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Meta-Analysis
. 2013 Nov 15;2013(11):CD010241.
doi: 10.1002/14651858.CD010241.pub2.

Pre-operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding

Yu Hwee Tan  1 , Anne Lethaby
Affiliations
Meta-Analysis

Pre-operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding

Yu Hwee Tan et al. Cochrane Database Syst Rev. .

Abstract

Background: Heavy menstrual bleeding is one of the most common reasons for referral of premenopausal women to a gynaecologist. Although medical therapy is generally first line, many women eventually will require further treatment. Endometrial ablation by hysteroscopic and more recent "second-generation" devices such as balloon, radiofrequency or microwave ablation offers a day-case surgical alternative to hysterectomy. Complete endometrial destruction is one of the main determinants of treatment success. Surgery is most effective if undertaken when endometrial thickness is less than four millimeters. One option is to perform the surgery in the immediate postmenstrual phase, which is not always practical. The other option is to use hormonal agents that induce endometrial thinning pre-operatively. The most commonly evaluated agents are goserelin (a gonadotrophin-releasing hormone analogue, or GnRHa) and danazol. Other GnRH analogues and progestogens have also been studied, although fewer data are available. It has been suggested that these agents will reduce operating time, improve the intrauterine operating environment and reduce absorption of fluid used for intraoperative uterine cavity distension. They may also improve long-term outcomes, including menstrual loss and dysmenorrhoea.

Objectives: To investigate the effectiveness and safety of pre-operative endometrial thinning agents (GnRH agonists, danazol, estrogen-progestins and progestogens) versus another agent or placebo when given before endometrial destruction in premenopausal women with heavy menstrual bleeding.

Search methods: The following electronic databases were searched to April 2013 for published and unpublished randomised controlled trials that met the inclusion criteria: the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO.Other electronic sources of trials included trial registers for ongoing and registered trials; citation indexes; conference abstracts in the Web of Knowledge; the LILACS database for trials from the Portuguese- and Spanish-speaking world; PubMed; and the OpenSIGLE database and Google for grey literature.All searches were performed in consultation with the MDSG Trials Search Co-ordinator.

Selection criteria: Randomised controlled trials (RCTs) were included if they compared the effects of these agents with one other, or with placebo or no treatment, on relevant intraoperative and postoperative treatment outcomes. Selection of trials was carried out independently by two review authors.

Data collection and analysis: Two review authors independently assessed studies for risk of bias and extracted data on surgical outcomes, effectiveness outcomes, proportion of women requiring further surgical therapy during follow-up, endometrial outcome measures, acceptability of use outcomes and quality of life. Data were analysed on an intention-to-treat basis. Dichotomous data were combined for meta-analysis with RevMan software using the Mantel-Haenszel method to estimate pooled risk ratios (RRs). Continuous data were combined for meta-analysis with RevMan software using an inverse variance method to estimate the pooled mean difference (MD) with 95% confidence interval (CI). The overall quality of evidence for the main findings was assessed with the use of GRADE working group methods.

Main results: Twenty studies with 1969 women were included in this review. These studies compared GnRHa, danazol and progestogens versus placebo or no treatment; GnRHa versus danazol, progestogens, GnRH antagonists or dilatation & curettage; and danazol versus progestogens. Four studies performed more than one comparison.When compared with no treatment, GnRHa used before hysteroscopic resection were associated with a higher rate of postoperative amenorrhoea at 12 months (RR 1.6, 95% CI 1.2 to 2.0, 7 RCTs, 605 women, moderate heterogeneity; I(2) = 40%) and at 24 months (RR 1.62, 95% CI 1.04 to 2.52, 2 RCTs, 357 women, no heterogeneity; I(2) = 0%), a slightly shorter duration of surgery (-3.5 minutes, 95% CI -4.7 to -2.3, 5 RCTs, 156 women, substantial heterogeneity; I(2) = 72%) and greater ease of surgery (RR 0.32, 95% CI 0.22 to 0.46, 2 RCTs, 415 women, low heterogeneity; I(2) = 4%). Postoperative dysmenorrhoea was reduced (RR 0.59, 95% CI 0.40 to 0.87, 2 RCTs, 133 women, no heterogeneity; I(2) = 0%). The use of GnRHa had no effect on intraoperative complication rates (RR 1.47, 95% CI 0.35 to 6.06, 5 RCTs, 592 women, no heterogeneity; I(2) = 0%), and participant satisfaction with this surgery was high irrespective of the use of pre-operative endometrial thinning agents (RR 0.99, 95% CI 0.93 to 1.05, 6 RCTs, 599 women, low heterogeneity; I(2) = 11%). GnRHa produced more consistent endometrial atrophy than was produced by danazol (RR 1.84, 95% CI 1.23 to 2.75, 2 RCTs, 142 women, no heterogeneity; I(2) = 0%). For other intraoperative and postoperative outcomes, any differences were minimal, and no benefits of GnRHa pretreatment were noted in studies in which women underwent second-generation ablation techniques. Both GnRHa and danazol produced side effects in a significant proportion of women, although few studies reported these in detail. Few randomised data were available to allow assessment of the effectiveness of progestogens as endometrial thinning agents. When reported, the long-term effects of endometrial thinning agents on benefits such as postoperative amenorrhoea were reduced with time.The main study weaknesses were that most participants received no follow-up beyond 24 months and that the studies used a small sample size. Heterogeneity for outcomes reported ranged from none to substantial. More than half the trials had no blinding of participants or outcome assessment. Most of the trials were determined to have uncertain selection and reporting bias, as they did not report allocation concealment and evidence of selective reporting was noted. The quality of reporting of adverse events was generally poor, but, when described in the studies, they included menopausal symptoms such as hot flushes, vaginal dryness, hirsutism, decreased libido and voice changes, as well as other side effects such as headache and weight gain.

