magnesium deficiency and its management: review of current knowledge

Magnesium is an important cofactor for metabolic reactions involving more than 300 enzymes, regulating a series of fundamental processes, such as myocardial contraction and blood pressure control, glucose regulation, participation in neuromuscular transmission. The prevalence of magnesium deficiency in various cohorts of fertile age women comprises up to 73.8 %. In clinical studies it was demonstrated that magnesium deficiency is associated with diseases and states such as dysmenorrhea, premenstrual syndrome (PMS), polycystic ovary syndrome (POS), climacteric syndrome, osteoporosis, use of combined oral contraceptives (COCs) and menopausal hormone therapy (MHT). Magnesium supplementation in combination with basic therapy can positively affect course and outcome of such pathologies. Magnesium organic salts could be used for countering magnesium deficiency. Among such agents, magnesium citrate has some advantage used in combination with pyridoxine (vitamin B6) providing additional effects. Health care professionals should be guided by the criteria for Mg-containing preparation selection, defined by the Russian Society of Obstetricians and Gynecologists (RSOG).

Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway.

It is important to monitor the association between menopausal hormone therapy (HT) use and breast cancer (BC) risk with contemporary estimates, and specifically focus on HT types and new drugs. We estimated hazard ratios (HR) of BC risk according to HT type, administration route and individual drugs, overall and stratified by body mass index (BMI), molecular subtype and detection mode, with non-HT use as reference. We included 1,275,783 women, 45+ years, followed from 2004, for a median of 12.7 years. Oral oestrogen combined with daily progestin was associated with the highest risk of BC (HR 2.42, 95% confidence interval (CI) 2.31-2.54), with drug-specific HRs ranging from Cliovelle®: 1.63 (95% CI 1.35-1.96) to Kliogest®: 2.67 (2.37-3.00). Vaginal oestradiol was not associated with BC risk. HT use was more strongly associated with luminal A cancer (HR 1.97, 95% CI 1.86-2.09) than other molecular subtypes, and more strongly with interval (HR 2.00, 95% CI: 1.83-2.30) than screen-detected (HR 1.33, 95% CI 1.26-1.41) BC in women 50-71 years. HRs for HT use decreased with increasing BMI. The use of oral and transdermal HT was associated with an increased risk of BC. The associations varied according to HT type, individual drugs, molecular subtype, detection mode and BMI.

Breast cancer risk assessment for prescription of Menopausal Hormone Therapy in women who have a family history of breast cancer

Background Menopausal Hormone Therapy (MHT) can alleviate menopausal symptoms but is associated with increased risk of breast cancer (BC). MHT prescription should be preceded by individualised risk/benefit evaluation; however, data outlining the impact of family history alongside different MHT therapeutic approaches are lacking. Aim To quantify the risks associated with MHT use in women with varying BC family histories of i) developing and ii) dying from BC. Design and setting An epidemiological modelling study (UK women). Method We used i) background risks of BC by age and family history, ii) relative risks for BC associated with MHT use, and iii) 10-year BC-specific net mortality rates to model the risk of developing and dying from BC between the ages of 50 and 80 in women with four different BC family history profiles: ‘average’, ‘modest’, ‘intermediate’, and ‘strong’. Results For a woman of ‘average’ family history taking no MHT, the cumulative BC risk (age 50-80) is 9.8%, and the risk of dying from the BC is 1.7%. Five years’ exposure to combined-cyclical MHT (age 50-55) increases these risks to 11.0% and 1.8%, respectively. For a woman with a ‘strong’ family history taking no MHT, the cumulative BC risk is 19.6%, and the risk of dying is 3.2%. With 5 years of MHT (age 50-55), this increases to 22.4% and 3.5%. Conclusion Both family history and MHT are associated with increased risk of BC. Estimates of the risks associated with MHT for women with different family histories can support decision-making around MHT prescription.

Association of muscle disorders in late postmenopausal women according to the type of experienced menopause.

