Gestagenes in the treatment of endometriosis: efficiency, safety, bioequivalence, transferability

Literature review




endometriosis, dienogest, adenomyosis, endometrioma


Endometriosis is a chronic disease that requires long-term treatment, the goal of which is effectively use drugs and avoids repeated surgical interventions.
The quality of patients’ life depends on the varying degrees of symptoms such as pelvic pain, dyspareunia, dysmenorrhea. Endometriosis causes infertility and perinatal complications. The symptoms of endometriosis often affect psychological and social well-being, and threaten the relationships, sexuality and mental health of women. Women with endometriosis have high levels of anxiety, depression, and other psychiatric disorders that can aggravate the severity of their pain.
The existing statistics on the endometriosis incidence is underestimated given the diagnostic difficulties. So far, there are no final, only generally an accepted method of treating endometriosis, and in most cases, treatment is only eliminates the symptoms. Today, it is desirable to take a conservative approach to treatment, avoiding surgery, and hormone therapy is recommended to relieve pain associated with endometriosis. An individual approach is important in the management of patients with endometriosis, taking into account the reproductive plans and needs of woman. Medical treatment methods should be used as much as possible, for example, dienogest 2 mg (in particular, Savis drug). Dienogest is a derivative of 19-nortestosterone, which has an antiproliferative effect on the endometriosis foci.
Savis is a drug specially formulated for the endometriosis treatment. Savis may be prescribed to relieve symptoms before and after surgery to prevent relapse. The safety profile of dienogest has been studied and data is constantly accumulating, given the popularity of its prescription.
The effectiveness of dienogest should be assessed primarily by its effect on pain and quality of life, on maintaining fertility, and on the possibility of avoiding or postponing surgery. This is important for various forms of endometriosis: endometriomas, extragenital endometriosis, adenomyosis.

Author Biography

A.M. Hryhorenko, National Pirogov Memorial Medical University; Medical Center “Innomed – Center for Endosurgery”, Vinnytsia

MD, professor, head of the course of oncogynecology and operative gynecology, Department of Obstetrics and Gynecology No. 2;


