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How endometriosis patients can be resistant to progesterone therapy and what to do about it

Endometriosis is a complex and often misunderstood condition affecting millions of women worldwide. While it's widely recognized for the excruciating pain it inflicts, there's a silent battle raging within the bodies of many sufferers – progesterone resistance. In this blog post, we delve into the intricacies of progesterone resistance in endometriosis, shedding light on its implications and offering hope for better management and treatmen

Understanding Progesterone Resistance: Progesterone is a hormone crucial for regulating the menstrual cycle and maintaining a healthy uterine environment. However, in women with endometriosis, the cells that line the uterus (endometrial cells) implant and grow outside the uterus, causing inflammation, scarring, and debilitating pain. Despite the role progesterone plays in controlling endometrial growth, many women with endometriosis exhibit resistance to its effects.

The Mechanisms at Play: Researchers have been unraveling the intricate mechanisms behind progesterone resistance in endometriosis. One leading theory suggests that the abnormal growths of endometrial tissue produce factors that disrupt progesterone signaling pathways, rendering the cells less responsive to its inhibitory effects. Additionally, genetic predispositions and environmental factors may contribute to this resistance, further complicating the picture. Environmental toxins such as dioxins, genetic and epigenetic changes and increased inflammation can lead to progesterone resistance.

Progesterone resistance seems to be associated with an overactivity of the progesterone receptor A (PRA) and Estrogen receptor-β (ER-β).

The Consequences: Progesterone resistance in endometriosis can have far-reaching consequences for women's health and quality of life. It may lead to persistent inflammation, exacerbating pain and other symptoms associated with the condition. Moreover, progesterone resistance can thwart traditional treatment approaches, making it challenging for patients and healthcare providers to effectively manage the disease.

Treatment options:

Micronized, bioidentical progesterone: in patients with progesterone resistance, much higher doses of bioidentical progesterone may be needed. Different forms include oral, sublingual, topical creams and vaginal suppositories.

Dienogest (17α-cyanomethyl-17β-hydroxyestra-4,9-dien-3-one) is efficacious in the treatment of endometriosis, attributed in part to its ability to overcome attenuated progesterone responses. DNG may overcome progesterone resistance by directly increasing the PR-B:PR-A RNA ratio in endometriotic cells and tissues. Estrogen receptor-β, which is increased in endometriotic tissue, is downregulated by DNG. As ER-β can repress estrogen-induced PR expression, decreasing ER-β with DNG may enhance progesterone sensitivity in patients with endometriosis.

Mirena IUD: The levonorgestrel intrauterine system (LNG-IUS) also has proven benefits, reducing moderate to severe dysmenorrhea in approximately 88% of patients compared with placebo. Eutopic and ectopic endometrial tissue biopsies after 6 months of LNG-IUS placement show a reduced cell-proliferation index in addition to decreased expression of ERα and PR-A. Symptomatic improvement of chronic pelvic pain seems equally promising, with some studies noting similar pain profiles in patients treated with LNG-IUS compared with GnRH analogues. Side effect profiles, similarly, are better in patients treated with LNG-IUS than with GnRH analogues.

Anti-inflammatory drugs: Statins have a proven capacity to decrease the proinflammatory mediators IL-1β, TNF-α and C-reactive protein. This class of drugs also inhibits angiogenic factors, further assuaging endometriotic lesion establishment and disease burden. Other antiinflammatory drugs such as ibuprofen or aspirin have been shown to lower infllammation in endometriosis patients.

Natural treatments: a highly antinflammatory, antioxidant rich diet can lower inflammation and improve progesterone response. A diet rich in polyphenols is recommended. Healing the gut and underlying inflammation can be helpful. Omega-3 rich foods can also be helpful. Turmeric, green tea, and berries, contain bioactive compounds with inflammation-inhibiting properties.

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