Association Between Hormone Replacement Therapy and Development of Endometrial Cancer: Results From a Prospective US Cohort Study
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SUBMITTER: Liang Y
PROVIDER: S-EPMC8801732 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTo review completed trials assessing effect of hormone replacement therapy on subsequent risk of stroke, assessing stroke by pathological type, severity, and outcome.DesignSystematic review of randomised controlled trials identified from the Cochrane Library, Embase, and Medline; reviews; and reference lists of relevant papers.Studies reviewed28 trials, with 39 769 subjects, were identified. REVIEW MEASURES: Rates for cerebrovascular events analysed with a random effects model. Sensitivity analyses for heterogeneity included phase of prevention (primary or secondary), type of hormone replacement therapy (oestrogen alone or combined with progesterone), type of oestrogen (estradiol or conjugated equine oestrogen), size of trial (< 5000 or > 5000 patients), length of follow up ( pound 3 years or > 3 years), sex (women only or men only), and trial quality (high or low).ResultsHormone replacement therapy was associated with significant increases in total stroke (odds ratio 1.29 (95% confidence interval 1.13 to 1.47), n = 28), non-fatal stroke (1.23 (1.06 to 1.44), n = 21), stroke leading to death or disability (1.56 (1.11 to 2.20), n = 14), ischaemic stroke (1.29 (1.06 to 1.56), n = 16), and a trend to more fatal stroke (1.28 (0.87 to 1.88), n = 22). It was not associated with haemorrhagic stroke (1.07 (0.65 to 1.75), n = 17) or transient ischaemic attack (1.02 (0.78 to 1.34), n = 22). Statistical heterogeneity was not present in any analysis.ConclusionsHormone replacement therapy was associated with an increased risk of stroke, particularly of ischaemic type. Among subjects who had a stroke, those taking hormone replacement therapy seemed to have a worse outcome. Hormone replacement therapy cannot be recommended for the primary or secondary prevention of stroke.
| S-EPMC548730 | biostudies-literature
Project description:The purpose of this study is to investigate the effect of hormone therapy (HT) on the oncological outcomes of endometrial cancer (EC) survivors. A systematic literature review was conducted in July 2021 to identify studies detailing the effect size for the relationship between HT use in EC and oncological outcomes (survival and disease recurrence). This included studies that evaluated the different recurrence rates among women treated for EC who subsequently underwent HT and those who did not. The collected studies were evaluated for quality, heterogeneity, and publication bias, and a pooled odds ratio (OR) or hazard ratio (HR) was calculated with a confidence interval of 95% (95% CI). In total, 5291 studies were collated, and after the review process, one randomized trial and seven observational studies were included, comprising 1801 EC survivors treated with HT and 6015 controls. The time-dependent analysis could be conducted for four studies, and considering the disease-free survival, the pooled HR of 0.90 (95% CI 0.28 to 2.87) showed no significant differences. However, among Black American women treated with continuous estrogen HT, the HR was 7.58 (95% CI 1.96 to 29.31), showing a significantly increased risk of recurrence for women in this ethnic group. Considering the pooled OR of all included studies 0.63 (95% CI 0.48 to 0.83), a significantly reduced risk of recurrence was found among EC survivors treated with HT. Considering the type of HT, the most risk-reducing was combined estrogen and progestin therapy and the cyclic regimen. Although supporting evidence is based mainly upon observational studies, evidence of no increased risk or even decreased risk was generally found, apart from in Black American women where a significantly increased recurrence risk was evident. The data are rather reassuring for the short-term administration of HT to symptomatic EC survivors. Future studies with a longer follow-up are necessary to better clarify the long-term effects of HT.
| S-EPMC8303659 | biostudies-literature
Project description:BackgroundMenopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study was to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study.MethodsWe used data from a case-control study nested within the French cohort E3N including 453 cases and 453 matched controls. Measures of mammographic density, history of MHT use during follow-up and information on potential confounders were available for all women. The association between MHT and mammographic density was evaluated by linear regression models. We applied mediation modelling techniques to estimate, under the hypothesis of a causal model, the proportion of the effect of MHT on BC risk mediated by percent mammographic density (PMD) for BC overall and by hormone receptor status.ResultsAmong MHT users, 4.2% used exclusively oestrogen alone compared with 68.3% who used exclusively oestrogens plus progestogens. Mammographic density was higher in current users (for a 60-year-old woman, mean PMD 33%; 95% CI 31 to 35%) than in past (29%; 27 to 31%) and never users (24%; 22 to 26%). No statistically significant association was observed between duration of MHT and mammographic density. In past MHT users, mammographic density was negatively associated with time since last use; values similar to those of never users were observed in women who had stopped MHT at least 8 years earlier. The odds ratio of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by PMD was 34% for any BC and became 48% when the correlation between BMI and PMD was accounted for. These effects were limited to hormone receptor-positive BC.ConclusionsOur results suggest that, under a causal model, nearly half of the effect of MHT on hormone receptor-positive BC risk is mediated by mammographic density, which appears to be modified by MHT for up to 8 years after MHT termination.