Authors' conclusions: Low-quality evidence suggests that endometrial thinning with GnRHa and danazol before hysteroscopic surgery improves operating conditions and short-term postoperative outcomes. GnRHa produced slightly more consistent endometrial thinning than was produced by danazol, although both achieved satisfactory results. The effect of these agents on longer-term postoperative outcomes was reduced with time. No benefits of GnRHa pretreatment were apparent with second-generation ablation techniques. Also, side effects were more common when these agents were used.

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Conflict of interest statement

Martin Sowter is the principal author of one of the studies included in the review. No other conflicts of interest have been reported.

Figures

1
1
Study flow diagram for 2002 to 2013 searches.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Forest plot of comparison: 1 GnRH analogues versus placebo or no treatment, outcome: 1.1 Intraoperative complications—uterine perforation.
5
5
Forest plot of comparison: 1 GnRH analogues versus placebo or no treatment, outcome: 1.2 Postoperative amenorrhoea at 12 months or less.
6
6
Forest plot of comparison: 1 GnRH analogues versus placebo or no treatment, outcome: 1.3 Postoperative amenorrhoea at 24 months or longer.
7
7
Forest plot of comparison: 1 GnRH analogues versus placebo or no treatment, outcome: 1.4 Requiring further surgery within 12 months of follow‐up.
8
8
Forest plot of comparison: 1 GnRH analogues versus placebo or no treatment, outcome: 1.5 Requiring further surgery ≥ 24 months of follow‐up.
9
9
Forest plot of comparison: 2 GnRH analogues versus danazol, outcome: 2.2 Postoperative amenorrhoea at 12 months or less.
10
10
Forest plot of comparison: 3 GnRH analogues versus progestogens, outcome: 3.2 Postoperative amenorrhoea at 12 months or less.
11
11
Forest plot of comparison: 6 Danazol versus no pretreatment, outcome: 6.2 Postoperative amenorrhoea at 12 months or less.
12
12
Forest plot of comparison: 6 Danazol versus no pretreatment, outcome: 6.3 Postoperative amenorrhoea at two years or more.
13
13
Forest plot of comparison: 6 Danazol versus no pretreatment, outcome: 6.4 Requiring further surgery at two years or more.
14
14
Forest plot of comparison: 7 Progestogens versus no pretreatment, outcome: 7.3 Postoperative amenorrhoea at two to four years.
15
15
Forest plot of comparison: 7 Progestogens versus no pretreatment, outcome: 7.4 Requiring further surgery at two to four years.
16
16
Forest plot of comparison: 8 Danazol versus progestogens, outcome: 8.2 Postoperative amenorrhoea at 12 months or less.
17
17
Forest plot of comparison: 9 GnRHa or danazol versus no pretreatment, outcome: 9.2 Postoperative amenorrhoea at 12 months or less.
1.1
1.1. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 1 Intraoperative complications—uterine perforation.
1.2
1.2. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 2 Postoperative amenorrhoea at 12 months or less.
1.3
1.3. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 3 Postoperative amenorrhoea at 24 months or longer.
1.4
1.4. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 4 Requiring further surgery within 12 months of follow‐up.
1.5
1.5. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 5 Requiring further surgery ≥ 24 months of follow‐up.
1.6
1.6. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 6 Endometrial thickness (ultrasound, mm).
1.8
1.8. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 8 Atrophic endometrial glands.
1.9
1.9. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 9 Optimal endometrial thinning (operator assessment).
1.10
1.10. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 10 Side effects.
1.11
1.11. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 11 Duration of operation (minutes).
1.12
1.12. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 12 Where operative difficulty encountered.
1.13
1.13. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 13 Distension medium absorption during surgery.
1.15
1.15. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 15 Women with moderate/heavy postoperative blood loss.
1.16
1.16. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 16 Postoperative dysmenorrhoea.
