Postoperative Hormone Replacement Therapy and Survival in Women with Ovarian Cancer.
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ABSTRACT:
SUBMITTER: Ji E
PROVIDER: S-EPMC9265037 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The American Women’s Health Initiative study published in July 2002 caused considerable concern among hormone replacement therapy (HRT) users and prescribers in many countries. This study is an exploratory research comparing the genome wide expression profile in whole blood samples according to HRT use. Within the Norwegian Women and Cancer study, 100 postmenopausal women (50 HRT users and 50 non-HRT users) born between 1943 and 1949 with normal to high body mass index and no other medication use were selected. After total RNA extraction, amplification and labelling, the samples were hybridized together with a common reference (Universal human reference RNA, Stratagen) to Agilent Human 1A oligoarrays (G4110b, Agilent Technologies, Palo Alto, CA) containing 20,173 unique genes. Differentially expressed genes were used to build a classifier using the nearest shrunken centroids method (PAM). Then, we tested the significant changes in single genes by different methods like t-test, Significance Analysis of Microarrays (SAM) and Bayesian ANOVA analysis (BAM). Results did not reveal any distinct gene list which predicted accurately HRT exposure (error rate = 0.45). Classifier performance slightly improved (error rate = 0.29) including only women who were using continuous combined HRT treatment. According to the small amplitude of expression alterations observed after HRT use in whole blood, large sample sizes are needed to identify significant single genes differentially expressed. However, significant enrichments in biologic process of genes with small changes after HRT use were observed (e.g. receptor and transporter activities, immune response, frizzled signalling pathway, actin filament organization, glycogen metabolism). Keywords: gene expression profile and exposure
2005-10-25 | GSE3492 | GEO
Project description:IntroductionHormone replacement therapy (HRT) can help women experiencing menopausal symptoms, but usage has declined due to uncertainty around risks of cancer and some cardiovascular diseases (CVD). Moreover, improved cancer survival rates mean that more women who survive cancer go on to experience menopausal symptoms. Understanding these relationships is important so that women and their clinicians can make informed decisions around the risks and benefits of HRT. This study's primary aim is to determine the association between HRT use after cancer diagnosis and the risk of cancer-specific mortality. The secondary aims are to investigate the risks of HRT on subsequent cancer, all-cause mortality and CVD.Methods and analysisWe will conduct a population-based longitudinal cohort study of 18-79 year-old women diagnosed with cancer between 1998 and 2020, using the QResearch database. The main exposure is HRT use, categorised based on compound, dose and route of administration, and modelled as a time-varying covariate. Analysis of HRT use precancer and postcancer diagnosis will be conducted separately. The primary outcome is cancer-specific mortality, which will be stratified by cancer site. Secondary outcomes include subsequent cancer diagnosis, CVD (including venous thrombo-embolism) and all-cause mortality. Adjustment will be made for key confounders such as age, body mass index, ethnicity, deprivation index, comorbidities, and cancer grade, stage and treatment. Statistical analysis will include descriptive statistics and Cox proportional hazards models to calculate HRs and 95% CIs.Ethics and disseminationEthical approval for this project was obtained from the QResearch Scientific Committee (Ref: OX24, project title 'Use of hormone replacement therapy and survival from cancer'). This project has been, and will continue to be, supported by patient and public involvement panels. We intend to the submit the findings for peer-reviewed publication in an academic journal and disseminate them to the public through Cancer Research UK.
| S-EPMC8330592 | biostudies-literature
Project description:Background: Findings by epidemiologic studies on menopausal hormone replacement therapy (HRT) and the risk of ovarian cancer are inconsistent. This study aimed to assess the association of menopausal HRT with the risk of ovarian cancer by histological subtype. Methods: A literature search was performed in PubMed, Web of Science, and EmBase for relevant articles published from inception to August 2018. Pooled relative risk ratios (RRs) with 95% confidence intervals (CIs) were determined with a random-effects model. Results: Thirty-six studies involving 4, 229, 061 participants were included in this meta-analysis. The pooled RR of ovarian cancer was 1.29 (95%CI 1.19-1.40, I 2 = 57.4%) for menopausal HRT. In subgroup analysis by study design, pooled RRs of ovarian cancer in cohort and case-control studies were 1.35 (95%CI 1.19-1.53) and 1.24 (95%CI 1.11-1.38), respectively. In subgroup analysis by continent, association of menopausal HRT with ovarian cancer was significant for North America (1.41 [1.23-1.61]), Europe (1.22 [1.12-1.34]), and Asia (1.76 [1.09-2.85]), but not Australia (0.96 [0.57-1.61]). Association differed across histological subtypes. Increased risk was only found for two common types, including serous (1.50 [1.35-1.68]) and endometrioid (1.48 [1.13-1.94]) tumors. Conclusion: This meta-analysis suggests that menopausal HRT may increase the risk of ovarian cancer, especially for serous and endometrioid tumors.
