Effect of Medical Therapies for Endometriosis on Bone Health: A Systematic Review and Meta-analysis

To evaluate the effect of endometriosis medical therapies on bone mineral density (BMD).

Electronic databases were searched from inception to July 2025 for clinical studies reporting the effect of hormonal treatments for endometriosis on BMD.

Eligible studies included randomized controlled trials (RCTs) and prospective and retrospective cohort studies involving women of reproductive age. Interventions assessed were gonadotropin-releasing hormone (GnRH) agonists with add-back therapy, dienogest, GnRH antagonists, and depot medroxyprogesterone acetate (DMPA). Risk of bias was evaluated with the Cochrane Risk of Bias Tool to evaluate RCTs, the Risk of Bias in Non-Randomized Studies of Interventions tool for nonrandomized trials, and the Newcastle-Ottawa Scale for cohort studies. A total of 1,153 studies were screened, of which 37 met inclusion criteria.

Pooled analysis of GnRH agonist showed a decrease in BMD at 6 months (-0.89%, 95% CI, -1.45 to -0.33, I2 =20.3%, 11 studies) and at 12 months (-1.50%, 95% CI, -2.68 to -0.31, I2 =40.5%, four studies). Subgroup analysis by GnRH agonist type decreased heterogeneity and showed that at 6 months both leuprolide (-1.33%, 95% CI, -1.92 to -0.74, I2 =0%, six studies) and goserelin (-0.42%, 95% CI, -1.00 to 0.16, I2 =11%, five studies) with add-back decreased BMD. Dienogest was associated with lower BMD at 6 months (-0.83%, 95% CI, -1.52 to -0.15, I2 =76.8%, six studies) and 12 months (-1.91%, 95% CI, -2.58 to -1.24. I2 =83.7%, four studies); however, there were high heterogeneity and inconsistency between studies. GnRH antagonist decreased BMD at 6 months (-2.17%, 95% CI, -3.44 to -0.90, I2 =97.3%, five studies), although most studies lacked add-back therapy. Data from four studies on DMPA could not be meta-analyzed. Risk of bias was low in studies included in the analysis.

Hormonal suppression for endometriosis treatment is associated with a decrease in BMD after 12 months of use, with each medical therapy having a unique effect. The clinical significance of these findings remains uncertain, highlighting the need for expert consensus for bone health management in patients on long-term hormonal therapy.

PROSPERO, CRD42024580675.