Current understanding on pharmacokinetics, clinical efficacy and safety of progestins for treating pain associated to endometriosis

References

• Ferrero S, Arena E, Morando A, et al. Prevalence of newly diagnosed endometriosis in women attending the general practitioner. Int J Gynaecol Obstet. 2010 Sep;110(3):203–207. PubMed PMID: 20546747.
   PubMed Web of Science ®Google Scholar
• Vercellini P, Vigano P, Somigliana E, et al. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014 May;10(5):261–275. PubMed PMID: 24366116.
   PubMed Web of Science ®Google Scholar
• Vercellini P, De Giorgi O, Pisacreta A, et al. Surgical management of endometriosis. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000 Jun;14(3):501–523. PubMed PMID: 10962639.
   PubMed Web of Science ®Google Scholar
• Vercellini P, Crosignani PG, Abbiati A, et al. The effect of surgery for symptomatic endometriosis: the other side of the story. Hum Reprod Update. 2009 Mar-Apr;15(2):177–188. PubMed PMID: 19136455.
   PubMed Web of Science ®Google Scholar
• Koga K, Takamura M, Fujii T, et al. Prevention of the recurrence of symptom and lesions after conservative surgery for endometriosis. Fertil Steril. 2015 Oct;104(4):793–801. PubMed PMID: 26354093.
   PubMed Web of Science ®Google Scholar
• Vercellini P, Somigliana E, Vigano P, et al. Endometriosis: current therapies and new pharmacological developments. Drugs. 2009;69(6):649–675. PubMed PMID: 19405548.
   PubMed Web of Science ®Google Scholar
• Menakaya U, Infante F, Condous G. Consensus on current management of endometriosis. Hum Reprod. 2013 Nov;28(11):3162–3163. PubMed PMID: 24014606.
   PubMed Web of Science ®Google Scholar
• Dunselman GA, Vermeulen N, Becker C, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014 Mar;29(3):400–412. PubMed PMID: 24435778.
   PubMed Web of Science ®Google Scholar
• Casper RF. Progestin-only pills may be a better first-line treatment for endometriosis than combined estrogen-progestin contraceptive pills. Fertil Steril. 2017;107(3):533–536.
   PubMed Web of Science ®Google Scholar
• Smuc T, Hevir N, Ribic-Pucelj M, et al. Disturbed estrogen and progesterone action in ovarian endometriosis. Mol Cell Endocrinol. 2009 Mar 25;301(1–2):59–64. PubMed PMID: 18762229.
   PubMed Web of Science ®Google Scholar
• Tosti C, Pinzauti S, Santulli P, et al. Pathogenetic mechanisms of deep infiltrating endometriosis. Reprod Sci. 2015 Sep;22(9):1053–1059. PubMed PMID: 26169038.
   PubMed Web of Science ®Google Scholar
• Greaves E, Temp J, Esnal-Zufiurre A, et al. Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis. Am J Pathol. 2015 Aug;185(8):2286–2297. PubMed PMID: 26073038; PubMed Central PMCID: PMCPMC4530129.
   PubMed Web of Science ®Google Scholar
• Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012 Sep;98(3):511–519. PubMed PMID: 22819144; PubMed Central PMCID: PMCPMC3836682.
   PubMed Web of Science ®Google Scholar
• Noel JC, Chapron C, Bucella D, et al. Estrogen and progesterone receptors in smooth muscle component of deep infiltrating endometriosis. Fertil Steril. 2010 Apr;93(6):1774–1777. PubMed PMID: 19217090; eng.
   PubMed Web of Science ®Google Scholar
• McKinnon BD, Bertschi D, Bersinger NA, et al. Inflammation and nerve fiber interaction in endometriotic pain. Trends Endocrinol Metab. 2015 Jan;26(1):1–10. PubMed PMID: 25465987.
   PubMed Web of Science ®Google Scholar
• Tafi E, Leone Roberti Maggiore U, Alessandri F, et al. Advances in pharmacotherapy for treating endometriosis. Expert Opin Pharmacother. 2015 Nov;16(16):2465–2483. PubMed PMID: 26569155.
   PubMed Web of Science ®Google Scholar
• Ferrero S, Alessandri F, Racca A, et al. Treatment of pain associated with deep endometriosis: alternatives and evidence. Fertil Steril. 2015 Oct;104(4):771–792. PubMed PMID: 26363387.
   PubMed Web of Science ®Google Scholar
• DiVasta AD, Laufer MR. The use of gonadotropin releasing hormone analogues in adolescent and young patients with endometriosis. Curr Opin Obstet Gynecol. 2013 Aug;25(4):287–292. PubMed PMID: 23770813.