  1. American Society for Reproductive Medicine. “Endometriosis and infertility: a committee opinion.” Fertil Steril 98 (2012): 591–8.
  2. Adachi, K., Takahashi, K., Nakamura, K., et al. “Postoperative administration of dienogest for suppressing recurrence of disease and relieving pain in subjects with ovarian endometriomas.” Gynecol Endocrinol 32.8 (2016): 646–9.
  3. Murji, A., Biberoğlu, K., Leng, J., et al. “Use of dienogest in endometriosis: a narrative literature review and expert commentary.” Curr Med Res Opin 36.5 (2020): 895–907. DOI: 10.1080/03007995.2020.1744120
  4. Johnson, N.P., Hummelshoj, L., World Endometriosis Society Montpellier Consortium. “Consensus on current management of endometriosis.” Hum Reprod 28.6 (2013): 1552–68.
  5. Ebert, A.D., Dong, L., Merz, M., et al. “Dienogest 2 mg Daily in the Treatment of Adolescents with Clinically Suspected Endometriosis: The VISanne Study to Assess Safety in ADOlescents.” J Pediatr Adolesc Gynecol 30.5 (2017): 560–7. DOI: 10.1016/j.jpag.2017.01.014
  6. Busacca, M., Chiaffarino, F., Candiani, M., et al. “Determinants of long-term clinically detected recurrence rates of deep, ovarian, and pelvic endometriosis.” Am J Obstet Gynecol 195.2 (2006): 426–32.
  7. Caruso, S., Iraci, M., Cianci, S., et al. “Comparative, open-label prospective study on the quality of life and sexual function of women affected by endometriosis-associated pelvic pain on 2 mg dienogest/30 microg ethinyl estradiol continuous or 21/7 regimen oral contraceptive.” J Endocrinol Invest 39.8 (2016): 923–31.
  8. Caruso, S., Iraci, M., Cianci, S., et al. “Effects of long-term treatment with dienogest on the quality of life and sexual function of women affected by endometriosis-associated pelvic pain.” J Pain Res 12 (2019): 2371–8.
  9. Chandra, A., Rho, A.M., Jeong, K., et al. “Clinical experience of long-term use of dienogest after surgery for ovarian endometrioma.” Obstet Gynecol Sci 61.1 (2018): 111–7.
  10. Del Forno, S., Mabrouk, M., Arena, A., et al. “Dienogest or norethindrone acetate for the treatment of ovarian endometriomas: can we avoid surgery?” Eur J Obstet Gynecol Reprod Biol 238 (2019): 120–4.
  11. Dunselman, G.A., Vermeulen, N., Becker, C., et al. “ESHRE guideline: management of women with endometriosis.” Hum Reprod 29.3 (2014): 400–12.
  12. Petraglia, F., Hornung, D., Seitz, C., et al. “Reduced pelvic pain in women with endometriosis: effcacy of long-term dienogest treatment.” Arch Gynecol Obstet 285.1 (2012): 167–73. DOI: 10.1007/s00404-011-1941-7
  13. Ferrero, S., Evangelisti, G., Barra, F. “Current and emerging treatment options for endometriosis.” Expert Opin Pharmacother 19.10 (2018): 1109–25.
  14. Foster, R.H., Wilde, M.I. “Dienogest.” Drugs 56.5 (1998): 825–33; discussion: 834–5.
  15. Gedeon Richter Plc. Randomized, open-label, 2-way crossover bioequivalence study of dienogest 2 mg film-coated tablet and visanne (reference) following a 2 mg dose in healthy subjects under fasting conditions. Final Integrated Clinical and Statistical Report, Version 01 (2 Oct 2015).
  16. Gedeon Richter. Zafrilla (dienogest) 2 mg tablets. Summary of Product Characteristics (Sep 2020).
  17. Guo, S.W. “Recurrence of endometriosis and its control.” Hum Reprod Update 15.4 (2009): 441–61.
  18. Harada, T., Momoeda, M., Taketani, Y., et al. “Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial.” Fertil Steril 90.5 (2008): 1583–8.
  19. Hirsch, M., Begum, M.R., Paniz, E., et al. “Diagnosis and management of endometriosis: a systematic review of international and national guidelines.” BJOG 125.5 (2018): 556–64.
  20. 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 157.2 (2011): 212–6.
  21. Koga, K., Takamura, M., Fujii, T., et al. “Prevention of the recurrence of symptom and lesions after conservative surgery for endometriosis.” Fertil Steril 104.4 (2015): 793–801.
  22. Kohler, G., Faustmann, T.A., Gerlinger, C., et al. “A dose-ranging study to determine the efficacy and safety of 1, 2, and 4 mg of dienogest daily for endometriosis.” Int J Gynaecol Obstet 108.1 (2010): 21–5.
  23. Koshiba, A., Mori, T., Okimura, H., et al. “Dienogest therapy during the early stages of recurrence of endometrioma might be an alternative therapeutic option to avoid repeat surgeries.” J Obstet Gynaecol Res 44.10 (2018): 1970–6.
  24. Lee, J.H., Song, J.Y., Yi, K.W., et al. “Effectiveness of dienogest for treatment of recurrent endometriosis: multicenter data.” Reprod Sci 25.10 (2018): 1515–22.
