Use of menopausal hormone therapy and ovarian cancer risk in a French cohort study

Author:

Fournier Agnès1ORCID,Cairat Manon1ORCID,Severi Gianluca12ORCID,Gunter Marc J3ORCID,Rinaldi Sabina3ORCID,Dossus Laure3ORCID

Affiliation:

1. “Exposome, Heredity, Cancer and Health” Team, Centre for Epidemiology and Population Health (CESP UMR 1018), Université Paris-Saclay, Inserm, Institut Gustave Roussy , Villejuif, France

2. Department of Statistics, Computer Science and Applications “G. Parenti”, University of Florence , Florence, Italy

3. Nutrition and Metabolism Branch, International Agency for Research on Cancer , Lyon, France

Abstract

Abstract Background Epidemiological studies have found that menopausal hormone therapy (MHT) use is associated with an increased ovarian cancer risk. However, whether different MHT types confer the same level of risk is unclear. We estimated the associations between different MHT types and the risk of ovarian cancer in a prospective cohort. Methods The study population included 75 606 postmenopausal women from the E3N cohort. Exposure to MHT was identified from self-reports in biennial questionnaires between 1992 and 2004 and from drug claim data matched to the cohort between 2004 and 2014. Hazard ratios and 95% confidence intervals (CIs) of ovarian cancer were estimated using multivariable Cox proportional hazards models with MHT as a time-varying exposure. Tests of statistical significance were 2-sided. Results Over an average 15.3 years follow-up, 416 ovarian cancers were diagnosed. Hazard ratios of ovarian cancer associated with ever use of estrogens combined with progesterone or dydrogesterone and ever use of estrogens combined with other progestagen were equal to 1.28 (95% CI = 1.04 to 1.57) and 0.81 (95% CI = 0.65 to 1.00), respectively (Phomogeneity = .003), compared with never use. The hazard ratio for unopposed estrogen use was 1.09 (95% CI = 0.82 to 1.46). We found no trend according to duration of use or time since last use except for estrogens combined with progesterone or dydrogesterone, which showed decreasing risk with increasing time since last use. Conclusion Different MHT types may impact ovarian cancer risk differentially. The possibility that MHT containing progestagens other than progesterone or dydrogesterone may confer some protection should be evaluated in other epidemiological studies.

Funder

French League against Cancer

French National Institute of Health and Medical Research

Mutuelle Générale de l’Education Nationale

Gustave Roussy Institute

French National Research Agency

French Ministry of Higher Education, Research and Innovation

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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