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The BMJ logoLink to The BMJ
. 2000 May 27;320(7247):1449–1452. doi: 10.1136/bmj.320.7247.1449

Endometriosis

Cynthia M Farquhar 1
PMCID: PMC1127642  PMID: 10827052

Abstract

Definition

Endometriosis is characterised by ectopic endometrial tissue, which can cause dysmenorrhoea, dyspareunia, non-cyclical pelvic pain, and subfertility. Diagnosis is made by laparoscopy. Most endometrial deposits are found in the pelvis (ovaries, peritoneum, uterosacral ligaments, pouch of Douglas, and rectovaginal septum). Extrapelvic deposits, including those in the umbilicus and diaphragm, are rare. Endometriomas are cysts of endometriosis within the ovary.

Interventions

In women with pain attributed to endometriosis

Beneficial:

Hormonal treatments (danazol, medroxyprogesterone, gestrinone, gonadotrophin releasing hormone analogues)

Combined ablation of endometrial deposits and uterine nerve

Postoperative hormonal treatment

Cystectomy for ovarian endometrioma (better than drainage)

Likely to be beneficial:

Oral contraceptive pill

Unknown effectiveness:

Dydrogesterone

Laparoscopic uterine nerve ablation (LUNA)

Laparoscopic ablation of endometrial deposits

Preoperative hormonal treatment

In women with subfertility attributed to endometriosis

Beneficial:

Laparoscopic ablation or excision of endometrial deposits

Cystectomy for ovarian endometrioma (better than drainage)

Unlikely to be beneficial:

Hormonal treatment

Postoperative hormonal treatment

Incidence/prevalence

In asymptomatic women, the prevalence ranges from 2% to 22%, depending on the diagnostic criteria used and the populations studied.14 In women with dysmenorrhoea, the incidence of endometriosis ranges from 40% to 60%, and in women with subfertility it ranges from 20% to 30%.2,5,6 The severity of symptoms and the probability of diagnosis increase with age.7 Incidence peaks at about age 40.8 Symptoms and laparoscopic appearance do not always correlate.9

Aetiology

The cause is unknown. Risk factors include early menarche and late menopause. Embryonic cells may give rise to deposits in the umbilicus, while retrograde menstruation may deposit endometrial cells in the diaphragm.10 11 Oral contraceptives reduce the risk of endometriosis, and this protective effect persists for up to a year after their discontinuation.9

Prognosis

We found one small randomised controlled trial (RCT) in which repeat laparoscopy was performed in the women treated with placebo. Over 12 months, endometrial deposits resolved spontaneously in a quarter, deteriorated in nearly half, and were unchanged in the remainder.12

Aims

To relieve pain (dysmenorrhoea, dyspareunia, and other pelvic pain) and to improve fertility, with minimal adverse effects.

Outcomes

American Fertility Society scores for size and number of deposits; recurrence rates; time between stopping treatment and recurrence; rate of adverse effects of treatment. In women with pain: relief of pain, assessed by visual analogue scale and subjective improvement. In women with subfertility: cumulative pregnancy rate, live birth rate. In women undergoing surgery: ease of surgical intervention (rated as easy, average, difficult, or very difficult).13

Methods

Clinical Evidence search and appraisal for systematic reviews, January 1999. We sought RCTs by electronic searching of databases, handsearching of 30 key journals, searching the reference lists of other RCTs, and identifying unpublished studies from abstracts, proceedings, and pharmaceutical companies. We used the search strategy and database of the Cochrane Menstrual Disorders and Subfertility Group to identify RCTs on Medline and Embase. We included RCTs that used adequate diagnostic criteria for inclusion of participants (endometriosis diagnosed either by laparoscopy or laparotomy in association with dysmenorrhoea, dyspareunia, other pelvic pain, or infertility) and clinical outcomes. Studies of assisted reproductive technologies were not included.

Question: What are the effects of hormonal treatments?

Four small systematic reviews found that all hormonal treatments except dydrogesterone were equally effective, compared with placebo, in reducing pain attributed to endometriosis. One systematic review of small RCTs found no evidence that hormonal treatments improved fertility. RCTs have found that six months' postoperative treatment with gonadotrophin releasing hormone analogues or a combination of danazol plus medroxyprogesterone reduces pain and delays the recurrence of pain significantly better than placebo. They found no evidence of an effect of postoperative gonadotrophin releasing hormone analogues on fertility.

