Menopause hormone therapy prescribing in ambulatory care visits among midlife and older U.S. women from 2018 to 2019.

The rates of prescription for menopause hormone therapy have been low in the U.S. since the 2002 Women's Health Initiative study, but no recent studies have assessed the prescribing of hormone therapy in the U.S. Using the National Ambulatory Medical Care Survey data from 2018 to 2019, we found that hormone therapy was prescribed in 3.8 % of U.S. visits by midlife and older women, with 60 % of these visits including estradiol-only prescriptions. Older age and Hispanic/Latina ethnicity were associated with decreased odds of prescribing, while White race and depression were associated with increased odds, indicating possible disparities in menopause care.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Primary Amenorrhea and Premature Ovarian Insufficiency.

This review focuses on primary amenorrhea and primary/premature ovarian insufficiency due to hypergonadotropic hypogonadism. Following a thoughtful, thorough evaluation, a diagnosis can usually be discerned. Pubertal induction and ongoing estrogen replacement therapy are often necessary. Shared decision-making involving the patient, family, and health-care team can empower the young person and family to successfully thrive with these chronic conditions.

Nonhormone therapies for vasomotor symptom management.

Vasomotor symptoms (VMS) are associated with adverse health consequences and can cause significant morbidity for postmenopausal women. Although hormone therapy remains the gold standard of VMS treatment in menopausal women, some women have contraindications to or may choose not to take hormone therapy. This article provides an up-to-date overview of the current evidence-based nonhormone therapies available for managing VMS. Evidence supporting various treatment options is reviewed, including lifestyle interventions, mind-body therapies, procedures, pharmacologic agents, and emerging therapies, such as neurokinin-receptor antagonists. The efficacy, safety, and clinical use of these treatments are detailed, offering insights for clinicians to make informed decisions in menopausal VMS management.

Menopausal hormone therapy and risk of venous thromboembolism: The story so far.

Menopausal hormone therapy (MHT) is known to increase the risk of venous thromboembolism (VTE), which includes deep vein thrombosis, pulmonary embolism, and less frequently cerebral vein thrombosis, but the absolute risk for a given patient is very low. After starting MHT, the risk of VTE seems to be at its highest, declining to the non-HRT user baseline level of risk after stopping. Whether estrogen-only or estrogen-progestin HRT combination is linked to a similar risk of VTE is unclear from the available evidence. The aim of this study is to evaluate the risks of developing VTE in relation to different types as well as different modes of administration of MHT through a database search including PubMed, MEDLINE, Google Scholar, Cochrane Library, and others in order to provide the women carers with the up-to-date and evidence-based guidelines and recommendations while counseling the post-menopausal women enquiring on use of hormonal therapies either to alleviate the menopausal symptoms or to prevent the long-term sequelae of estrogen deficiency.

On sait que l'hormonothérapie ménopausique (MHT) augmente le risque de thromboembolie veineuse (TEV), qui comprend la thrombose veineuse profonde, l'embolie pulmonaire et, moins fréquemment, la thrombose veineuse cérébrale, mais le risque absolu pour un patient donné est très faible. Après le début du MHT, le risque de TEV semble être à son plus haut niveau, diminuant jusqu'au niveau de risque de base des non-utilisatrices de THS après l'arrêt. Les preuves disponibles ne permettent pas de savoir si un THS à base d'œstrogène seul ou d'association œstroprogestative est lié à un risque similaire de TEV. Le but de cette étude est d'évaluer les risques de développer une TEV par rapport à différents types ainsi qu'à différents modes d'administration du MHT grâce à une recherche dans des bases de données comprenant PubMed, MEDLINE, Google Scholar, Cochrane Library et autres afin de fournir aux femmes les soignants avec les lignes directrices et recommandations à jour et fondées sur des preuves tout en conseillant les femmes ménopausées qui se renseignent sur l'utilisation de thérapies hormonales, soit pour soulager les symptômes de la ménopause, soit pour prévenir les séquelles à long terme d'une carence en œstrogènes.

Risks and benefits of hormone therapy after menopause for cognitive decline and dementia: A conceptual review.

OBJECTIVE: The effects on the brain of hormone therapy after the onset of menopause remain uncertain. The effects may be beneficial, neutral, or harmful. We provide a conceptual review of the evidence. METHODS: We 1) provide a brief history of the evidence, 2) discuss some of the interpretations of the evidence, 3) discuss the importance of age at menopause, type of menopause, and presence of vasomotor symptoms, and 4) provide some clinical recommendations. RESULTS: The evidence and the beliefs about hormone therapy and dementia have changed over the last 30 years or more. Five recent observation studies suggested that hormone therapy is associated with an increased risk of dementia, and the association appears not to change with the timing of initiation of therapy. These harmful associations may be explained by a causal effect of hormone therapy on the brain or by several confounding mechanisms. We suggest that the use of hormone therapy should be customized for different subgroups of women. It may be important to subgroup women based on age at onset of menopause, type of menopause, and presence or absence of vasomotor symptoms. In addition, the effects may vary by type, dose, route, and duration of administration of estrogens and by the concurrent use of progestogens. DISCUSSION: The relation of hormone therapy with the risk of dementia is complex. Hormone therapy may have beneficial, neutral, or harmful effects on the brain. Hormone therapy should be guided by the clinical characteristics of the women being treated.