1.17
1.17. Analysis
Comparison 1 GnRH analogues versus placebo or no treatment, Outcome 17 Satisfaction with outcome.
2.2
2.2. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 2 Postoperative amenorrhoea at 12 months or less.
2.3
2.3. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 3 Postoperative amenorrhoea at 24 months.
2.4
2.4. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 4 Requesting further surgery during follow‐up.
2.5
2.5. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 5 Endometrial thickness (ultrasound).
2.7
2.7. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 7 Atrophic endometrial glands.
2.8
2.8. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 8 Satisfactory thinning (hysteroscopy).
2.9
2.9. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 9 Optimal endometrial thinning (operator assessment).
2.10
2.10. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 10 Complete atrophy (hysteroscopy).
2.11
2.11. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 11 Side effects.
2.12
2.12. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 12 Weight gain.
2.13
2.13. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 13 Duration of operation (minutes).
2.14
2.14. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 14 Where operative difficulty encountered.
2.15
2.15. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 15 Distension medium absorption during surgery.
2.16
2.16. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 16 Postoperative blood loss—objective.
2.17
2.17. Analysis
Comparison 2 GnRH analogues versus danazol, Outcome 17 Satisfaction with outcome.
3.2
3.2. Analysis
Comparison 3 GnRH analogues versus progestogens, Outcome 2 Postoperative amenorrhoea at 12 months or less.
3.3
3.3. Analysis
Comparison 3 GnRH analogues versus progestogens, Outcome 3 Postoperative amenorrhoea at 24 months.
3.4
3.4. Analysis
Comparison 3 GnRH analogues versus progestogens, Outcome 4 Requiring further surgery at two years of follow‐up.
3.5
3.5. Analysis
Comparison 3 GnRH analogues versus progestogens, Outcome 5 Endometrial thickness (ultrasound).
3.7
3.7. Analysis
Comparison 3 GnRH analogues versus progestogens, Outcome 7 Endometrial atrophy (histology).
3.8
3.8. Analysis
Comparison 3 GnRH analogues versus progestogens, Outcome 8 Optimal endometrial thinning (operator assessment).
3.9
3.9. Analysis
Comparison 3 GnRH analogues versus progestogens, Outcome 9 Duration of operation (minutes).
3.10
3.10. Analysis
Comparison 3 GnRH analogues versus progestogens, Outcome 10 Satisfaction with outcome.
4.1
4.1. Analysis
Comparison 4 GnRH analogue versus GnRH antagonist, Outcome 1 Intraoperative complications.
4.2
4.2. Analysis
Comparison 4 GnRH analogue versus GnRH antagonist, Outcome 2 Postoperative amenorrhoea at 12 months or less.
4.3
4.3. Analysis
Comparison 4 GnRH analogue versus GnRH antagonist, Outcome 3 Postoperative amenorrhoea and/or hypomenorrhoea at 12 months or less.
4.4
4.4. Analysis
Comparison 4 GnRH analogue versus GnRH antagonist, Outcome 4 Requiring further surgery within 12 months of follow‐up.
4.5
4.5. Analysis
Comparison 4 GnRH analogue versus GnRH antagonist, Outcome 5 Endometrial thickness (ultrasound).
4.6
4.6. Analysis
Comparison 4 GnRH analogue versus GnRH antagonist, Outcome 6 Side effects.
4.7
4.7. Analysis
Comparison 4 GnRH analogue versus GnRH antagonist, Outcome 7 Duration of operation (minutes).
4.8
4.8. Analysis
Comparison 4 GnRH analogue versus GnRH antagonist, Outcome 8 Good operative view.
4.10
4.10. Analysis
Comparison 4 GnRH analogue versus GnRH antagonist, Outcome 10 Postoperative dysmenorrhoea.
4.11
4.11. Analysis
Comparison 4 GnRH analogue versus GnRH antagonist, Outcome 11 Satisfaction with outcome.
5.2
5.2. Analysis
Comparison 5 GnRH analogue versus dilatation & curettage, Outcome 2 Normal bleeding or less at 12 months.
5.3
5.3. Analysis
Comparison 5 GnRH analogue versus dilatation & curettage, Outcome 3 Postoperative amenorrhoea at 12 months or less.
5.4
5.4. Analysis
Comparison 5 GnRH analogue versus dilatation & curettage, Outcome 4 Requiring further surgery within 12 months of follow‐up.
5.6
5.6. Analysis
Comparison 5 GnRH analogue versus dilatation & curettage, Outcome 6 Side effects—presence of PMS symptoms.
5.7
5.7. Analysis
