ArticlesEndometrial cancer and hormone-replacement therapy in the Million Women Study
Introduction
Use of oestrogen-only hormone-replacement therapy (HRT) increases the risk of endometrial cancer.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 To counteract this effect, many postmenopausal women who have not had a hysterectomy use combined HRT—regimens containing progestagens and oestrogens. Epidemiological evidence suggests that use of such combined oestrogen-progestagen therapy attenuates, and perhaps even reverses, the oestrogen-associated increase in endometrial cancer.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 However, published findings are sparse and mostly come from the USA, where HRT preparations often differ from those available elsewhere. Furthermore, tibolone, a synthetic steroid with oestrogenic, progestagenic, and androgenic properties, has not been licensed in the USA, but is prescribed for HRT in many countries, and has been linked to an increased risk of endometrial cancer.14, 15 We report here on the relation between use of different types of HRT and incidence of endometrial cancer in the Million Women Study, a cohort study including about one of every four women in the UK who were aged 50–64 years in 1996–2001.16, 17
Section snippets
Data collection, follow-up, and definitions
Between May, 1996, and March, 2001, more than a million women joined the study.16, 17 They completed a recruitment questionnaire containing questions about sociodemographic and other personal factors, including use of HRT. A follow-up questionnaire was sent to study participants 2–3 years after recruitment, to update information on use of HRT and other factors. These questionnaires can be viewed on the study website. To date, 1·3 million study participants have been flagged on the NHS Central
Results
716 738 postmenopausal women with no previous cancer or hysterectomy were recruited in 1996–2001, flagged on the NHS Central Registers, and followed up for incident cancer. Average age at entry into the study was 57·5 years. 320 953 women (45%) reported that they had ever used HRT, and among them 22% last used continuous combined preparations, 45% last used cyclic combined preparations, 9% last used tibolone, 4% last used oestrogen-only HRT, 2% last used other or more than one HRT type, and 18%
Discussion
In this large cohort study, the types of HRT commonly used in the UK were shown to have sharply contrasting effects on the risk of developing endometrial cancer. Compared with never users of HRT, the overall incidence of endometrial cancer was increased in users of tibolone and oestrogen-only therapy and decreased in users of continuous combined HRT. However, the effect of the commonly used types of HRT varied, depending on a woman's body-mass index. Among women who were not overweight, use of
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