Endometriosis-associated bone loss: re-evaluating the potential role of systemic inflammation and hypoestrogenic therapies.

Abstract

Endometriosis is frequently managed with hormonal suppression that can induce hypoestrogenism during a period when many patients are still accruing peak bone mass. This narrative review summarizes current clinical and mechanistic evidence on bone health in endometriosis and its treatments and discusses a preliminary conceptual framework for risk stratification and monitoring. This review discusses two hypothetical converging pathways: (1) an intrinsic pathway in which chronic systemic inflammation may shift bone remodeling toward resorption (via cytokine-mediated effects on osteoclastogenic and Wnt signaling pathways and oxidative stress), and (2) an iatrogenic pathway in which ovarian suppression, most notably with gonadotropin-releasing hormone agonists/antagonists and some progestin-based regimens, reduces estrogen exposure and can lead to measurable short-term bone mineral density loss. Available observational data generally do not show clinically meaningful bone mineral density deficits or excess fracture incidence in untreated endometriosis, but treatment-associated bone mineral density loss is well documented; long-term fracture outcomes and bone-quality measures remain insufficiently studied. We compare the skeletal safety signals across commonly used therapies, discuss the role and limitations of add-back therapy, and highlight when baseline evaluation and follow-up assessment (including consideration of trabecular bone score) may be warranted in higher-risk patients.