Depot Medroxyprogesterone Acetate and Risk of Meningioma in the US

Tianqi Xiao, MD1,2; Pranav Kumar, BA1,2; Mina Lobbous, MD, MSPH2,3; et al 

2025년09월02일

JAMA Neurol. Published online: September 2, 2025.

DOI:10.1001/jamaneurol.2025.3011

Abstract

Importance  There lacks data clarifying the meningioma risk conferred by depot medroxyprogesterone acetate in the US.

Objective  To examine the relative risk of meningioma diagnosis in women using depot medroxyprogesterone acetate and other related progestins.

Design, Setting, and Participants  This retrospective population-based cohort study used data from TriNetX, a US national database of 68 health care organizations. Data were analyzed from December 2004 to December 2024. The incidence of meningioma diagnosis was compared between treatment groups through propensity-score matched analyses. Participants included a sample of females with use of only 1 of the following progestins/contraceptives: depot medroxyprogesterone acetate, oral medroxyprogesterone acetate, combined oral contraceptives, intrauterine devices, progestin only pills, or subdermal implantable contraceptive. The control group included females without use of these hormonal treatments. Of the 118 289 082 total patients in TriNetX at the time of analysis, 61 588 239 patients were female and eligible.

Exposures  Patients were defined using diagnostic codes from the International Classification of Diseases, Current Procedural Terminology, and RxNorm codes within TriNetX.

Main Outcome and Measure  The main outcome was meningioma diagnosis. Relative risks and number needed to harm were calculated.

Results  There were 10 425 438 patients that met inclusion criteria with a mean age of 33.4 years at inclusion. After propensity score matching, 88 667 patients with mean age of 26.2 years at inclusion were in the depot medroxyprogesterone acetate group. Use of depot medroxyprogesterone acetate had a relative risk of 2.43 (95% CI, 1.77-3.33) for meningioma diagnosis compared with controls. Notably, this risk was confined for patients with longer than 4 years of exposure or starting the prescription at ages older than 31 years. Oral medroxyprogesterone acetate had increased relative risk of 1.18 (95% CI, 1.10-1.27) compared with controls. No increased risk of meningioma diagnosis was found with any other contraceptive. The number needed to harm for the depot medroxyprogesterone acetate was 1152 patients and 3020 patients for oral medroxyprogesterone acetate.

Conclusions and Relevance  In this study, women receiving depot medroxyprogesterone acetate had a greater relative risk of subsequent meningioma diagnosis, especially with prolonged exposures and starting the medication at older ages. The high number needed to harm suggests low clinical risk overall.

Key Points

Question  What is the association between the use of injectable depot medroxyprogesterone acetate and a meningioma diagnosis for women in the US?

Findings  This population-based cohort study of a national US database demonstrated that women using depot medroxyprogesterone acetate had a statistically significant increased relative risk of developing a meningioma diagnosis when compared with women using oral medroxyprogesterone acetate, other contraceptives, and healthy controls without use of these contraceptives. No increased risk of meningioma diagnosis was found with any other contraceptive.

Meaning  In this study, women who used depot medroxyprogesterone acetate had an increased risk for developing a meningioma.

Table 4.  Meningioma Incidence Risk Following Propensity-Matched Analysis of Contraceptive Use

Forest Plot of the Relative Risks (RRs) for Meningioma Diagnosis Across Propensity-Score Matched Analyses With 95% CIs

COC indicates combined oral contraceptives; Cu, copper; dMPA, depot medroxyprogesterone acetate; IUD, intrauterine device; LGN, levonorgestrel; oMPA, oral medroxyprogesterone acetate; POP, progesterone only pill; SDI, subdermal implant.

요약

·         중요성 : 미국에서는 데포-메드록시프로게스테론 아세테이트(DMPA) 사용이 뇌수막종(meningioma) 발생 위험에 어떤 영향을 미치는지에 대한 명확한 데이터가 부족하다.

·         목적 : DMPA 및 기타 관련 프로게스틴(progestins) 사용 여성에서 뇌수막종 진단의 상대 위험도(relative risk, RR)를 평가하는 것

·         연구 설계, 환경 및 참여자 :

-연구 설계: 후향적 인구 기반 코호트 연구

-데이터베이스: 미국 TriNetX (68개 의료기관, 약 1억 1,828만명 데이터)

-연구 기간: 2004년 12월 ~ 2024년 12월

-연구 대상:

※ 여성 61,588,239명 중, 아래 단일 피임 방법만 사용한 환자 포함

▪ DMPA (주사제)

▪ 경구용 메드록시프로게스테론 아세테이트(oral MPA)

▪  복합 경구 피임약(combined oral contraceptives)

▪  자궁내 장치(IUD)

▪  프로게스틴 단일제 경구약(progestin-only pills)

▪  피하 이식형 피임제(subdermal implant)

※ 대조군: 해당 호르몬 피임제를 사용하지 않은 여성

·         노출 :

-국제질병분류(ICD), 시술코드(CPT), 약제코드(RxNorm)를 기반으로 DMPA 및 다른 피임약 사용자 분류

·         주요 평가지표 : 

-1차 평가지표: 뇌수막종(meningioma) 진단 여부

-상대위험도(RR), 95% 신뢰구간(CI), 그리고 유해발생필요수(Number Needed to Harm, NNH) 계산.

·          결과 : 

-최종 분석 대상자: 10,425,438명 (포함 기준 충족)

▪ 평균 연령: 33.4세

-성향점수매칭(Propensity Score Matching) 후:

▪ DMPA 사용자: 88,667명

▪ 평균 연령: 26.2세

-주요 결과

▪ DMPA 사용 → 뇌수막종 위험 2.43배 증가

(RR 2.43, 95% CI 1.77–3.33)

▪ 이 위험 증가는 4년 이상 장기 사용 또는 31세 이후 시작한 경우에서 더 뚜렷하게 나타남.

▪ 경구 MPA: 위험 1.18배 증가

  (RR 1.18, 95% CI 1.10–1.27)

▪ 기타 피임 방법(복합 경구약, IUD, 프로게스틴 단일제, 피하 이식형): 유의미한 위험 증가 없음

-Number Needed to Harm (NNH):

▪ DMPA: 1,152명당 1명 추가 발생 

▪ 경구 MPA: 3,020명당 1명 추가 발생

·         결론 및 의의 :

-DMPA 사용 여성에서 뇌수막종 진단 위험이 증가하였으나, 이는 장기간 사용 또는 31세 이후 시작한 경우에서만 뚜렷함.

-그러나 NNH가 매우 크다(>1,000)는 점에서, 절대 위험(absolute risk)은 낮아 임상적으로 전체적인 위험은 크지 않음. 

-고위험군(예: 고연령, 장기 DMPA 사용자)에서는 주의 깊은 모니터링이 필요함.