Endometriosis is a ‘’hormone-sensitive’’ disease. The disease is ‘’dependent’’ on oestrogens, as we observe raised levels of oestrogens as well as changes in the oestrogen receptors of women with endometriosis¹. We also observe ‘’progesterone resistance’’ as a result of dysfunction of its receptors². Apart from the dependence on oestrogens and the progesterone resistance, patients with endometriosis present higher levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines³. The aforementioned lead to a hyper-inflammatory ‘’micro-environment’’.

Based on the above, medical management with hormones is the first-line management as well as a useful strategy post-operatively. However, medical management has, for the time being, various disadvantages: it only works in a number of patients⁴, is associated with side-effects⁵, and works as contraception (a problem for women that wish to get pregnant imminently).

The good results offered by radical surgical excision of endometriosis lesions^6-9, may also be explained (at least partially) by the role of hormones and the hyper-inflammatory ‘’micro-environment’’. It has been demonstrated that the surgical excision of endometriosis lesions leads to a measurable reduction in the levels of pro-inflammatory cytokines¹⁰.

Since we have touched upon the role of oestrogens in endometriosis, we can now discuss one of the most promising theories. According to the ‘’Oestrogen-threshold Theory’’¹¹, if we manage to keep the oestradiol (E2, oestrogen) levels between 30 and 60 pg/mL, we could achieve ‘’a perfect compromise’’ between improvement of endometriosis symptoms and unpleasant side-effects from low oestrogen levels.  The use of the new, promising drugs (Gnrh antagonists) is based on this principle¹².

References:

1. Chantalat E, Valera MC, Vaysse C, Noirrit E, Rusidze M, Weyl A, Vergriete K, Buscail E, Lluel P, Fontaine C, Arnal JF, Lenfant F. Estrogen Receptors and Endometriosis. Int J Mol Sci. 2020 Apr 17;21(8):2815.
2. Patel, B.G.; Rudnicki, M.; Yu, J.; Shu, Y.; Taylor, R.N. Progesterone resistance in endometriosis: Origins, consequences and interventions. Acta Obstet. Gynecol. Scand. 2017, 96, 623–632.
3. Gazvani R, Templeton A. Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction. 2002; 123:217–226.
4. Donnez, J.; Dolmans, M.-M. GnRH Antagonists with or without Add-Back Therapy: A New Alternative in the Management of Endometriosis? Int. J. Mol. Sci. 2021, 22, 11342.
5. Millochau J.C., Abo C., Darwish B., Huet E., Dietrich G., Roman H. Continuous Amenorrhea May Be Insufficient to Stop the Progression of Colorectal Endometriosis. J. Minim. Invas. Gynecol. 2016;23:839–842.
6. Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis: A committee opinion. Fertil. Steril. 2014, 101, 927–935.
7. Dunselman, G.A.; Vermeulen, N.; Becker, C.; Calhaz-Jorge, C.; D’Hooghe, T.; De Bie, B.; Heikinheimo, O.; Horne, A.W.; Kiesel, L.; Nap, A.; et al. ESHRE guideline: Management of women with endometriosis. Hum. Reprod. 2014, 29, 400–412.
8. Leyland, N.; Casper, R.; Laberge, P.; Singh, S.S. Endometriosis: Diagnosis and management. J. Obstet. Gynecol. Can. 2010, 32, S1–S3.
9. Keckstein, J.; Becker, C.M.; Canis, M.; Feki, A.; Grimbizis, G.F.; Hummelshoj, L.; Nisolle, M.; Roman, H.; Saridogan, E.; Tanos, V. et al. Recommendations for the surgical treatment of endometriosis. Part 2: Deep endometriosis. Hum. Reprod. Open. 2020, 2020, hoaa002.
10. Monsanto SP, Edwards AK, Zhou J, Nagarkatti P, Nagarkatti M, Young SL, Lessey BA, Tayade C. Surgical removal of endometriotic lesions alters local and systemic proinflammatory cytokines in endometriosis patients. Fertil Steril. 2016 Apr;105(4):968-977.
11. Barbieri, R.L. Hormone treatment of endometriosis: The estrogen threshold hypothesis. Am. J. Obstet. Gynecol. 1992, 166, 740–745.
12. Donnez J, Dolmans MM. GnRH Antagonists with or without Add-Back Therapy: A New Alternative in the Management of Endometriosis? Int J Mol Sci. 2021 Oct 20;22(21):11342.