Current use of HRT linked to increased risk of ovarian cancer and death in 'The Million Women Study'

Key Points

In the large cohort study referred to as the "The Million Women Study" published in the journal Lancet, the use of hormone replacement therapy (HRT) in postmenopausal women was demonstrated to increase the risk of ovarian cancer and death from ovarian cancer by 20% and 23%, respectively, compared to nonuse of HRT.

The investigators stated that previously published studies assessing the relationship between HRT and the risk of ovarian cancer were inconclusive and lacked statistical power due to an insufficient number of enrolled patients receiving HRT.

This analysis evaluated 948,576 postmenopausal women without a baseline diagnosis of cancer who were selected from the 1.3 million participants enrolled in The Million Women Study. Patient data regarding social, demographic, and lifestyle factors, including the use of HRT, were collected at recruitment and again after 3 years of follow-up. Average follow-up was 5.3 years for incident ovarian cancer and 6.9 years for death.

It was demonstrated that current HRT users had a greater risk of both developing (relative risk=1.20; 95% CI, 1.09–1.32; P=.0002) and dying from (relative risk=1.23; 95% CI, 1.09–1.38; P=.0006) ovarian cancer than patients who had never received HRT. Although there was a statistically significant correlation between the risk of ovarian cancer and the duration of HRT, there was no significant correlation between the risk of ovarian cancer and the preparation, mode of administration, or constituents (estrogen alone or combined with progestin) of the prescribed HRT.

Past use of HRT was not associated with an increased risk of ovarian cancer (relative risk=0.98; 95% CI, 0.88–1.11) or death from ovarian cancer (relative risk=0.97; 95% CI, 0.84–1.11).

According to the authors, the results of this study translate into an estimated 1 additional case of ovarian cancer in approximately 2,500 users of HRT and 1 additional death due to ovarian cancer in approximately 3,300 users of HRT over a 5-year period.

The authors stated that the increased risk of ovarian cancer with use of HRT needs to be considered in addition to the increased risks of breast and endo-metrial cancer that accompany use of HRT. "The total incidence of these 3 cancers in the study population is 63% higher in current users of HRT than in [patients who never used HRT] (31 vs 19 per 1,000 over 5 years). Thus, when ovarian, endometrial, and breast cancer are taken together, use of HRT results in a material increase in the incidence of these common cancers."

Ovarian cancer accounts for approximately 4% of all cancers in women and is the fourth-leading cause of cancer-related death among women in the United States. It is estimated that there will be 22,430 new cases of ovarian cancer and 15,280 deaths from ovarian cancer in the United States in 2007.

SOURCES

Beral V, Bull D, Green J, Reeves; for the Million Women Study Collaborators. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet. 2007;369:1703–1710.

National Cancer Institute website. http:// http://www.cancer.gov/cancertopics/types/ovarian/. Accessed August 8, 2007.