| S-EPMC8053286 | biostudies-literature
Project description:IntroductionAssociations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use.MethodsWithin the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed.ResultsFor risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ?49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ?65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ?22.5 kg/m2) than for more overweight women (BMI ?25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime.ConclusionsAn elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors.
| S-EPMC3446339 | biostudies-literature
Project description:ObjectiveCarpal tunnel syndrome (CTS) is the most common compressive focal mononeuropathy, and the increased incidence in postmenopausal and pregnant women suggests its association with oestrogen. The objective of this study is to evaluate the relationship between hormone replacement therapy (HRT) and the occurrence of CTS.DesignPopulation-based case-control study.SettingNationwide health insurance programme operated by the government with a near 100% coverage rate.ParticipantsWe identified women ≥45 years old in the Health Insurance Research Database of Taiwan, which contains data on a representative sample of one million enrollees. After exclusion of those who were diagnosed with CTS before the prescription of HRT, a total of 118 309 participants were included and followed up for 15 years starting from 1 January 1996. Both HRT and occurrence of CTS were identified using the insurance claims.Main outcome measuresWe identified incident patients of CTS and evaluated the association between HRT and CTS by calculating the OR.ResultsOf the 4535 participants who developed CTS during the study period, 2334 (51.5%) were HRT recipients. In participants without CTS, the proportion of HRT recipients was 28.1%, yielding an OR of 2.72 with a 95% CI of 2.56 to 2.88. After adjustment for age, diabetes, rheumatoid arthritis, hypothyroidism, gout and obesity, the OR of CTS associated with HRT was 2.04 (95% CI 1.91 to 2.17). While HRT, diabetes, rheumatoid arthritis and gout had similar effects on CTS across all age groups, hypothyroidism and obesity had different effects on different groups.ConclusionThis study observed a positive association between HRT and CTS, independent of age, diabetes, rheumatoid arthritis, hypothyroidism, gout and obesity. While the ORs of CTS associated with HRT were similar across age groups, those associated with hypothyroidism and obesity were not, indicating effect modifications by age.
| S-EPMC8728457 | biostudies-literature
Project description:AimsRandomized controlled trials (RCTs) have shown that the risk of stroke and venous thromboembolism (VTE) is increased with hormone replacement therapy (HRT); the effect on coronary heart disease (CHD) remains unclear.Methods and resultsRCTs of HRT were identified. Event rates for cerebrovascular disease [stroke, TIA (transient ischaemic attack)], CHD (myocardial infarction, unstable angina, sudden cardiac death), and VTE (pulmonary embolism, deep vein thrombosis) were analysed. Sensitivity analyses were performed by type of HRT (mono vs. dual) and subject age. 31 trials (44 113 subjects) were identified. HRT was associated with increases in stroke (odds ratio, OR, 1.32, 95% confidence intervals, CI, 1.14-1.53) and VTE (OR 2.05, 95% CI 1.44-2.92). In contrast, CHD events were not increased (OR 1.02, 95% CI 0.90-1.11). Ordinal analyses confirmed that stroke severity was increased with HRT (OR 1.31, 95% CI 1.12-1.54). Although most trials included older subjects, age did not significantly affect risk. The addition of progesterone to oestrogen doubled the risk of VTE.ConclusionHRT is associated with an increased risk of stroke, stroke severity, and VTE, but not of CHD events. Although most trials studied older patients, increased risk was not related to age. Combined HRT increases the risk of VTE compared with oestrogen monotherapy.
