The largest double-blind randomized controlled trial of combined HRT/HT was the Women's Health Initiative (N = 16,608). This study found that, after an average follow-up of 5.6 years, women taking combined HRT/HT (compared with women randomly assigned to placebo) had a nonstatistically significant increased risk of invasive ovarian cancer (hazard ratio [HR] = 1.58; 0.77–3.24), with a wide confidence interval.
A collaborative analysis of case-control studies, analyzing data from 2,200 women with ovarian cancer and 8,900 control women from 12 U.S. studies, reported an association between fertility drug use and invasive ovarian cancer. The use of fertility drugs was associated with an increased risk of ovarian cancer, primarily in women who did not have a subsequent pregnancy. Two case-control studies published subsequent to the collaborative analysis did not find an association between fertility drug use and risk of ovarian cancer.[29,30]
A retrospective cohort study of women evaluated for infertility observed an increased risk of invasive or borderline malignant ovarian tumors associated with prolonged use of clomiphene. Another retrospective cohort of more than 12,000 women evaluated for infertility found an increased risk of ovarian cancer compared with the general population (standardized incidence ratio 1.98; 95% CI, 1.4–2.6). There was no excess risk with the use of clomiphene or gonadotropins. Although the risks of ovarian cancer were slightly higher among women with 15 or more years from first exposure, the number of exposed cases were small (five exposed cases and three exposed cases, respectively) and observed rate ratios were not statistically significant.
Several other cohort studies of women undergoing infertility treatment have not observed an excess risk of ovarian cancer.[32,33,34] In one study, women with unexplained infertility who were not exposed to fertility drugs had an excess risk of ovarian and uterine cancers.
A cohort study among nurses did not observe a risk of ovarian cancer associated with perineal talc use (RR = 1.09; 95% CI, 0.86–1.37). A meta-analysis of 16 studies observed an increased risk with the use of talc (RR = 1.33; 95% CI, 1.16–1.45); however, there was no evidence of a dose response.