{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:16:27Z","timestamp":1788491787513,"version":"build-2803163510"},"reference-count":229,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T00:00:00Z","timestamp":1774051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Endometriosis is associated with nociceptive pain, as well as peripheral and central sensitization. Evidence-based treatment suggestions for controlling endometriosis should be based on the convergence of the best scientific evidence, physicians\u2019 clinical expertise, and the values and priorities of individual patients. In this non-systematic, comprehensive narrative review, data from available randomized controlled trials and meta-analyses on hormonal treatment for symptomatic endometriosis are interpreted through the lens of clinical experience. The role of patients in defining therapeutic trade-off balances is also taken into consideration. Most symptomatic patients benefit from hormonal therapy, including first-line (progestogens and estrogen-progestogen combinations) and second-line (GnRH agonists and antagonists) medications, to relieve nociceptive pain. To reduce the risk of venous and arterial thrombosis and avoid stimulating lesions, it is preferable to use combinations containing body-identical estrogens rather than ethinyl-estradiol. The main adverse effect of first-line medications is irregular bleeding, which adversely impacts efficacy, tolerability, and adherence. If progestogens and estrogen-progestogens do not improve health-related quality of life (HRQoL), promptly stepping up to GnRH analogues combined with add-back therapy is indicated. Add-on rather than upfront combination therapy is suggested. Separating the analogues and add-back therapy allows for choosing the compounds that best suit the characteristics of individual patients. Transdermal body-identical estradiol use is proposed in combination with both progestogens and GnRH analogues. Similar satisfactory outcomes are achieved with GnRH agonists and antagonists. Evidence on the use of neuromodulatory drugs to treat neuropathic and nociplastic pain is derived from studies of other chronic pain conditions and shows limited effectiveness. The two mainstays of hormonal therapy are (i) ovariostasis and (ii) amenorrhea. \u201cMedical treatment failure\u201d should not be declared unless a shift from first-line to second-line medications has been undertaken whenever these conditions are not met. For severely symptomatic adolescents and young women, secondary prevention through ovariostasis and amenorrhea should be pursued promptly to improve HRQoL, halt lesion progression, and preserve reproductive potential.<\/jats:p>","DOI":"10.3390\/jcm15062408","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T09:48:42Z","timestamp":1774259322000},"page":"2408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Medical Treatment for Endometriosis: One Size Does Not Fit All"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4195-0996","authenticated-orcid":false,"given":"Paolo","family":"Vercellini","sequence":"first","affiliation":[{"name":"Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi, 20122 Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3239-3799","authenticated-orcid":false,"given":"Noemi","family":"Salmeri","sequence":"additional","affiliation":[{"name":"Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi, 20122 Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1788-9670","authenticated-orcid":false,"given":"Veronica","family":"Bandini","sequence":"additional","affiliation":[{"name":"Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi, 20122 Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Conca","sequence":"additional","affiliation":[{"name":"Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi, 20122 Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3674-5912","authenticated-orcid":false,"given":"Paola","family":"Vigan\u00f2","sequence":"additional","affiliation":[{"name":"Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi, 20122 Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgardo","family":"Somigliana","sequence":"additional","affiliation":[{"name":"Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi, 20122 Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9806-3741","authenticated-orcid":false,"given":"Michele","family":"Vignali","sequence":"additional","affiliation":[{"name":"Academic Centre for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi, 20122 Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.52054\/FVVO.15.3.090","article-title":"Evidence-Based and Experience-Based Medicine, Which Comes First: The Chicken or the Egg?","volume":"15","author":"Ata","year":"2023","journal-title":"Facts Views Vis. 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