Abstract
Introduction
Ectopic endometrial tissue is found in 1.5% to 6.2% of women of reproductive age, in up to 60% of those with dysmenorrhoea, and in up to 30% of women with subfertility, with a peak incidence at around 40 years of age. However, symptoms may not correlate with laparoscopic findings.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of hormonal treatments given at diagnosis of endometriosis? What are the effects of hormonal treatments before surgery for endometriosis? What are the effects of non-hormonal medical treatments for endometriosis? What are the effects of surgical treatments for endometriosis? What are the effects of hormonal treatment after conservative surgery for endometriosis? What are the effects of hormonal treatment after oophorectomy (with or without hysterectomy) for endometriosis? What are the effects of treatments for ovarian endometrioma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 40 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: combined oral contraceptives, danazol, dydrogesterone, gestrinone, gonadorelin analogues, aromatase inhibitors, hormonal treatment before surgery, hormonal treatment, laparoscopic cystectomy, laparoscopic removal of endometriotic deposits (alone or with uterine nerve ablation), laparoscopic removal plus presacral neurectomy, laparoscopic uterine nerve ablation, non-steroidal anti-inflammatory drugs, presacral neurectomy alone, and progestogens other than dydrogesterone.
Key Points
Ectopic endometrial tissue is found in 1.5% to 6.2% of women of reproductive age, in up to 60% of those with dysmenorrhoea, and up to 30% of women with subfertility, with a peak incidence at around 40 years of age. However, symptoms may not correlate with laparoscopic findings.
Without treatment, endometrial deposits may resolve spontaneously in up to one third of women, deteriorate in nearly half, and remain unchanged in the remainder.
Oral contraceptives reduce the risk of endometriosis, whereas an early menarche and late menopause increase the risk.
Hormonal treatments (such as combined oral contraceptives, progestogens, and danazol, gestrinone, and gonadorelin analogues) can reduce the pain attributed to endometriosis when given at diagnosis. However, adverse effects are common, particularly with danazol, gestrinone, and gonadorelin analogues.
Combined oral contraceptives may be less effective than gonadorelin analogues, but they are less likely to reduce bone mineral density or to cause other adverse effects, such as hot flushes and vaginal dryness.
We do not know whether giving the progestogen dydrogesterone at diagnosis is effective in the treatment of endometriosis, or whether hormonal treatment given before surgery makes it easier to perform surgery or reduces subsequent pain.
Laparoscopic removal of endometrial deposits reduces pain and improves quality of life compared with no removal, but it can be complicated by adhesions and damage to other pelvic structures.
Combining laparoscopic removal of deposits with uterine nerve ablation may improve pain relief compared with diagnostic laparoscopy alone, but we don't know whether uterine nerve ablation alone is of any benefit in reducing symptoms.
The hormonal treatments danazol, medroxyprogesterone acetate, gonadorelin analogues, and aromatase inhibitors may reduce pain and other symptoms when given for 6 months after conservative surgery, although studies of other hormonal treatments have given conflicting results.
We don't know whether hormone replacement therapy prevents or promotes recurrence of endometriosis in women who have had oophorectomy.
Laparoscopic excision of endometrial cysts in the ovary may reduce pelvic pain and recurrence of cysts compared with laparoscopic drainage and cyst wall electrosurgical ablation, with similar risks of adverse effects.
About this condition
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. Severity of endometriosis is defined by the American Fertility Society: this review uses the terms mild (stage I and II), moderate (stage III), and severe (stage IV). Endometriomas are cysts of endometriosis within the ovary. This review assesses dysmenorrhoea, dyspareunia (painful sexual intercourse), dyschezia (painful defecation), and non-cyclical pelvic pain associated with endometriosis. For infertility associated with endometriosis, see review on female infertility.