Benefits

In women with pain attributed to endometriosis: We found four systematic reviews (search dates 1998, 1996, 1997, 1997) comparing six months' continuous suppression of ovulation (using danazol, gestrinone, medroxyprogesterone acetate, dydrogesterone, oral contraceptives, or gonadotrophin releasing hormone analogues) and placebo.1417 None of the reviews included more than 200 women. They found that except for dydrogesterone, which was given at two different dosages in the luteal phase, with no evidence of effect, all treatments were equally effective at reducing severe and moderate pain at six months. We found no placebo controlled RCTs of oral contraceptives. One RCT compared oral contraceptives and gonadotrophin releasing hormone analogues in 49 women.18 It found no differences in rate of relief for all types of pain except menstrual pain, for which oral contraceptive was better. In women with subfertility attributed to endometriosis: We found one systematic review (search date 1996), which identified four RCTs in a total of 244 women.19The trials evaluated six months' treatment with danazol, medroxyprogesterone, or gonadotrophin releasing hormone analogues compared with placebo. They found no evidence of an effect on the probability of pregnancy (odds ratio for pregnancy compared with placebo 0.83; 95% confidence interval 0.50 to 1.39). In women who have undergone surgery: We found no systematic review. We found three placebo controlled RCTs of gonadotrophin releasing hormone analogues in a total of 443 women who had undergone surgery for endometriosis.2022 The smallest trial (n=65) evaluated three months' treatment and found no difference in pain relief; the two larger trials (n=109, n=269) evaluated six months' treatment and found that gonadotrophin releasing hormone analogues significantly reduced pain scores (P=0.008)21and delayed the recurrence of pain by more than 12 months.21,22Two of the trials evaluated fertility (n=65, n=269) and found no difference in pregnancy rates or time to conception.20,22One RCT in 60 women found that postoperative treatment with a combination of danazol (600 mg/day) and medroxyprogesterone (100 mg/day) reduced pain more than placebo six months after surgery.23

Harms

Gonadotrophin releasing hormone analogues: Adverse effects occurred in 11% of women taking gonadotrophin releasing hormone analogues,14 which are associated with hypo-oestrogenic symptoms such as hot flushes and vaginal dryness. RCTs have found that adding oestrogen, progesterone, or tibolone significantly relieves hot flushes caused by gonadotrophin releasing hormone analogues (by 50% or more on symptom scores).13,24,25 Danazol: Adverse effects occurred in 15% of women taking danazol.15 Danazol is associated with androgenic symptoms of acne, weight gain, and hirsutism and with decreased breast size, muscle cramps, and hunger. Gestrinone is associated with a higher frequency of hot flushes than are gonadotrophin releasing hormone analogues, and also with greasy skin and hirsutism.15 Medroxyprogesterone: The trials gave no information on adverse effects of medroxyprogesterone.

Comment

The trials were mainly small, with no long term follow up. Most trials compared gonadotrophin releasing hormone analogues with danazol. No summary statistics could be calculated because the trials compared different drugs with placebo or with no treatment.

Question: What are the effects of surgical treatments?

Option: Laparascopic uterine nerve ablation (LUNA)

We found insufficient evidence on the effects of laparascopic uterine nerve ablation in women with pain attributed to endometriosis.

Benefits

We found one systematic review (search date 1998), which identified two small RCTs in women with endometriosis. These found no difference in pain relief between women treated with laparascopic uterine nerve ablation and those who were not.26

Harms

The trials gave no information on adverse effects. Potential harms include denervation of pelvic structures and uterine prolapse.26

Comment

The trials may have been too small to rule out a beneficial effect.26

Option: Laparoscopic ablation of endometrial deposits

We found insufficient evidence on the effects of laparoscopic ablation of deposits on its own. One RCT found that at six months ablation of deposits combined with laparascopic uterine nerve ablation reduced pain more than diagnostic laparoscopy. One RCT found that laparoscopic surgery increased fertility more than diagnostic laparoscopy.

