A prospective study of postmenopausal hormone use and ovarian cancer risk

Abstract

The relationship between postmenopausal hormone use (PMH) and ovarian cancer risk is unclear, particularly for specific hormone formulations, but recent studies suggest that there is a positive association. We conducted a prospective observational study with 82 905 postmenopausal women, including 389 ovarian cancers, in the Nurses' Health Study from 1976 to 2002. Compared with never users of PMH, both current and past users of X5 years had a significantly elevated risk of ovarian cancer (RR ¼ 1.41, 95% confidence interval (CI) 1.07 -1.86 and relative risk (RR) ¼ 1.52, 95% CI 1.01 -2.27, respectively). Examined by hormone type in continuous years, use of unopposed estrogen was associated with a significant increase in the risk of epithelial ovarian cancer (P for trend o0.001; RR for 5-year increment of use ¼ 1.25, 95% CI 1.12 -1.38). Use of estrogen plus progestin (RR for 5-year increment of use ¼ 1.04, 95% CI 0.82 -1.32) was not significantly associated with ovarian cancer risk. Generally, results were similar for serous tumours (RR for 5-year increment of unopposed estrogen use ¼ 1.23, 95% CI 1.07 -1.40) and slightly stronger for endometrioid tumours (RR for 5-year increment of unopposed estrogen use ¼ 1.53, 95% CI 1.20 -1.94). Recency of use was not significantly associated with ovarian cancer risk, but statistical power was limited here.

Hormone therapy and ovarian cancer: incidence and survival

“…In contrast, several studies published since this metaanalysis have suggested that long-term use of E-alone may increase risk [5,7,15,29,30]. In a cohort study, Lacey et al detected a significantly increased risk of ovarian cancer in women who had used estrogen therapy for 10-19 years (HR=1.8, 95% CI: 1.1-3.0) or more than 20 years (HR=3.2, 95% CI: 1.7-5.7) compared to never users [15].…”

“…In a cohort study, Lacey et al detected a significantly increased risk of ovarian cancer in women who had used estrogen therapy for 10-19 years (HR=1.8, 95% CI: 1.1-3.0) or more than 20 years (HR=3.2, 95% CI: 1.7-5.7) compared to never users [15]. Danforth and colleagues detected a two-fold increased risk among users of 5 or more years duration [5], and the recent findings from the Million Women study also suggested an elevated risk with long-duration (≥5 years) of use (relative risk-1.53, 95% CI 1.27-1.84). In the current data, we detected a statistically significant increased risk of ovarian cancer associated with E-alone use, though we could demonstrate no clear dose-response relationship with increasing duration.…”

“…Results from studies conducted in the U.S. [5,11,[13][14][15]31,32], Australia [33], Norway [8], Sweden [29], and U.K [7] have been inconclusive regarding the relationship between EP and ovarian cancer. Overall, we detected no associations with EP use.…”

“…While positive associations between HT and endometrial and breast cancer incidence are well-established [3,4], the relationship with ovarian cancer is less clear. Some studies have shown a modestly increased risk of ovarian cancer associated with HT [5][6][7], but other studies have found no association [8][9][10][11]. A meta-analysis conducted nearly 10 years ago suggested a 15% increased risk of ovarian cancer associated with ever use of HT [12].…”

“…A meta-analysis conducted nearly 10 years ago suggested a 15% increased risk of ovarian cancer associated with ever use of HT [12]. More recently, studies have investigated the type of hormone preparation used [5,7,[13][14][15]. The WHI trial detected an elevated, but not statistically significant, association between estrogen plus progestin therapy (EP) and ovarian cancer [hazard ratio (HR) 1.58, 95% CI 0.77-3.24] [13]; however, during the 5.6-year follow-up period, there were only 32 women diagnosed with ovarian cancer.…”