| S-EPMC2515884 | biostudies-literature
Project description:BackgroundThe molecular mechanisms underlying window of implantation (WOI) displacement in patients with recurrent implantation failure (RIF) remain unclear. This study aims to explore the transcriptomic signatures of endometrium with normal and displaced WOIs and to identify the causes of endometrial receptivity (ER) abnormalities and WOI displacement in RIF patients.MethodsIn this study, 40 RIF patients were recruited and underwent personalized embryo transfer (pET) guided by the predicted results of endometrial receptivity diagnosis (ERD) model. Transcriptome analysis of endometrium from patients with clinical pregnancies after pET was performed to identify differentially expressed genes (DEGs) associated with WOI displacement. Gene expression data from HRT and natural cycle endometrium were compared to identify specific gene expression patterns of ER-related genes during WOI.ResultsThe ERD results indicated that 67.5% of RIF patients (27/40) were non-receptive in the conventional WOI (P+5) of the HRT cycle. The clinical pregnancy rate in RIF patients improved to 65% (26/40) after ERD-guided pET, indicating the effectiveness of transcriptome-based WOI prediction. Among the 26 patients with clinical pregnancy, the gene expression profiles of P+5 endometrium from advanced (n=6), normal (n=10) and delayed (n=10) WOI groups were significantly different from each other. Furthermore, 10 DEGs identified among P+5 endometrium of 3 groups were involved in immunomodulation, transmembrane transport and tissue regeneration, which could accurately classify the endometrium with different WOIs. Additionally, a large number of ER-related genes showed significant correlation and similar gene expression patterns in P+3, P+5, and P+7 endometrium from HRT cycles and LH+5, LH+7, and LH+9 endometrium from natural cycles.ConclusionOur study shows that ER-related genes share similar gene expression patterns during WOI in both natural and HRT cycles, and their aberrant expression is associated with WOI displacements. The improvement of pregnancy outcomes in RIF patients by adjusting ET timing according to ERD results demonstrates the importance of transcriptome-based endometrial receptivity assessment and the clinical efficiency of ERD model.
| S-EPMC10863671 | biostudies-literature
Project description:ObjectiveOral 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.MethodEligible 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.ResultsWe 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 vs 1.9). The GRS was associated with VTE risk (HR comparing 4th quartile to 1st: 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.ConclusionThe VTE GRS might inform clinical guidance regarding the balance of risks and benefits of HT use, especially among younger women.
| S-EPMC8881382 | biostudies-literature
Project description:BackgroundGiven the known deleterious effects seen with bicarbonate supplementation for acidemia, we hypothesized that utilizing high bicarbonate concentration replacement solution in continuous venovenous hemofiltration (CVVH) would be independently associated with higher mortality.MethodsIn a propensity score-matched historical cohort study conducted at a single tertiary care center from December 9, 2006, through December 31, 2009, a total of 287consecutive adult critically ill patients with Stage III acute kidney injury (AKI) requiring CVVH were enrolled. We excluded patients on maintenance dialysis, those who received other modalities of continuous renal replacement therapies, and patients that received a mixed of 22 and 32 mEq/L bicarbonate solution pre- and post-filter. The primary outcome was in-hospital and 90-day mortality rates.ResultsAmong enrollees, 68 were used 32 mEq/L bicarbonate solution, and 219 received 22mEq/L bicarbonate solution for CVVH. Patients on 32 mEq/L bicarbonate solution were more often non-surgical, had lower pH and bicarbonate level but had higher blood potassium and phosphorus levels in comparison with those on 22 mEq/L bicarbonate solution. After adjustment for the baseline characteristics, the use of 32 bicarbonate solution was significantly associated with increased in-hospital (HR = 1.94; 95% CI 1.02-3.79) and 90-day mortality (HR = 1.50; 95% CI 1.03-2.14). There was a significant increase in the hospital (p = .03) and 90-day (p = .04) mortality between the 22 vs. 32 mEq/L bicarbonate solution groups following propensity matching.ConclusionOur data showed there is a strong association between using high bicarbonate solution and mortality independent of severity of illness and comorbid conditions. These findings need to be evaluated further in prospective studies.
| S-EPMC5619733 | biostudies-literature
Project description:Background: Previous studies have suggested that prenatal inflammation could damage the immature brain of preterm infants. In this study, we aimed to investigate whether funisitis could affect childhood neurodevelopment. We hypothesized that childhood neurodevelopment would vary across groups with or without funisitis. Material sand Methods: Using data from the U.S. Collaborative Perinatal Project (1959-1976), 29,725 subjects with available intelligence quotient (IQ) were studied. Detailed placental examinations were conducted according to a standard protocol with quality control procedures. Multivariate logistic regression models were applied to evaluate the relationship between funisitis and IQ at age 4 or 7 years after adjusting for confounders. Results: Early preterm birth children with funisitis had a 3.0-fold (95% confidence interval 1.2, 7.3) risk of low full-scale IQ (<70) at age 4 years, which disappeared until age 7 years. Term birth children with funisitis had 1.9-fold (95% confidence interval 1.2, 3.0) risk of low performance IQ at age 7 years, but they did not have increased risk of low full-scale IQ. No difference in IQ score was found in late preterm birth children. Conclusion: Funisitis may injure the developmental brain of infants, leading to the relative low IQ in childhood at age 4, but the negative effect is only existed in performance IQ at age of 7.
| S-EPMC6584799 | biostudies-literature