Benefits

In women with pain attributed to endometriosis: We found no systematic review and no RCTs evaluating laparoscopic ablation of deposits alone. We found one RCT comparing the combination of ablation of deposits plus laparascopic uterine nerve ablation with diagnostic laparoscopy in 63 women.27,28This found that combined ablation reduced pain at six months (median decrease in pain score 2.85 for ablation, 0.05 for diagnostic laparoscopy; P=0.01). In women with subfertility attributed to endometriosis: We found no systematic review. We found one RCT comparing laparoscopic ablation or excision of endometriotic deposits and diagnostic laparoscopy in 341 women with subfertility attributed to mild or moderate endometriosis.29 This found that laparoscopic surgery increased cumulative pregnancy rates (relative risk of pregnancy after 36 weeks 1.7, 1.2 to 2.6; NNT 8). Laser versus diathermy ablation: We found no RCTs.

Harms

The trials gave no information on adverse effects.2729 Potential harms include adhesions, reduced fertility, and damage to other pelvic structures.

Comment

Further RCTs comparing ablation alone and ablation plus laparascopic uterine nerve ablation are under way (C Sutton and R Dover, personal communication). A systematic review of laser versus diathermy ablation is planned (C Farquhar and N Johnson, personal communication).

Question: What are the effects of preoperative hormonal treatment?

One RCT found no evidence that preoperative treatment with gonadotrophin releasing hormone analogues facilitated surgery.

Benefits

We found no systematic review. We found one RCT comparing three months' preoperative treatment with a gonadotrophin releasing hormone analogue and no treatment in 75 women with moderate or severe endometriosis.30 There was no difference in ease of surgery between the two groups.

Harms

See above under hormonal treatments.

Comment

The trial may have been too small to rule out a clinically important effect.

Question: What are the effects of treatments for ovarian endometrioma?

Option: Laparoscopic drainage or laparoscopic cystectomy

One RCT found that pain and fertility improved more with cystectomy than with drainage, and there was no evidence of a difference in complication rates.

Benefits

We found no systematic review. We found one RCT comparing laparoscopic cystectomy and laparoscopic drainage in 64 women.31 In women with pain attributed to endometrioma: The trial found that cystectomy reduced recurrence of pain at two years (odds ratio 0.2, 0.05 to 0.77) and increased the pain free interval after operation (median interval 19 months v 9.5 months; P<0.05). In women with subfertility attributed to endometrioma: Cystectomy increased the pregnancy rate (66.7% v 23.5%; odds ratio 8.25, 1.15 to 59; P<0.05).

Harms

The trial reported no intraoperative or postoperative complications in either group.

Comment

None.  

Key messages

  • Four small systematic reviews found that all hormonal treatments except dydrogesterone were equally effective, compared with placebo, in reducing pain attributed to endometriosis

  • One systematic review of small RCTs found no evidence that hormonal treatments improved fertility

  • Six months' postoperative treatment with gonadotrophin releasing hormone analogues or a combination of danazol and medroxyprogesterone significantly reduces pain and delays the recurrence of pain compared with placebo, but there is no evidence of an effect of postoperative gonadotrophin releasing hormone analogues on fertility

  • We found insufficient evidence on the effects of laparoscopic uterine nerve ablation in women with pain attributed to endometriosis and on the effects of laparoscopic ablation of deposits on its own

  • One RCT found no evidence that preoperative treatment with gonadotrophin releasing hormone analogues facilitated surgery

  • One RCT found that pain and subfertility caused by ovarian endometrioma were improved more by cystectomy than by drainage

Acknowledgments

We thank women's health section advisers Mike Dixon, Edinburgh, and Richard Johnson, Stoke on Trent.

Footnotes

Competing interests: CF was reimbursed in 1995 by ICI, the manufacturer of Zoladex, for helping to develop educational programmes.