Exogenous Estrogen in the Development of Head and Neck Cancer.

Importance: Sex differences in head and neck cancer (HNC) incidence suggest a potential contribution of sex hormones. Objective: To assess the role of exogenous estrogen exposure in the development of HNC in female patients. Design, Settings, and Participants: This large multicenter cohort study using clinical records from the TriNetX real-world database included 20 years of data (through May 31, 2023) from 87 health care organizations. The TriNetX database was searched for medical records for female patients with and without exogenous estrogen exposure according to their chronological age. Cohort 1 included 731 366 female patients aged 18 to 45 years old with regular oral contraceptive (OC) intake and cohort 2 included 3 886 568 patients in the same age group who did not use OC. Cohort 3 comprised 135 875 female patients at least 50 years old receiving hormone replacement therapy (HRT), whereas cohort 4 included 5 875 270 patients at least 50 years old without HRT. Propensity score matching was performed for the confounders age, alcohol dependence, and nicotine dependence. Data analyses were performed in May 2023. Main Outcome and Measures: Diagnosis of HNC (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision: C00-C14), and after propensity score matching (1:1 nearest-neighbor greedy matching), a risk analysis to investigate risk differences and risk ratios (RRs) with a 95% CI. Results: Among the 718 101 female patients in each of cohorts 1 and 2 (mean [SD] age at diagnosis, 25.9 [6.7] years), those with OC intake had a higher risk of an HNC diagnosis (RR, 1.47; 95% CI, 1.21-1.78) than those without OC use. Among the 131 835 female patients in each of cohorts 3 and 4 (mean [SD] age, 67.9 [12.0] years), those with postmenopausal HRT intake had a lower risk of an HNC diagnosis (RR, 0.77; 95% CI, 0.64-0.92) than those without HRT use. Conclusions and Relevance: The findings of this cohort study illustrate a positive association between OC and a negative association between HRT and the development of HNC in female patients. Given the limitations of the TriNetX database, future research should include detailed information on the intake of OC and HRT and reproductive health information (eg, age at menarche/menopause, number of pregnancies) to more accurately define the strength and direction of the possible association between exogeneous estrogen exposure and the development of HNC in female patients.

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

Introduction: Despite evidence from preclinical studies suggesting estrogen's neuroprotective effects, the use of menopausal hormone therapy (MHT) to support cognitive function remains controversial. Methods: 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. Results: 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. Discussion: 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.

OBJECTIVE: To examine the association between menopause hormone therapy (MHT) and physical performance among women from the Canadian Longitudinal Study on Aging. STUDY DESIGN: Cross-sectional study of 12,506 postmenopausal Canadian women. MAIN OUTCOME MEASURES: Grip 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. RESULTS: Compared with those who never used MHT, prior or current use was associated with better performance on the timed up and go test (ß: -0.19; 95%CI: -0.28; -0.11) and faster gait speed (ß = 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. CONCLUSIONS: MHT 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.

Association between menopausal hormone therapy and the risk of gastric cancer: A Korean nationwide population-based cohort study.

OBJECTIVE: Gastric cancer (GC) is more common in men than women, but also more common among postmenopausal than premenopausal women. The protective effect of reproductive hormones against GC remains unclear. Therefore, we evaluated the association between menopausal hormone therapy (MHT) and the risk of GC in women. METHODS: We investigated the national cohort data of women aged over 40 years who underwent health checkups by the Korean National Health Insurance Service in 2009. After excluding individuals with missing data and those previously diagnosed with cancer, 1,354,621 postmenopausal women were included and divided into groups according to their MHT history. We followed the study population until 2018 and analyzed the hazard ratios (HR) with 95 % confidence intervals (CIs) for the incidence rate of GC in a multivariate adjusted model. RESULTS: The number of women with and without a history of MHT was 214,723 (15.9 %) and 1,139,898 (84.1 %), respectively. During the mean 8.32 ± 0.8 years of follow-up, a total of 12,496 GC cases developed in the study population (10,962 MHT non-users; 1534 MHT users). In the adjusted model, MHT was associated with a 12 % decrease in the development of GC relative to non-use of MHT (HR 0.88; 95 % CI 0.83-0.93). Exposure to MHT for >2 years was linked to a reduction in GC risk, particularly when initiated before the age of 50, giving a 45 % risk reduction. CONCLUSIONS: According to our large-scale prospective national cohort study, exogenous MHT is associated with a decreased risk of GC in postmenopausal women.

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.