Comparison 5 GnRH analogue versus dilatation & curettage, Outcome 7 Postoperative dysmenorrhoea.
5.8
5.8. Analysis
Comparison 5 GnRH analogue versus dilatation & curettage, Outcome 8 Satisfaction with outcome.
6.2
6.2. Analysis
Comparison 6 Danazol versus no pretreatment, Outcome 2 Postoperative amenorrhoea at 12 months or less.
6.3
6.3. Analysis
Comparison 6 Danazol versus no pretreatment, Outcome 3 Postoperative amenorrhoea at two years or more.
6.4
6.4. Analysis
Comparison 6 Danazol versus no pretreatment, Outcome 4 Requiring further surgery at two years or more.
6.5
6.5. Analysis
Comparison 6 Danazol versus no pretreatment, Outcome 5 Endometrial thickness (ultrasound).
6.7
6.7. Analysis
Comparison 6 Danazol versus no pretreatment, Outcome 7 Atrophic endometrial glands.
6.8
6.8. Analysis
Comparison 6 Danazol versus no pretreatment, Outcome 8 Optimal endometrial thinning (operator assessment).
6.10
6.10. Analysis
Comparison 6 Danazol versus no pretreatment, Outcome 10 Duration of operation (minutes).
6.11
6.11. Analysis
Comparison 6 Danazol versus no pretreatment, Outcome 11 Distension medium absorption during surgery (mL).
6.12
6.12. Analysis
Comparison 6 Danazol versus no pretreatment, Outcome 12 Satisfaction with outcome.
7.2
7.2. Analysis
Comparison 7 Progestogens versus no pretreatment, Outcome 2 Postoperative amenorrhoea at 12 months or less.
7.3
7.3. Analysis
Comparison 7 Progestogens versus no pretreatment, Outcome 3 Postoperative amenorrhoea at two to four years.
7.4
7.4. Analysis
Comparison 7 Progestogens versus no pretreatment, Outcome 4 Requiring further surgery at two to four years.
7.5
7.5. Analysis
Comparison 7 Progestogens versus no pretreatment, Outcome 5 Endometrial thickness (ultrasound).
7.7
7.7. Analysis
Comparison 7 Progestogens versus no pretreatment, Outcome 7 Atrophic endometrial glands.
7.8
7.8. Analysis
Comparison 7 Progestogens versus no pretreatment, Outcome 8 Optimal endometrial thinning (operator).
7.11
7.11. Analysis
Comparison 7 Progestogens versus no pretreatment, Outcome 11 Satisfaction with outcome.
8.2
8.2. Analysis
Comparison 8 Danazol versus progestogens, Outcome 2 Postoperative amenorrhoea at 12 months or less.
8.3
8.3. Analysis
Comparison 8 Danazol versus progestogens, Outcome 3 Postoperative amenorrhoea at two years.
8.4
8.4. Analysis
Comparison 8 Danazol versus progestogens, Outcome 4 Requiring further surgery at two years of follow‐up.
8.5
8.5. Analysis
Comparison 8 Danazol versus progestogens, Outcome 5 Endometrial thickness (ultrasound).
8.7
8.7. Analysis
Comparison 8 Danazol versus progestogens, Outcome 7 Atrophic endometrial glands.
8.8
8.8. Analysis
Comparison 8 Danazol versus progestogens, Outcome 8 Optimal endometrial thinning (operator).
8.10
8.10. Analysis
Comparison 8 Danazol versus progestogens, Outcome 10 Duration of operation (minutes).
8.11
8.11. Analysis
Comparison 8 Danazol versus progestogens, Outcome 11 Satisfaction with outcome.
9.2
9.2. Analysis
Comparison 9 GnRHa or danazol versus no pretreatment, Outcome 2 Postoperative amenorrhoea at 12 months or less.
9.3
9.3. Analysis
Comparison 9 GnRHa or danazol versus no pretreatment, Outcome 3 Amenorrhoea at five years.
9.4
9.4. Analysis
Comparison 9 GnRHa or danazol versus no pretreatment, Outcome 4 Improvement (light bleeding/amenorrhoea) at five years.
9.5
9.5. Analysis
Comparison 9 GnRHa or danazol versus no pretreatment, Outcome 5 Requiring further surgery at one year.
9.6
9.6. Analysis
Comparison 9 GnRHa or danazol versus no pretreatment, Outcome 6 Requiring further surgery at five years.
9.7
9.7. Analysis
Comparison 9 GnRHa or danazol versus no pretreatment, Outcome 7 Endometrial thickness (mm).
9.8
9.8. Analysis
Comparison 9 GnRHa or danazol versus no pretreatment, Outcome 8 Side effects.
9.9
9.9. Analysis
Comparison 9 GnRHa or danazol versus no pretreatment, Outcome 9 Duration of operation (minutes).
9.10
9.10. Analysis
Comparison 9 GnRHa or danazol versus no pretreatment, Outcome 10 Postoperative menorrhagia.
9.11
9.11. Analysis
Comparison 9 GnRHa or danazol versus no pretreatment, Outcome 11 Satisfaction with outcome at 12 months of follow‐up.
9.12
9.12. Analysis
Comparison 9 GnRHa or danazol versus no pretreatment, Outcome 12 Satisfaction with outcome at five years.
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Update of

