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Menopausal Hormone Replacement Therapy and the Risk of Ovarian Cancer: A Meta-Analysis.

ABSTRACT: 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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC6902084 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Menopausal Hormone Replacement Therapy and the Risk of Ovarian Cancer: A Meta-Analysis.

Liu Yang Y Ma Lan L Yang Xiaoling X Bie Jia J Li Dongya D Sun Chunyi C Zhang Jie J Meng Yushi Y Lin Jie J

Frontiers in endocrinology 20191203

<b>Background:</b> 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. <b>Methods:</b> 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 determ ...[more]

PMID: 31849838

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Project description:BackgroundHalf the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk.MethodsIndividual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use.FindingsDuring prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31-1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29-1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40-1·66; p<0·0001) and endometrioid (1·42, 1·20-1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07-1·46, p=0·005).InterpretationThe increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.FundingMedical Research Council, Cancer Research UK.

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.

Project description:BackgroundPublished findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence.MethodsPrincipal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users.FindingsDuring prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1-4 (oestrogen-progestagen RR 1·60, 95% CI 1·52-1·69; oestrogen-only RR 1·17, 1·10-1·26), and were twice as great during years 5-14 (oestrogen-progestagen RR 2·08, 2·02-2·15; oestrogen-only RR 1·33, 1·28-1·37). The oestrogen-progestagen risks during years 5-14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21-2·40 vs 1·93, 1·84-2·01; heterogeneity p<0·0001). For a given preparation, the RRs during years 5-14 of current use were much greater for oestrogen-receptor-positive tumours than for oestrogen-receptor-negative tumours, were similar for women starting MHT at ages 40-44, 45-49, 50-54, and 55-59 years, and were attenuated by starting after age 60 years or by adiposity (with little risk from oestrogen-only MHT in women who were obese). After ceasing MHT, some excess risk persisted for more than 10 years; its magnitude depended on the duration of previous use, with little excess following less than 1 year of MHT use.InterpretationIf these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50-69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.FundingCancer Research UK and the Medical Research Council.

Dataset Information

Menopausal Hormone Replacement Therapy and the Risk of Ovarian Cancer: A Meta-Analysis.

Publications

Menopausal Hormone Replacement Therapy and the Risk of Ovarian Cancer: A Meta-Analysis.

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