{"paper_id":"35eb1704-beb3-4982-833b-d003588821f3","body_text":"Dydrogesterone as an Option in the Medical\nTreatment of Endometriosis: A Brief Comment\nD i d r o g e s t e r o n ac o m oo p ç ã on ot r a t a m e n t oc l í n i c od a\nendometriose: Um breve comentário\nBruno Ramalho de Carvalho 1\n1 Bruno Ramalho – R e p r o d u ç ã oH u m a n a ,B r a s í l i a ,D F ,B r a z i l\nRev Bras Ginecol Obstet 2022;44(8):802 –803.\nAddress for correspondence Bruno Ramalho de Carvalho, MD, MSc,\nBruno Ramalho – Reprodução Humana, SGAS 614, Conjunto C, Sala\n177, 70200-740, Edifício Vitrium, Asa Sul, Brasília, Distrito Federal,\nBrazil (e-mail: bruno@brunoramalho.med.br).\nDear Editor,\nEndometriosis-related pain and morbidity are assumed to\ncause substantial impact on quality of life. Due to its chronic -\nity, the disease is expected to be clinically managed in a long-\nterm individualized plan, considering easy access, cost-effec -\ntiveness, acceptance, and adherence, regardless of surgical\ninterventions, when (and if) they are necessary.\nA better health-related quality of life is the main goal of\nthe endometriosis treatment. It may be reached, individual-\nly, by relieving chronic pelvic pain, either acyclic, dysmenor-\nrhea or dyspareunia, reducing the use of analgesics, and\neventually protecting fertilit y. The opt imized treatment of\nthe disease often combines hormonal and surgical\napproaches, but the current literature\n1 shows an inclination\ntowards the use of medical strategies as first choices, ulti-\nmately postponing, or even avoiding, the need for surgery.\nAiming to inhibit the growth of endometriotic lesions,\nmedical alternatives like selective progesterone receptor\nmodulators, antiangiogenic factors and immunomodulators\nhave been studied in recent years.\n2 As a matter of fact,\nestrogens combined with progestagens or progestagens\nalone still seem to be the most used agents to suppress\novarian function and disease activity,\n2 but there is a lack of\ncomparative information to determine a best choice among\nthe available molecules. Despite the different potencies to\nsuppress the hypothalamic -pituitary-ovarian axis, progesta-\ngens in general may be similarly effective to control endo-\nmetriosis. Individualization of the treatment is, then,\nexpected to be the less expensive, with minimal adverse\neffects and maximal adherence.\n3,4\nDydrogesterone is a retroprogesterone characterized by\nhigh selectivity for progesterone receptors and potent pro-\ngestagenic activity. According to the medical lea flet, it may\nbe prescribed in two regimens in the treatment of endome-\ntriosis, namely: a cyclical regimen, from the 5th to the 25th\ndays of the menstrual cycle, and a continuous one, both with\ndaily doses ranging from 10 mg to 30 mg.\n5 However, knowl-\nedge on the comparative ef ficacy of the two protocols is also\nscarce, and the recently published ORCHIDEA Study1 brought\ninteresting data to light.\nAs the primary outcome, a signi ficant decrease in the\nintensity of chronic pelvic pain was observed among women\nreceiving dydrogesterone in the daily doses of 20 mg or 30\nmg. By assessing women experience after treatment cycle 6,\nit was also observed a reduction in the number of days of\nanalgesics use, and the severity of dysmenorrhea, as much as\nimprovements in sexual well-being.1 In other words, the\nstudy pointed to a comparable gain in quality of life between\nthe two daily doses, whether in cyclical or continuous\nregimens, at least for the first 6 months.