   PubMed Web of Science ®Google Scholar
• Ferrero S, Remorgida V, Maganza C, et al. Aromatase and endometriosis: estrogens play a role. Ann N Y Acad Sci. 2014 May;1317:17–23. PubMed PMID: 24738993.
   PubMed Web of Science ®Google Scholar
• Reis FM, Petraglia F, Taylor RN. Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis. Hum Reprod Update. 2013 Jul-Aug;19(4):406–418. PubMed PMID: 23539633; PubMed Central PMCID: PMCPMC3682670.
   PubMed Web of Science ®Google Scholar
• Grandi G, Mueller MD, Bersinger NA, et al. The association between progestins, nuclear receptors expression and inflammation in endometrial stromal cells from women with endometriosis. Gynecol Endocrinol. 2017;33:712–715. (1473-0766 (Electronic)). eng.
   PubMed Web of Science ®Google Scholar
• Grandi G, Mueller M, Bersinger N, et al. Progestin suppressed inflammation and cell viability of tumor necrosis factor-alpha-stimulated endometriotic stromal cells. Am J Reprod Immunol. 2016 Oct;76(4):292–298. PubMed PMID: 27515307.
   PubMed Web of Science ®Google Scholar
• Katayama H, Katayama T, Uematsu K, et al. Effect of dienogest administration on angiogenesis and hemodynamics in a rat endometrial autograft model. Hum Reprod. 2010 Nov;25(11):2851–2858. PubMed PMID: 20813806.
   PubMed Web of Science ®Google Scholar
• Schweppe KW. Current place of progestins in the treatment of endometriosis-related complaints. Gynecol Endocrinol. 2001 Dec;15(Suppl 6):22–28. PubMed PMID: 12227883.
   PubMedGoogle Scholar
• Ferrero S, Remorgida V, Venturini PL. Current pharmacotherapy for endometriosis. Expert Opin Pharmacother. 2010 May;11(7):1123–1134. PubMed PMID: 20230308.
   PubMed Web of Science ®Google Scholar
• Berlanda N, Somigliana E, Vigano P, et al. Safety of medical treatments for endometriosis. Expert Opin Drug Saf. 2016 Jan;15(1):21–30. PubMed PMID: 26576479.
   PubMed Web of Science ®Google Scholar
• Chwalisz K, Surrey E, Stanczyk FZ. The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis. Reprod Sci. 2012 Jun;19(6):563–571. PubMed PMID: 22457429.
   PubMed Web of Science ®Google Scholar
• Singh H, Uniyal JP, Jha P, et al. Pharmacokinetics of norethindrone acetate in women. Am J Obstet Gynecol. 1979 Oct 1;135(3):409–414. PubMed PMID: 484634.
   PubMed Web of Science ®Google Scholar
• Prasad KV, Rao BS, Sivakumar B, et al. Pharmacokinetics of norethindrone in Indian women. Contraception. 1979 Jul;20(1):77–90. PubMed PMID: 477319.
   PubMed Web of Science ®Google Scholar
• Food and Drugs Administration. AYGESTIN® (norethindrone acetate) tablets, USP. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/018405s023lbl.pdf
   Google Scholar
• Chu MC, Zhang X, Gentzschein E, et al. Formation of ethinyl estradiol in women during treatment with norethindrone acetate. J Clin Endocrinol Metabol. 2007;92(6):2205–2207.
   PubMed Web of Science ®Google Scholar
• Vercellini P, Pietropaolo G, De Giorgi O, et al. Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate. Fertil Steril. 2005 Nov;84(5):1375–1387. PubMed PMID: 16275232.
   PubMed Web of Science ®Google Scholar
• Ferrero S, Camerini G, Ragni N, et al. Norethisterone acetate in the treatment of colorectal endometriosis: a pilot study. Hum Reprod. 2010;25(1):94–100.
   PubMed Web of Science ®Google Scholar
• Ferrero S, Remorgida V, Venturini PL, et al. Norethisterone acetate versus norethisterone acetate combined with letrozole for the treatment of ovarian endometriotic cysts: a patient preference study. Eur J Obstet Gynecol Reprod Biol. 2014 Mar;174:117–122. PubMed PMID: 24388845.
   PubMed Web of Science ®Google Scholar
• Morotti M, Venturini PL, Biscaldi E, et al. Efficacy and acceptability of long-term norethindrone acetate for the treatment of rectovaginal endometriosis. Eur J Obstet Gynecol Reprod Biol. 2017 Mar 27;213:4–10. PubMed PMID: 28384540.