  25. Lee, S.R., Yi, K.W., Song, J.Y., et al. “Efficacy and safety of long-term use of dienogest in women with ovarian endometrioma.” Reprod Sci 25.3 (2018): 341–6.
  26. Leyland, N., Casper, R., Laberge, P., et al. “Endometriosis: diagnosis and management.” J Obstet Gynaecol Can 32 (7 Suppl 2) (2010): S1–32. 10.1016/S1701-2163(16)34589-3
  27. McCormack, P.L. “Dienogest: a review of its use in the treatment of endometriosis.” Drugs 70.16 (2010): 2073–88.
  28. Momoeda, M., Harada, T., Terakawa, N., et al. “Long-term use of dienogest for the treatment of endometriosis.” J Obstet Gynaecol Res 35.6 (2009): 1069–76.
  29. 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 39.5 (2013): 985–90.
  30. Nakamura, M., Katsuki, Y., Shibutani, Y., Oikawa, T. “Dienogest, a synthetic steroid, suppresses both embryonic and tumor-cell-induced angiogenesis.” Eur J Pharmacol 386.1 (1999): 33–40.
  31. National Institute for Health and Care Excellence. “Endometriosis: diagnosis and management.” Available from: [].
  32. Oettel, M., Breitbarth, W., Elger, W., et al. “The Pharmacological profile of dienogest.” EU J Contraception and Reprod Health Care 3 (1998): 1–12.
  33. Okada, H., Nakajima, T., Yoshimura, T., et al. “The inhibitory effect of dienogest, a synthetic steroid, on the growth of human endometrial stromal cells in vitro.” Mol Hum Reprod 7.4 (2001): 341–7.
  34. Ota, Y., Andou, M., Yanai, S., et al. “Long-term administration of dienogest reduces recurrence after excition of endometrioma.” J Endometr Pelvic Pain Disord 7.2 (2015): 63–7.
  35. Ouchi, N., Akira, S., Mine, K., et al. “Recurrence of ovarian endometrioma after laparoscopic excision: risk factors and prevention.” J Obstet Gynaecol Res 40.1 (2014): 230–6.
  36. Park, S.Y., Kim, S.H., Chae, H.D., et al. “Efficacy and safety of dienogest in patients with endometriosis: a single-center observational study over 12 months.” Clin Exp Reprod Med 43.4 (2016): 215–20.
  37. Leonardo-Pinto, J.P., Benetti-Pinto, C.L., Yela, D.A. “When solving dyspareunia is not enough to restore sexual function in women with deep infiltrating endometriosis treated with dienogest.” J Sex Marital Ther 45.1 (2019): 44–9.
  38. Pontis, A., D’Alterio, M.N., Pirarba, S., et al. “Adenomyosis: a systematic review of medical treatment.” Gynecol Endocrinol 32.9 (2016): 696–700.
  39. Qaseem, A., Forciea, M.A., McLean, R.M., et al. “Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians.” Ann Intern Med 166.11 (2017): 818–39.
  40. Römer, T. “Long-term treatment of endometriosis with dienogest: retrospective analysis of efficacy and safety in clinical practice.” Arch Gynecol Obstet 298.4 (2018): 747–53.
  41. Schindler, A.E. “Dienogest in long-term treatment of endometriosis.” Int J Womens Health 3 (2011): 175–84.
  42. Seitz, C., Gerlinger, C., Faustmann, T., et al. “Safety of dienogest in the long-term treatment of endometriosis: a one-year, open-label, follow-up study.” Fertil Steril 92 (2009): S107.
  43. Seracchioli, R., Mabrouk, M., Manuzzi, L., et al. “Post-operative use of oral contraceptive pills for prevention of anatomical relapse or symptom recurrence after conservative surgery for endometriosis.” Hum Reprod 24.11 (2009): 2729–35.
  44. Strowitzki, T., Faustmann, T., Gerlinger, C., et al. “Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study.” Eur J Obstet Gynecol Reprod Biol 151.2 (2010): 193–8.
  45. 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 25.3 (2010): 633–41.
  46. Sugimoto, K., Nagata, C., Hayashi, H., et al. “Use of dienogest over 53 weeks for the treatment of endometriosis.” J Obstet Gynaecol Res 41.12 (2015): 1921–6.
  47. Takaesu, Y., Nishi, H., Kojima, J., et al. “Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis.” J Obstet Gynaecol Res 42.9 (2016): 1152–8.
  48. Bayer Inc. Visanne. Summary of product characteristics. Pymble (NSW): Bayer Australia (2016).
  49. Yamanaka, A., Hada, T., Matsumoto, T., et al. “Effect of dienogest on pain and ovarian endometrioma occurrence after laparoscopic resection of uterosacral ligaments with deep infiltrating endometriosis.” Eur J Obstet Gynecol Reprod Biol 216 (2017): 51–5.



How to Cite

Hryhorenko, A. (2021). Gestagenes in the treatment of endometriosis: efficiency, safety, bioequivalence, transferability: Literature review. REPRODUCTIVE ENDOCRINOLOGY, (61), 72–75.