Medical Therapies for Endometriosis Differentially Inhibit Stem Cell Recruitment

Objective: To determine the effect of the 3 well-known endometriosis treatments on stem cell recruitment to endometriotic lesions. Study Design: C57BL/6 mice (aged 8 weeks, n = 20) underwent bone marrow transplant following submyeloablation with 5-fluorouracil using 20 × 106 bone marrow stem cells from green fluorescent protein (GFP) mice. Two weeks after transplantation, experimental endometriosis was created in mice by suturing segments of the uterine horn into the peritoneal cavity. Mice were then randomized to receive treatment with medroxyprogesterone acetate (MPA), leuprolide acetate (Gonadotrophin-Releasing Hormone Analogue [GnRHa]), letrozole, or vehicle control (dimethyl sulfoxide). After 3 weeks of treatment, the mice were killed and the endometriosis lesions evaluated. Results: All 3 treatments resulted in a significant reduction in lesion volume and weight. Estrogen deprivation using GnRHa or letrozole resulted in greater lesion regression than the progestin MPA. The GFP+/CD45− bone marrow-derived stem cells (BMDSCs) engrafted the lesions of endometriosis. Estrogen deprivation using GnRHa or letrozole significantly reduced BMDSC engraftment in the endometriosis lesions. MPA failed to significantly reduce stem cell number in endometriosis. Conclusion: The superiority of estrogen deprivation over progestin therapy in depriving the lesions of stem cells may have implications for the long-term treatment of endometriosis. Reduced stem cell engraftment is likely to result in long-term regression of the lesions, whereas progestins may only prevent their growth acutely.