   PubMed Web of Science ®Google Scholar
• Scala C, Leone Roberti Maggiore U, Barra F, et al. Norethindrone acetate versus extended-cycle oral contraceptive (Seasonique((R))) in the treatment of endometriosis symptoms: a prospective open-label comparative study. Eur J Obstet Gynecol Reprod Biol. 2018 Feb 1;222:89–94. PubMed PMID: 29408753.
   PubMed Web of Science ®Google Scholar
• Neumann F. Pharmacology and potential use of cyproterone acetate. Horm Metab Res. 1977 Jan;9(1):1–13. PubMed PMID: 66176.
   PubMed Web of Science ®Google Scholar
• Hümpel M, Wendt H, Dogs G, et al. Intraindividual comparison of pharmacokinetic parameters of d-norgestrel, lynestrenol and cyproterone acetate in 6 women. Contraception. 1977 08 01;16(2):199–215.
   Web of Science ®Google Scholar
• Frolich M, Van Schie MG, Brand EC. Sex hormone binding globulin: binding capacity and studies on the binding of cyproterone acetate and other steroids. Clin Chim Acta. 1978 Jul 15;87(2):239–244. PubMed PMID: 566170
   PubMed Web of Science ®Google Scholar
• Moran C, Alcivia JC, Garcia-Hernandez E, et al. Treatment of endometriosis with cyproterone acetate. Preliminary report. Arch Med Res. 1996;27(4):535–538.
   PubMed Web of Science ®Google Scholar
• Vercellini P, De Giorgi O, Mosconi P, et al. Cyproterone acetate versus a continuous monophasic oral contraceptive in the treatment of recurrent pelvic pain after conservative surgery for symptomatic endometriosis. Fertil Steril. 2002;77(1):52–61.
   PubMed Web of Science ®Google Scholar
• Stone SC. Desogestrel. Clin Obstet Gynecol. 1995 Dec;38(4):821–828. PubMed PMID: 8616978.
   PubMed Web of Science ®Google Scholar
• Scala C, Leone Roberti Maggiore U, Remorgida V, et al. Drug safety evaluation of desogestrel. Expert Opin Drug Saf. 2013 May;12(3):433–444. PubMed PMID: 23560561.
   PubMed Web of Science ®Google Scholar
• Hasenack HG, Bosch AM, Kaar K. Serum levels of 3-keto-desogestrel after oral administration of desogestrel and 3-keto-desogestrel. Contraception. 1986 Jun;33(6):591–596. PubMed PMID: 2945700.
   PubMed Web of Science ®Google Scholar
• Madden S, Back DJ, Martin CA, et al. Metabolism of the contraceptive steroid desogestrel by the intestinal mucosa. Br J Clin Pharmacol. 1989 Mar;27(3):295–299. PubMed PMID: 2524206; PubMed Central PMCID: PMCPMC1379826.
   PubMed Web of Science ®Google Scholar
• Back DJ, Grimmer SF, Shenoy N, et al. Plasma concentrations of 3-keto-desogestrel after oral administration of desogestrel and intravenous administration of 3-keto-desogestrel. Contraception. 1987 Jun;35(6):619–626. PubMed PMID: 2959449.
   PubMed Web of Science ®Google Scholar
• Kuhnz W, Pfeffer M, al-Yacoub G. Protein binding of the contraceptive steroids gestodene, 3-keto-desogestrel and ethinylestradiol in human serum. J Steroid Biochem. 1990 Feb;35(2):313–318. PubMed PMID: 2308344.
   PubMedGoogle Scholar
• Verhoeven CH, Gloudemans RH, Peeters PA, et al. Excretion and metabolism of desogestrel in healthy postmenopausal women. J Steroid Biochem Mol Biol. 2001 Nov;78(5):471–480. PubMed PMID: 11738557.
   PubMed Web of Science ®Google Scholar
• Razzi S, Luisi S, Ferretti C, et al. Use of a progestogen only preparation containing desogestrel in the treatment of recurrent pelvic pain after conservative surgery for endometriosis. Eur J Obstetrics Gynecol Reprod Biol. 2007;135(2):188–190.
   PubMed Web of Science ®Google Scholar
• Remorgida V, Abbamonte LH, Ragni N, et al. Letrozole and desogestrel-only contraceptive pill for the treatment of stage IV endometriosis. Aust New Zealand J Obstet Gynaecol. 2007;47(3):222–225.
