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

Jade Desilets, Rosa Lakabi, Lakabi R, Olsthoorn A, Alisha Olsthoorn, Matelski J, John Matelski, Chris Walsh, Murji A, Ally Murji, Miazga E, Elizabeth Miazga
Obstetrics and gynecology · 2026 · vol. 148(2) , pp. 205–215 · doi:10.1097/AOG.0000000000006241 · PMID:41855532
meta-analysis OA: closed public-domain-us
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⚙ AI-generated summary by claude@2026-06, 2026-06-13 ⓘ

This systematic review and meta-analysis found that hormonal therapies for endometriosis, including GnRH agonists, dienogest, and GnRH antagonists, are associated with decreased bone mineral density after 6 and 12 months of use.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-13 · read from full text ⓘ

This systematic review and meta-analysis evaluated how medical therapies for endometriosis affect bone mineral density, drawing on clinical studies (RCTs and prospective/retrospective cohorts) of reproductive-age women that assessed GnRH agonists with add-back, dienogest, GnRH antagonists, and depot medroxyprogesterone acetate, with searches conducted through July 2025. Across 37 included studies, pooled results showed decreases in BMD with GnRH agonists at 6 and 12 months, with subgroup analyses indicating reductions even with add-back, while dienogest was also associated with lower BMD; GnRH antagonists decreased BMD at 6 months, and DMPA results could not be meta-analyzed. The authors note high heterogeneity and inconsistencies for several comparisons, and the clinical significance of the BMD changes is uncertain. This paper is centrally about endometriosis — it systematically reviews hormonal suppression treatments for endometriosis and their effects on bone health (BMD).

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Abstract

OBJECTIVE: To evaluate the effect of endometriosis medical therapies on bone mineral density (BMD). DATA SOURCES: Electronic databases were searched from inception to July 2025 for clinical studies reporting the effect of hormonal treatments for endometriosis on BMD. METHODS OF STUDY SELECTION: 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. TABULATION, INTEGRATION, AND RESULTS: 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. CONCLUSION: 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. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42024580675.
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Objective

To evaluate the effect of endometriosis medical therapies on bone mineral density (BMD). DATA SOURCES: Electronic databases were searched from inception to July 2025 for clinical studies reporting the effect of hormonal treatments for endometriosis on BMD.

Methods

OF STUDY SELECTION: 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. TABULATION, INTEGRATION, AND RESULTS: 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.

Conclusion

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. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42024580675.

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Condition tags

endometriosis

MeSH descriptors

Bone Density Bone Density Bone Density Bone Density Bone Density Bone Density Bone Density Bone Density Bone Density Bone Density Bone Density Bone Density Bone Density Bone Density Bone Density Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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