Hormone therapy and ovarian cancer

JAMA. 2009 Jul 15;302(3):298-305. doi: 10.1001/jama.2009.1052.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Administration, Oral
  • Aged
  • Cohort Studies
  • Denmark / epidemiology
  • Drug Administration Schedule
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogens / administration & dosage*
  • Female
  • Humans
  • Incidence
  • Middle Aged
  • Ovarian Neoplasms / epidemiology*
  • Perimenopause
  • Poisson Distribution
  • Postmenopause
  • Progestins / administration & dosage*
  • Registries
  • Risk
  • Time Factors


  • Estrogens
  • Progestins