   PubMed Web of Science ®Google Scholar
• Maggiore ULR, Remorgida V, Scala C, et al. Desogestrel-only contraceptive pill versus sequential contraceptive vaginal ring in the treatment of rectovaginal endometriosis infiltrating the rectum: a prospective open-label comparative study. Acta Obstet Gynecol Scand. 2014;93(3):239–247.
   PubMed Web of Science ®Google Scholar
• Morotti M, Remorgida V, Venturini PL, et al. Progestogen-only contraceptive pill compared with combined oral contraceptive in the treatment of pain symptoms caused by endometriosis in patients with migraine without aura. Eur J Obstet Gynecol Reprod Biol. 2014 Aug;179:63–68. PubMed PMID: 24965982.
   PubMed Web of Science ®Google Scholar
• Ferrero S, Pretta S, Bertoldi S, et al. Increased frequency of migraine among women with endometriosis. Hum Reprod. 2004 Dec;19(12):2927–2932. PubMed PMID: 15513980.
   PubMed Web of Science ®Google Scholar
• Food and Drugs Administration. MPLANON® (etonogestrel implant) 68 mg for subdermal use only. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021529s004lbl.pdf
   Google Scholar
• Bennink HJ. The pharmacokinetics and pharmacodynamics of Implanon, a single-rod etonogestrel contraceptive implant. Eur J Contracept Reprod Health Care. 2000 Sep;5(Suppl 2):12–20. PubMed PMID: 11246602.
   PubMedGoogle Scholar
• Wenzl R, van Beek A, Schnabel P, et al. Pharmacokinetics of etonogestrel released from the contraceptive implant Implanon. Contraception. 1998 Nov;58(5):283–288. PubMed PMID: 9883383.
   PubMed Web of Science ®Google Scholar
• Ponpuckdee J, Taneepanichskul S. The effects of implanon in the symptomatic treatment of endometriosis. J Med Assoc Thai. 2005 Oct;88 Suppl 2:S7–S10. PubMed PMID: 17722311; eng.
   PubMedGoogle Scholar
• Walch K, Unfried G, Huber J, et al. Implanon versus medroxyprogesterone acetate: effects on pain scores in patients with symptomatic endometriosis–a pilot study. Contraception. 2009 Jan;79(1):29–34. PubMed PMID: 19041438.
   PubMed Web of Science ®Google Scholar
• Beerthuizen R, van Beek A, Massai R, et al. Bone mineral density during long-term use of the progestagen contraceptive implant Implanon compared to a non-hormonal method of contraception. Hum Reprod. 2000 Jan;15(1):118–122. PubMed PMID: 10611199.
   PubMed Web of Science ®Google Scholar
• Monteiro-Dantas C, Espejo-Arce X, Lui-Filho JF, et al. A three-year longitudinal evaluation of the forearm bone density of users of etonogestrel- and levonorgestrel-releasing contraceptive implants. Reprod Health. 2007 Nov 12;4:11. PubMed PMID: 17997844; PubMed Central PMCID: PMCPMC2200638.
   PubMedGoogle Scholar
• Westhoff C. Depot-medroxyprogesterone acetate injection (Depo-Provera): a highly effective contraceptive option with proven long-term safety. Contraception. 2003 Aug;68(2):75–87. PubMed PMID: 12954518.
   PubMed Web of Science ®Google Scholar
• Dragoman MV, Gaffield ME. The safety of subcutaneously administered depot medroxyprogesterone acetate (104mg/0.65mL): A systematic review. Contraception. 2016 Sep;94(3):202–215. PubMed PMID: 26874275.
   PubMed Web of Science ®Google Scholar
• Ruan X, Seeger H, Mueck AO. The pharmacology of dienogest. Maturitas. 2012 Apr;71(4):337–344. PubMed PMID: 22364708.
   PubMed Web of Science ®Google Scholar
• Food and Drugs Administration. PROVERA® (medroxyprogesterone acetate) tablets, USP. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/011839s079s080lbl.pdf
   Google Scholar
• Food and Drugs Administration. DEPO-PROVERA CI® (medroxyprogesterone acetate) injectable suspension, for intramuscular use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020246s036lbl.pdf
   Google Scholar
• Halpern V, Combes SL, Dorflinger LJ, et al. Pharmacokinetics of subcutaneous depot medroxyprogesterone acetate injected in the upper arm. Contraception. 2014 01 01;89(1):31–35.
   PubMed Web of Science ®Google Scholar
• Roland M, Leisten D, Kane R. Endometriosis therapy with medroxyprogesterone acetate. J Reprod Med. 1976 Oct;17(4):249–252. PubMed PMID: 978656.