Incidence/ Prevalence
The diagnosis of endometriosis is based on surgical visualisation of the disease; therefore, the true prevalence of the disease in the general population is unknown. Variations in estimates of prevalence are thought to be mostly because of differences in diagnostic thresholds and criteria between studies, and in variations in childbearing age between populations, rather than underlying genetic differences.The estimated prevalence of endometriosis in the general population is 1.5% to 6.2%. In women with dysmenorrhoea, the incidence of endometriosis is 40% to 60%, and in women with subfertility it is 20% to 30%. The severity of symptoms and the probability of diagnosis increase with age. Incidence peaks at about 40 years of age. Symptoms and laparoscopic appearance do not always correlate.
Aetiology/ Risk factors
The cause of endometriosis is unknown. Risk factors include early menarche and late menopause. Embryonic cells may give rise to deposits in the umbilicus, whereas retrograde menstruation may deposit endometrial cells in the diaphragm. Use of oral contraceptives reduces the risk of endometriosis, and this protective effect persists for up to 1 year after their discontinuation.
Prognosis
We found two RCTs in which laparoscopy was repeated after treatment in women given placebo. Over 6 to 12 months, endometrial deposits resolved spontaneously in up to one third of women, deteriorated in nearly half, and were unchanged in the remainder.
Aims of intervention
To relieve pain (dysmenorrhoea, dyspareunia, and other pelvic pain), with minimal adverse effects.
Outcomes
Symptoms of endometriosis: including relief of chronic pain (assessed by a visual analogue scale ranging from 0 to 10, and subjective improvement). The different types of chronic pelvic pain include dysmenorrhoea, non-menstrual pelvic pain [both mid-cycle and non-cyclic pain], dyspareunia, and dyschezia; endometrial deposits: American Fertility Society scores for size and number of deposits; recurrence rate: time between stopping treatment and recurrence; in women having surgery: ease of surgical intervention: rated by the surgeon as easy, average, difficult, or very difficult; adverse effects of treatment.
Methods
Clinical Evidence search and appraisal December 2009. For this review, the following were used for the identification of studies: Medline 1966 to December 2009, Embase 1980 to December 2009, and The Cochrane Library 2009, Issue 4. Additional searches were carried out on the NHS Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and the National Institute for Health and Clinical Excellence (NICE) guidance websites. Abstracts of studies retrieved in the search were assessed independently by two information specialists. Predetermined criteria were used to identify relevant studies. Study design criteria included systematic reviews and RCTs, which were at least single blind. We excluded all studies described as "open", "open label" or "non-blinded", unless the interventions could not be "blinded". The minimum number of individuals in each trial was 20. The size of follow-up was 80% or more. There was no minimum length of follow-up. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table 1.
GRADE evaluation of interventions for endometriosis
| Important outcomes | Symptoms of endometriosis (including chronic pelvic pain, dysmenorrhoea, non menstrual pelvic pain, dyspareunia and dyschezia, and other symptoms), recurrence, endometrial deposits, ease of surgery, adverse effects | ||||||||
| Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of hormonal treatments given at diagnosis of endometriosis? | |||||||||
| 1 (100) | Symptoms of endometriosis | Combined oral contraceptive v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (130) | Symptoms of endometriosis | Combined oral contraceptive v progestogens | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for no comparisons between groups |
| 3 (292) | Symptoms of endometriosis | Combined oral contraceptives v gonadorelin analogues | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results |
| 2 (98) | Symptoms of endometriosis | Gonadorelin analogues v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality point deducted for sparse data and incomplete reporting of results |
| 1 (35) | Symptoms of endometriosis | Danazol v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data. |
| 1 (269) | Symptoms of endometriosis | Danazol v gestrinone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 7 (535) | Symptoms of endometriosis | Danazol v gonadorelin analogues | 4 | 0 | 0 | 0 | 0 | High | |
| 3 (426) | Endometrial deposits | Danazol v gonadorelin analogues | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (55) | Symptoms of endometriosis | Gestrinone v gonadorelin analogues | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for sparse data. Consistency point deducted for conflicting results at different end points |
| 1 (33) | Symptoms of endometriosis | Medroxyprogesterone acetate v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (80) | Symptoms of endometriosis | Medroxyprogesterone acetate v combined oral contraceptives plus danazol | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for conflicting results |
