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Current Drug Therapy Recommendations for the Treatment of Endometriosis

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Abstract

The principal symptoms and signs of endometriosis are tissue lesions and pelvic pain. These occur to varying degrees, with a chronic pattern and a tendency for deterioration with time. Patients with endometriosis often also have fertility problems, but the relationship between this and the signs and symptoms of the disease is inconsequent; the basic pathophysiology is not exactly known. Although an immunological defect resulting in an inflammatory reaction around discharged menstrual debris in the pelvic cavity has been shown, no treatments based on this process are available.

Estrogen often plays an important role in the progression of lesions and pain. Therefore, the aim of treatment usually has been to downregulate the ovaries and/or give antiestrogenic drugs as an alternative to surgical removal. As complete downregulation of the ovaries and hypoestrogenaemia does not seem to be crucial, achievement of amenorrhoea seems to be sufficient. This means that women may continue to have circulating estrogen levels so that severe hypoestrogenic adverse effects such as bone déminéralisation, dry vagina, psychiatric symptoms or anabolic/androgenic effects of gestagens can be avoided. However, as both symptoms and the dependence of hormones may vary between and within women, the treatment needs to be individualised.

There are a number of available treatments for endometriosis on the market and it is important for the doctor to know how to reach the therapeutic window of these treatments for each woman. It is also important to inform the patient about the different possibilities so that the treatment with the least impact on her quality of life can be chosen. When the therapeutic window has been identified, the treatment may then either be continued for a long period of time or be repeated when needed.

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References

  1. Fukaya T, Hoshiai H, Yajima A. Is pelvic endometriosis always associated with chronic pain? A retrospective study of 618 cases diagnosed by laparoscopy. Am J Obstet Gynecol 1993; 169: 719–22

    PubMed  CAS  Google Scholar 

  2. Rawson JMR. Prevalence of endometriosis in asymptomatic women. J Reprod Med 1991; 36: 513–5

    PubMed  CAS  Google Scholar 

  3. Vercellini P, Bocciolone L, Crosignani PG. Is mild endometriosis always a disease? Hum Reprod 1992; 7: 627–9

    PubMed  CAS  Google Scholar 

  4. Wardle PG, Hull MG. Is endometriosis a disease? Baillieres Clin Obstet Gynaecol 1993; 7: 673–85

    Article  PubMed  CAS  Google Scholar 

  5. Koninckx PR. Is mild endometriosis a condition occuring intermittently in all women? Human Reprod 1994; 9: 2202–5

    CAS  Google Scholar 

  6. Koninckx PR, Oosterlynck D, D’Hooghe T, et al. Deeply infiltrating endometriosis is a disease whereas mild endometriosis could be considered a non-disease. Ann N Y Acad Sci 1994; 734: 333–41

    Article  PubMed  CAS  Google Scholar 

  7. Balasch J, Creus M, Fabregues F, et al. Visible and non-visible endometriosis at laparoscopy in fertile and infertile women and in patients with chronic pelvic pain: a prospective study. Hum Reprod 1996; 11: 387–91

    Article  PubMed  CAS  Google Scholar 

  8. Hill JA. Immunology and endometriosis. Obstet Gynecol Clin North Am 1997; 24: 291–306

    Article  PubMed  CAS  Google Scholar 

  9. Redwine DB. Age-related evolution in colour appearance of endometriosis. Fertil Steril 1987; 48: 1062–3

    PubMed  CAS  Google Scholar 

  10. Bergqvist A, Fernö M. Estrogen and progesterone receptors in endometriotic tissue and endometrium: comparison according to localization and recurrence. Fertil Steril 1993; 60: 63–8

    PubMed  CAS  Google Scholar 

  11. Bergqvist A. Hormonal regulation of endometriosis and the rationales and effects of gonadotrophin-releasing hormone agonist treatment: a review. Human Reprod 1995; 10: 446–52

    Article  CAS  Google Scholar 

  12. Perper MM, Nezhat F, Goldstein H, et al. Dysmenorrhea is related to the number of implants in endometriosis patients. Fertil Steril 1995, 63: 500–3

    PubMed  CAS  Google Scholar 

  13. Vercellini P, Trespidi L, De Giorgi O, et al. Endometriosis and pelvic pain: relation to disease stage and localization. Fertil Steril 1996, 65: 299–304

    PubMed  CAS  Google Scholar 

  14. Stovall DW, Bowser LM, Archer DF, et al. Endometriosis-associated pelvic pain: evidence for an association between the stage of disease and a history of chronic pelvic pain. Fertil Steril 1997, 68: 13–8