Musculoskeletal disorders frequently affect postmenopausal women. This study aims to compare muscle disorders between women according to the type of experienced menopause: premature (PM) or normal age of menopause (NAM). This was a cross-sectional study conducted in nine Latin American countries in which late postmenopausal women (55 to 70 years) were surveyed with a general questionnaire, the Menopause Rating Scale (MRS: item #4 exploring musculoskeletal discomfort), and the trength, assistance with walking, rising from a chair, climbing stairs, and falling questionnaire (risk of sarcopenia). A total of 644 women were included: 468 who had NAM, and 176 who had PM (116 spontaneous and 60 surgical). The overall mean age of the participants was 60.9 ± 4.2 years. Women who had PM experienced more musculoskeletal discomfort (33.5% vs 20.9%, P < 0.001) and a higher likelihood of sarcopenia (35.2% vs 19.9%, P < 0.001) than women who had a NAM. Women who had surgical PM exhibited a higher prevalence of severe musculoskeletal discomfort (46.7% vs 29.3%, P < 0.02) and a higher likelihood of sarcopenia (45.0% vs 27.6%, P < 0.02) than women who had a NAM. After adjusting for covariates (age, body mass index, menopausal hormone therapy use, physical activity, education, cigarette consumption, use of antidepressants, sexual activity, comorbidities, and having a partner), our logistic regression model determined that spontaneous PM was not associated with higher odds of musculoskeletal discomfort and higher odds of sarcopenia. On the other hand, women who had surgical PM were more likely to experience musculoskeletal discomforts (odds ratio: 2.26; 95% confidence interval: 1.22-4.17) and higher odds for sarcopenia (odds ratio: 2.05; 95% confidence interval: 1.16-3.65) as compared to women who experienced a NAM. Women experiencing surgical PM have a higher likelihood of developing muscle disorders. This underscores the potential significance of hormonal levels in influencing musculoskeletal health during postmenopause.

Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk.

Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk. We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated. The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 × 10-14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 × 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk. MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.

Prediagnostic use of menopausal hormone therapy and long-term survival of localized epithelial ovarian cancer: The Extreme study.

Use of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long-term MHT use, especially estrogen therapy (ET), was associated with improved long-term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long-term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000-2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo-values, 5- and 10-year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5-year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10-year survival. Use of MHT was not significantly associated with an improved 5- or 10-year survival in women with localized EOC (5-year relative survival probability = 0.95, 95% CI: 0.89-1.02; 10-year relative survival probability = 0.92, 95% CI: 0.84-1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long-term survival of localized EOC.

Abstract 2202: Association of multi-morbidity with incident cancer diagnoses

Abstract Background: Multi-morbidity (MM), which is usually defined as a simple count of the number of different diseases an individual has, has previously been identified as a risk factor for some incident cancer diagnoses. This study aimed to use more sophisticated machine learning techniques to classify MM into disease clusters and to investigate their association with incident colorectal (CRC), breast (BC), lung (LC) and prostate (PrC) cancer diagnoses. Methods: Participants in UK Biobank with a hospital (HES) record and no prevalent cancer were included in the study. Self-reported (SR), HES and primary-care (GP) recorded diseases were converted to phecodes. Sex-stratified latent class analyses (LCA) was used to identify disease clusters in the SR data. Associations between clusters and selected cancer diagnoses was undertaken using Cox proportional hazards modelling, adjusting for age, ethnicity, socio-economic status, year and region of recruitment, body mass index, smoking history, alcohol consumption and menopausal hormone therapy use (women only). The analyses were validated using HES and GP data. Results: The analysis included 158,951 women and 127,406 men. Just over 30% (49,061) of women and 37% (48,110) of men had MM (≥2 diseases) at recruitment. LCA identified 10 disease clusters in women, the most common of which was related to respiratory disease, largely comprising asthma (9344; 19.1%). Nine disease clusters were identified in men, the most common of which was related to heart disease (9358; 19.5%), and largely comprising ischemic heart disease and hypertension. No association between disease cluster and incident CRC or BC was identified. In women, LC risk was associated with several disease clusters: respiratory (Hazard Ratio 1.57 (95% confidence interval 1.28 - 1.91) p&amp;lt;0.001), arthritis/gut (1.46 (1.15 - 1.85) p=0.002), hyperlipidemia (1.51 (1.19 - 1.92) p=0.001, cardiac (1.74 (1.40 - 2.17) p&amp;lt;0.001) and type 2 diabetes (T2DM) (1.56 (1.16 - 2.09) p=0.003). In men, LC was associated with disease clusters of hyperlipidemia/hypertension (1.23 (1.02 - 1.48) p=0.03), cardiac (1.40 (1.18 - 1.66) p&amp;lt;0.001), T2DM (1.26 (1.02 - 1.56) p=0.03), respiratory (2.74 (2.21 - 3.39) p&amp;lt;0.001) and cardiometabolic/arthritis (1.81 (1.08 - 3.03) p=0.02). T2DM (0.80 (0.68 - 0.87) p&amp;lt;0.001) was associated with an inverse risk of PrC. Cluster distribution was similar in HES and GP data, with the association between the cardiac and the arthritis clusters replicated for LC in women, and the respiratory cluster for LC and T2DM cluster for PrC in men. Conclusion: Clusters of MM were identified in a large cancer-free population, which were replicated using different sources of healthcare data. Several disease clusters were associated with incident LC and, to a lesser extent, PrC. Further work to understand the potential causal nature of these associations is needed. Citation Format: Megan C. Conroy, Gillian K. Reeves, Naomi E. Allen. Association of multi-morbidity with incident cancer diagnoses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2202.

