According to the Women's Health Initiative Study , a randomized, double-blind, placebo-controlled trial including 16 608 postmenopausal women, the hazard ratio for invasive ovarian cancer in women assigned to estrogen and progestin compared with placebo was 1.58 (95% CI 0.77 to 3.24)
In a cohort study in the UK, 948 576 postmenopausal women without previous cancer or bilateral oophorectomy were followed-up for an average of 5.3 years for incident ovarian cancer and 6.9 years for death. 30% of women were current users and 20% past users of hormone replacement therapy (HRT). During follow-up, 2 273 incident ovarian cancers and 1 591 deaths from the malignancy were recorded. Ovarian cancer was more frequent with current users than never users (RR 1.20, 95% CI 1.09 to1.32 for incident disease and RR 1.23, 95% CI 1.09 to 1.38 for death). The relative risks did not vary appreciably by socioeconomic status, reproductive history, previous use of oral contraceptives, body-mass index, or alcohol and tobacco consumption. For current users, incidence of ovarian cancer increased with increasing duration of use, but did not differ significantly by type of preparation used. Risks associated with HRT varied according to tumour histology (p<0.0001), and in women with epithelial tumours the relative risk for current versus never use of HRT was greater for serous than for mucinous, endometroid, or clear cell tumours. Past users of HRT were not at an increased risk of ovarian cancer (RR 0.98, 95% CI 0.88 to 1.11 for incident and 0.97, 95% CI 0.84 to 1.11 for fatal disease). Over 5 years, the standardised incidence rates for ovarian cancer in current and never users of HRT were 2.6 (95% CI 2.4 to 2.9) and 2.2 (95% CI 2.1 to 2.3) per 1000, respectively; death rates were 1.6 (95% CI 1.4 to 1.8) and 1.3 (95% CI 1.2 to 1.4) per 1 000, respectively – i.e. one extra ovarian cancer in roughly 2 500 users and one extra cancer death in roughly 3 300 users.
A systematic review including 10 studies (9 case-control studies and one cohort study) with a total of 256 257 cases of invasive cancer, 1 case-control study of invasive and borderline cancers (1 684 patients) and 1 case-control study with borderline cancers only (2 882 patients) was abstracted in DARE. Ever use of HRT was associated with an increased risk of developing invasive epithelial ovarian cancer (RR 1.15, 95% CI 1.05 to 1.27). Some heterogeneity was present. Inclusion of studies with borderline carcinoma produced similar results. No trend on increasing risk with increased duration was observed. According to a cohort study of 44 241 postmenopausal women , the ever use of estrogen-only was associated with an increased risk of ovarian cancer (rate ratio 1.6, 95% CI 1.2 to 2.0). There was a 7% increase of risk ratio per year of use. The RR for estrogen plus progestin use was 1.1 (5% CI 0.64 to 1.7).
Comment: The quality of evidence is downgraded by inconsistency (variability in results across studies).