\n4\nRegarding adverse events, the ORCHIDEA Study 1 found\nmild uterine bleeding as the most frequent one (1.1%), as it is\nexpected for other progestagen-only treatment regimens,\nespecially in the continuous model. However, despite being\nrelated to a better control of uterine bleeding, vaginal\ndischarge and irritation, and coital well-being, than other\nprogestagens, adverse events like headache, dizziness, ab-\ndominal pain, flatulence, and nausea may be more frequent\nwith dydrogesterone,\n6 and this must be better evaluated in\nfuture well-designed studies.\nreceived\nApril 27, 2022\naccepted after revision\nMay 2, 2022\npublished online\nJuly 15, 2022\nDOI https://doi.org/\n10.1055/s-0042-1751075.\nISSN 0100-7203.\n© 2022. Federação Brasileira de Ginecologia e Obstetrícia. All rights\nreserved.\nThis is an open access article published by Thieme under the terms of the\nCreative Commons Attribution License, permitting unrestricted use,\ndistribution, and reproduction so long as the original work is properly cited.\n(https://creativecommons.org/licenses/by/4.0/)\nThieme Revinter Publicações Ltda., Rua do Matoso 170, Rio de\nJaneiro, RJ, CEP 20270-135, Brazil\nLetter to the Editor\nTHIEME\n802\nArticle published online: 2022-07-15\n\nThe earlier results of the application of dydrogesterone in\nwomen with endometriosis were published more than four\ndecades ago,\n7 but such a use has been notedly explored with\nmore interest in the lastfifteen years. The study by Trivedi et al.\n(2007)8 was the first to convincingly demonstrate significant\nimprovements in pelvic pain, dysmenorrhea and dyspareunia,\nand a 74% rate of satisfaction in the postlaparoscopic follow-up\nat 3 to 6 months.\nA recently published meta-analysis 9 of 19 studies (1,709\nwomen) confronted different regimens of dydrogesterone to\ngonadotropin-releasing hormone (GnRH) agonists, aroma-\ntase inhibitors or anti-progestagens against endometriosis.\nDespite the suggestion that dydrogesterone is the most\neffective among them for dysmenorrhea, little could be\nobtained regarding de finite conclusions, since the available\nstudies are generally small, non-randomized and heteroge-\nneous. Of note, a special view on the ef ficacy of dydrogester-\none to treat sexual dysfunction in women with\nendometriosis is expected from large cohorts with long\nterm follow ups, since the preliminary data are encourag-\ning.\n10 Following the same reasoning, the ability of dydro-\ngesterone to prevent the increase in size of ovarian\nendometriomas must be reassured by robust studies. 11\nIt is true that the absence of clinically relevant activity on\nestrogen, glucocorticoid, mineralocorticoid, or androgenic\nreceptors may be a positive characteristic of dydrogesterone\nin currently recommended daily doses versus other proges-\ntagens. In addition to favoring the lower occurrence of\nadverse events, that pharmacological pro file may be safer\nfor women in childbearing age, in the absence of contracep-\ntion.\n6,12 Moreover, the good oral bioavailability and the\ntheoretical lower risk of developing breast or endometrial\ncancer compared to other progestagens\n6 are aspects to be\nconsidered for a first clinical treatment choice.\nHowever, it should be argued that any progestagen may be\ninitially considered suf ficient against the symptoms of en-\ndometriosis. Then, what is expected from science is to fill the\ngaps by the confrontation of different progestins commonly\nused for treating endometriosis, such as the contemporary\ndienogest,13 or the molecules from previous generations.