Abstract P231: Are Resiliency and Religiosity/Spirituality Associated With Better Sleep Outcomes in Midlife Latinas?

Background: The disproportionate cardiovascular disease (CVD) burden among Latinas is not completely explained. An important health behavior in CVD prevention is sleep. In the United States (U.S.), Latinas experience unique sociocultural stressors that may impact sleep, particularly in midlife. Yet, little is known about protective factors such as resiliency and religiosity/spirituality among midlife Latinas. Aims: To assess the relation of resiliency and religiosity/spirituality with sleep disturbances in midlife Latinas. Methods: We conducted a cross-sectional analysis using baseline data from 49 participants in a pilot study to reduce CVD risk in midlife Latinas. Participants were Latinas aged 40-60 years who were perimenopausal or early postmenopausal, free of CVD, with no menopause hormone therapy use in the prior three months. Women were recruited from community settings. The frequency of sleep disturbances (trouble falling asleep, waking early, or nocturnal awakenings) over the past two weeks was assessed, and a sum score was created (0-16). The 6-item Brief Resilience Scale was used to assess the perceived ability to “bounce back” or recover from hardship. Religiosity/spirituality was determined by self-report (how important is religion/spirituality to you). Multivariable linear regression models were performed at p&lt;0.15, adjusting for sociodemographic. Results: Participants were on average aged 47.1±4.5 years, 47% had less than a high school education, and 98% were born outside of the continental U.S. Sixty-nine percent of women experienced trouble falling asleep. The mean sleep score was 6.9±4.6. In adjusted models, we found an inverse relationship between resiliency and sleep (ß[SE]= -0.33[0.13],p=0.01). Religiosity/spirituality was not related to sleep disturbances (ß[SE]= 1.15[1.60],p=0.48). Conclusions: In this analysis of midlife Latinas, higher resiliency was associated with poorer sleep. Findings suggest that the ability to “bounce back” after hardship and religiosity/spirituality may not buffer the negative impact of stress on sleep. Further research is necessary with objective sleep measures to identify protective factors for sleep disturbances that may subsequently improve CVD risk in midlife Latinas.

Use of menopausal hormone therapy beyond age 65 years and its effects on women's health outcomes by types, routes, and doses.

The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths. Using prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and Cox regression analyses adjusted for time-varying characteristics of the women, we examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular diseases, and dementia. Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%). For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer by 10%-19%, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer (45% or adjusted hazards ratio, 0.55; 95% CI, 0.50-0.60), ovarian cancer (21%), ischemic heart disease (5%), CHF (5%), and venous thromboembolism (5%), whereas E+ progesterone exhibited risk reduction only in CHF (4%). Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen.

The unique risk factor profile of triple negative breast cancer: a comprehensive meta-analysis.

Triple-negative breast cancer (TNBC) has a poor prognosis compared to other breast cancer subtypes. This systematic review and meta-analysis examines whether known risk factors for breast cancer are also associated with TNBC in adult females. EMBASE, Medline, SCOPUS, and grey literature were queried with no limit on the date or language of publication. The exposures of interest included parity, breastfeeding, duration of breastfeeding, age at menarche, age at first live birth, oral contraceptive (OC) use, duration of OC use, use of menopausal hormone therapy (MHT), family history, body mass index (BMI), alcohol use, smoking and breast density. The main outcome of interest was TNBC. Study quality was determined using the Newcastle-Ottawa scale for case control studies and cohort studies. We estimated weighted odds ratios from random effects models to study the exposure-outcome associations. Protocol was registered under the number: PROSPERO 2021 CRD42021254594. Thirty-three studies were included. Family history, longer duration of oral contraceptive use, and higher breast density were significantly associated with increased risk for TNBC, whereas, later age at menarche, later age at first birth and breastfeeding were protective against TNBC. Parity, MHT, alcohol, smoking, and BMI were not significantly associated with TNBC overall, but higher parity was associated with higher risk among Black women. Our findings highlight that TNBC has a distinct risk-factor profile compared to overall breast cancer. This can be the foundational work in identification of actionable TNBC risk factors to improve prevention and early detection of these poor prognosis breast tumors.

Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use.

To compare weight loss response and changes in cardiometabolic risk markers in postmenopausal women using semaglutide with and without menopause hormone therapy (HT) use. Retrospective cohort study of postmenopausal women treated with semaglutide for overweight or obesity for ≥3 months. Endpoints: total body weight loss percentage (TBWL%) at 3, 6, 9, and 12 months after semaglutide initiation; and percentage of women achieving ≥5% and ≥10% TBWL and changes in cardiometabolic risk markers (glucose, blood pressure, and lipids) at 12 months. There were 16 women on HT and 90 on no-HT; mean age 56 ± 8 vs 59 ± 8 yr, P = 0.2 and mean BMI 36 ± 5 vs 39 ± 8 kg/m 2 , P = 0.1; respectively. Among women on no-HT, White race, dyslipidemia, and depression were more prevalent. Women on HT had a higher TBWL% at 3, 6, 9, and 12 months: 7 ± 3% vs 5 ± 4%, P = 0.01; 13 ± 6% vs 9 ± 5%, P = 0.01; 15 ± 6% vs 10 ± 6%, P = 0.02; and 16 ± 6% vs 12 ± 8%, P = 0.04; respectively. After adjusting for potential confounders, this association remained significant across time. At 12 months, a greater percentage of women on HT achieved ≥5% and ≥10% TBWL. Both groups experienced an improvement in cardiometabolic risk markers. In postmenopausal women with overweight or obesity treated with semaglutide, HT use was associated with an improved weight loss response. This association was maintained when adjusted for confounders. Larger studies should be conducted to confirm these results.

Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition.

Despite evidence from preclinical studies suggesting estrogen's neuroprotective effects, the use of menopausal hormone therapy (MHT) to support cognitive function remains controversial. We used random-effect meta-analysis and multi-level meta-regression to derive pooled standardized mean difference (SMD) and 95% confidence intervals (C.I.) from 34 randomized controlled trials, including 14,914 treated and 12,679 placebo participants. Associations between MHT and cognitive function in some domains and tests of interest varied by formulation and treatment timing. While MHT had no overall effects on cognitive domain scores, treatment for surgical menopause, mostly estrogen-only therapy, improved global cognition (SMD=1.575, 95% CI 0.228, 2.921; P=0.043) compared to placebo. When initiated specifically in midlife or close to menopause onset, estrogen therapy was associated with improved verbal memory (SMD=0.394, 95% CI 0.014, 0.774; P=0.046), while late-life initiation had no effects. Overall, estrogen-progestogen therapy for spontaneous menopause was associated with a decline in Mini Mental State Exam (MMSE) scores as compared to placebo, with most studies administering treatment in a late-life population (SMD=-1.853, 95% CI -2.974, -0.733; P = 0.030). In analysis of timing of initiation, estrogen-progestogen therapy had no significant effects in midlife but was associated with improved verbal memory in late-life (P = 0.049). Duration of treatment >1 year was associated with worsening in visual memory as compared to shorter duration. Analysis of individual cognitive tests yielded more variable results of positive and negative effects associated with MHT. These findings suggest time-dependent effects of MHT on certain aspects of cognition, with variations based on formulation and timing of initiation, underscoring the need for further research with larger samples and more homogeneous study designs.

Menopause hormone therapy and physical performance: The Canadian Longitudinal Study on Aging

ObjectiveTo examine the association between menopause hormone therapy (MHT) and physical performance among women from the Canadian Longitudinal Study on Aging. Study designCross-sectional study of 12,506 postmenopausal Canadian women. Main outcome measuresGrip strength (kg), gait speed (m/s), timed up and go (s), chair rise (s), and balance (s) were assessed following standard procedures. The association between MHT and physical performance was evaluated using linear regression models adjusted for age, education, study site, smoking, alcohol consumption, body mass index, diabetes, hypertension, and hysterectomy. Sensitivity analyses were conducted according to age at study visit (<65 vs. ≥65 years), body mass index (<25 kg/m2 vs. ≥25 kg/m2), physical activity level (less vs. more active), duration and type of MHT, and time of starting MHT after menopause. ResultsCompared with those who never used MHT, prior or current use was associated with better performance on the timed up and go test (β: −0.19; 95%CI: −0.28; −0.11) and faster gait speed (β = 0.01, 95%CI = 0.00; 0.02). No association was found for grip strength, balance, and chair rise. Results did not change by body mass index, physical activity, or duration of MHT use. When stratified by age at study visit, the effect remained significant only in among those aged 65 years or more. Starting MHT <5 years after menopause was associated with better physical performance. ConclusionsMHT was associated with better physical performance in gait speed and timed up and go tests. The cross-sectional design of the study limits causal interpretation. Prospective studies are needed to confirm our results.

Eligibility criteria for using menopausal hormone therapy in breast cancer survivors: a safety report based on a systematic review and meta-analysis.

Menopause hormone therapy (MHT) effectively alleviates menopausal symptoms. However, it is generally not recommended for breast cancer survivors, although the scientific evidence is scarce. This study aimed to establish eligibility criteria for use of the MHT in breast cancer survivors based on a systematic review and meta-analysis of the literature. We conducted exhaustive literature searches until June 2022 in MEDLINE, The Cochrane Library, and EMBASE, using a tailored strategy with a combination of controlled vocabulary and search terms related to breast cancer survivors and MHT. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessed the risk of bias using the Cochrane and Risk of Bias in Non-randomized Studies - of Interventions tools. The quality of the evidence was graded according to grading quality of evidence and strength of recommendations criteria (A, high; B, moderate; C, low; and D, very low). We categorized MHT use into four levels: category 1 (no restrictions on use), category 2 (the benefits outweigh the risks), category 3 (the risks generally outweigh the benefits), and category 4 (MHT should not be used). A total of 12 studies met the eligibility criteria. Analysis of the three randomized clinical trials using combined MHT or tibolone revealed no significant differences concerning tumor recurrence (relative risk [RR], 1.46; 95% CI, 0.99-2.24). A combined analysis of randomized clinical trials, prospective, and retrospective trials found no elevated risk of recurrence (RR, 0.85; 95% CI, 0.54-1.33) or death (RR, 0.91; 95% CI, 0.38-2.19). The eligibility criteria for patients with hormone receptor (HR)-positive tumors fell into categories 3B and 3C for combined MHT or estrogen alone and 4A for tibolone. For HR-negative tumors, the category was 2B and 2C. Our findings suggest that MHT could be a viable treatment alternative for breast cancer survivors experiencing menopausal symptoms, especially those with HR-negative tumors. Personalized management is recommended for each peri/postmenopausal woman facing a diminished quality of life because of menopause symptoms. Further randomized trials are needed before considering changes to current standards of care.

Bone health in women with premature ovarian insufficiency/early menopause: a 23-year longitudinal analysis.

Bone health in women with premature ovarian insufficiency/early menopause: a 23-year longitudinal analysis.

Does menopause hormone therapy improve symptoms of depression? Findings from a specialized menopause clinic.

Depressive symptoms are commonly reported during the perimenopause and in the early postmenopausal years. Although menopausal hormone therapy (MHT) is considered the most effective treatment option for vasomotor symptoms, its effect on mood-related symptoms is less established. This study aims to assess interval change in depressive symptoms after initiation of MHT treatment in women seeking care at a Canadian specialized menopause clinic. Women and female-presenting people attending the St. Joseph's Healthcare Menopause Clinic in Hamilton, Ontario, were invited to participate in this study. Participants (n = 170) completed a self-report questionnaire, which included their medical history as well as validated tools for bothersome symptoms at their initial visit. A shortened version was administered at the follow-up visit 3 to 12 months later with the same validated tools. We sought to examine interval changes on the Center for Epidemiological Studies Depression Scale based on type of treatment used and MHT dose, while controlling for relevant demographic variables (smoking, education level, age). There was a high rate of depressive symptoms in those seeking specialized menopause care (62%). MHT use was associated with significantly improved depressive symptoms, both alone and in addition to an antidepressant medication ( P < 0.001). Younger age, lower education attainment, and smoking were all associated with higher depression scores. This study supports the use of MHT to improve depressive symptoms experienced by those seeking specialized menopause care. Further investigation into timing of treatment initiation may facilitate a personalized treatment approach to improve quality of life of women in the peri- and postmenopausal years.

