Progesterone Resistance and Targeting the Progesterone Receptors: A Therapeutic Approach to Endometriosis

Nick Pullen
In: Endometriosis - Basic Concepts and Current Research Trends · 2012 · doi:10.5772/29021 · W1523215578
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This review examines progesterone receptor antagonists as a therapeutic strategy for endometriosis, exploring pre-clinical and clinical evidence regarding their mechanism and efficacy.

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This chapter reviews the molecular mechanisms underlying progesterone resistance in endometriosis, highlighting how altered expression and function of progesterone receptor isoforms contribute to disease progression. It details the downregulation of PR-B and the relative preservation or upregulation of PR-A, which disrupts normal hormonal signaling and promotes inflammation and cell proliferation. The authors discuss therapeutic strategies aimed at restoring progesterone sensitivity through selective progesterone receptor modulators and other targeted agents to manage symptoms and lesion growth. This paper is centrally about endometriosis — specifically focusing on progesterone resistance as a key pathophysiological feature and potential target for treatment.

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Abstract

Endometriosis is characterised by the benign growth of endometrial glands and stroma on the surface of peritoneal tissues and other organs. It is generally regarded as an aberrant estrogen-dependent growth condition, which presents with symptoms of chronic pelvic pain, bleeding and infertility. Steroidal progestogens are already widely used in the treatment of the condition, dienogest (Visanne) the most recent of which has gained EU approval for clinical use (McCormack, 2010). Progestogens appear to work by both directly inhibiting the functional effects of estrogen on endometrial cell proliferation, and also suppressing ovarian function, to induce anovulatory amenorrhoea. The efficacy of this class of agents in patients with endometriosis, however, is relatively modest and the tolerability (breakthrough bleeding and bloating) as well as concerns on the long term safety (risk of breast cancer and thromboembolism, effect on bone mineral density) has also limited their broader utility. Progesterone receptor antagonists (PRAs) have emerged in recent years as an alternative approach to treating the disease. This class of agents has contrasting effects on reproductive function compared with progestogens. This review will focus on what we know about the PRA mechanism of action from pre-clinical in vitro and in vivo evidence and how clinical data have shaped confidence in this class of agents as a new approach to treating endometriosis symptoms and disease progression1.
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Open access Submitted: 03 March 2011 Published: 09 May 2012 DOI: 10.5772/29021 From the Edited Volume Edited by Koel Chaudhury and Baidyanath Chakravarty Submitted: 03 March 2011 Published: 09 May 2012 © 2012 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Discover 2026 Nobel Laureate Francis Halzen’s chapter on IntechOpen >

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endometriosischronic_pelvic_paininfertility

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