| 1 (48) | Symptoms of endometriosis | Medroxyprogesterone acetate v gonadorelin analogues | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (271) | Symptoms of endometriosis | Dienogest v gonadorelin analogues | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (82) | Symptoms of endometriosis | Levonorgestrel-releasing intrauterine system v gonadorelin analogue | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (34) | Symptoms of endometriosis | Medroxyprogesterone acetate v danazol | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (22) | Symptoms of endometriosis | Dydrogesterone v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| What are the effects of hormonal treatments before surgery for endometriosis? | |||||||||
| 1 (48) | Symptoms of endometriosis | Hormone treatment before surgery v no hormonal treatment | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 2 (123) | Ease of surgery | Hormone treatment before surgery v no hormonal treatment | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (75) | Symptoms of endometriosis | Hormonal treatment before surgery v hormonal treatment after surgery | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| What are the effects of non-hormonal medical treatments for endometriosis? | |||||||||
| 1 (24) | Symptoms of endometriosis | NSAIDs v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| What are the effects of surgical treatments for endometriosis? | |||||||||
| 1 (63) | Symptoms of endometriosis | Laparoscopic removal plus laparoscopic uterine nerve ablation (LUNA) v diagnostic laparoscopy | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 5 (506) | Symptoms of endometriosis | Laparoscopic ablation plus LUNA v laparoscopic removal alone | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (39) | Symptoms of endometriosis | Laparoscopic removal alone v diagnostic laparoscopy or no treatment | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (24) | Symptoms of endometriosis | Laparoscopic excision v laparoscopic ablation | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (35) | Symptoms of endometriosis | Laparoscopic removal v gonadorelin analogue | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 3 (245) | Symptoms of endometriosis | Laparoscopic removal plus presacral neurectomy v laparoscopic removal alone | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (67) | Adverse effects (complications of surgery) | Laparoscopic uterine nerve ablation v laparoscopic presacral neurectomy | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| What are the effects of hormonal treatment after conservative surgery for endometriosis? | |||||||||
| 3 (332 at most) | Symptoms of endometriosis | Hormonal treatment after surgery v surgery alone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting |
| 1 (222) | Symptoms of endometriosis | Combined oral contraceptives v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting |
| 1 (70) | Recurrence | Combined oral contraceptives v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 3 (165) | Symptoms of endometriosis | Danazol v placebo | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for conflicting results |
| 6 (at least 764) | Symptoms of endometriosis | Gonadorelin analogues v placebo | 4 | 0 | –1 | –1 | 0 | Low | Consistency point deducted for conflicting results. Directness point deducted for inclusion of different interventions and study durations |
| 1 (60) | Symptoms of endometriosis | Medroxyprogesterone acetates v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (40) | Symptoms of endometriosis | Levonorgestrel intrauterine system v no hormonal treatment | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (40) | Symptoms of endometriosis | Danazol v gonadorelin analogue | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (60) | Recurrence | Gonadorelin analogues v placebo/expectant management | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (97) | Recurrence | Aromatase inhibitors plus gonadorelin analogues v gonadorelin analogues alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of result |
| What are the effects of hormonal treatment after oophorectomy (with or without hysterectomy) for endometriosis? | |||||||||
| 1 (172) | Recurrence | HRT v no treatment | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and lack of blinding. Directness point deducted as most women had hysterectomy |
| What are the effects of treatments for ovarian endometrioma? | |||||||||
| 2 (164) | Recurrence of endometriosis | Laparoscopic excision of cyst v laparoscopic ablation | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion. Consistency: similarity of results across studies. Directness: generalisability of population or outcomes. Effect size: based on relative risk or odds ratio.
Glossary
- High-quality evidence
Further research is very unlikely to change our confidence in the estimate of effect.
- Laparoscopic cystectomy
During laparoscopy, the cyst wall of the endometrioma is excised or stripped.
- Laparoscopic drainage
During laparoscopy, the endometrioma contents are drained out.