    Article  PubMed  CAS  Google Scholar 

  15. Vercellini P. Endometriosis: what a pain it is. Semin Reprod Endocrinol 1997; 15: 251–61

    Article  PubMed  CAS  Google Scholar 

  16. Redwine DB. Endometriosis persisting after castration: clinical characteristics and results of surgical management. Obstet Gynecol 1994; 83: 405–13

    PubMed  CAS  Google Scholar 

  17. Namnoum AB, Hickman TN, Goodman SB, et al. Incidence of symptom recurrence after hysterectomy for endometriosis. Fertil Steril 1995; 64: 898–902

    PubMed  CAS  Google Scholar 

  18. Waller KG, Shaw RW. Gonadotrophin-releasing hormone analogues for the treatment of endometriosis: long term follow-up. Fertil Steril 1993; 59: 511–4

    PubMed  CAS  Google Scholar 

  19. Hornstein MD, Hemmings R, Yuzpe AA, et al. Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis. Fertil Steril 1997; 68: 860–4

    Article  PubMed  CAS  Google Scholar 

  20. Shaw RW. Evaluation of treatment with gonadotrophin-releasing hormone analogues. In RW Shaw, editor. Endometriosis: current understanding and management. Oxford: Blackwell Science, 1995: 206–34

    Google Scholar 

  21. Adamson GD, Kwei L, Edgren RA. Pain of endometriosis: effects of nafarelin and danazol therapy. Int J Fertil Menopaus Stud 1994; 39: 215–7

    CAS  Google Scholar 

  22. Dlugi AM, Miller JD, Knittle J. Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Lupron Study Group. Fertil Steril 1990; 54: 419–27

    PubMed  CAS  Google Scholar 

  23. Eldred JM, Haynes PJ, Thomas EJ. A randomized double-blind placebo-controlled trial of the effects on bone metabolism of the combination of nafarelin acetate and norethisterone. Clin Endocrinol 1992; 37: 354–9

    Article  CAS  Google Scholar 

  24. Kiilholma P, Tuimala R, Kivinen S, et al. Comparison of the gonadotropin-releasing hormone agonist goserelin acetate alone versus goserelin combined with estrogen-progestogen add-back therapy in the treatment of endometriosis. Fertil Steril 1995; 64: 903–8

    PubMed  CAS  Google Scholar 

  25. Mukherjee T, Barad D, Turk R, et al. A randomized, placebo-controlled study on the effect of cyclic intermittent etidronate therapy on the bone mineral density changes associated with six months of gonadotropin-releasing hormone agonist treatment. Am J Obstet Gynecol 1996; 175: 105–9

    Article  PubMed  CAS  Google Scholar 

  26. Hornstein MD, Surrey ES, Weisberg GW, et al. Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Lupron Add-Back Study Group. Obstet Gynecol 1998; 91: 16–24

    Article  PubMed  CAS  Google Scholar 

  27. Bergqvist A, Bergh T, Hogström L, et al. The effects of trip-torelin versus placebo on the symptoms of endometriosis. Fertil Steril 1998; 69: 702–8

    Article  PubMed  CAS  Google Scholar 

  28. Van Leusden HA. Impact of different GnRH analogs in benign gynecological disorders related to their chemical structure, delivery system and dose. Gynecol Endocrinol 1994; 8: 215–22

    Article  PubMed  Google Scholar 

  29. Dawood MY. Hormonal therapies for endometriosis: implications for bone metabolism. Acta Obstet Gynecol Scand 1994; 159 Suppl.: 22–34

    CAS  Google Scholar 

  30. Dochi T, Lees B, Sidhu M, et al. Bone density and endometriosis. Fertil Steril 1994; 61: 175–7

    PubMed  CAS  Google Scholar 

  31. Sowers M, Eyre D, Hollis BW, et al. Biochemical markers of bone turnover in lactating and nonlactating postpartum women. J Clin Endocrinol Metab 1995; 80: 2210–6

    Article  PubMed  CAS  Google Scholar 

  32. Lopez JM, Gonzalez G, Reyes V, et al. Bone turnover and density in healthy women during breastfeeding and after weaning. Osteroporos Int 1996; 6: 153–9

    Article  CAS  Google Scholar 

  33. Hashimoto K, Nozaki M, Inoue Y, et al. The chronological change of vertebral bone loss following oophorectomy using dual energy X-ray absorptiometry: the correlation with specific markers of bone metabolism. Maturitas 1995; 22: 185–91

    Article  PubMed  CAS  Google Scholar 

  34. Yildiz A, Sahin I, Gol K, et al. Bone loss rate in lumbar spine: a comparison between natural and surgically induced menopause. Int J Gynaecol Obstet 1996; 55: 153–9

