{"paper_id":"d4f12649-b3db-47be-bd74-dfea13115d3e","body_text":"ABSTRACT\nIntroduction\nDysmenorrhea is a painful symptom associated with uterine contractions and menstrual bleeding and is treated by administering analgesic drugs. Since progesterone receptors (PRs) have a major role in regulating uterine tissues (myometrium and endometrium) physiology, oral contraceptives are used off-label for treating primary or secondary dysmenorrhea. The development of selective progesterone receptor modulators (SPRMs), a class of synthetic steroids with agonistic, antagonistic, or mixed effects in targeting PRs in different tissues, stimulated their possible clinical use for treating secondary dysmenorrhea related to uterine diseases (endometriosis, adenomyosis, uterine fibroids).\nAreas covered\nThe present review examines the development of the clinical trials and observational studies done with the different SPRMs for the treatment of dysmenorrhea in patients with uterine diseases.\nExpert opinion\nMifepristone, telapristone acetate and vilaprisan have antagonistic activity on PRs, whereas ulipristal acetate and asoprisnil have both potent antagonist and partial agonist effects.\nSince no studies have been done on primary dysmenorrhea, the different SPRMs have been evaluated in the treatment of endometriosis, adenomyosis and uterine fibroid-related dysmenorrhea.\nArticle highlights\nProgesterone is a central target for therapeutic interventions in the context of uterine diseases.\nThere are no studies on the clinical use of SPRMs for the treatment of primary dysmenorrhea.\nStudies on SPRMs’ use for treating endometriosis-, adenomyosis-, and uterine fibroids-related dysmenorrhea are available (mifepristone, ulipristal acetate, asoprisnil, telapristone acetate, vilaprisan).\nThe ability to selectively modulate progesterone activity without inducing hypoestrogenism makes SPRMs an attractive option for long-term treatment.\nSide effects and long-term safety (hepatotoxicity and PAECs) represent the major limit for SPRMs use.\nDeclaration of interest\nThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.\nReviewer disclosure\nPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.","source_license":"public-domain-us","license_restricted":false}