- Laparoscopic removal of endometrial deposits
A surgical procedure where a long tube with a fibreoptic telescope (the laparoscope) is inserted into a woman's abdomen to ablate (destroy) or excise (cut out) the endometrial deposits around the ovaries and uterus in order to relieve pain.
- Laparoscopic uterine nerve ablation (LUNA)
The cutting of nerves in the uterus to stop chronic pain. This is carried out laparoscopically through a small incision in the abdomen, so the outside surface of the uterus and uterine nerves can be seen.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Presacral neurectomy (PSN)
The cutting of the presacral nerve (superior hypogastric nerve plexus) that lies in front of the sacrum behind the peritoneum. This can be undertaken laparoscopically or at open surgery.
- Severity of endometriosis: mild (stage I and II); moderate (stage III): severe (stage IV):
Determination of the stage or degree of endometrial involvement is based on the American Fertility Society scale of weighted point scale of estimations, evaluating the degree of involvement of the peritoneum, ovaries, and fallopian tubes. According to the allocated score, endometriosis is categorised as follows. American Fertility Society score of 1 to 15 points; American Fertility Society score of 16 to 40 points; American Fertility Society score of >40 points.
- Total abdominal hysterectomy
Open operation through the abdominal wall to remove the uterus. In some situations, this is performed in conjunction with a bilateral salpingo-oophorectomy, the removal of both ovaries and fallopian tubes.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Subfertility in women with endometriosis (see review on female infertility)
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Simone Ferrero, San Martino Hospital and University of Genoa, Genoa, Italy.
Valentino Remorgida, San Martino Hospital and University of Genoa, Genoa, Italy.
Pier Luigi Venturini, San Martino Hospital and University of Genoa, Genoa, Italy.
References
- 1.American Fertility Society. Revised American Fertility Society (RAFS) classification of endometriosis. Fertil Steril 1985;43:351–352. [DOI] [PubMed] [Google Scholar]
- 2.Mahmood TA, Templeton A. Prevalence and genesis of endometriosis. Hum Reprod 1991;6:544–549. [DOI] [PubMed] [Google Scholar]
- 3.Moen MH, Schei B. Epidemiology of endometriosis in a Norwegian county. Acta Obstet Gynecol Scand 1997;76:559–562. [DOI] [PubMed] [Google Scholar]
- 4.Ballard KD, Seaman HE, de Vries CS, et al. Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study - Part 1. BJOG: Int J Obstet Gynecol 2008;115:1382–1391. [DOI] [PubMed] [Google Scholar]
- 5.Ferrero S, Arena E, Morando A, et al. Prevalence of newly diagnosed endometriosis in women attending the general practitioner. Int J Gynaecol Obstet 2010;110:203–207. [DOI] [PubMed] [Google Scholar]
- 6.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]
- 7.Ajossa S, Mais V, Guerriero S, et al. The prevalence of endometriosis in premenopausal women undergoing gynecological surgery. Clin Exp Obstet Gynecol 1994;21:195–197. [PubMed] [Google Scholar]
- 8.Waller KG, Lindsay P, Curtis P, et al. The prevalence of endometriosis in women with infertile partners. Eur J Obstet Gynecol Reprod Biol 1993;48:135–139. [DOI] [PubMed] [Google Scholar]
- 9.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] [PubMed] [Google Scholar]
- 10.Vessey MP, Villard-Mackintosh L, Painter R. Epidemiology of endometriosis in women attending family planning clinics. BMJ 1993;306:182–184. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.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] [Google Scholar]