This review is one of 87 chapters from the second issue of Clinical Evidence www.evidence.org

Clinical Evidence is published by BMJ Publishing Group and American College of Physicians-American Society of Internal Medicine. The second issue is available now, and Clinical Evidence will be updated and expanded every six months. Individual subscription rate, issues 3 and 4, £75/$140; institution rate £160/$245. For more information including how to subscribe, please visit the Clinical Evidence website at www.evidence.org

References

  • 1.Mahmood TA, Templeton A. Prevalence and genesis of endometriosis. Hum Reprod. 1991;6:544–549. doi: 10.1093/oxfordjournals.humrep.a137377. [DOI] [PubMed] [Google Scholar]
  • 2.Gruppo italiano per lo studio dell'endometriosi. Prevalence and anatomical distribution of endometriosis in women with selected gynaecological conditions: results from a multicentric Italian study. Hum Reprod. 1994;9:1158–1162. [PubMed] [Google Scholar]
  • 3.Moen MH, Schei B. Epidemiology of endometriosis in a Norwegian county. Acta Obstet Gynecol Scand. 1997;76:559–562. doi: 10.3109/00016349709024584. [DOI] [PubMed] [Google Scholar]
  • 4.Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997;24:235–258. doi: 10.1016/s0889-8545(05)70302-8. [DOI] [PubMed] [Google Scholar]
  • 5.Ajossa S, Mais V, Guerriero S, Paoletti AM, Caffiero A, Murgia C, et al. The prevalence of endometriosis in premenopausal women undergoing gynecological surgery. Clin Exp Obstet Gynecol. 1994;21:195–197. [PubMed] [Google Scholar]
  • 6.Waller KG, Lindsay P, Curtis P, Shaw RW. The prevalence of endometriosis in women with infertile partners. Eur J Obstet Gynecol Reprod Biol. 1993;48:135–139. doi: 10.1016/0028-2243(93)90254-a. [DOI] [PubMed] [Google Scholar]
  • 7.Berube S, Marcoux S, Maheux R. Characteristics related to the prevalence of minimal or mild endometriosis in infertile women. Canadian Collaborative Group on Endometriosis. Epidemiology. 1998;9:504–510. doi: 10.1097/00001648-199809000-00006. [DOI] [PubMed] [Google Scholar]
  • 8.Vessey MP, Villard-Mackintosh L, Painter R. Epidemiology of endometriosis in women attending family planning clinics. BMJ. 1993;306:182–184. doi: 10.1136/bmj.306.6871.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Vercellini P, Trespidi L, DeGiorgi O, Cortesi I, Parazzini F, Crosignani PG. Endometriosis and pelvic pain: relation to disease stage and localization. Fertil Steril. 1996;65:299–304. [PubMed] [Google Scholar]
  • 10.Rock JA, Markham SM. Pathogenesis of endometriosis. Lancet. 1992;340:1264–1267. doi: 10.1016/0140-6736(92)92959-j. [DOI] [PubMed] [Google Scholar]
  • 11.McLaren J, Prentice A. New aspects of pathogenesis of endometriosis. Curr Obstet Gynaecol. 1996;6:85–91. [Google Scholar]
  • 12.Cooke ID, Thomas EJ. The medical treatment of mild endometriosis. Acta Obstet Gynecol Scand Suppl. 1989;150:27–30. [PubMed] [Google Scholar]
  • 13.Compston JE, Yamaguchi K, Croucher PI, Garrahan NJ, Lindsay PC, Shaw RW. The effects of gonadotrophin-releasing hormone agonists on iliac crest cancellous bone structure in women with endometriosis. Bone. 1995;16:261–267. doi: 10.1016/8756-3282(94)00038-2. [DOI] [PubMed] [Google Scholar]
  • 14.Prentice A, Deary AJ, Goldbeck-Wood S. Cochrane Library. Issue 3. Oxford: Update Software; 1999. Gonadotrophin releasing hormone analogues (GnRHAs) for painful symptoms associated with endometriosis. . (Search date August 1998.) [Google Scholar]
  • 15.Prentice A, Deary AJ, Goldbeck-Wood S, Smith SK. Cochrane Library. Issue 1. Oxford: Update Software; 1999. Progestagens and antiprogestagens for painful symptoms associated with symptomatic endometriosis. . (Search date September 1996.) [Google Scholar]
