Effect of Medical Therapies for Endometriosis on Bone Health: A Systematic Review and Meta-analysis.
Hormonal therapies for endometriosis may lead to a decrease in bone mineral density, but the clinical significance of this finding is unclear and warrants further investigation.
Where it sits
this study against the rest of the goserelin corpusSummary and findings
This systematic review and meta-analysis evaluated the effect of medical therapies for endometriosis on bone mineral density (BMD) in women of reproductive age. The study included various hormonal treatments, including GnRH agonists, dienogest, and DMPA. The findings indicated a decrease in BMD associated with these therapies over time.
Abstract
<h4>Objective</h4>To evaluate the effect of endometriosis medical therapies on bone mineral density (BMD).<h4>Data sources</h4>Electronic databases were searched from inception to July 2025 for clinical studies reporting the effect of hormonal treatments for endometriosis on BMD.<h4>Methods of study selection</h4>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.<h4>Tabulation, integration, and results</h4>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.<h4>Conclusion</h4>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.<h4>Systematic review registration</h4>PROSPERO, CRD42024580675.
Background
This paper addresses the impact of hormonal therapies for endometriosis on bone health, specifically bone mineral density (BMD). Prior research has indicated that hormonal treatments can influence BMD, but the extent and clinical significance of these effects were not well established. This study is important as it synthesizes existing data to provide insights into the potential risks associated with long-term hormonal therapy in women with endometriosis.
Methods
The study design was a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies. The population included women of reproductive age receiving various hormonal treatments for endometriosis. A total of 1,153 studies were screened, and 37 met the inclusion criteria. The primary outcome measure was the change in BMD at 6 and 12 months, with various hormonal therapies assessed.
Results
The pooled analysis indicated a decrease in BMD of -0.89% at 6 months and -1.50% at 12 months. Subgroup analyses showed that leuprolide and goserelin also decreased BMD, with leuprolide showing a reduction of -1.33% at 6 months. Goserelin's effect was -0.42% at 6 months, which was not statistically significant. Dienogest and GnRH antagonists also demonstrated reductions in BMD, with the latter showing a decrease of -2.17% at 6 months.
Interpretation
The findings suggest that hormonal therapies for endometriosis are associated with a decrease in BMD, particularly with GnRH agonists and antagonists. While some results are statistically significant, the clinical significance of these changes is uncertain, especially given the small effect sizes and high heterogeneity in some analyses. The study's limitations, including the lack of data on DMPA and potential biases, further complicate the interpretation of these results for clinical practice.
Key findings
- -0.89% BMD at 6 months, 95% CI -1.45 to -0.33, I2 =20.3%, n=11 studies
- -1.50% BMD at 12 months, 95% CI -2.68 to -0.31, I2 =40.5%, n=4 studies
- -1.33% BMD with leuprolide at 6 months, 95% CI -1.92 to -0.74, I2 =0%, n=6 studies
- -0.42% BMD with goserelin at 6 months, 95% CI -1.00 to 0.16, I2 =11%, n=5 studies
- -0.83% BMD with dienogest at 6 months, 95% CI -1.52 to -0.15, I2 =76.8%, n=6 studies
- -2.17% BMD with GnRH antagonist at 6 months, 95% CI -3.44 to -0.90, I2 =97.3%, n=5 studies
Limitations
- high heterogeneity in some analyses
- lacked data on DMPA for meta-analysis
- uncertain clinical significance of findings