  • doi: 10.1002/14651858.CD010241

References

References to studies included in this review

Alborzi 2002 {published data only}
    1. Alborzi S, Parsanezhad ME, Dehbashi S. A comparison of hysteroscopic endometrial ablation for abnormal uterine bleeding in two groups of patients with or without endometrial preparation. Middle East Fertility Journal 2002;75(3):620‐2.
Bhatia 2008 {published data only}
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Donnez 1997 {published data only}
    1. Donnez J, Vilos G, Gannon MJ, Maheaux R, Emanuel MH, Istre O. Goserelin acetate (Zoladex) plus endometrial ablation for dysfunctional uterine bleeding: a 3‐year follow‐up evaluation. Fertility and Sterility 2001;75(3):620‐2. - PubMed
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English 1998 {published data only}
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Fraser 1996 {published and unpublished data}
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Garry 1996 {published data only}
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Jack 2005 {published data only}
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Kriplani 2001 {published data only}
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Kriplani 2002 {published data only}
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Lissak 1999 {published data only}
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Rai 2000 {published data only}
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Romer 1996 {published data only}
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Shawki 2002 {published data only}
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Sorensen 1997 {published data only}
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Sowter 1997 {published data only}
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Sutton 1994 {published data only}
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Taskin 1996 {published data only}
    1. Taskin O, Yalcinoglu A, Kucuk S, Burak F, Ozekici U, Wheeler JM. The degree of fluid absorption during hysteroscopic surgery in patients pretreated with Goserelin. Journal of the American Association of Gynecologic Laparoscopists 1996;3(4):555‐9. - PubMed
Taskin 1998 {published data only}
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Vercellini 1996 {published data only}
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Vilos 2010 {published data only}
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References to studies excluded from this review

