Investigating the Potential Effect of Hormone Replacement Therapy as a Risk Factor for Meningiomas

Introduction: Meningiomas are known to express estrogen and progesterone receptors. Long-term estrogen or progesterone hormone replacement therapy (HRT), regardless of biological sex, may be a risk factor for their development. However, the literature has not reached a consensus on this association. In this study, we aim to elucidate the association between HRT and meningioma incidence among various patient populations.

Methods: The National Inpatient Survey (NIS) dataset from 2016-2019 was queried to identify four patient groups: 1) Males receiving HRT (ICD-10 Z79.890) experiencing gender identity disorders (GID) (ICD-10 F64), 2) Male patients neither receiving HRT nor experience GID, 3) Female patients not receiving HRT, and 4) Female patients receiving HRT. Patients with hypothyroidism and testosterone deficiencies were excluded to avoid confounding of the ICD-10 code. 1:1 propensity matching was conducted to match male patients and match female patients by demographics and meningioma risk factors. Chi-square and Fisher’s exact tests were utilized for univariate analysis, and multivariate logistic regression was utilized to control for covariates.

Results: 12,598 male patients were identified, of whom 6,299 (50.0%) were receiving HRT for GID. Four (0.1%) male patients on HRT developed meningiomas compared to six (0.1%) patients without HRT or GID: no significant difference was noted (p=0.752). 34,530 female patients were identified, of whom 17,265 (50.0%) were receiving estrogen or progesterone HRT. Sixty-one (0.4%) female patients receiving HRT developed meningiomas, compared to 57 (0.3%) female patients not receiving HRT. The difference in meningioma incidence was not significant (p=0.782). On multivariate analysis of the female cohort, HRT use was not associated with development of meningiomas (p=0.699).

Conclusion : No significant differences in meningioma incidence between patients receiving HRT and patients not receiving HRT were identified, irrespective of sex. These trends point to a likely lack of association between HRT use and meningiomas. Further longitudinal studies should be conducted to clearly characterize outcomes of cisgender and transgender patients receiving HRT.