   PubMed Web of Science ®Google Scholar
• Moghissi KS, Boyce CR. Management of endometriosis with oral medroxyprogesterone acetate. Obstet Gynecol. 1976 Mar;47(3):265–267. PubMed PMID: 1250555.
   PubMed Web of Science ®Google Scholar
• Luciano AA, Turksoy RN, Carleo J. Evaluation of oral medroxyprogesterone acetate in the treatment of endometriosis. Obstet Gynecol. 1988 Sep;72(3 Pt 1):323–327. PubMed PMID: 2970029.
   PubMed Web of Science ®Google Scholar
• Telimaa S, Puolakka J, Ronnberg L, et al. Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis. Gynecol Endocrinol. 1987 Mar;1(1):13–23. PubMed PMID: 2972167.
   PubMedGoogle Scholar
• Telimaa S, Ronnberg L, Kauppila A. Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery. Gynecol Endocrinol. 1987 Dec;1(4):363–371. PubMed PMID: 2972171.
   PubMedGoogle Scholar
• Bergqvist A, Theorell T. Changes in quality of life after hormonal treatment of endometriosis. Acta Obstet Gynecol Scand. 2001 Jul;80(7):628–637. PubMed PMID: 11437721.
   PubMed Web of Science ®Google Scholar
• Harrison RF, Barry-Kinsella C. Efficacy of medroxyprogesterone treatment in infertile women with endometriosis: a prospective, randomized, placebo-controlled study. Fertil Steril. 2000 Jul;74(1):24–30. PubMed PMID: 10899492.
   PubMed Web of Science ®Google Scholar
• Brown J, Kives S, Akhtar M. Progestagens and anti-progestagens for pain associated with endometriosis. Cochrane Database Syst Rev. 2012;(3):CD002122. PubMed PMID: 22419284.
   PubMed Web of Science ®Google Scholar
• Vercellini P, De Giorgi O, Oldani S, et al. Depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol for long-term treatment of pelvic pain associated with endometriosis. Am J Obstet Gynecol. 1996;175(2):396–401.
   PubMed Web of Science ®Google Scholar
• Wong AYK, Tang LCH, Chin RKH. Levonorgestrel-releasing intrauterine system (Mirena®) and Depot medroxyprogesterone acetate (Depoprovera) as long-term maintenance therapy for patients with moderate and severe endometriosis: a randomised controlled trial. Aust New Zealand J Obstet Gynaecol. 2010;50(3):273–279.
   PubMed Web of Science ®Google Scholar
• Crosignani PG, Luciano A, Ray A, et al. Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. Hum Reprod. 2006;21(1):248–256.
   PubMed Web of Science ®Google Scholar
• Schlaff WD, Carson SA, Luciano A, et al. Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain. Fertil Steril. 2006;85(2):314–325.
   PubMed Web of Science ®Google Scholar
• Stager MM, Cromer BA. Management of clinical side effects of DMPA. J Pediatr Adolesc Gynecol. 2000 Aug;13(3):147–149. PubMed PMID: 10989335.
   PubMedGoogle Scholar
• Jain J, Jakimiuk AJ, Bode FR, et al. Contraceptive efficacy and safety of DMPA-SC. Contraception. 2004 Oct;70(4):269–275. PubMed PMID: 15451329.
   PubMed Web of Science ®Google Scholar
• Kaunitz AM, Darney PD, Ross D, et al. Subcutaneous DMPA vs. intramuscular DMPA: a 2-year randomized study of contraceptive efficacy and bone mineral density. Contraception. 2009;80(1):7–17.
   PubMed Web of Science ®Google Scholar
• Guilbert ER, Brown JP, Kaunitz AM, et al. The use of depot-medroxyprogesterone acetate in contraception and its potential impact on skeletal health. Contraception. 2009 Mar;79(3):167–177. PubMed PMID: 19185668.
   PubMed Web of Science ®Google Scholar
• Gynecologists TACoOa. Committee opinion - depot medroxyprogesterone acetate and bone effects. 2014.
   Google Scholar
• Harada T, Taniguchi F. Dienogest: a new therapeutic agent for the treatment of endometriosis. Womens Health (Lond). 2010 Jan;6(1):27–35. PubMed PMID: 20001868. The American College of Obstetricians and Gynecologists. Committee opinion - depot medroxyprogesterone acetate and bone effects. 2014. Available from: https://www.acog.org/-/media/Committee-Opinions/Committee-on-Adolescent-Health-Care/co602.pdf?dmc=1
   PubMedGoogle Scholar
• Board ME PUBLIC ASSESSMENT REPORT of the Medicines Evaluation Board in the Netherlands Visanne, tablets, 2 mg Bayer BV, The Netherlands. Available from: https://db.cbg-meb.nl/Pars/h104058.pdf
   Google Scholar
• McCormack PL. Dienogest: a review of its use in the treatment of endometriosis. Drugs. 2010 Nov 12;70(16):2073–2088. PubMed PMID: 20964453.
