Progesterone resistance can cause endometriosis

Progesterone resistance can cause endometriosis

Impaired progesterone signaling can be one of the mechanisms of endometriosis development; therefore, therapies directed toward correcting this progesterone inaction can be promising for endometriosis treatment and prevention.

Key Points


  • Progesterone response is impaired in women with endometriosis.
  • The exact mechanism of progesterone impairment is unknown but genetic and epigenetic regulation of progesterone receptors, along with inflammation and environmental factors were implicated.
  • Understanding the mechanism of inadequate progesterone response will enable the development of future therapeutics for endometriosis.


  • Loss of progesterone signaling in endometrial tissue is believed to play a part in endometriosis development. Understanding progesterone resistance/impaired signaling will enable the development of effective treatment strategies for preventing and managing endometriosis.  

What’s done here?

  • This review summarizes the evidence supporting progesterone resistance in endometriosis and discusses possible strategies to correct the progesterone action in endometrial tissue to alleviate the symptoms of endometriosis.

Key results:

  • Although the exact mechanism is unknown, progesterone resistance is evident in endometriosis.
  • Causes of progesterone resistance in endometriosis include congenital, genetics, epigenetics as well as inflammation, retrograde menses, and environmental toxins like dioxin.
  • Several strategies are suggested for alleviating the progesterone resistance such as the use of synthetic progestins and other approaches that enhance progesterone response by targeting underlying cellular and molecular events.

Lay Summary

Progesterone is a steroid hormone produced by the corpus luteum of ovaries. Abnormal progesterone signaling (i.e., progesterone resistance) in the endometrium has been implicated in the establishment of eutopic and ectopic endometrial implants. Several causes for faulty progesterone signaling have been suggested: (1) congenial – resulting from maternal and neonatal preconditioning, which means newborn progesterone resistance may persist through adolescence; (2) inflammation – as progesterone action is crucial for decreasing inflammation in the endometrium; (3) retrograde menses – via peritoneal inflammation; (4) genetics – several polymorphisms (genetic variations) found in the progesterone receptor gene are implicated as the genetic cause of progesterone resistance; (5) epigenetic modifications and microRNAs – may contribute to the regulation of some critical genes leading to progesterone resistance; (6) dioxin – an environmental toxin which is suspected to induce progesterone resistance; and (7) retinoid resistance – diet-derived lipids that mediate the action of progesterone in the endometrium.

No matter the cause, impaired progesterone signaling leads to ineffective hormonal therapy in women with endometriosis. Some therapeutic strategies to correct the defective progesterone action include the use of synthetic progestins such as dienogest or medicated uterine devices. These interventions to enhance progesterone responsiveness in endometriosis, however, provide limited benefits. Understanding the underlying cellular and molecular basis of progesterone resistance may lead to the identification of novel therapeutics to prevent and treat endometriosis as well as to the establishment of biomarkers to predict response to these innovative therapies.    

Research Source:

progesterone progesterone resistance endometrium


EndoNews highlights the latest peer-reviewed scientific research and medical literature that focuses on endometriosis. We are unbiased in our summaries of recently-published endometriosis research. EndoNews does not provide medical advice or opinions on the best form of treatment. We highly stress the importance of not using EndoNews as a substitute for seeking an experienced physician.