Progesterone receptor ligands for the treatment of endometriosis

Estrogen dependence and progesterone resistance play a crucial role in the origin and development of endometriosis. Therefore, hormonal therapies are currently the most effective treatment. Progestins are considered the first-line ap-proach, especially for a long-term management. Progestins are synthetic compounds that mimic the effects of progester-one by binding progesterone receptors. Continuous use of progestins leads to the suppression of ovarian steroidogenesis with anovulation and low serum levels of ovarian steroids, causing endometrial pseudodecidualization. Moreover, they act by interfering on several endometriosis pathogenetic pathways, decreasing inflammation, provoking apoptosis in endometriotic cells, stimulating atrophy or regression of endometrial lesions, inhibiting angiogenesis, and decreasing expression of metalloproteinases, thus diminishing the invasiveness of endometriotic implants. Progestins are effective for pain relief and improvement of the quality of life (QoL). The side effects are limited, and the compounds are available in different formulations and routes of administration and represent, in most cases, an inexpensive treatment option. Di-enogest, Medroxyprogesterone acetate and Norethisterone acetate are the labeled progestins for endometriosis, but other progestins, such as Dyhidrogesterone, Levonorgestrel and Desogestrel, have been shown to be effective in the treatment of endometriosis-associated pain. The present review aims to describe the available and emerging evidences on proges-tins used for the treatment of endometriosis.

Automated summary

Estrogen dependence and progesterone resistance are essential in the development of endometriosis, making hormonal therapies the most effective treatment. Progestins, as synthetic compounds, mimic the effects of progesterone and are the first-line approach for long-term management. They suppress ovarian steroidogenesis, decrease inflammation, induce apoptosis in endometriotic cells, and inhibit angiogenesis, ultimately relieving pain and improving the quality of life. Available progestin options include Di-enogest, Medroxyprogesterone acetate, and Norethisterone acetate, but other progestins such as Dyhidrogesterone, Levonorgestrel, and Desogestrel have also shown efficacy in treating endometriosis-associated pain. This review aims to summarize the evidence on the use of progestins for endometriosis treatment.