   PubMed Web of Science ®Google Scholar
• Shin D, Lee S, Lim KS, et al. Pharmacokinetic study of single and multiple oral administrations of 2 mg dienogest in healthy Korean women. Contraception. 2013 Jun;87(6):750–755. PubMed PMID: 23218856; eng.
   PubMed Web of Science ®Google Scholar
• Bizzarri N, Remorgida V, Leone Roberti Maggiore U, et al. Dienogest in the treatment of endometriosis. Expert Opin Pharmacother. 2014 Sep;15(13):1889–1902. PubMed PMID: 25069386.
   PubMed Web of Science ®Google Scholar
• Cosson M, Querleu D, Donnez J, et al. Dienogest is as effective as triptorelin in the treatment of endometriosis after laparoscopic surgery: results of a prospective, multicenter, randomized study. Fertil Steril. 2002 Apr;77(4):684–692. PubMed PMID: 11937116.
   PubMed Web of Science ®Google Scholar
• Harada T, Momoeda M, Taketani Y, et al. Dienogest is as effective as intranasal buserelin acetate for the relief of pain symptoms associated with endometriosis–a randomized, double-blind, multicenter, controlled trial. Fertil Steril. 2009 Mar;91(3):675–681. PubMed PMID: 18653184.
   PubMed Web of Science ®Google Scholar
• Takaesu Y, Nishi H, Kojima J, et al. Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis. J Obstet Gynaecol Res. 2016 Sep;42(9):1152–1158. PubMed PMID: 27225336.
   PubMed Web of Science ®Google Scholar
• Andres MDP, Lopes LA, Baracat EC, et al. Dienogest in the treatment of endometriosis: systematic review. Arch Gynecol Obstet. 2015 Sep;292(3):523–529. PubMed PMID: 25749349; eng.
   PubMed Web of Science ®Google Scholar
• Kitawaki J, Kusuki I, Yamanaka K, et al. Maintenance therapy with dienogest following gonadotropin-releasing hormone agonist treatment for endometriosis-associated pelvic pain. Eur J Obstet Gynecol Reprod Biol. 2011 Aug;157(2):212–216. PubMed PMID: 21474232.
   PubMed Web of Science ®Google Scholar
• Lang J, Yu Q, Zhang S, et al. Dienogest for treatment of endometriosis in Chinese women: a placebo-controlled, randomized, double-blind phase 3 study. J Womens Health (Larchmt). 2017 Oct 30. PubMed PMID: 29083258; eng.
   Google Scholar
• Morotti M, Sozzi F, Remorgida V, et al. Dienogest in women with persistent endometriosis-related pelvic pain during norethisterone acetate treatment. Eur J Obstet Gynecol Reprod Biol. 2014 Dec;183:188–192. PubMed PMID: 25461377.
   PubMed Web of Science ®Google Scholar
• Leone Roberti Maggiore U, Ferrero S, Candiani M, et al. Bladder endometriosis: a systematic review of pathogenesis, diagnosis, treatment, impact on fertility, and risk of malignant transformation. Eur Urol. 2017 May;71(5):790–807. PubMed PMID: 28040358.
   PubMed Web of Science ®Google Scholar
• Angioni S, Nappi L, Pontis A, et al. Dienogest. A possible conservative approach in bladder endometriosis. Results of a pilot study. Gynecol Endocrinol. 2015;31(5):406–408.
   PubMed Web of Science ®Google Scholar
• Leonardo-Pinto JP, Benetti-Pinto CL, Cursino K, et al. Dienogest and deep infiltrating endometriosis: the remission of symptoms is not related to endometriosis nodule remission. Eur J Obstetrics Gynecol Reprod Biol. 2017;211:108–111.
   PubMed Web of Science ®Google Scholar
• Vercellini P, Bracco B, Mosconi P, et al. Norethindrone acetate or dienogest for the treatment of symptomatic endometriosis: a before and after study. Fertil Steril. 2015 Dec 8. PubMed PMID: 26677792.
   Web of Science ®Google Scholar
• Strowitzki T, Faustmann T, Gerlinger C, et al. Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program. Int J Women’s Health. 2015;7:391–401.