- 12.Rock JA, Markham SM. Pathogenesis of endometriosis. Lancet 1992;340:1264–1267. [DOI] [PubMed] [Google Scholar]
- 13.McLaren J, Prentice A. New aspects of pathogenesis of endometriosis. Curr Obstet Gynaecol 1996;6:85–91. [Google Scholar]
- 14.Cooke ID, Thomas EJ. The medical treatment of mild endometriosis. Acta Obstet Gynecol Scand Suppl 1989;150:27–30. [PubMed] [Google Scholar]
- 15.Harrison RF, Barry-Kinsella C. Efficacy of medroxyprogesterone treatment in infertile women with endometriosis: a prospective, randomized, placebo-controlled study. Fertil Steril 2000;74:24–30. [DOI] [PubMed] [Google Scholar]
- 16.Audebert A, Descampes P, Marret H, et al. Pre or post operative medical treatment with nafarelin in stage III–IV endometriosis: a French multicentred study. Eur J Obstet Gynecol Reprod Biol 1998;79:145–148. [DOI] [PubMed] [Google Scholar]
- 17.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 2008;90:1583–1588. [DOI] [PubMed] [Google Scholar]
- 18.Vercellini P, Crosignani PG, Somigliana E, et al. Medical treatment for rectovaginal endometriosis: what is the evidence? Hum Reprod 2009;24:2504–2514. [DOI] [PubMed] [Google Scholar]
- 19.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 Obstet Gynecol Reprod Biol 2007;135:188–190. [DOI] [PubMed] [Google Scholar]
- 20.Davis L, Kennedy SS, Moore J, et al. Modern combined oral contraceptives for pain associated with endometriosis. In: The Cochrane Library: Issue 4, 2009. Chichester UK; John Wiley & Sons Ltd. Search date 2007. [DOI] [PubMed] [Google Scholar]
- 21.Parazzini F, Di Cintio E, Chatenoud L, et al. Estroprogestin vs. gonadotrophin agonists plus estroprogestin in the treatment of endometriosis-related pelvic pain: a randomized trial. Eur J Obstet Gynecol Reprod Biol 2000;88:11–14. [DOI] [PubMed] [Google Scholar]
- 22.Zupi E, Marconi D, Sdracia M, et al. Add-back therapy in the treatment of endometriosis-associated pain. Fertil Steril 2004;82:1303–1308. [DOI] [PubMed] [Google Scholar]
- 23.Vercellini P, Trespidi L, Colombo A, et al. 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]
- 24.Prentice A, Deary AJ, Goldbeck-Wood S, et al. Gonadotrophin releasing hormone analogues for pain associated with endometriosis. In: The Cochrane Library: Issue 4, 2009. Chichester, UK: John Wiley & Sons Ltd. Search date 1998. [Google Scholar]
- 25.Prentice A, Deary AJ, Bland E. Progestagens and antiprogestagens for pain associated with endometriosis. In: The Cochrane Library: Issue 4, 2009. Chichester, UK: John Wiley & Sons Ltd. Search date 2000. [Google Scholar]
- 26.Selak V, Farquhar C, Prentice A, et al. Danazol for pelvic pain associated with endometriosis. In: The Cochrane Library: Issue 4, 2009. Chichester, UK: John Wiley & Sons Ltd. Search date 2007. [Google Scholar]
- 27.Bergqvist A, Theorell T. Changes in quality of life after hormonal treatment of endometriosis. Acta Obstet Gynecol Scand 2001;80:628–637. [PubMed] [Google Scholar]
- 28.Cheng MH, Yu BKJ, Chang SP, et al. A randomized, parallel, comparative study of the efficacy and safety of nafarelin versus danazol in the treatment of endometriosis in Taiwan. J Chin Med Assoc 2005;68:307–314. [DOI] [PubMed] [Google Scholar]
- 29.Bromham DR, Bookere MW, Rose GR, et al. Updating the clinical experience in endometriosis – the European perspective. Br J Obstet Gynaecol 1995;102(suppl):12–16. [DOI] [PubMed] [Google Scholar]
- 30.Sagsveen M, Farmer JE, Prentice A, et al. Gonadotrophin-releasing hormone analogues for endometriosis: bone mineral density. In: The Cochrane Library: Issue 4, 2009. Chichester, UK: John Wiley & Sons Ltd. Search date 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Compston JE, Yamaguchi K, Croucher PI, et al. The effects of gonadotrophin-releasing hormone agonists on iliac crest cancellous bone structure in women with endometriosis. Bone 1995;16:261–267. [DOI] [PubMed] [Google Scholar]