    Article  PubMed  CAS  Google Scholar 

  35. Revilla R, Revilla M, Hernandez ER, et al. Evidence that the loss of bone mass induced by GnRH agonists is not totally recovered. Maturitas 1995; 22: 145–50

    Article  PubMed  CAS  Google Scholar 

  36. Adashi EY. Long-term gonadotrophin-releasing hormone agonist therapy: the evolving issue of steroidal add-back paradigms. Hum Reprod Update 1994; 9: 1380–97

    CAS  Google Scholar 

  37. Steingold KA, Cedars M, Lu JK, et al. Treatment of endometriosis with a long-acting gonadotropin-releasing hormone agonist. Obstet Gynecol 1987; 69: 403–11

    PubMed  CAS  Google Scholar 

  38. Lemay A, Brideau NA, Forest JC, et al. Cholesterol fractions and apolipoproteins during endometriosis treatment by a gonadotrophin releasing hormone (GnRH-agonist implant or by danazol. Clin Endocrinol 1991; 35: 305–10

    Article  CAS  Google Scholar 

  39. Ravn P, Bergqvist A, Hansen MA, et al. Treatment of endometriosis with the luteinizing hormone-releasing hormone agonist nafarelin: effect on bone turnover and bone mass. Menopause: JNorth Am Menopause Soc 1994; 1: 11–7

    Google Scholar 

  40. Surrey ES, Voigt B, Fournet N, et al. Prolonged gonadotropin-releasing hormone agonist treatment of symptomatic endometriosis: the role of cyclic sodium etidronate and low-dose norethindrone ‘add-back’ therapy. Fertil Steril 1995; 63: 747–55

    PubMed  CAS  Google Scholar 

  41. West CP, Baird DT. Suppression of ovarian activity by Zoladex depot (ICI 118630): a long-acting luteinizing hormone releasing hormone agonist analogue. Clin Endocrinol 1987; 26: 213–20

    Article  CAS  Google Scholar 

  42. Barbieri RL. Hormone treatment of endometriosis: the estrogen threshold hypothesis. Am J Obstet Gynecol 1992; 166: 740–5

    PubMed  CAS  Google Scholar 

  43. Hull ME, Barbieri RL. Nafarelin in the treatment of endometriosis. Gynecol Obstet Invest 1994; 37: 263–4

    Article  PubMed  CAS  Google Scholar 

  44. Bergqvist A, Jacobson J, Harris S. A double-blind randomized study of the treatment of endometriosis with nafarelin versus nafarelin plus norethisterone. Gynecol Endocrinol 1997; 11: 187–94

    Article  PubMed  CAS  Google Scholar 

  45. Edmonds DK. Add-back therapy in the treatment of endometriosis: the European experience. Br J Obstet Gynecol 1996; 103 Suppl.: 10–3

    CAS  Google Scholar 

  46. Friedman AJ, Hornstein MD. Gonadotropin-releasing hormone agonist plus estrogen-progestin ‘add-back’ therapy for endo-metriosis-related pelvic pain. Fertil Steril 1993; 60: 236–41

    PubMed  CAS  Google Scholar 

  47. Caird LE, West CP, Lumsden MA, et al. Medroxyprogesterone acetate with Zoladex for long-term treatment of fibroids: effects on bone density and patient acceptability. Human Reprod 1997; 12: 436–40

    Article  CAS  Google Scholar 

  48. Howell R, Edmonds DK, Dowsett M, et al. Gonadotropin-releasing hormone analogue (goserelin) plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial. Fertil Steril 1995; 64: 474–81

    PubMed  CAS  Google Scholar 

  49. Overton CE, Lindsay PC, Johal B, et al. A randomized, double-blind, placebo-controlled study of luteal phase dydro-gesterone (Duphaston) in women with minimal to mild endometriosis. Fertil Steril 1994; 62: 701–7

    PubMed  CAS  Google Scholar 

  50. Vercellini P, Cortesi I, Crosignani PG. Progestins for symptomatic endometriosis: a critical analysis of the evidence. Fertil Steril 1997; 68: 393–401

    Article  PubMed  CAS  Google Scholar 

  51. Bergqvist A, Landgren B-M, Diczfalusy E. A Clinical pharma-cokinetic and pharmacodynamic study of three progestogens in the treatment of endometriosis. New Trends Gynecol Obstet 1988; 4: 65–84

    Google Scholar 

  52. Teichmann AT, Cremer P, Wieland H, et al. Lipid metabolic changes during hormonal treatment of endometriosis. Maturitas 1988; 10: 27–33

