Table 3.
Protective epigenetic effects of nonsurgical therapies for endometriosis
| Therapies | Epigenetic roles | Active ingredient | Patient/objects | Clinical outcome | References |
|---|---|---|---|---|---|
| COX-2 inhibitors | Diminishes COX-2 hypomethylation in the eutopic endometriosis | Rofecoxib | Women | Endometriosis-related pelvic pains significantly decreased with no recurrence | Cobellis et al (186); Ota et al (188) |
| Celecoxib | Human endometrial cells | Decrease COX-2 activity via a decrease in the production of PGE2 and VEGF | Cobellis et al (186) | ||
| Nimesulide | Endometrial stromal cells | Prevent ectopic endometrial stromal cell proliferation | Kong et al (225) | ||
| Aromatase inhibitor | Counters estrogen-driven epigenetic changes | Letrozole | Women | Improve endometrium receptivity and uterine health | Steiner et al (209) |
| P4-based therapy | Help maintain epigenetic homeostasis linked to endometriosis | OCP | Women | The endometrioma volume dramatically decreased in the OCP group compared with the placebo | Harada et al (195) |
| Progestin | Women | Trigger the HPO and consequently influence the pathophysiology of the endometriosis | Casper et al (198); Buggio et al (197) | ||
| GnRH antagonists | Help maintain epigenetic homeostasis linked to hypoestrogenism in endometriosis and endometrial fibrosis | Leuprolide acetate | Women | Improve endometrium receptivity and subside undiagnosed endometriosis | Steiner et al (209) |
| Linzagolix | Women | Significantly reduced pain related to endometriosis | Dababou et al (204) | ||
| Relugolix | Women | Significantly improved endometriosis-associated pain | Giudice et al (205) | ||
| Elagolix | Women | Effectively alleviate endometriosis lesions and endometriosis-associated pelvic pain | Diamond et al (207); Taylor et al (206) | ||
| Histone/DNA methylation modulators | Directly related to the pathophysiology and progression of endometriosis | EZH2 antagonist | Human endometrial and endometriotic cells | Reduced migration and proliferation of endometriotic epithelial cells | Colón-Caraballo et al (52) |
| EZH2 inhibitor (tazemetostat) | Female rats | Reduce the number of endometriotic vesicles | Seguinot-Tarafa et al (53) | ||
| Modulates DNA methylation and histone modification-related proteins functions in endometriotic cells | AH 6809 and AH23848 (PGE2 receptors antagonist) | Human endometriotic epithelial and stromal cell | Inhibits adhesion, invasion, growth, and survival endometriotic cells by modifying integrins, MMPs, and TIMPs, cell cycle, survival, and intrinsic apoptotic pathways | Arosh et al (221) | |
| SIRT1 is an epigenetic mediator in the endometrium of women with endometriosis | EX-527 (SIRT1 inhibitor) | Mouse endometriosis model | Endometriotic lesions were diminished significantly with EX-527 treatment via downregulating STRT1 | Rezk et al (148) | |
Abbreviations: AH23848, thromboxane receptor blocker; AH 6809, 6-isopropoxy-9-oxoxanthene-2-carboxylic acid; COX-2, cyclooxygenase 2; EZH2, histone methyltransferase; HPO, hypothalamic-pituitary-ovarian axis; MMP, matrix metalloproteinase; OCP, estrogen-progestin oral contraceptive pill; PGE2, prostaglandin E2; SIRT1, sirtuin-1; TIMP, metalloprotease inhibitor.