- 32.Gregoriou O, Konidaris S, Vitoratos N, et al. Gonadotropin-releasing hormone analogue plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial. Int J Fertil Womens Med 1997;42:406–411. [PubMed] [Google Scholar]
- 33.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] [PubMed] [Google Scholar]
- 34.Cheung TH, Lo KW, Yim SF, et al. Dose effects of progesterone in add-back therapy during GnRHa treatment. J Reprod Med 2005;50:35-40. [PubMed] [Google Scholar]
- 35.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;91:675–681. [DOI] [PubMed] [Google Scholar]
- 36.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;20:1993–1998. [DOI] [PubMed] [Google Scholar]
- 37.Yap C, Furness S, Farquhar C. Pre and post operative medical therapy for endometriosis surgery. In: The Cochrane Library: Issue 4, 2009. Chichester, UK: John Wiley & Sons Ltd. Search date 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Shaw R, Garry R, McMillan L, et al. A prospective randomized open study comparing goserelin (Zoladex) plus surgery and surgery alone in the management of ovarian endometriomas. Gynaecol Endosc 2001;10:151–157. [Google Scholar]
- 39.Nawathe A, Patwardhan S, Yates D, et al. Systematic review of the effects of aromatase inhibitors on pain associated with endometriosis. BJOG: Int J Obstet Gynecol 2008;115:818–822. [DOI] [PubMed] [Google Scholar]
- 40.Allen C, Hopwell S, Prentice A. Non-steroidal anti-inflammatory drugs for pain in women with endometriosis. In: The Cochrane Library: Issue 4, 2009. Chichester, UK: John Wiley & Sons Ltd. Search date 2005. [DOI] [PubMed] [Google Scholar]
- 41.Cobellis L, Razzi S, De Simone S, et al. The treatment with a COX-2 specific inhibitor is effective in the management of pain related to endometriosis. Eur J Obstet Gynecol Reprod Biol 2004;116:100–102. [DOI] [PubMed] [Google Scholar]
- 42.Jacobson TZ, Barlow DH, Garry R, et al. Laparoscopic surgery for pelvic pain associated with endometriosis. In: The Cochrane Library: Issue 4, 2009. Chichester, UK: John Wiley & Sons Ltd. Search date 2001. [Google Scholar]
- 43.Sutton CJG, Ewen SP, Whitelaw N, et al. 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] [PubMed] [Google Scholar]
- 44.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] [PubMed] [Google Scholar]
- 45.Proctor M, Latthe PM, Farquhar CM, et al. Surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhoea. In: The Cochrane Library: Issue 4, 2009. Chichester, UK: John Wiley & Sons Ltd. Search date 2004. [Google Scholar]
- 46.Johnson NP, Farquhar CM, Crossley S, et al. A double-blind randomised controlled trial of laparoscopic uterine nerve ablation for women with chronic pelvic pain. Br J Obstet Gynaecol 2004;111:950–959. [DOI] [PubMed] [Google Scholar]
- 47.Abbott J, Hawe J, Hunter D, et al. Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial. Fertil Steril 2004;82:878–884. [DOI] [PubMed] [Google Scholar]
- 48.Wright J, Lotfallah H, Jones K, et al. A randomized trial of excision versus ablation for mild endometriosis. Fertil Steril 2005;83:1830–1836. [DOI] [PubMed] [Google Scholar]
- 49.Lalchandani S, Baxter A, Phillips K. Is helium thermal coagulator therapy for the treatment of women with minimal to moderate endometriosis cost-effective? A prospective randomised controlled trial. Gynecol Surg 2005;2:255–258. [Google Scholar]