| S-EPMC6902084 | biostudies-literature
Project description:BackgroundFrequently, patients treated for Ovarian Cancer (OC) undergo menopause with subsequent symptoms. This review scrutinised the impact of Hormone Replacement Therapy (HRT) on the Overall Survival (OS) and Progression-Free Survival (PFS) of patients diagnosed with OC.MethodsA systematic literature search was conducted in the most popular English databases. Inclusion and exclusion criteria were applied to select publications that evaluate OS and PFS in these patients. End-point analysis targeted values of log(HR) and its Standard Error (SE).ResultsUp to 1 September 2022, 11 studies were included in the qualitative synthesis. Eight publications, totalling 4191 patients, were included in the meta-analyses. Eight studies were considered for the OS analysis and pooled an HR of 0.66 with respective 95% CI between 0.57 and 0.76, with a p-value < 0.00001 at a Z value of 5.7, in favour of the HRT group. Results for PFS showed an overall HR of 0.73 in favour of the HRT group; CI between 0.57 and 0.95, p = 0.02 at a Z value of 2.36. Further subgroup analyses highlighted the non-inferiority of this treatment.ConclusionsPatients treated for OC that receive HRT for menopausal symptoms after various treatments appeared to have better OS than never-users.
| S-EPMC9856775 | biostudies-literature
Project description:The effect of hormone replacement therapy (HRT) on the malignant transformation of postmenopausal endometriosis remains unclear. This study aimed to investigate the impact of HRT on ovarian cancer occurrence in postmenopausal women with de novo endometriosis or a history of endometriosis. A total of 10,304 women that received HRT (the HRT group) and 10,304 that did not (the control group) were selected by 1:1 matching those that met the study criteria. Incidences of ovarian cancer (0.3% in the HRT group and 0.5% in the control group) and cumulative incidence rates of ovarian cancer were similar in the two groups. The overall mean duration of HRT was 1.4 ± 2.2 years, but the duration of HRT in women with ovarian cancer was 2.2 ± 2.9 years. After adjusting for co-variables, receipt of HRT, duration of HRT, combined use of estrogen and progesterone, and tibolone were not found to be risk factors for ovarian cancer. However, the use of estrogen alone was found to be a significant risk factor for ovarian cancer (HR 2.898; 95% CI 1.251-6.715; p = 0.013). With the exception of HRT using estrogen alone, HRT did not increase the risk of ovarian cancer in postmenopausal women with a history of endometriosis or de novo endometriosis.
| S-EPMC10046182 | biostudies-literature
Project description:BACKGROUND: The risks/benefits balance of hormone replacement therapy is controversial. Information can influence consumers' knowledge and behavior; research findings about hormone replacement therapy are uncertain and the messages provided by the media are of poor quality and incomplete, preventing a fully informed decision making process. We therefore felt that an explicit, rigorous and structured assessment of the information needs on this issue was urgent and we opted for the organisation of a national consensus conference (CC) to assess the current status of the quality of information on hormone replacement therapy (HRT) and re-visit recent research findings on its risks/benefits. METHODS: We chose a structured approach based on the traditional CC method combined with a structured preparatory work supervised by an organising committee (OC) and a scientific board (SB). The OC and SB chose the members of the CC's jury and appointed three multidisciplinary working groups (MWG) which were asked to review clinical issues and different aspects of the quality of information. Before the CC, the three MWGs carried out: a literature review on the risk/benefit profile of HRT and two surveys on the quality of information on lay press and booklets targeted to women. A population survey on women's knowledge, attitude and practice was also carried out. The jury received the documents in advance, listened the presentations during the two-day meeting of the CCs, met immediately after in a closed-door meeting and prepared the final document. Participants were researchers, clinicians, journalists as well as consumers' representatives. RESULTS: Key messages in the CC's deliberation were: a) women need to be fully informed about the transient nature of menopausal symptoms, about HRT risks and benefits and about the availability of non-pharmacological interventions; b) HRT is not recommended to prevent menopausal symptoms; c) the term "HRT" is misleading and "post menopausal hormone therapy" should be the preferred definition. CONCLUSION: This CC led to the identification of specific information drawbacks. Women are exposed to messages that are often partial, non evidence-based nor transparently developed. The structured and participative methodology of this CC allowed a multidisciplinary perspective and a substantial lay people input.
