Translational Insights into the Pathogenesis, Molecular Biomarkers, and Targeted Therapeutics of Endometriosis in Non-Human Primate Models: A Systematic Review

Yohanes Adam Elsoin, Hermawan Wibisono
In: Sriwijaya Journal of Obstetrics and Gynecology · 2026 · vol. 4(2) , pp. 56–71 · doi:10.59345/sjog.v4i2.380 · W7225663450
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Abstract

Background: Endometriosis is a chronic, estrogen-dependent gynecological dis-order affecting 10–15% of reproductive-aged women worldwide. Unlike rodents, Old World non-human primates (NHPs) menstruate spontaneously and develop lesions that are histologically indistinguishable from human disease. Objective: To evaluate NHP evidence on the pathogenesis, molecular and imaging biomarkers, and targeted therapeutics of endometriosis. Methods: This review followed PRISMA 2020 and Synthesis Without Meta-analysis (SWiM) guidelines. Four databases were searched through July 2026 for original NHP endometriosis studies. Risk of bias (five domains) and certainty (GRADE narrative) were appraised. Results: Of 426 records, 20 studies (N = 299 NHPs: 132 olive baboons, 96 rhe-sus macaques, 55 cynomolgus macaques, and 16 mixed macaques) were synthe-sized in four clusters. In Cluster 1 (k = 5, N = 85), rosiglitazone (−51.8% lesion area), letrozole, the 17β-HSD1 inhibitor PBRM (−67% red lesions), and dienogest reduced lesion burden or central pain sensitization; testosterone with a Western-style diet accelerated Stage III/IV endometrioma. In Cluster 2 (k = 4, N = 61; Low certainty), bentamapimod and rhTNFbp-1 regressed active lesions, anti-TNF-α mAb c5N did not improve fecundity (18% vs. 30% placebo), and intraperitoneal mesenchymal stem cells worsened endometriosis scores (P = 0.02). Cluster 3 (k = 8, N = 109) described collective invasion, mitochondrial depletion, Treg:Th17 dysbiosis, 92.9% induction by intrauterine puncture, and oviductal Anoctamin-1 attenuation. Cluster 4 (k = 3, N = 44) reported serum miRNAs, CXCL13, and PET/CT imaging. Conclusion: NHP models offer high translational fidelity for developing fertility-sparing therapeutics and biomarkers; small, short-term studies limit certainty.

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