JB & JS open access · 2026
Hormone Replacement Therapy Is Associated with Increased Risk of Anterior Cruciate Ligament Tear in Midlife Women in the United States.
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Playter Katharine P, Gordon Olivia L, Matzkin Elizabeth G
Аннотация
BACKGROUND: Across the female lifespan, the incidence of anterior cruciate ligament (ACL) tears has demonstrated a bimodal age distribution, and this may be related to fluctuating lifetime estrogen. However, this relationship-and the role of hormone replacement therapy (HRT) and its potentially modifying effect on ACL tear risk-has been underreported. The purpose of this study was to (1) characterize the ACL tear risk pattern in women compared with men in a national database and (2) assess the relationship between HRT and the risk of ACL tear among midlife women.
METHODS: A retrospective cohort study was conducted using the Merative© MarketScan Commercial database. The data set was queried for women 40 to 55 years of age with insurance claims between January 1, 2019, and December 31, 2023. The exposure of interest was any systemic supplemental estrogen. The primary outcome was any ACL tear following the index date. The nearest neighbor 5:1 propensity score was used to generate matched groups with and without exposure to supplemental estrogen.
RESULTS: Of 384,582 included individuals, 16,751 were taking HRT. Analysis of aggregate ACL tear events, normalized by person-time, demonstrated a bimodal distribution in women, with peaks during adolescence (16-20 years old) and midlife (40-50 years old). Conditional logistic regression analysis demonstrated that women in the supplemental estrogen-exposed group had a significantly higher risk of any ACL tear (OR: 1.26, 95% CI: 1.02-1.55) and ACL reconstruction (OR: 1.5, 95% CI: 1.07-2.11) compared with the control group.
CONCLUSIONS: Estrogen-containing HRT was associated with significantly increased risk of ACL tear when controlling for age, comorbidities, and perimenopausal or menopausal status. The relationship between HRT and ACL tear risk is likely multifactorial, and these findings support the need for further prospective studies to better characterize this relationship.
LEVEL OF EVIDENCE: Level III-Retrospective, observational cohort. See Instructions for Authors for a complete description of levels of evidence.
METHODS: A retrospective cohort study was conducted using the Merative© MarketScan Commercial database. The data set was queried for women 40 to 55 years of age with insurance claims between January 1, 2019, and December 31, 2023. The exposure of interest was any systemic supplemental estrogen. The primary outcome was any ACL tear following the index date. The nearest neighbor 5:1 propensity score was used to generate matched groups with and without exposure to supplemental estrogen.
RESULTS: Of 384,582 included individuals, 16,751 were taking HRT. Analysis of aggregate ACL tear events, normalized by person-time, demonstrated a bimodal distribution in women, with peaks during adolescence (16-20 years old) and midlife (40-50 years old). Conditional logistic regression analysis demonstrated that women in the supplemental estrogen-exposed group had a significantly higher risk of any ACL tear (OR: 1.26, 95% CI: 1.02-1.55) and ACL reconstruction (OR: 1.5, 95% CI: 1.07-2.11) compared with the control group.
CONCLUSIONS: Estrogen-containing HRT was associated with significantly increased risk of ACL tear when controlling for age, comorbidities, and perimenopausal or menopausal status. The relationship between HRT and ACL tear risk is likely multifactorial, and these findings support the need for further prospective studies to better characterize this relationship.
LEVEL OF EVIDENCE: Level III-Retrospective, observational cohort. See Instructions for Authors for a complete description of levels of evidence.