| S-EPMC2698849 | biostudies-literature
Project description:ObjectiveTo estimate the effect of estrogen-only and combined hormone replacement therapy (HRT) on the hazards of overall and age-specific all-cause mortality in healthy women aged 46-65 at first prescription.DesignMatched cohort study.SettingElectronic primary care records from The Health Improvement Network (THIN) database, UK (1984-2017).Population105 199 HRT users (cases) and 224 643 non-users (controls) matched on age and general practice.MethodsWeibull-Double-Cox regression models adjusted for age at first treatment, birth cohort, type 2 diabetes, hypertension and hypertension treatment, coronary heart disease, oophorectomy, hysterectomy, body mass index, smoking and deprivation status.Main outcome measuresAll-cause mortality.ResultsA total of 21 751 women died over an average of 13.5 years follow-up per participant, of whom 6329 were users and 15 422 non-users. The adjusted hazard ratio (HR) of overall all-cause mortality in combined HRT users was 0.91 (95% CI 0.88-0.94), and in estrogen-only users was 0.99 (0.93-1.07), compared with non-users. Age-specific adjusted HRs for participants aged 46-50, 51-55, 56-60 and 61-65 years at first treatment were 0.98 (0.92-1.04), 0.87 (0.82-0.92), 0.88 (0.82-0.93) and 0.92 (0.85-0.98) for combined HRT users compared with non-users, and 1.01 (0.84-1.21), 1.03 (0.89-1.18), 0.98 (0.86-1.12) and 0.93 (0.81-1.07) for estrogen-only users, respectively.ConclusionsCombined HRT was associated with a 9% lower risk of all-cause mortality and estrogen-only formulation was not associated with any significant changes.Tweetable abstractEstrogen-only HRT is not associated with all-cause mortality and combined HRT reduces the risks.
| S-EPMC9298998 | biostudies-literature
Project description:Results from the epidemiologic studies on the relationship between hormone replacement therapy (HRT) and the risk of kidney cancer in women were not completely consistent. This meta-analysis aimed to evaluate the relationship between HRT and risk of kidney cancer in women. We performed a meta-analysis of observational studies to assess this association. The PubMed and Embase databases were searched from their inception to January 29, 2020, to identify relevant studies that fit the pre-stated inclusion criteria; reference lists from the retrieved articles were also been reviewed. Relative risks (RRs) with corresponding 95% CIs were extracted and combined using random effects models. Furthermore, dose-response, sensitivity analyses, publication bias, and subgroup analysis by study design, regional location, and exposure assessment method were conducted. Thirteen articles involving 6 cohort studies and 8 case-control studies were included in our meta-analysis. Overall, 4194 women were diagnosed with kidney cancer among 648 107 participants. The pooled RR for kidney cancer was 1.08 (95% CI: 0.96-1.22) in those who were administered HRT compared to those who had not. Subgroup analysis indicated the overall result was not influenced by study type, regional location, or adjusted variables. Dose-response analysis showed a nonlinear relationship between HRT and kidney cancer (P = .0021) and the risk of kidney cancer decreased by 15% to 28% with 12 to 18 years of HRT use. No evidence of publication bias was found (P for Egger =.111). Our meta-analysis showed that HRT use is inversely associated with kidney cancer risk in a dose-dependent fashion.
| S-EPMC7366413 | biostudies-literature
Project description:The American Women's Health Initiative study published in July 2002 caused considerable concern among hormone replacement therapy (HRT) users and prescribers in many countries. This study is an exploratory research comparing the genome wide expression profile in whole blood samples according to HRT use. Within the Norwegian Women and Cancer study, 100 postmenopausal women (50 HRT users and 50 non-HRT users) born between 1943 and 1949 with normal to high body mass index and no other medication use were selected. After total RNA extraction, amplification and labelling, the samples were hybridized together with a common reference (Universal human reference RNA, Stratagen) to Agilent Human 1A oligoarrays (G4110b, Agilent Technologies, Palo Alto, CA) containing 20,173 unique genes. Differentially expressed genes were used to build a classifier using the nearest shrunken centroids method (PAM). Then, we tested the significant changes in single genes by different methods like t-test, Significance Analysis of Microarrays (SAM) and Bayesian ANOVA analysis (BAM). Results did not reveal any distinct gene list which predicted accurately HRT exposure (error rate = 0.45). Classifier performance slightly improved (error rate = 0.29) including only women who were using continuous combined HRT treatment. According to the small amplitude of expression alterations observed after HRT use in whole blood, large sample sizes are needed to identify significant single genes differentially expressed. However, significant enrichments in biologic process of genes with small changes after HRT use were observed (e.g. receptor and transporter activities, immune response, frizzled signalling pathway, actin filament organization, glycogen metabolism). Experiment Overall Design: Indirect design with Stratagene reference Experiment Overall Design: 47 non HRT users and 42 HRT users Experiment Overall Design: No technical replicates
2007-11-28 | E-GEOD-3492 | biostudies-arrayexpress
Project description:PurposePrior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival.MethodsData from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery.ResultsUse of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend <0.01 for duration of MHT use). Residual disease mediated some (17%) of the relationship between MHT and survival.ConclusionsPre-diagnosis MHT use for 5+ years was a favorable prognostic factor for women with ovarian cancer. This large study is consistent with prior smaller studies, and further work is needed to understand the underlying mechanism.
| S-EPMC7487048 | biostudies-literature