Breast cancer risk in postmenopausal women using estradiol-progestogen therapy

Obstet Gynecol. 2009 Jan;113(1):65-73. doi: 10.1097/AOG.0b013e31818e8cd6.


Objective: To estimate the risk for breast cancer in Finnish women using postmenopausal estradiol (E2)-progestogen therapy.

Methods: All Finnish women over 50 years using E2-progestogen therapy for at least 6 months in 1994-2005 (N=221,551) were identified from the national medical reimbursement register and followed up for breast cancer incidence (n=6,211 cases) through the Finnish Cancer Registry to the end of 2005. The risk for breast cancer in E2-progestogen therapy users was compared with that in the general population.

Results: The standardized incidence ratio for all types of breast cancer was not elevated within the first 3 years of use, but it rose to 1.31 (95% confidence interval 1.20-1.42) for the use from 3-5 years and to 2.07 (1.84-2.30) with 10 or more years of use. Exposure to sequential progestogen for 5 years or more was accompanied with a lower risk elevation (1.78, 1.64-1.90) than exposure to continuous use (2.44, 2.17-2.72). Oral and transdermal use of E2-progestogen therapy was associated with comparable risk elevations for breast cancer. The use of norethisterone acetate was accompanied with a higher risk after 5 years of use (2.03, 1.88-2.18) than that of medroxyprogesterone acetate (1.64, 1.49-1.79). The risk of lobular breast cancer increased sooner than that for ductal cancer and was detectable for E2-progestogen therapy use less than 3 years (1.35, 1.18-1.53). There was no excess risk of breast cancer with distant metastases among E2-progestogen therapy users.

Conclusion: The use of E2-progestogen therapy is associated with an increased risk for breast cancer after 3 years of use. The risk is lower for sequential than for continuous use, but comparable for oral and transdermal use. The risk elevation may not be uniform for all progestogens.

Level of evidence: II.

Publication types

  • Comment
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / chemically induced*
  • Breast Neoplasms / epidemiology
  • Carcinoma, Ductal, Breast / chemically induced
  • Carcinoma, Lobular / chemically induced
  • Drug Administration Schedule
  • Estradiol / administration & dosage*
  • Estradiol / adverse effects
  • Estrogen Replacement Therapy / adverse effects*
  • Female
  • Finland / epidemiology
  • Humans
  • Incidence
  • Middle Aged
  • Postmenopause
  • Progestins / administration & dosage
  • Progestins / adverse effects*
  • Risk Factors


  • Progestins
  • Estradiol