\nThe information available to date is still insuf ficient to\nestablish the clinical superiority of one molecule over the\nothers. The ORCHIDEA Study 1 reported that dydrogesterone\nmay relieve endometriosis-related chronic pelvic pain for at\nleast 6 months of use in the regimen of preference. As\naforementioned, the best progestagen for the treatment of\nendometriosis will be the one that is affordable, efficient, and\nwell-accepted by each woman. Therefore, dydrogesterone is\nas welcome as any other progestagen in the search for the\nbest individualized approach.\nConflict of Interests\nThe author has no con flict of interests to declare.\nReferences\n1 Sukhikh GT, Adamyan LV, Dubrovina SO, Baranov II, Bezhenar VF,\nKozachenko AV, et al. Prolonged cyclical and continuous regi-\nmens of dydrogesterone are effective for reducing chronic pelvic\npain in women with endometriosis: results of the ORCHIDEA\nstudy. Fertil Steril. 2021;116(06):1568 –1577. Doi: 10.1016/j.\nfertnstert.2021.07.1194\n2 Rafique S, Decherney AH. Medical management of endometri-\nosis. Clin Obstet Gynecol. 2017;60(03):485 –496. Doi: 10.1097/\nGRF.0000000000000292\n3 Falcone T, Flyckt R. Clinical management of endometriosis.\nObstet Gynecol. 2018;131(03):557 –571. Doi: 10.1097/\nAOG.0000000000002469\n4 Eaton JL. Round-the-clock or start-and-stop: Does the regimen\nmatter when dydrogesterone is used to treat chronic pelvic pain\ndue to endometriosis? Fertil Steril. 2021;116(06):1578 –1579.\nDoi: 10.1016/j.fertnstert.2021.10.018\n5 Duphaston® [Internet]. São PauloAbbott Laboratórios do Bra-\nsil2021 [cited 2022 Apr 7]. Available from: https://dam.abbott.\ncom/pt-br/documents/pdfs/nossas-bulas/D/BU-29-DUPHAS-\nTON-bula-profissional-FINAL.pdf\n6 Ott J, Egarter C, Aguilera A. Dydrogesterone after 60 years: a\nglance at the safety pro file. Gynecol Endocrinol. 2022;38(04):\n279–287. Doi: 10.1080/09513590.2021.2016692\n7 Johnston WI. Dydrogesterone and endometriosis. Br J Obstet\nGynaecol. 1976;83(01):77 –80. Doi: 10.1111/j.1471-0528.1976.\ntb00734.x\n8 Trivedi P, Selvaraj K, Mahapatra PD, Srivastava S, Malik S. Effective\npost-laparoscopic treatment of endometriosis with dydrogester-\none. Gynecol Endocrinol. 2007;23(Suppl 1):73 –76\n9 Peng C, Huang Y, Zhou Y. Dydrogesterone in the treatment of\nendometriosis: evidence mapping and meta-analysis. Arch Gynecol\nObstet. 2021;304(01):231–252. Doi: 10.1007/s00404-020-05900-z\n10 Yalçın Bahat P, Yücel B, Yuksel Ozgor B, Kadiro ğ ulları P, Topbas\nSelçuki NF, Çakmak K, et al. The effect of dydrogesterone on sexual\nfunction in endometriosis. J Obstet Gynaecol. 2021;1-4:1 –4. Doi:\n10.1080/01443615.2021.1958765\n11 Kitawaki J, Koga K, Kanzo T, Momoeda M. An assessment of the\nefficacy and safety of dydrogesterone in women with ovarian\nendometrioma: An open-label multicenter clinical study. Reprod\nMed Biol. 2021;20(03):345 –351. Doi: 10.1002/rmb2.12391\n12 Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR,\nSchweppe KW, et al. Classi fication and pharmacology of proges-\ntins. Maturitas. 2008;61(1-2):171 –180. Doi: 10.1016/j.maturi-\ntas.2008.11.013\n13 Andres MdeP , Lopes LA, Baracat EC, Podgaec S. Dienogest in the\ntreatment of endometriosis: systematic review. Arch Gynecol\nObstet. 2015;292(03):523–529. Doi: 10.1007/s00404-015-3681-6\nRev Bras Ginecol Obstet Vol. 44 No. 8/2022 © 2022. Federação Bras ileira de Ginecologia e Obstetrícia. All rights reserved.\nDydrogesterone as an Option in the Medical Treatment of Endometriosis Carvalho 803","source_license":"CC0","license_restricted":false}