   Web of Science ®Google Scholar
• Lee DY, Lee JY, Seo JW, et al. Gonadotropin-releasing hormone agonist with add–back treatment is as effective and tolerable as dienogest in preventing pain recurrence after laparoscopic surgery for endometriosis. Arch Gynecol Obstet. 2016;294(6):1257–1263.
   PubMed Web of Science ®Google Scholar
• Momoeda M, Harada T, Terakawa N, et al. Long-term use of dienogest for the treatment of endometriosis. J Obstet Gynaecol Res. 2009;35(6):1069–1076.
   PubMed Web of Science ®Google Scholar
• Strowitzki T, Marr J, Gerlinger C, et al. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial. Hum Reprod. 2010 Mar;25(3):633–641. PubMed PMID: 20089522.
   PubMed Web of Science ®Google Scholar
• Vercellini P, Vigano P, Somigliana E. The role of the levonorgestrel-releasing intrauterine device in the management of symptomatic endometriosis. Curr Opin Obstet Gynecol. 2005 Aug;17(4):359–365. PubMed PMID: 15976541.
   PubMed Web of Science ®Google Scholar
• Food and Drugs Administration. MIRENA® (levonorgestrel-releasing intrauterine system). Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021225s019lbl.pdf
   Google Scholar
• Seeber B, Ziehr SC, Gschliebetaer A, et al. Quantitative levonorgestrel plasma level measurements in patients with regular and prolonged use of the levonorgestrel-releasing intrauterine system. Contraception. 2012 Oct;86(4):345–349. PubMed PMID: 22402256.
   PubMed Web of Science ®Google Scholar
• Gomes MKO, Rosa-E-Silva JC, Garcia SB, et al. Effects of the levonorgestrel-releasing intrauterine system on cell proliferation, Fas expression and steroid receptors in endometriosis lesions and normal endometrium. Hum Reprod. 2009;24(11):2736–2745.
   PubMed Web of Science ®Google Scholar
• Engemise SL, Willets JM, Taylor AH, et al. Changes in glandular and stromal estrogen and progesterone receptor isoform expression in eutopic and ectopic endometrium following treatment with the levonorgestrel-releasing intrauterine system. Eur J Obstetrics Gynecol Reprod Biol. 2011;157(1):101–106.
   PubMed Web of Science ®Google Scholar
• Fedele L, Bianchi S, Zanconato G, et al. Use of a levonorgestrel-releasing intrauterine device in the treatment of rectovaginal endometriosis. Fertil Steril. 2001;75(3):485–488.
   PubMed Web of Science ®Google Scholar
• Gomes MK, Ferriani RA, Rosa e Silva JC, et al. The levonorgestrel-releasing intrauterine system and endometriosis staging. Fertil Steril. 2007 May;87(5):1231–1234. PubMed PMID: 17292364.
   PubMed Web of Science ®Google Scholar
• Ferreira RA, Vieira CS, Rosa ESJC, et al. Effects of the levonorgestrel-releasing intrauterine system on cardiovascular risk markers in patients with endometriosis: a comparative study with the GnRH analogue. Contraception. 2010 Feb;81(2):117–122. PubMed PMID: 20103448.
   PubMed Web of Science ®Google Scholar
• Petta CA, Ferriani RA, Abrao MS, et al. Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Hum Reprod. 2005 Jul;20(7):1993–1998. PubMed PMID: 15790607.
   PubMed Web of Science ®Google Scholar
• Lan S, Ling L, Jianhong Z, et al. Analysis of the levonorgestrel-releasing intrauterine system in women with endometriosis. J Int Med Res. 2013 Jun;41(3):548–558. PubMed PMID: 23660087.
   PubMed Web of Science ®Google Scholar
• Lockhat FB, Emembolu JO, Konje JC. The efficacy, side-effects and continuation rates in women with symptomatic endometriosis undergoing treatment with an intra-uterine administered progestogen (levonorgestrel): a 3 year follow-up. Hum Reprod. 2005 Mar;20(3):789–793. PubMed PMID: 15608040; eng.
   PubMed Web of Science ®Google Scholar
• Tanmahasamut P, Rattanachaiyanont M, Angsuwathana S, et al. Postoperative levonorgestrel-releasing intrauterine system for pelvic endometriosis-related pain: a randomized controlled trial. Obstet Gynecol. 2012 Mar;119(3):519–526. PubMed PMID: 22314873.
   PubMed Web of Science ®Google Scholar
• Morelli M, Sacchinelli A, Venturella R, et al. Postoperative administration of dienogest plus estradiol valerate versus levonorgestrel-releasing intrauterine device for prevention of pain relapse and disease recurrence in endometriosis patients. J Obstet Gynaecol Res. 2013 May;39(5):985–990. PubMed PMID: 23551827; eng.
   PubMed Web of Science ®Google Scholar
• Cho S, Jung JA, Lee Y, et al. Postoperative levonorgestrel-releasing intrauterine system versus oral contraceptives after gonadotropin-releasing hormone agonist treatment for preventing endometrioma recurrence. Acta Obstet Gynecol Scand. 2014 Jan;93(1):38–44. PubMed PMID: 24605384; eng.
   PubMed Web of Science ®Google Scholar
• Kim ML, Cho YJ, Kim MK, et al. The efficacy of long-term maintenance therapy with a levonorgestrel-releasing intrauterine system for prevention of ovarian endometrioma recurrence. Int J Gynaecol Obstet. 2016 Sep;134(3):256–259. PubMed PMID: 27346551; eng.
   PubMed Web of Science ®Google Scholar
• Chen YJ, Hsu TF, Huang BS, et al. Postoperative maintenance levonorgestrel-releasing intrauterine system and endometrioma recurrence: a randomized controlled study. Am J Obstet Gynecol. 2017 Jun;216(6):582.e1–582.e9. PubMed PMID: 28209488; eng.
   Web of Science ®Google Scholar
• Bayoglu Tekin Y, Dilbaz B, Altinbas SK, et al. Postoperative medical treatment of chronic pelvic pain related to severe endometriosis: levonorgestrel-releasing intrauterine system versus gonadotropin-releasing hormone analogue. Fertil Steril. 2011 Feb;95(2):492–496. PubMed PMID: 20883991.
   PubMed Web of Science ®Google Scholar
• Ferrero S. Endometriosis: modern management of an ancient disease. Eur J Obstet Gynecol Reprod Biol. 2017 Feb;209:1–2. PubMed PMID: 28094070.
   PubMed Web of Science ®Google Scholar
• Guerriero S, Condous G, Van den Bosch T, et al. Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group. Ultrasound Obstet Gynecol. 2016 Jun 28. PubMed PMID: 27349699.
   Web of Science ®Google Scholar
• Upson K, Allison KH, Reed SD, et al. Biomarkers of progestin therapy resistance and endometrial hyperplasia progression. Am J Obstet Gynecol. 2012 Jul;207(1):36 e1–8. PubMed PMID: 22727345; PubMed Central PMCID: PMCPMC3398620.
   Web of Science ®Google Scholar
• Clark MK, Sowers MR, Nichols S, et al. Bone mineral density changes over two years in first-time users of depot medroxyprogesterone acetate. Fertil Steril. 2004 Dec;82(6):1580–1586. PubMed PMID: 15589863.
   PubMed Web of Science ®Google Scholar
• Scholes D, LaCroix AZ, Ichikawa LE, et al. Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception. Arch Pediatr Adolesc Med. 2005 Feb;159(2):139–144. PubMed PMID: 15699307.
   PubMedGoogle Scholar
• Modesto W, Bahamondes MV, Bahamondes L. Prevalence of low bone mass and osteoporosis in long-term users of the injectable contraceptive depot medroxyprogesterone acetate. J Womens Health (Larchmt). 2015 Aug;24(8):636–640. PubMed PMID: 26098552.
   PubMed Web of Science ®Google Scholar
• Meier C, Brauchli YB, Jick SS, et al. Use of depot medroxyprogesterone acetate and fracture risk. J Clin Endocrinol Metab. 2010 Nov;95(11):4909–4916. PubMed PMID: 20685865.
   PubMed Web of Science ®Google Scholar
• Lanza LL, McQuay LJ, Rothman KJ, et al. Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture. Obstet Gynecol. 2013 Mar;121(3):593–600. PubMed PMID: 23635623.
   PubMed Web of Science ®Google Scholar
• Vestergaard P, Rejnmark L, Mosekilde L. The effects of depot medroxyprogesterone acetate and intrauterine device use on fracture risk in Danish women. Contraception. 2008 Dec;78(6):459–464. PubMed PMID: 19014791.
   PubMed Web of Science ®Google Scholar
• Pontis A, D’Alterio MN, Pirarba S, et al. Adenomyosis: a systematic review of medical treatment. Gynecol Endocrinol. 2016 Sep;32(9):696–700. PubMed PMID: 27379972.
   PubMed Web of Science ®Google Scholar
• Muzii L. Medicated intrauterine systems for treatment of endometriosis-associated pain. J Minim Invasive Gynecol. 2006 Nov-Dec;13(6):535–538. PubMed PMID: 17097576.
   PubMed Web of Science ®Google Scholar