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

Minh Tung Phung & Malcolm C. Pike et al. · 2021-02-22

Abstract

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 (Ptrend < 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.

Funding
A Pooled Analysis to Identify New Ovarian Cancer Risk FactorsEpidemiology of Ovarian Cancer:New HypothesesDana-Farber/Harvard Cancer Center Ovarian Cancer SPOREOVARIAN CANCER RISK AND SURVIVAL IN BRCA CARRIERSPathologyOvarian Cancer and Gonadotropin SignalingGenes, Hormones & Environment in an Ovarian Cancer ModelThe Molecular Epidemiology Of Ovarian CancerSteroid Hormone Genes and Ovarian Cancer RiskRegulatory T Cell Function in Ovarian CancerSURVEILLANCE EPIDEMIOLOGY & END RESULTS PROGRAMProject 1University of Michigan Rogel Cancer Center Support Grant 2023-2028General Clinical Research CenterInflammation and Ovarian CancerThe Progesterone Receptor Gene and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskCancer Research Training and Education CoordinationInterpretable Machine Learning to Identify Alzheimer's Disease Therapeutic TargetsHormone Therapy and Risk of Ovarian CancerSURVEILLANCE EPIDEMIOLOGY AND END RESULTSGenes, Hormones & Environment in an Ovarian Cancer ModelDana-Farber/Harvard Cancer Center Ovarian Cancer SPORESteroid Hormone Genes and Ovarian Cancer RiskEpidemiology of Ovarian Cancer:New HypothesesCollaborative Genetic Study of Ovarian Cancer RiskIn vitro and In Vivo screening of chemopreventive agentsCancer Genetic Network (CGN)Inflammation and Ovarian CancerOVARIAN CANCER RISK AND SURVIVAL IN BRCA CARRIERSThe Molecular Epidemiology Of Ovarian CancerNIH Grant P01-CA17054National Center for Research Resources FundingGeneral Clinical Research CenterU.S. Army Medical Research and Material Command Grant DAMD17–01–1-0729U.S. Department of Defense Grant DAMD17–02–1-0669U.S. Department of Defense Grant DAMD17–02–1-0666U.S. Department of Defense Grant W81XWH-10–1-02802

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P30 CA008748

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P50 CA159981

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M01 RR000056

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R01 CA095023

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R01-CA054419

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P50-CA105009

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R01-CA112523

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R01-CA087538

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R01-CA058598

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N01-CN-55424

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N01-PC-67001

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R01-CA095023

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K07-CA080668

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R01-CA076016

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M01-RR000056