Estrogen Replacement and Ovarian Cancer

Byron's Comments:

More widespread damage by the medical profession.

Study Title:

Hormone Therapy and Ovarian Cancer

Study Abstract:

Context Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration.

Objective To assess risk of ovarian cancer in perimenopausal and postmenopausal women receiving different hormone therapies.

Design and Setting Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register of Medicinal Product Statistics provided individually updated exposure information. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. Information on confounding factors and effect modifiers was from other national registers. Poisson regression analyses with 5-year age bands included hormone exposures as time-dependent covariates.

Participants A total of 909 946 women without hormone-sensitive cancer or bilateral oophorectomy.

Main Outcome Measure Ovarian cancer.

Results In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian cancers, of which 2681 were epithelial cancers, were detected. Compared with women who never took hormone therapy, current users of hormones had incidence rate ratios for all ovarian cancers of 1.38 (95% confidence interval [CI], 1.26-1.51) and 1.44 (95% CI, 1.30-1.58) for epithelial ovarian cancer. The risk declined with years since last use: 0 to 2 years, 1.22 (95% CI, 1.02-1.46); more than 2 to 4 years, 0.98 (95% CI, 0.75-1.28); more than 4 to 6 years, 0.72 (95% CI, 0.50-1.05), and more than 6 years, 0.63 (95% CI, 0.41-0.96). For current users the risk of ovarian cancer did not differ significantly with different hormone therapies or duration of use. The incidence rates in current and never users of hormones were 0.52 and 0.40 per 1000 years, respectively, ie, an absolute risk increase of 0.12 (95% CI, 0.01-0.17) per 1000 years. This approximates 1 extra ovarian cancer for roughly 8300 women taking hormone therapy each year.

Conclusion Regardless of the duration of use, the formulation, estrogen dose, regimen, progestin type, and route of administration, hormone therapy was associated with an increased risk of ovarian cancer.

From press release:

Compared with women who have never taken hormone therapy, those who currently take it or who have taken it in the past are at increased risk of ovarian cancer, regardless of the duration of use, the formulation, estrogen dose, regimen or route of administration, according to a new study.

Primary prevention of ovarian cancer is challenging because little is known about its cause. Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy (HT), according to background information in the article. Data have been limited on the differing effects of formulations, regimens and routes of administration.

Lina Steinrud Mørch, M.Sc., of Rigshospitalet, Copenhagen University, Denmark, and colleagues conducted a study to examine the risk of ovarian cancer associated with hormone therapy use. The study included all Danish women age 50 through 79 years from 1995 through 2005 through linkage to Danish national registers. Prescription data from the National Register of Medicinal Product Statistics provided individually updated information on HT use. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. The analysis included a total of 909,946 women without hormone-sensitive cancer or who had not had both ovaries removed. At the end of follow-up, 63 percent of the women had not been taking HT, 22 percent were previous users of hormones, and 9 percent current users of hormones. Among the current users, 46 percent had used hormones for more than 7 years.

During an average of 8 years of follow-up, 3,068 ovarian cancers were detected . Of these, 2,681 were epithelial tumors (a type of ovarian cancer). Compared with never users, current users of HT had an overall 38 percent increased risk of ovarian cancer. When restricting the analyses to epithelial ovarian cancer, the relative risk among current HT users was 44 percent higher, with previous HT users having a 15 percent increased risk compared with women who had never used HT. The risk for ovarian cancer and epithelial ovarian cancer did not increase significantly with increasing durations of HT.

The risk of ovarian cancer declined with longer time since last HT use. The risk of ovarian cancer did not differ significantly by formulation, regimen, type of progestin or route of administration.

The absolute risk indicated approximately 1 extra ovarian cancer for roughly 8,300 women taking hormone therapy each year. “If this association is causal, use of hormones has resulted in roughly 140 extra cases of ovarian cancer in Denmark over the mean follow-up of 8 years, i.e., 5 percent of the ovarian cancers in this study. Even though this share seems low, ovarian cancer remains highly fatal, so accordingly this risk warrants consideration when deciding whether to use HT,” the authors write.


Study Information:

Lina Steinrud Mørch, MSc; Ellen Løkkegaard, MD, PhD; Anne Helms Andreasen, MSc; Susanne Krüger-Kjær, MD, DrMSci; Øjvind Lidegaard, MD, DrMSci. Hormone Therapy and Ovarian Cancer JAMA 2009 July 302(3):298-305.

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