The Mechanism of Single Progesterone as Add-Back Therapy to GnRH-a Administration

Ruxia Shi
In: World Journal of Gynecology & Womens Health · 2019 · vol. 1(5) · doi:10.33552/wjgwh.2019.01.000521 · W2907416310
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⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-07 ⓘ

This study investigated the mechanism of single progesterone as an add-back therapy to gonadotropin-releasing hormone agonist administration for endometriosis treatment.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text ⓘ

This paper is an opinion-style review on the mechanistic rationale for using a single progesterone add-back regimen—norethindrone acetate (1.25–2.5 mg daily)—during gonadotropin-releasing hormone agonist (GnRH-a) treatment in women with endometriosis, discussing broader add-back regimens and the concept of maintaining estrogen within a tissue-specific “estrogen dosage window.” It describes GnRH-a–induced low estrogen and argues that add-back aims to preserve estrogen around normal levels to reduce perimenopausal side effects and avoid stimulation of ectopic endometrial growth, while specifically analyzing norethindrone as a 19-nortestosterone derivative with progesterone activity plus androgen and partial estrogen activity that may contribute to effects such as hemostasis and reduced pelvic congestion/bleeding. A key limitation is that the text does not provide direct clinical trial data for the single-progesterone regimen, presenting instead a theoretical/clinical conference–based explanation of why it might work. Relevance to endometriosis: endometriosis is the central context for GnRH-a add-back therapy in the paper, and the single progesterone (norethindrone acetate) regimen is discussed as part of add-back strategies specifically to address endometriosis-related treatment challenges.

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Abstract

Endometriosis (EMS) is a common estrogen-dependent gynecological disorder, which affects quality of life and fertility of productive-aged women [1]. Current treatment of EMS is mainly based on surgery and post-operative maintenance treatment of ovarian suppressive agents.
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Acknowledgement

This work was supported by a grant from Major Science and Technology Project of Changzhou Health and Family Planning Commission(ZD201812). Conflict of Interest No conflict of interest.

References

1. Nirgianakis K, Bersinger NA, McKinnon B, Kostov P , Imboden S, et al. (2013) Regression of the inflammatory microenvironment of the peritoneal cavity in women with endometriosis by GnRHa treatment. Eur J Obstet Gynecol Reprod Biol 170(2): 550-554. 2. Almassinokiani F, Mehdizadeh A, Sariri E, Rezaei M, Almasi A, et al. (2013) Effects of simvastatin in prevention of pain recurrences after surgery for endometriosis. Med Sci Monit 19: 534-539. 3. The Chinese medical association branch of obstetrics and gynecology endometriosis group (2007) The diagnosis and treatment of endometriosis. Chin J Obstet Gynecol 42 (9): 645-647. 4. Leng JH, Lang JH, Yang JX (2000) Progress of diagnosis and treatment of endometriosis. Chin J Obstet Gynecol 35 (1): 53-55. 5. Liu DY, Gu MJ, Shu JZ, Shi YX, Wang CY, et al. (2006) Effect of triptorelin and an extended-interval dosing regimen in the treatment of patients with endometriosis and adenomyoma. Chin J Obstet Gynecol 41 (10): 657-659. 6. Yang DZ and Wang MY (2010) Proceedings of the third national meeting on endometriosis and chronic pelvic pain. Chin J Obstet Gynecol 45 (4): 243-245. 7. Khan KN, Kitajima M, Hiraki K, Fujishita A, Nakashima M, et al. (2010) Cell proliferation effect of GnRH agonist on pathological lesions of women with endometriosis, adenomyosis and uterine myoma. Hum Reprod 25 (11): 2878–2890. 8. Wang YQ, Zhang SF, Chen X, Zhu J, Hua KQ, et al. (2009) Effects and safety of gonadotrophin-releasing hormone agonist combined with estradiol Citation: Ruxia Shi, Jiming Chen, Junling Liu, Weiwei Wei, Ying Cao, et al. The Mechanism of Single Progesterone as Add-Back Therapy to GnRH-a Administration. W J Gynecol Women’s Health. 1(5): 2018. WJGWH.MS.ID.000521. DOI: 10.33552/WJGWH.2019.01.000521. World Journal of Gynecology & Women’s Health Volume 1-Issue 5 Page 3 of 3 patch and oral medroxyprogesterone acetate on endometriosis. Chinese J Obstet Gynecol 44 (7): 7-9. 9. Liu PS, Li X, Liu Y, Hong-luan M, Yu-lan S (2008) Ximingting tablets in the treatment of women with climacteric syndrome. J Shandong Univ 46(8): 791-794. 10. Zhou L and Liu YJ (2011) Progress of black cohosh treatment for peri- menopausal syndrome. Res Integ Tradit Chin West Med 3(3): 150-152. 11. Endometriosis Collaboration Group, Obstetrics and Gynecology Branch, Chinese Medical Association (2015). Chin J Obstet Gynecol 50(3): 161- 169. 12. Barbieri RL (1992) Hormone treatment of endometriosis: the estrogen threshold hypothesis. Am J Obster Gynecol 166(2): 740-745.

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endometriosis

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