An Update on Pathophysiology and Medical Management of Endometriosis

Abstract

Endometriosis is an inflammatory oestrogen dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The modern advance in treatment of endometriosis management is tackling the debilitating pain it causes, besides the infertility in patients desiring fertility in reproductive age group. This can be achieved by surgical or medical means, although in most cases a combination of both treatments is required. Usually, long term treatment is required in most cases. Unfortunately in most cases, pain symptoms recur between 6months and 12 months once treatment is stopped. A lot of research has gone in understanding the pathogenesis and further medical management of endometriosis besides surgery to be useful in relieving pain and use in patients desiring fertility besides hormonal treatments used earlier like hormonal contraceptives (oral, transdermal or vaginal administration), progestogens, danazol, Gonadotrophic releasing hormone agonist (GnRH), aromatase inhibitors. Newer agents like antiangiogenic drugs, phytochemical agents like resveratrol, TNF-α inhibitors, GnRH antagonists like egalogolix, statins, antiinflammatory agents like COX2 Inhibitors and PPARγ inhibitors like pioglitazone etc., with recent work of combined efficacy of telmesartan of both PPARγ partial agonism along with angiotensin 1 receptor agonism having more efficacy, role of immunomodulators like rapamycin, lipoxin 4 and pentoxyphylline, GnRH antagonists like egalogolix are still under study undergoing phase III trials although preliminary results show promising results with fewer side effects as compared to similar duration of GnRH agonist and much less BMD side effects. Increasing number of trials show the safety of SPRM's, along with efficacy although disadvantage is suppression of fertility so cannot be used for women desiring fertility. Currently, only mifepristone and ulipristal have received FDA approval for indication in fibroid treatment, MTP and not for endometriosis as yet. The advantages and disadvantages of all the recent advances are discussed in an update in the pathophysiology as well medical treatment of endometriosis.

The Potential Effect of Fucoidan on Inhibiting Epithelial-to-Mesenchymal Transition, Proliferation, and Increase in Apoptosis for Endometriosis Treatment: In Vivo and In Vitro Study

“…Endometriosis is an inflammatory disease caused by increased TNF-α and IL-1β, which reduce the protein expression of Bax and increase Bcl-2 to inhibit the apoptosis of endometriotic lesions [ 18 ]. A previous study indicated that FC inhibited inflammation and induced apoptosis of cancer cells.…”

“…Through macrophage or directly, estrogen can induce endometriotic-cell-secreted pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). When the inflammatory factor increases, the ability of anti-apoptosis, proliferation, invasion, and the migration ability is elevated in endometriosis cells [ 18 ]. In addition, TNF-α and IL-1β could induce NF-κB expression and further regulate vascular endothelial growth factor (VEGF) expression.…”

“…In addition, TNF-α and IL-1β could induce NF-κB expression and further regulate vascular endothelial growth factor (VEGF) expression. Increased vascular endothelial growth factor (VEGF) expression could also induce angiogenesis and EMT [ 18 , 19 , 20 ].…”

Should All Patients With Endometriosis Undergo Surgery?

“…It not only reduces pain but also improves the microenvironment of adnexa and peritoneal, thereby increasing fertility. 1,2 Based on our results, those with endometriosis who underwent laparoscopic surgery had the rate spontaneous pregnancy of 46.3% within a year after surgery. 3 However, it should be noted that the recurrence rate increased within a year in the absence of pregnancy.…”

“…3 However, it should be noted that the recurrence rate increased within a year in the absence of pregnancy. 1,4 Careful monitoring should be performed during the first year after surgery to increase the potency of fertility, and providing adjuvant hormonal therapy when necessary to reduce the risk of recurrence. 4,5 Medical treatment should be given for those who do not expect pregnancy to prevent recurrence.…”