    Article  PubMed  CAS  Google Scholar 

  53. Telimaa S, Apter D, Reinila M, et al. Placebo-controlled comparison of hormonal and biochemical effects of danazol and high-dose medroxyprogesterone acetate. Eur J Obstet Gynecol Reprod Biol 1990; 36: 97–105

    Article  PubMed  CAS  Google Scholar 

  54. Vercillini P, De Giorgi O, Oldani S, et al. Depot medroxyprogesterone acetete 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: 396–401

    Article  Google Scholar 

  55. Landgren B-M, Diczfalusy E. Hormonal effects of the 300μg norethisterone (NET) minipill. 1. Daily steroid levels in 43 subjects during a pretreatment cycle and during the second month of NET administration. Contraception 1980; 21: 87–113

    Article  PubMed  CAS  Google Scholar 

  56. Telimaa S, Penttila I, Poulakka J, et al. Circulating lipid and lipoprotein concentrations during danazol and high-dose medroxyprogesterone acetate therapy of endometriosis. Fertil Steril 1989; 52: 31–5

    PubMed  CAS  Google Scholar 

  57. Rosano GM, Sarrel PM. Ovarian hormones and the cardiovascular system: recent findings. Cardiologia 1994; 39: 275–9

    PubMed  CAS  Google Scholar 

  58. Gestrinone Italian Study Group. Gestrinone versus a gonadotropin-releasing hormone agonist for the treatment of pelvic pain associated with endometriosis: a multicenter, randomized, double-blind study. Fertil Steril 1996; 66: 911–9

    Google Scholar 

  59. Barbieri RL, Evans S, Kistner RW. Danazol in the treatment of endometriosis: analysis of 100 cases with a 4-year follow-up. Fertil Steril 1982; 37: 737–46

    PubMed  CAS  Google Scholar 

  60. Cirkel U. Medical treatment of symptomatic endometriosis. Hum Reprod Suppl 1996; 11: 89–101

    Article  CAS  Google Scholar 

  61. Vercillini P, Trespidi L, Panazza S, et al. Very low dose danazol for relief of endometriosis-associated pelvic pain: a pilot study. Fertil Steril 1994; 62: 1136–42

    Google Scholar 

  62. Döberl A, Bergqvist A, Jeppsson S, et al. Regression of endo-metriosis following shorter treatment with, or lower dose of danazol: comparison of pre-and post-treatment laparoscopic findings in the Scandinavian multicentre study. Acta Obstet Gynecol Scand 1984; 123 Suppl.: 51–8

    Article  Google Scholar 

  63. Hornstein MD, Yuzpe AA, Burry KA, et al. Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain. Fertil Steril 1995; 63: 955–62

    PubMed  CAS  Google Scholar 

  64. Zorn JR, Mathieson J, Risquez F, et al. Treatment of endometriosis with a delayed release preparation of the agonist D-Trp6-luteinizing hormone-releasing hormone: long-term follow-up in a series of 50 patients. Fertil Steril 1990; 53: 401–6

    PubMed  CAS  Google Scholar 

  65. Adamson GD, Heinrichs WL, Henzl MR, et al. Therapeutic efficacy and bone mineral density response during and following a three-month re-treatment of endometriosis with nafarelin (Synarel). Am J Obstet Gynecol 1997; 177: 1413–8

    Article  PubMed  CAS  Google Scholar 

  66. Hornstein MD, Yuzpe AA, Burry KA, et al. Retreatment with nafarelin for recurrent endometriosis symptoms: efficacy, safety and bone mineral density. Fertil Steril 1997; 67: 1013–8

    Article  PubMed  CAS  Google Scholar 

  67. Dawood MY. Dysmenorrhoea and prostaglandin’s: pharmacological and therapeutic considerations. Drugs 1981; 22: 42–56

    Article  PubMed  CAS  Google Scholar 

  68. Duleba AT, Keltz MD, Olive DL. Evaluation and management of chronic pelvic pain. J Am Assoc Gynecol Laparosc 1996; 3: 205–27

    Article  PubMed  CAS  Google Scholar 

  69. Owen PR. Prostaglandin synthetase inhibitors in the treatment of primary dysmenorrhea. Am J Obstet Gynecol 1984; 148: 96–103

    PubMed  CAS  Google Scholar 

  70. Bergqvist A. Different types of extregenital endometriosis: a review. Gynecol Endocrinol 1993; 7: 1–15

    Article  Google Scholar 

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    Agneta Bergqvist

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Bergqvist, A. Current Drug Therapy Recommendations for the Treatment of Endometriosis. Drugs 58, 39–50 (1999). https://doi.org/10.2165/00003495-199958010-00004

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