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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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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Condition tags

endometriosischronic_pelvic_paininfertility

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