Depot-Medroxyprogesterone Acetate Use Is Associated with Decreased Risk of Ovarian Cancer: The Mounting Evidence of a Protective Role of Progestins

Cancer Epidemiol Biomarkers Prev. 2021 May;30(5):927-935. doi: 10.1158/1055-9965.EPI-20-1355. Epub 2021 Feb 22.


Background: Combined oral contraceptive use is associated with a decreased risk of invasive epithelial ovarian cancer (ovarian cancer). There is suggestive evidence of an inverse association between progestin-only contraceptive use and ovarian cancer risk, but previous studies have been underpowered.

Methods: The current study used primary data from 7,977 women with ovarian cancer and 11,820 control women in seven case-control studies from the Ovarian Cancer Association Consortium to evaluate the association between use of depot-medroxyprogesterone acetate (DMPA), an injectable progestin-only contraceptive, and ovarian cancer risk. Logistic models were fit to determine the association between ever use of DMPA and ovarian cancer risk overall and by histotype. A systematic review of the association between DMPA use and ovarian cancer risk was conducted.

Results: Ever use of DMPA was associated with a 35% decreased risk of ovarian cancer overall (OR, 0.65; 95% confidence interval, 0.50-0.85). There was a statistically significant trend of decreasing risk with increasing duration of use (P trend < 0.001). The systematic review yielded six studies, four of which showed an inverse association and two showed increased risk.

Conclusions: DMPA use appears to be associated with a decreased risk of ovarian cancer in a duration-dependent manner based on the preponderance of evidence. Further study of the mechanism through which DMPA use is associated with ovarian cancer is warranted.

Impact: The results of this study are of particular interest given the rise in popularity of progestin-releasing intrauterine devices that have a substantially lower progestin dose than that in DMPA, but may have a stronger local effect.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Carcinoma, Ovarian Epithelial / epidemiology
  • Carcinoma, Ovarian Epithelial / prevention & control*
  • Case-Control Studies
  • Contraceptive Agents, Hormonal / administration & dosage*
  • Female
  • Humans
  • Medroxyprogesterone Acetate / administration & dosage*
  • Middle Aged
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / prevention & control*
  • Progestins / pharmacology
  • Risk Assessment


  • Contraceptive Agents, Hormonal
  • Progestins
  • Medroxyprogesterone Acetate