Hormone Therapy and Different Ovarian Cancers

Lina Steinrud Mørch; Ellen Løkkegaard; Anne Helms Andreasen; Susanne Krüger Kjær; Øjvind Lidegaard


Am J Epidemiol. 2012;175(12):1234-1242. 

In This Article

Abstract and Introduction


Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from 1995–2005. The women were 50–79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers, including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women taking unopposed oral estrogen therapy had increased risks of both serous tumors (incidence rate ratio (IRR) = 1.7, 95% confidence interval: 1.4, 2.2) and endometrioid tumors (IRR = 1.5, 95% confidence interval: 1.0, 2.4) but decreased risk of mucinous tumors (IRR = 0.3, 95% confidence interval: 0.1, 0.8). Similar increased risks of serous and endometrioid tumors were found with estrogen/progestin therapy, whereas no association was found with mucinous tumors. Consistent with results from recent cohort studies, the authors found that ovarian cancer risk varied according to tumor histology. The types of ovarian tumors should be given attention in future studies.


Ovarian cancer is the most lethal of gynecologic cancers. Unfortunately, little is known about its etiology. In recent meta-analyses, investigators have concluded that women taking postmenopausal hormone therapy (HT) have an increased risk of ovarian cancer compared with never users.[1,2] Two large prospective studies, the Million Women Study and Danish Sex Hormone Register Study, found an overall increased risk of 30%–40%.[3,4]

Less is known about the association between hormone use and the risk of different histologic subtypes of epithelial ovarian cancer. Other risk factors for ovarian cancer have been found to differ between mucinous and nonmucinous ovarian tumors, supporting the hypothesis of different etiologies.[5,6] However, previous studies on HT and different types of ovarian tumors were mainly case-control studies, and the numbers of cases were small, especially for mucinous tumors.[1,7–10] Most prospective cohort studies either did not examine tumor type[1,4] or had incomplete information on histology.[11]

Recently, Danforth et al.[12] found that estrogen-only therapy (ET) was more strongly associated with the risk of endometrioid tumors than with the risk of other types of epithelial tumors in the Nurses' Health Study (NHS). The Million Women Study found that with HT use, the highest risk was for serous tumors, whereas there was a lower risk of mucinous tumors.[3] Knowledge about the associations between HTs and subtypes of ovarian cancer will add to the understanding of how HT acts as a promoter of ovarian cancer carcinogenesis. Moreover, if different types of ovarian tumors are to be viewed as separate diseases, that fact should be considered when creating the study designs for future research. Therefore, the aim of the present study was to explore the risks of HT associated with different histologic types of ovarian cancer.


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