Alford 1996 {published data only}
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Cicenelli 2007 {published data only}
    1. Cicinelli E, Pinto V, Tinelli R, Saliani N, Leo V, Cianci A. Rapid endometrial preparation for hysteroscopic surgery with oral desogestrel plus vaginal raloxifene: a prospective, randomized pilot study. Fertility and Sterility 2007;88(3):698‐701. - PubMed
Cooper 1996 {published data only}
    1. Cooper KG, Pinion SB, Bhattacharya S, Parkin DE. The effects of gonadotrophin releasing hormone analogue (goserelin) and prostaglandin E1 (misoprostol) on cervical resistance prior to transcervical resection of the endometrium. British Journal of Obstetrics and Gynaecology 1996;103:375‐8. - PubMed
Cooper 2001 {published data only}
    1. Cooper J, Brill A, Fulop T. Is endometrial pretreatment necessary in NovaSure 3‐D endometrial ablation?. Gynaecological Endoscopy 2001;10:179‐82.
Florio 2010 {published data only}
    1. Florio P, Imperatore A, Litta P, Franchini M, Calzolari S, Angioni S. The use of nomegestrol acetate in rapid preparation of endometrium before operative hysteroscopy in pre‐menopausal women. Steroids 2010;75(12):912‐7. - PubMed
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Florio 2012 {published data only}
    1. Florio P, Filippeschi M, Imperatore A, Mereu L, Franchini M, Calzolari S, et al. The practicability and surgeons' subjective experiences with vaginal danazol before an operative hysteroscopy. Steroids 2012;77(5):528‐33. - PubMed
Gabbanini 2009 {published data only}
    1. Gabbanini M, Altomare A, Franchini M, Pinzauti S, Imperatore A, Petraglia F, et al. Endometrial preparation before operative hysteroscopy in pre‐menopausal women: a randomized, double‐blind, placebo controlled comparison of vaginal and oral administration of danazol. 18th Annual Congress of the European Society for Gynaecological Endoscopy. Florence, Italy, 2009; Vol. 6:S42.
Mavrelos 2010 {published data only}
    1. Mavrelos D, Ben‐Nagi J, Davies A, Lee C, Salim R, Jurkovic D. The value of pre‐operative treatment with GnRH analogues in women with submucous fibroids: a double‐blind, placebo‐controlled randomized trial. Human Reproduction 2010;25(9):2264‐9. - PubMed
Muzii 2010 {published data only}
    1. Muzii L, Boni T, Bellati F, Marana R, Ruggiero A, Zullo MA, et al. GnRH analogue treatment before hysteroscopic resection of submucous myomas: a prospective, randomized, multicenter study. Fertility and Sterility 2010;94(4):1496‐9. - PubMed
Perino 1993 {published data only}
    1. Perino A, Chianchiano N, Petrionio M, Cittadini E. Role of leuprolide acetate depot in hysteroscopic surgery: a controlled study. Fertility and Sterility 1993;59:507‐10. - PubMed
Rich 1995 {published data only}
    1. Rich AD, Manyonda IT, Patel R, Amias AG. A comparison of the efficacy of danazol, norethisterone, cyproterone acetate and medroxyprogesterone acetate in endometrial thinning prior to ablation: a pilot study. Gynaecological Endoscopy 1995;4:59‐61.
Serden 1992 {published data only}
    1. Serden SP, Brooks PG. Preoperative therapy in preparation for endometrial ablation. Journal of Reproductive Medicine 1992;37:679‐81. - PubMed
Triolo 2006 {published data only}
    1. Triolo O, Vivo A, Benedetto V, Falcone S, Antico F. Gestrinone versus danazol as preoperative treatment for hysteroscopic surgery: a prospective randomized evaluation. Fertility and Sterility 2006;85(4):1027‐31. - PubMed
Trivedi 1999 {published data only}
    1. Trivedi P, Rocha I, Padhye A. Is routine preoperative preparation necessary for hysteroscopic endometrial resection?. Gynaecological Endoscopy 1999;8(5):287‐91.
Vercellini 1994 {published data only}
    1. Vercellini P, Trespidi L, Bramante T, Panazza S, Mauro F, Crosignani PG. Gonadotrophin releasing hormone agonist treatment before hysteroscopic endometrial resection. International Journal of Gynaecology and Obstetrics 1994;45(3):235‐9. - PubMed
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References to studies awaiting assessment

Gannon 1994 {published data only}
    1. Gannon MJ, Johnson N, Buchan PC, O'Donovan P, Neale R, Bryce F, et al. The EBOR trial. 27th British Congress of Obstetrics and Gynaecology. Dublin, Ireland, 2‐7 July 1995:Abstract 215.
    1. Gannon MJ, Johnson N, Drife JO, Neale R, Watters J, Lilford RL. Preparation of the endometrium for ablation: Danol, Zoladex or nothing. European Congress of Gynaecological Endoscopic Surgery. Rome, Italy, 15‐18 June 1994.
Mayonda 1994 {published data only}
    1. Mayonda I, Rich D, Patel R, Amias A. Endometrial thinning before ablation: is danazol the best progestagenic agent?. Journal of Obstetrics & Gynecology 1994;14(5):364‐5.
McDonald 1994 {published data only}
    1. McDonald R. Endometrial resection: does pre‐operative goserelin influence outcome?. Journal of Obstetrics & Gynecology 1994;14(5):363.
Nagele 1995 {published data only}
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