- 50.Wong AYK, Tang L. An open and randomized study comparing the efficacy of standard danazol and modified triptorelin regimens for postoperative disease management of moderate to severe endometriosis. Fertil Steril 2004;81:1522–1527. [DOI] [PubMed] [Google Scholar]
- 51.Loverro G, Carriero C, Rossi AC, et al. A randomized study comparing triptorelin or expectant management following conservative laparoscopic surgery for symptomatic stage III-IV endometriosis. Eur J Obstet Gynecol Reprod Biol 2008;136:194–198. [DOI] [PubMed] [Google Scholar]
- 52.Morgante G. Low-dose danazol after combined surgical and medical therapy reduces the incidence of pelvic pain in women with moderate and severe endometriosis. Hum Reprod 1999;14:2371–2374. [DOI] [PubMed] [Google Scholar]
- 53.Vercellini P, Frontino G, de Giorgi O, et al. Comparison levonorgestrel-releasing intrauterine device versus expectant management after conservative surgery for symptomatic endometriosis: a pilot study. Fertil Steril 2003;80:305–309. [DOI] [PubMed] [Google Scholar]
- 54.Sesti F, Pietropolli A, Capozzolo T, et al. Hormonal suppression treatment or dietary therapy versus placebo in the control of painful symptoms after conservative surgery for endometriosis stage III-IV. A randomized comparative trial. Fertil Steril 2007;88:1541–1547. [DOI] [PubMed] [Google Scholar]
- 55.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] [PubMed] [Google Scholar]
- 56.Muzii L, Marana R, Caruana P, et al. Postoperative administration of monophasic combined oral contraceptives after laparoscopic treatment of ovarian endometriosis: a prospective, randomized trial. Am J Obstet Gynecol 2000;183:588–592. [DOI] [PubMed] [Google Scholar]
- 57.Bianchi S, Busacca M, Agnoli B, et al. Effects of 3 month therapy with danazol after laparoscopic surgery for stage III/IV endometriosis: a randomized study. Hum Reprod 1999;14:1335–1337. [DOI] [PubMed] [Google Scholar]
- 58.Parazzini F, Fedele L, Busacca M, et al. Postsurgical medical treatment of advanced endometriosis: results of a randomized clinical trial. Am J Obstet Gynecol 1994;171:1205–1207. [DOI] [PubMed] [Google Scholar]
- 59.Busacca M, Somigliana E, Bianchi S, et al. Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage III–IV: a randomized controlled trial. Hum Reprod 2001;16:2399–2402. [DOI] [PubMed] [Google Scholar]
- 60.Loverro G, Santillo V, Pansini MV, et al. Are GnRH agonists helpful in the therapy of endometriosis after surgical treatment? Hum Reprod 2001;16(1 suppl):96. [Google Scholar]
- 61.Hornstein MD, Hemmings R, Yuzpe AA, et al. Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis. Fertil Steril 1997;68:860–864. [DOI] [PubMed] [Google Scholar]
- 62.Vercellini P, Crosignani PG, Fadini R, et al. A gonadotrophin-releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis. Br J Obstet Gynaecol 1999;106:672–677. [DOI] [PubMed] [Google Scholar]
- 63.Soysal S, Soysal ME, Ozer S, et al. The effects of post-surgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial. Hum Reprod 2004;19:160–167. [DOI] [PubMed] [Google Scholar]
- 64.Al KadriH, Hassan S, Al-Fozan HM, et al. Hormone therapy for endometriosis and surgical menopause. In: The Cochrane Library: Issue 4, 2009. Chichester, UK: John Wiley & Sons Ltd. Search date 2008. [DOI] [PubMed] [Google Scholar]
- 65.Hart RJ, Hickey M, Maouris P, et al. Excisional surgery versus ablative surgery for ovarian endometriomata. In: The Cochrane Library: Issue 4, 2009. Chichester, UK: John Wiley & Sons Ltd. Search date 2004. [Google Scholar]
- 66.Matorras R, Elorriaga MA, Pijoan JI, et al. Recurrence of endometriosis in women with bilateral adnexectomy (with or without total hysterectomy) who received hormone replacement therapy. Fertil Steril 2002;77:303–308. [DOI] [PubMed] [Google Scholar]