  • 16.Selak V, Farquhar C, Prentice A. Danazol versus placebo for the treatment of endometriosis. Cochrane Library. Issue 1. Oxford: Update Software, 1998. (Search date February 1997.)
  • 17.Moore J, Kennedy S, Prentice A. Cochrane Library. Issue 3. Oxford: Update Software; 1999. Modern combined oral contraceptives for the treatment of painful symptoms associated with endometriosis. . (Search date August 1997.) [Google Scholar]
  • 18.Vercellini P, Trespidi L, Colombo A, Vendola N, Marchini M, Crosignani PG. A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. Fertil Steril. 1993;60:75–79. [PubMed] [Google Scholar]
  • 19.Hughes E, Fedorkow D, Collins J. Cochrane Library. Issue 3. Oxford: Update Software; 1999. Ovulation suppression versus placebo in the treatment of endometriosis. . (Search date February 1996.) [Google Scholar]
  • 20.Parazzini F, Fedele L, Busacca M, Falsetti L, Pellegrini S, Venturini PL, et al. Postsurgical medical treatment of advanced endometriosis: results of a randomized clinical trial. Am J Obstet Gynecol. 1994;171:1205–1207. doi: 10.1016/0002-9378(94)90133-3. [DOI] [PubMed] [Google Scholar]
  • 21.Hornstein MD, Hemmings R, Yuzpe AA, Heinrichs WL. Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis. Fertil Steril. 1997;68:860–864. doi: 10.1016/s0015-0282(97)00360-9. [DOI] [PubMed] [Google Scholar]
  • 22.Vercellini P, Crosignani PG, Fadini R, Radici E, Belloni C, Sismondi P. A gonadotrophin-releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis. Br J Obstet Gynaecol. 1999;106:672–677. doi: 10.1111/j.1471-0528.1999.tb08366.x. [DOI] [PubMed] [Google Scholar]
  • 23.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;1:363–371. doi: 10.3109/09513598709082709. [DOI] [PubMed] [Google Scholar]
  • 24.Gregoriou O, Konidaris S, Vitoratos N, Papadias C, Papoulias I, Chryssicopoulos A. Gonadotropin-releasing hormone analogue plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial. Int J Fertil Womans Med. 1997;42:406–411. [PubMed] [Google Scholar]
  • 25.Taskin O, Yalcinoglu AI, Kucuk S. Effectiveness of tibolone on hypoestrogenic symptoms induced by goserelin treatment in patients with endometriosis. Fertil Steril. 1997;67:40–45. doi: 10.1016/s0015-0282(97)81853-5. [DOI] [PubMed] [Google Scholar]
  • 26.Wilson M, Farquhar CM, Sinclair O. Cochrane Library. Issue 3. Oxford: Update Software; 1999. Surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhoea. . (Search date August 1998.) [DOI] [PubMed] [Google Scholar]
  • 27.Sutton CJG, Ewen SP, Whitelaw N, Haines P. A prospective, randomised, double-blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal, mild and moderate endometriosis. Fertil Steril. 1994;62:696–700. doi: 10.1016/s0015-0282(16)56990-8. [DOI] [PubMed] [Google Scholar]
  • 28.Sutton CJG, Pooley AS, Ewen SP. Follow-up report on a randomised, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal to moderate endometriosis. Fertil Steril. 1997;68:170–174. doi: 10.1016/s0015-0282(97)00403-2. [DOI] [PubMed] [Google Scholar]
  • 29.Marcoux S, Maheux R, Berube S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. N Engl J Med. 1997;337:217–222. doi: 10.1056/NEJM199707243370401. [DOI] [PubMed] [Google Scholar]
  • 30.Audebert A, Descampes P, Marret H, Ory-Lavollee L, Bailleul F, Hamamah S. Pre or post operative medical treatment with nafarelin in stage III-IV endometriosis: a French multicentered study. Eur J Obstet Gynecol Reprod Biol. 1998;79:145–148. doi: 10.1016/s0301-2115(98)00028-1. [DOI] [PubMed] [Google Scholar]
  • 31.Beretta P, Franchi M, Ghezzi F, Busacca M, Zupi E, Bolis P. Randomized clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation. Fertil Steril. 1998;70:1176–1180. doi: 10.1016/s0015-0282(98)00385-9. [DOI] [PubMed] [Google Scholar]

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