An assessment of the efficacy and safety of dydrogesterone in women with ovarian endometrioma: An open-label multicenter clinical study

Jo Kitawaki, Kaori Koga, Takumi Kanzo, Mikio Momoeda, Jo Kitawaki, Kaori Koga, Takumi Kanzo, Mikio Momoeda

Abstract

Purpose: To assess the efficacy and safety of dydrogesterone in Japanese women with ovarian endometrioma in a real-world setting.

Methods: The post-marketing study involved 15 sites in Japan. Dydrogesterone 10 mg twice daily orally was administered for 21 days (day 5-25 of each menstrual cycle) for 4 cycles. The primary outcome measure was the change in ovarian endometrioma volume from baseline. Secondary outcome measures included total dysmenorrhea score (0 = absent to 3 = severe), severity of dysmenorrhea pain [0-10cm visual analog scale (VAS)], serum carbohydrate antigen 125 (CA-125) levels, and safety.

Results: The study group comprised women with an endometrioma aged 20 to 49 (47.4% cases aged ≥40 years). Endometrioma volume was reduced in 50% (26/52), unchanged in 25% (13/52), and increased in 25% (13/52) of women from baseline to the end of cycle 5; three-quarters of patients thus had either reduced or unchanged ovarian endometrioma volume. Dydrogesterone significantly reduced total dysmenorrhea scores and severity of dysmenorrhea pain VAS during treatment compared with baseline. CA-125 levels were not significantly changed during the study. The incidence of adverse events and adverse drug reactions in 59 subjects was 13.6% and 11.9%.

Conclusions: Dydrogesterone prevented an increase in endometrioma size in many women, and it also significantly improved total dysmenorrhea scores and severity of dysmenorrhea pain, and was well tolerated. The ClinicalTrials.gov identifier of the study was NCT02921763.

Keywords: dydrogesterone; dysmenorrhea; endometriosis; ovarian endometrioma; post‐marketing study.

Conflict of interest statement

Takumi Kanzo is an employee of Mylan EPD G.K, Tokyo, Japan. The other authors have no conflicts of interest to disclose related to this work.

© 2021 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.

Figures

FIGURE 1
FIGURE 1
Patient disposition
FIGURE 2
FIGURE 2
Mean (+SD) volume of ovarian endometriomas from before treatment initiation to end of Cycle 5 (efficacy analysis set) in three subgroups: endometriomal volume increased (‐⸳‐□‐⸳‐), unchanged (‐‐○‐‐), or decreased (‐●‐)
FIGURE 3
FIGURE 3
Mean change in dysmenorrhea score over time (Wilcoxon signed‐rank test (vs −1 cycle), *: P < .01, **: P < .001)
FIGURE 4
FIGURE 4
Mean change in the severity of dysmenorrhea pain (VAS) at each cycle (Wilcoxon signed‐rank test (vs −1 cycle), *: P < .01, **: P < .001)