Hormone replacement therapy and breast cancer incidence in Korean women

ObjectivesAfter the 2002 Women's Health Initiative (WHI) study, the global use of menopausal hormone therapy (MHT) declined, and despite subsequent studies indicating a low risk of breast cancer, concerns about MHT usage persist. We examined the relationship between changes in MHT use and changes in the incidence of breast cancer from 2002 to 2020 in South Korea. Study designThis study used tumor registry information from 2002 to 2020 from the Korean Statistical Information Service and analyzed the incidence rate of invasive breast cancer in women, who were divided into two age groups: <50 and >50 years. The numbers of MHT prescriptions in Korea between 2002 and 2020 was determined from pharmacy data. ResultsThe incidence of breast cancer per 100,000 women in South Korea increased from 34.3 in 2002 to 96.4 in 2020. Breast cancer incidence rates increased annually in both groups of women (those aged under and over 50 years), with no significant difference between the two (p = 0.614). Prescriptions for estrogen therapy (ET) in 2020 were 52.7 % lower than those in 2002. Prescriptions for estrogen-progesterone therapy (EPT) decreased by 27.9 % over the same period. Conversely, tibolone prescriptions, which had initially decreased by 25.4 % in 2004, subsequently showed a steady increase and were 93.6 % higher in 2020 than in 2002. ConclusionThe incidence of breast cancer increased annually in Korean women of all ages; however, the use of ET and EPT for MHT has declined since 2002, particularly the use of EPT after 2010. MHT, especially EPT, did not significantly increase the incidence of breast cancer in Korean women.

Menopausal hormone therapy and risk of sarcoidosis: a population-based nested case–control study in Sweden

Sarcoidosis incidence peaks in women between 50 and 60 years old, which coincides with menopause, suggesting that certain sex hormones, mainly estrogen, may play a role in disease development. We investigated whether menopausal hormone therapy (MHT) was associated with sarcoidosis risk in women and whether the risk varied by treatment type. We performed a nested case–control study (2007–2020) including incident sarcoidosis cases from the Swedish National Patient Register (n = 2593) and matched (1:10) to general population controls (n = 20,003) on birth year, county, and living in Sweden at the time of sarcoidosis diagnosis. Dispensations of MHT were obtained from the Swedish Prescribed Drug Register before sarcoidosis diagnosis/matching. Adjusted odds ratios (aOR) of sarcoidosis were estimated using conditional logistic regression. Ever MHT use was associated with a 25% higher risk of sarcoidosis compared with never use (aOR 1.25, 95% CI 1.13–1.38). When MHT type and route of administration were considered together, systemic estrogen was associated with the highest risk of sarcoidosis (aOR 1.51, 95% CI 1.23–1.85), followed by local estrogen (aOR 1.25, 95% CI 1.11–1.42), while systemic estrogen-progestogen combined was associated with the lowest risk compared to never users (aOR 1.12, 95% CI 0.96–1.31). The aOR of sarcoidosis did not differ greatly by duration of MHT use. Our findings suggest that a history of MHT use is associated with increased risk of sarcoidosis, with women receiving estrogen administered systemically having the highest risk.

Association with menopausal hormone therapy and asymptomatic gallstones in US women in the third National Health and Nutrition Examination Study

15% of US adults have gallstones, most of which are clinically “silent”. Several studies show that menopausal hormone therapy (MHT) increases symptomatic gallstones and cholecystectomy risk. MHT use may be contraindicated in women with gallstones and population studies may be biased by “confounding by contraindication” while the true association between MHT and gallstones remains underestimated. We sought to examine whether MHT use was associated with asymptomatic gallstones using instrumental variable (IV) analysis to account for confounding by contraindication. We used 2018 postmenopausal women from the Third National Health and Nutrition Examination Survey to estimate associations of MHT use with asymptomatic gallstones. A traditional logistic regression analysis was compared to instrumental variable (IV) analysis to account for confounding by contraindication. 12% of women with asymptomatic gallstones and 25% of women without gallstones were current MHT users (P < 0.001). The traditional analysis suggested a decreased odds of asymptomatic gallstones in current versus never users (OR 0.58, 95% CI 0.37, 0.89), but increased odds (OR 1.51, 95% CI 0.44, 5.16) in the IV analysis. The traditional analysis consistently underestimated the odds of asymptomatic gallstones with MHT use compared to the IV analysis. Accounting for confounding by contraindication, we found a suggestive, though imprecise, positive association between MHT use and asymptomatic gallstones among postmenopausal women. Failure to consider contraindication can produce incorrect results.