References

    1. Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Viganò P. Endometriosis. Nat Rev Dis Primers. 2018;4:9. 10.1038/s41572-018-0008-5
    1. Ferrero S, Evangelisti G, Barra F. Current and emerging treatment options for endometriosis. Expert Opin Pharmacother. 2018;19:1109‐1125.
    1. Camara O, Herrmann J, Egbe A, et al. Treatment of endometriosis of uterosacral ligament and rectum through the vagina: description of a modified technique. Hum Reprod. 2009;24:1407‐1413.
    1. Crosignani P, Olive D, Bergqvist A, Luciano A. Advances in the management of endometriosis: an update for clinicians. Hum Reprod Update. 2006;12:179‐189.
    1. Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10:261‐275.
    1. Bishop PM. A new oral progestogen in the treatment of dysmenorrhoea. Proc R Soc Med. 1961;54:752‐754.
    1. Bell ET, Loraine JA. Effect of dydrogesterone on hormone excretion in patients with dysmenorrhoea. Lancet. 1965;1:403‐406.
    1. Fairweather DV. Duphaston in dysmenorrhoea; the results of a double blind clinical trial. J Obstet Gynaecol Br Commonw. 1965;72:193‐195.
    1. Iacovides S, Avidon I, Baker FC. What we know about primary dysmenorrhea today: a critical review. Hum Reprod Update. 2015;21:762‐778.
    1. Farquhar C, Prentice A, Singla A, Selak V. Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev. 2007;(4):CD000068.
    1. Brown J, Pan A, Hart RJ. Gonadotrophin‐releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev. 2010;(12):CD008475.
    1. Harada T, Momoeda M, Taketani Y, Hoshiai H, Terakawa N. Low‐dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo‐controlled, double‐blind, randomized trial. Fertil Steril. 2008;90:1583‐1588.
    1. Brown J, Farquhar C. An overview of treatments for endometriosis. JAMA. 2015;313:296‐297.
    1. Harada T. Dysmenorrhea and endometriosis in young women. Yonago Acta Med. 2013;56:81‐84.
    1. Harada T, Momoeda M. Evaluation of an ultra‐low‐dose oral contraceptive for dysmenorrhea: a placebo‐controlled, double blind, randomized trial. Fertil Steril. 2016;106:1807‐1814.
    1. Mabrouk M, Solfrini S, Frascà C, et al. A new oral contraceptive regimen for endometriosis management: preliminary experience with 24/4‐day drospirenone/ethinylestradiol 3 mg/20 mcg. Gynecol Endocrinol. 2012;28:451‐454.
    1. Harada T, Kosaka S, Elliesen J, Yasuda M, Ito M, Momoeda M. Ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen for the management of endometriosis‐associated pelvic pain: a randomized controlled trial. Fertil Steril. 2017;108:798‐805.
    1. Schindler AE. Dienogest in long‐term treatment of endometriosis. Int J Womens Health. 2011;3:175‐184.
    1. Vercellini P, Fedele L, Pietropaplo G, Frontino G, Somigliana E, Crosignani PG. Progestogens for endometriosis: forward to the past. Hum Reprod Update. 2003;9:387‐396.
    1. Schweppe KW. The place of dydrogesterone in the treatment of endometriosis and adenomyosis. Maturitas. 2009;65(Suppl 1):S23‐S27.
    1. Brown J, Kives S, Akhtar M. Progestagens and anti‐progestagens for pain associated with endometriosis. Cochrane Database Syst Rev. 2012;(3):CD002122.
    1. Chen FP, Soong YK, Lee N, et al. The use of serum CA‐125 as a marker for endometriosis in patients with dysmenorrhea for monitoring therapy and for recurrence of endometriosis. Acta Obstet Gynecol Scand. 1998;77:665‐670.
    1. Overton CE, Lindsay PC, Balroop Johal MB, et al. A randomized, double‐blind, placebo‐controlled study of luteal phase dydrogesterone (Duphaston) in women with minimal to mild endometriosis. Fertil Steril. 1994;62:701‐707.
    1. Johnston WIH. Dydrogesterone and endometriosis. Br J Obstet Gynaec. 1976;83:77‐80.
    1. Kaiser E, Wagner THA. Die Behandlung der Endometriose mit Dydrogesteron. TW Gynaekologie. 1989;2:386‐388.
    1. Walker SM. The treatment of endometriosis with dydrogesterone. Br J Clin Pract. 1983;S24:40‐46.
    1. Tumasian KP, Bēspoyasnaya VV, Voronovskaya IV. Treatment of endometriosis in female infertility. Lik Sprava. 2001;3:103‐105.
    1. Cornillie FJ, Puttemans P, Brosens IA. Histology and ultrastructure of human endometriotic tissues treated with dydrogesterone (Duphaston). Eur J Obstet Gynecol Reprod Biol. 1987;26:39‐55.
    1. Taniguchi F, Ota I, Iba Y, et al. The efficacy and safety of dydrogesterone for treatment of dysmenorrhea: An open‐label multicenter clinical study. J Obstet Gynaecol Res. 2018;45:168‐175.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa