Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2017 Nov 15;11(11):CD000547.
doi: 10.1002/14651858.CD000547.pub2.

Preoperative medical therapy before surgery for uterine fibroids

Anne Lethaby  1 , Lucian Puscasiu, Beverley Vollenhoven
Affiliations
Meta-Analysis

Preoperative medical therapy before surgery for uterine fibroids

Anne Lethaby et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive.Fibroid growth is stimulated by oestrogen. Gonadotropin-hormone releasing analogues (GnRHa) induce a state of hypo-oestrogenism that shrinks fibroids , but has unacceptable side effects if used long-term. Other potential hormonal treatments, include progestins and selective progesterone-receptor modulators (SPRMs).This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments.

Objectives: To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids.

Search methods: We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials.

Selection criteria: We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids.

Data collection and analysis: We used standard methodological procedures expected by The Cochrane Collaboration.

Main results: We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low-quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD -175 mL, 95% CI -219.0 to -131.7; 13 studies; 858 participants; I² = 67%; low-quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate-quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate-quality evidence).Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (-9.59 minutes, 95% CI 15.9 to -3.28; 6 studies; 617 participants; I² = 57%; low-quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate-quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low-quality evidence).GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low-quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low-quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (-47% with GnRHa compared to -20% and -22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low-quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate-quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate-quality evidence) or haemoglobin levels (MD -0.2, 95% CI -0.6 to 0.2; 188 participants; moderate-quality evidence).There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI -5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low-quality evidence).The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB-2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high-quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low-quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low-quality evidence; asoprisnil: MD -166.9 mL; 95% CI -277.6 to -56.2; 1 study; 22 participants; low-quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured.

Authors' conclusions: A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid-related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost-effectiveness and distinguish between groups of women with fibroids who would most benefit.

PubMed Disclaimer

Conflict of interest statement

Anne Lethaby: None known.

Lucian Puscasiu (LP) is a co‐author of an included trial in this review (Donnez 2012a). LP has received publication and speaking fees as well as travel expenses and fees in connection with ESMYA launch symposium in March 2012 in Barcelona from the company Gedeon‐Richter. LP also received investigator's fees from the company ICON during the PEARL I study.

Beverley Vollenhoven: None known.

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
4
4
Forest plot of comparison: 1 GnRHa treatment versus placebo or no pretreatment (preoperative outcomes), outcome: 1.1 Uterine volume (mL) (preoperative).
5
5
Forest plot of comparison: 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), outcome: 2.1 Duration of surgery (minutes).
6
6
Forest plot of comparison: 3 GnRHa treatment versus no pretreatment or placebo before myomectomy (operative and postoperative), outcome: 3.1 Duration of surgery (minutes).
1.1
1.1. Analysis
Comparison 1 GnRHa treatment versus placebo or no pretreatment (preoperative outcomes), Outcome 1 Uterine volume (mL) (preoperative).
1.3
1.3. Analysis
Comparison 1 GnRHa treatment versus placebo or no pretreatment (preoperative outcomes), Outcome 3 Fibroid volume (mL) (preoperative).
1.5
1.5. Analysis
Comparison 1 GnRHa treatment versus placebo or no pretreatment (preoperative outcomes), Outcome 5 Haemoglobin (preoperative).
1.7
1.7. Analysis
Comparison 1 GnRHa treatment versus placebo or no pretreatment (preoperative outcomes), Outcome 7 Total frequency of adverse events.
1.8
1.8. Analysis
Comparison 1 GnRHa treatment versus placebo or no pretreatment (preoperative outcomes), Outcome 8 Individual adverse events.
2.1
2.1. Analysis
Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), Outcome 1 Duration of surgery (minutes).
2.3
2.3. Analysis
Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), Outcome 3 Intraoperative blood loss (mL).
2.5
2.5. Analysis
Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), Outcome 5 Proportion with blood transfusions.
2.6
2.6. Analysis
Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), Outcome 6 Proportion with postoperative complications.
2.7
2.7. Analysis
Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), Outcome 7 Proportion with individual complications.
2.8
2.8. Analysis
Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), Outcome 8 Proportion with difficult surgery.
2.9
2.9. Analysis
Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), Outcome 9 Proportion undergoing vaginal rather than abdominal procedure.
2.10
2.10. Analysis
Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), Outcome 10 Proportion with vertical incision.
2.11
2.11. Analysis
Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), Outcome 11 Duration of hospital stay (days).
2.13
2.13. Analysis
Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), Outcome 13 Postoperative haemoglobin.
3.1
3.1. Analysis
Comparison 3 GnRHa treatment versus no pretreatment or placebo before myomectomy (operative and postoperative), Outcome 1 Duration of surgery (minutes).
3.3
3.3. Analysis
Comparison 3 GnRHa treatment versus no pretreatment or placebo before myomectomy (operative and postoperative), Outcome 3 Intraoperative blood loss (mL).
3.4
3.4. Analysis
Comparison 3 GnRHa treatment versus no pretreatment or placebo before myomectomy (operative and postoperative), Outcome 4 Proportion with blood transfusions.
3.5
3.5. Analysis
Comparison 3 GnRHa treatment versus no pretreatment or placebo before myomectomy (operative and postoperative), Outcome 5 Proportion with postoperative complications.
3.6
3.6. Analysis
Comparison 3 GnRHa treatment versus no pretreatment or placebo before myomectomy (operative and postoperative), Outcome 6 Proportion with vertical incision.
3.7
3.7. Analysis
Comparison 3 GnRHa treatment versus no pretreatment or placebo before myomectomy (operative and postoperative), Outcome 7 Duration of hospital stay (days).
3.8
3.8. Analysis
Comparison 3 GnRHa treatment versus no pretreatment or placebo before myomectomy (operative and postoperative), Outcome 8 Proportion with postoperative recurrence of myomas.
3.9
3.9. Analysis
Comparison 3 GnRHa treatment versus no pretreatment or placebo before myomectomy (operative and postoperative), Outcome 9 Postoperative haemoglobin.
4.1
4.1. Analysis
Comparison 4 GnRHa treatment versus no pretreatment or placebo prior to resection, Outcome 1 Duration of surgery (minutes).
4.2
4.2. Analysis
Comparison 4 GnRHa treatment versus no pretreatment or placebo prior to resection, Outcome 2 Difficulty of surgery (VAS).
4.3
4.3. Analysis
Comparison 4 GnRHa treatment versus no pretreatment or placebo prior to resection, Outcome 3 Fibroid recurrence.
5.2
5.2. Analysis
Comparison 5 GnRHa treatment versus other medical therapies prior to any surgery, Outcome 2 Fibroid volume.
5.4
5.4. Analysis
Comparison 5 GnRHa treatment versus other medical therapies prior to any surgery, Outcome 4 Haemoglobin at end of preoperative treatment.
5.5
5.5. Analysis
Comparison 5 GnRHa treatment versus other medical therapies prior to any surgery, Outcome 5 Reduction in bleeding to PBAC < 75.
5.6
5.6. Analysis
Comparison 5 GnRHa treatment versus other medical therapies prior to any surgery, Outcome 6 Adverse events.
6.3
6.3. Analysis
Comparison 6 SPRM versus placebo, Outcome 3 Haemoglobin (g/dL).
6.4
6.4. Analysis
Comparison 6 SPRM versus placebo, Outcome 4 Reduction in menstrual bleeding (PBAC < 75).
6.5
6.5. Analysis
Comparison 6 SPRM versus placebo, Outcome 5 Change in menstrual blood loss from baseline to treatment end.
6.6
6.6. Analysis
Comparison 6 SPRM versus placebo, Outcome 6 Serious adverse events.
6.7
6.7. Analysis
Comparison 6 SPRM versus placebo, Outcome 7 Other adverse events.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Audebert 1994 {published data only}
    1. Audebert AJM, Madenelat P, Querleu D, Pontonnier G, Racinet C, Renaud R, et al. Deferred versus immediate surgery for uterine fibroids: clinical trial results. British Journal of Obstetrics and Gynaecology 1994;101(Suppl):29‐32. - PubMed
Balasch 1995 {published data only}
    1. Balasch J, Manau D, Mimó J, Duran M, Puerto B, Vanrell JA. Trial of routine gonadotropin releasing hormone agonist treatment before abdominal hysterectomy for leiomyoma. Acta Obstetricia et Gynecologica Scandinavica 1995;74(7):562‐5. - PubMed
Baytur 2007 {published data only}
    1. Baytur YB, Ozbilgin K, Cilaker S, Lacin S, Kurtul O, Oruc S, et al. A comparative study of the effect of raloxifene and gosereline on uterine leiomyoma volume changes and estrogen receptor, progesterone receptor, bcl‐2 and p53 expression immunohistochemically in premenopausal women. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2007;135(1):94‐103. - PubMed
Benagiano 1996 {published data only}
    1. Benagiano G, Kivinen ST, Fadini R, Cronje H, Klintorp S, Spuy Z. Zoladex (goserelin acetate) and the anemic patient: results of a multicenter fibroid study. Fertility and Sterility 1996;66(2):223‐9. - PubMed
Bustos López 1995 {published data only}
    1. Bustos López HH, Miranda Rodríguez JA, Kably Ambe A, Serviere Zaragoza C, Espinoza de los Monteros A, Alvarado Durán A. Pre‐operative medical treatment of uterine leiomyomatosis with hypophysiary gonadotropin releasing hormone analogues [Tratamiento médico preoperatorio de leiomiomatosis uterina con análogos de hormona liberadora de gonadotropinas hipofisiarias]. Ginecología y Obstetricia de México 1995;63(8):356‐64. - PubMed
Cagnacci 1994 {published data only}
    1. Cagnacci A, Paoletti AM, Soldani R, Angiolucci M, Arangino S, Falqui A, et al. Role of goserelin‐depot in the clinical management of uterine fibroids. Clinical and Experimental Obstetrics & Gynecology 1994;21(4):263‐5. - PubMed
Campo 1999 {published data only}
    1. Campo S, Garcea N. Laparoscopic myomectomy in premenopausal women with and without preoperative treatment using gonadotropin‐releasing hormone analogues. Human Reproduction (Oxford, England) 1999;14(1):44‐8. - PubMed
Cetin 1995 {published data only}
    1. Cetin MT, Vardar MA, Demir SC. Kibar M. Administration of preoperative gonadotropin releasing hormone agonist (buserelin) for uterine leiomyomas. Annals of Medical and Health Sciences Research 1995;4:102‐8.
D'Anna 1994 {published data only}
    1. D'Anna R, Palmara V, Lo Re C, Scilipoti A, Leonardi I. Short treatment with leuprolide acetate depot before hysterectomy for uterine leiomyomata [Breve trattamento con leuprolide acetato depot prima di intervento chirurgico per leiomiomatosi uterina]. Minerva Ginecologica 1994;46(6):343‐6. - PubMed
De Falco 2009 {published data only}
    1. Falco M, Staibano S, Mascolo M, Mignogna C, Improda L, Ciociola F, et al. Leiomyoma psuedocapsule after presurgical treatment with gonadotropin‐releasing hormone agonists: relationship between clinical features and immunohistochemical changes. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2009;144(1):44‐7. - PubMed
Donnez 2003 {published data only}
    1. Donnez J, Vivancos B, Kudela M, Audebert A, Jadoul P. A randomized, placebo‐controlled, dose‐ranging trial comparing fulvestrant with goserelin in premenopausal patients with uterine fibroids awaiting hysterectomy. Fertility and Sterility 2003;79(6):1380‐9. - PubMed
Donnez 2012a {published data only}
    1. Donnez J, Tatarchuk TF, Bouchard P, Puscasiu L, Zakharenko NF, Ivanova T, et al. PEARL I Study Group. Ulipristal acetate versus placebo for fibroid treatment before surgery. New England Journal of Medicine 2012;366(5):409‐20. - PubMed
Donnez 2012b {published data only}
    1. Donnez J, Tomaszewski J, Vázquez F, Bouchard P, Lemieszczuk B, Baró F, et al. PEARL II Study Group. Ulipristal acetate versus leuprolide acetate for uterine fibroids. New England Journal of Medicine 2012;366(5):421‐32. - PubMed
Engman 2009 {published data only}
    1. Engman M, Granberg S, Williams AR, Meng CX, Lalitkumar PGL, Gemzell‐Danielsson K. Mifepristone for treatment of uterine leiomyoma. A prospective randomised placebo controlled trial. Human Reproduction (Oxford, England) 2009;24(8):1870‐9. - PubMed
Fedele 1990 {published data only}
    1. Fedele L, Vercellini P, Bianchi S, Brioschi D, Dorta M. Treatment with GnRH agonists before myomectomy and the risk of short‐term myoma recurrence. British Journal of Obstetrics and Gynaecology 1990;97(5):393‐6. - PubMed
Friedman 1989 {published data only}
    1. Friedman AJ, Daly M, Juneau‐Norcross M, Fine C, Rein MS. Recurrence of myomas after myomectomy in women pretreated with leuprolide acetate depot or placebo. Fertility and Sterility 1992;58(1):205‐8. - PubMed
    1. Friedman AJ, Rein MS, Harrison‐Atlas D, Garfield JM, Doubilet PM. A randomized, placebo‐controlled, double‐blind study evaluating leuprolide acetate depot treatment before myomectomy. Fertility and Sterility 1989;52(5):728‐33. - PubMed
Gerris 1996 {published data only}
    1. Gerris J, Degueldre M, Peters AAW, Romao F, Stjernquist M, al‐Taher H. The place of Zoladex in deferred surgery for uterine fibroids. Zoladex Myoma Study Group. Hormone Research 1996;45(6):279‐84. - PubMed
Golan 1993 {published data only}
    1. Golan A, Bukovsky I, Pansky M, Schneider D, Weinraub Z, Caspi E. Pre‐operative gonadotropin‐releasing hormone agonist treatment in surgery for uterine leiomyomata. Human Reproduction (Oxford, England) 1993;8(3):450‐2. - PubMed
    1. Golan A, Bukovsky I, Schneider D, Pansky M, Caspi E. Preoperative GnRH‐analog treatment in surgery for uterine myomas. 3rd International Sympoisum on Gynaecological Endocrinology, Switzerland, 25‐28 Feb 1993. 1993:15.
Hudecek 2012 {published data only}
    1. Hudecek R, Ivanová Z, Smerdová M, Pánková S, Krajcovicová R. Effect of GnRH analogues pre‐treatment on myomectomy outcomes in reproductive age women. Ceska Gynekologie 2012;77(2):109‐17. - PubMed
Levens 2008 {published data only}
    1. Levens ED, Potlog‐Nahari C, Armstrong AY, Wesley R, Premkumar A, Blithe DL, et al. CDB‐2914 for uterine leiomyomata treatment. Obstetrics and Gynecology 2008;111(5):1129‐36. - PMC - PubMed
Lumsden 1994 {published data only}
    1. Lumsden MA, West CP, Thomas E, Coutts J, Hillier H, Thomas N, et al. Treatment with the gonadotropin releasing hormone‐agonist goserelin before hysterectomy for uterine fibroids. British Journal of Obstetrics and Gynaecology 1994;101(5):438‐42. - PubMed
Mavrelos 2010 {published data only}
    1. Mavrelos D, Ben‐Nagi J, Davies A, Lee C, Salim R, Jurkovic D. The value of preoperative treatment with GnRH analogues in women with submucous fibroids: a double blind placebo controlled randomised trial. Human Reproduction (Oxford, England) 2010;25(9):2264‐9. - PubMed
Muneyyirci‐Delale 2007 {published data only}
    1. Muneyyirci‐Delale O, Richard‐Davis G, Morris T, Armstrong J. Goserelin acetate 10.8 mg plus iron monotherapy prior to surgery in premenopausal women with iron deficiency anemia due to uterine leiomyomas: results from a phase III, randomized, multicenter, double blind, controlled trial. Clinical Therapeutics 2007;29(8):1682‐91. - 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, randomised, multicenter study. Fertility and Sterility 2010;94(4):1496‐9. - PubMed
Nikolov 1999 {published data only}
    1. Nikolov A, Karag'osov I. Comparative study on the efficacy of preoperative use of GnRH agonists in patients with uterine fibromyomas. Akuserstvo i Ginekologija 1999;38(4):38‐42. - PubMed
    1. Nikolov N, Karag'osov I. Preoperative use of Zoladex for treatment of uterine fibromyomas (abstract). Acta Obstetricia et Gynecologica Scandinavica 1997;76(Suppl):31.
Reinsch 1994 {published data only}
    1. Reinsch RC, Murphy AA, Morales AJ, Yen SSC. The effects of RU 486 and leuprolide acetate on uterine artery blood flow in the fibroid uterus: a prospective randomised study. American Journal of Obstetrics and Gynecology 1994;170(6):1623‐8. - PubMed
Sayyah‐Melli 2007 {published data only}
    1. Sayyah‐Melli M, Farzadi L, Madarek EO. Comparison of the effect of gonadotropin‐releasing hormone analog (Diphereline) and Cabergoline (Dostinex) treatment on uterine myoma regression. Saudi Medical Journal 2007;28(3):445‐50. - PubMed
Sayyah‐Melli 2009 {published data only}
    1. Sayyah‐Melli M, Tehrani‐Gadim S, Dastranj‐Tabrizi A, Gatrehsamani F, Morteza G, Ouladesahebmadarek E, et al. Comparison of the effect of gonadotropin‐releasing hormone agonist and dopamine receptor agonist on uterine myoma growth. Saudi Medical Journal 2009;30(8):1024‐33. - PubMed
Seraccholi 2003 {published data only}
    1. Seracchioli R, Venturoli S, Colombo F, Bagnoli A, Vianello F, Govoni F, et al. GnRH agonist treatment before total laparoscopic hysterectomy for large Uteri. Journal of the American Association of Gynecologic Laparoscopists 2003;10(3):316‐9. - PubMed
Shaw 1989 {published data only}
    1. Shaw RW. Mechanism of LHRH analogue action in uterine fibroids. Hormone Research 1989;32(Suppl 1):150‐3. - PubMed
Shaw 1996 {unpublished data only}
    1. Shaw RW. Placebo controlled comparison of the effectiveness of the microparticles depot formulation of buserelin in the pre‐operative management of patients with uterine fibroids. Clinical/biometric report, Hoechst Marion Roussel, UK Ltd 1996.
Stovall 1994 {published data only}
    1. Stovall TG, Ling FW, Henry LC, Woodruff MR. A randomised trial evaluating leuprolide acetate before hysterectomy as treatment for leiomyomas. American Journal of Obstetrics and Gynecology 1991;164(6 Pt 1):1420‐5. - PubMed
    1. Stovall TG, Summitt Jr RL, Washburn SA, Ling FW. Gonadotropin‐releasing hormone agonist use before hysterectomy. American Journal of Obstetrics and Gynecology 1994;170(6):1744‐51. - PubMed
Stovall 1995 {published data only}
    1. Stovall TG, Muneyyirci‐Delale O, Summitt Jr RL, Scialli AR. GnRH agonist and iron versus placebo and iron in the anemic patient before surgery for leiomyomas: a randomized controlled trial. Leuprolide Acetate Study Group. Obstetrics and Gynecology 1995;86(1):65‐71. - PubMed
Vercellini 1998 {published data only}
    1. Vercellini P, Crosignani PG, Mangioni C, Imparato E, Ferrari A, Giorgi O. Treatment with a gonadotrophin releasing hormone agonist before hysterectomy for leiomyomas: results of a multicentre, randomised controlled trial. British Journal of Obstetrics and Gynaecology 1998;105(11):1148‐54. - PubMed
Vercellini 2003 {published data only}
    1. Vercellini P, Trespidi L, Zaina B, Vicentini S, Stellato G, Crosignani PG. Gonadotropin‐releasing hormone agonist treatment before abdominal myomectomy: a controlled trial. Fertility and Sterility 2003;79(6):1390‐5. - PubMed
Verspyck 2000 {published data only}
    1. Verspyck E, Marpeau L, Lucas C. Leuporelin depot 3.75 mg versus lynestrenol in the preoperative treatment of symptomatic uterine myomas: a multicentre randomised trial. European Journal of Obstetrics, Gynecology, and Reproductive BIology 2000;89(1):7‐13. - PubMed
Wilkens 2008 {published data only}
    1. Wilkens J, Chwalisz K, Han C, Walker J, Cameron IT, Ingamells S, et al. Effects of the selective progesterone receptor modulator asoprisnil on uterine artery blood flow, ovarian activity and clinical symptoms in patients with uterine leiomyomata scheduled for hysterectomy. Journal of Clinical Endocrinology and Metabolism 2008;93(12):4664‐71. - PubMed
Zullo 1998 {published data only}
    1. Zullo F, Pellicano M, Stefano R, Zupi E, Mastrantonio P. A prospective randomised study to evaluate leuprolide acetate treatment before laparascopic myomectomy: efficacy and ultrasonographic predictors. American Journal of Obstetetrics and Gynecology 1998;178(1 Pt 1):108‐12. - PubMed
    1. Zullo F, Pellicano M, Carlo C, Stefano R, Mastrantonio P, Nappi C. GnRH‐a pretreatment and laparoscopic intramural myomectomy: efficacy and ultrasonographic correlations (abstract). American Society for Reproductive Medicine. 1996:S134.

References to studies excluded from this review

Bassaw 2014 {published data only}
    1. Bassaw B, Mohammed N, Jaggat A, SIngh‐Bhola M, Ramkissoon A, Singh P, et al. Experience with a gonadotropin‐releasing hormone agonist prior to myomectomy ‐ comparison of twice‐ vs thrice‐monthly doses and a control group. Journal of Obstetrics and Gynaecology 2014;34(5):415‐9. - PubMed
Benagiano 1992 {published data only}
    1. Benagiano G, Morini A, Primiero FM. Fibroids: overview of current and future treatment options. Journal of Obstetrics and Gynaecology 1992;99(Suppl 7):18‐22. - PubMed
Bizzari 2015 {published data only}
    1. Bizzarri N, Ghirardi V, Remorgida V, Venturini PL, Ferrero S. Three‐month treatment with triptorelin, letrozole and ulipristal acetate before hysteroscopic resection of uterine myomas: prospective comparative pilot study. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2015;192:22‐6. - PubMed
Bondi 2016 {published data only}
    1. Bondi C, Maggiore LRU, Alessandri F, Venturini PL, Vellone VG, Ferrero S. Three‐month treatment with ulipristal acetate prior to laparoscopic myomectomy of large uterine myomas. Human Reproduction 2016;31(Suppl 1):i467. - PubMed
Coddington 2009 {published data only}
    1. Coddington CC, Grow D, Ahmed MS, Toner JP, Cook E, Diamond MP. Gonadotropin‐releasing hormone agonist pretreatment did not decrease postoperative adhesion formation after abdominal myomectomy in a randomized control trial. Fertility and Sterility 2009;91(5):1909‐13. - PubMed
De Falco 2006 {published data only}
    1. Falco M, Staibano S, D'Armiento FP, Mascolo M, Salvatore G, Busiello A. Preoperative treatment of uterine leiomyomas: clinical findings and expression of transforming growth factor‐beta3 and connective tissue growth factor. Journal of the Society for Gynecologic Investigation 2006;13(4):297‐300. - PubMed
Di Lieto 2005 {published data only}
    1. Lieto A, Falco M, Mansueto G, Rosa G, Pollio F, Staibano S. Preoperative administration of GnRH‐a plus tibolone to premenopausal women with uterine fibroids: evaluation of the clinical response, the immunohistochemical expression of PDGF, bFGF and VEGF and the vascular pattern. Steroids 2005;70(2):95‐102. - PubMed
Donnez 2014 {published data only}
    1. Donnez J, Vazquez F, Tomaszewski J, Nouri K, Bouchard P, Fauser BCJM, et al. the PEARL III and PEARL III extension study group. Long term treatment of uterine fibroids with ulipristal acetate. Fertility and Sterility 2014;10(6):1565‐73. - PubMed
Elzaher 2013 {published data only}
    1. Elzaher MA, Moawad A, Madkour WA, Ali M, Salah Eldin Abdel Hamid AM, Zaheer H. Does medical debulking with gonadotropin‐releasing hormone agonist facilitate vaginal hysterectomy with a moderate enlarged uterus? A randomised controlled study. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2013;169(2):326‐30. - PubMed
Ferrero 2016a {published data only}
    1. Ferrero S, Racca A, Tafi E, Alessandri F, Venturini PL, Maggiore LRU, et al. Ulipristal acetate before high complexity hysteroscopic myomectomy: a retrospective comparative study. Journal of Minimally Invasive Gynecology 2016;23(3):390‐5. - PubMed
Ferrero 2016b {published data only}
    1. Ferrero S, Racca A, Tafi E, Scala C, Alessandri F, Venturini PL, et al. Ulipristal acetate versus triptorelin prior to laparoscopic myomectomy: prospective study. Journal of Minimally Invasive Gynecology 2016;23(7 Suppl 1):S199.
Hasan 2014 {published data only}
    1. Hasan M, Nasir A, Saba E. Color Doppler misoprostol response study (CDMRS): an evaluation tool for patients awaiting myomectomy. Journal of Medical Ultrasound 2014;22(2):78‐82.
Hutsikava 2016 {published data only}
    1. Hutsikava L. The preoperative treatment of women with myoma of the uterus using ulipristal acetate. Gynecological Endocrinology 2016;32(Suppl 1):50.
Leone Roberti Maggiore 2014 {published data only}
    1. Leone Roberti Maggiore U, Scala C, Venturini PL, Ferrero S. Preoperative treatment with letrozole in patients undergoing laparoscopic myomectomy of large uterine myomas: a prospective non randomised study. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2014;181:157‐62. - PubMed
Mizutani 2005 {published data only}
    1. Mizutani T, Sugihara A, Honma H, Komura H, Nakamuro K, Terada N. Effect of steroid add‐back therapy on the proliferative activity of uterine leiomyoma cells under gonadotropin‐releasing hormone agonist therapy. Gynecological Endocrinology 2005;20(2):80‐3. - PubMed
Nakano 1998 {published data only}
    1. Nakano H, Kawasima M, Okada S, Igarashi T, Maejima M, Ogino M. The study of the effect of presurgical GnRH agonist treatment for women with uterine leiomyoma ‐ effect on the myoma volume and the operation. Japanese Journal of Fertility and Sterility 1998;43:289‐93.
Palomba 2001 {published data only}
    1. Palomba S, Massimiliano P, Affinito P, Carlo C, Zullo F, Nappi C. Effectiveness of short term administration of tibolone plus gonadotropin‐releasing hormone analogue on the surgical outcome of laparoscopic myomectomy. Fertility and Sterility 2001;75(2):429‐33. - PubMed
    1. Palomba S, Morelli M, Nola R, Santagata M, Oliverio A, Sena T, et al. Short‐term administration of tibolone plus GnRH analog before laparoscopic myomectomy. Journal of the American Association of Gynecologic Laparoscopists 2002;9(2):170‐4. - PubMed
Parsanezhad 2010 {published data only}
    1. Parsanezhad ME, Azmoon M, Alborzi S, Rajaeefard A, Zarei A, Kazerooni T, et al. A randomised controlled clinical trial comparing the effects of aromatase inhibitor (letrazole) and gonadotropin‐releasing hormone agonist (triptorelin) on uterine leiomyoma volume and hormonal status. Fertility and Sterility 2010;93(1):192‐8. - PubMed
Russo 1998 {published data only}
    1. Russo P, Ciolli P, Atlante M, Carico EE, Mancini R, Russo R, et al. Clinical use of leuprolide acetate depot in a group of gynecologic patients in the preoperative period. Minerva Ginecologica 1998;50(11):499‐502. - PubMed
Rutgers 1995 {published data only}
    1. Rutgers J, Spong C, Sinow R, Heiner J. Leuprolide acetate treatment and myoma arterial size. Obstetrics and Gynecology 1995;86(3):386‐8. - PubMed
Simon 2016 {published data only}
    1. Simon J, Catherino WH, Segars J, Blakesley R, Chan A, Sniukiene V, et al. First US‐based phase 3 study of ulipristal acetate (UPA) for symptomatic uterine fibroids (UF): results of VENUS‐1. Fertility and Sterility 2016;106(3):e376.
Tabatabai 2015 {published data only}
    1. Tabatabai A, Karimi‐Zarchi M, Meibodi B, Vaghefi M, Yazdian P, Zeidabadi M, et al. Effects of a single rectal dose of Misoprostol prior to abdominal hysterectomy in women with symptomatic leiomyoma: a randomised double blind clinical trial. Electronic Physician 2015;7(6):1372‐5. - PMC - 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 randomised evaluation. Fertility and Sterility 2006;85(4):1027‐31. - PubMed
Weeks 2000 {published data only}
    1. Weeks A, Duffy S, Walker J. A double‐blind randomised trial of leuprorelin acetate prior to hysterectomy for dysfunctional uterine bleeding. British Journal of Obstetrics and Gynaecology 2000;107(3):323‐8. - PubMed
    1. Weeks AD, Duffy SRG, Walker JJ. Uterine ultrasonographic changes with gondatrophin‐releasing hormone agonists. American Journal of Obstetrics and Gynecology 1999;180(1):8‐13. - PubMed
Ylikorkala 1995 {published data only}
    1. Ylikorkala O, Tiitinen A, Hulkko S, Kivinen S, Nummi S. Decrease in symptoms, blood loss and uterine size with nafarelin acetate before abdominal hysterectomy: a placebo‐controlled, double‐blind study. Human Reproduction 1995;10(6):1470‐4. - PubMed

References to studies awaiting assessment

Gambardella 1995 {published data only}
    1. Gambardella F, Capicotto V, Cuneo P, Daminani A, Proto M. Using analogous preoperative Gn‐RH in the treatment of symptomatic uterine leiomyomatosis [Uso preoperatorio degli analoghi del Gn‐RH nel trattamento della leiomiomatosi uterina sintomatica]. Giornarle Italiano di Ostetrica e Ginecologica 1995;11:658‐62.

References to ongoing studies

Bigatti 2014 {published data only}
    1. Bigatti G, Iemmello R, Desgro M, Pollini S, Santirocco M. Progesterone preoperative treatment before myomectomy with the Intrauterine Bigatti Shaver (IBS). Gynecological Surgery 2014;11(1 Suppl 1):119‐20.
NCT01873378 {unpublished data only}
    1. NCT01873378. GnRH agonist pretreatment in hysteroscopic myomectomy. clinicaltrials.gov/ct2/show/NCT01873378 (first received 1 June 2013).
NCT02288130 {unpublished data only}
    1. NCT02288130. Ulipristal acetate vs GnRHa prior to laparoscopic myomectomy (MYOMEX). clinicaltrials.gov/ct2/show/NCT02288130 (first received 6 November 2014).

Additional references

Baird 2003
    1. Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. American Journal of Obstetrics and Gynecology 2003;188(1):100‐7. - PubMed
Buttram 1981
    1. Buttram VC Jr, Reiter RC. Uterine leiomyomas: etiology, symptomatology, and management. Fertility and Sterility 1981;36(4):433‐45. - PubMed
Campo 2005
    1. Campo S, Campo V, Gambadauro P. Short term and long term results of resectoscopic myomectomy with and without pretreatment with GnRH analogs in premenopausal women. Acta Obstetricia et Gynecologica Scandinavica 2005;84(8):756‐60. - PubMed
Carls 2008
    1. Carls GS, Lee DW, Ozminkowski RJ, Wang S, Gibson TB, Stewart E. What are the total costs of surgical treatment for uterine fibroids?. Journal of Women's Health 2008;17(7):1119‐32. - PubMed
Chen 2011
    1. Chen I, Motan T, Kiddoo D. Gonadotropin‐releasing hormone agonist in laparoscopic myomectomy: systematic review and meta‐analysis of randomised controlled trials. Journal of Minimally Invasive Gynecology 2011;18(3):303‐9. - PubMed
Friedman 1990
    1. Friedman AJ, Lobel SM, Rein MS, Barbieri RL. Efficacy and safety considerations in women with uterine leiomyomas treated with gonadotrophin‐releasing hormone agonists: the estrogen window hypothesis. American Journal of Obstetrics and Gynecology 1990;163(4 Part 1):1114‐9. - PubMed
Geirsson 1993
    1. Geirsson RT. Intrauterine volume measurement techniques and uteroplacental growth. In: Chervenak FA, Isaacson GC, Campbell S editor(s). Ultrasound in Obstetrics and Gynecology. Boston: Little, Brown and Company, 1993:405‐12.
GRADEpro GDT 2015 [Computer program]
    1. McMaster University (developed by Evidence Prime). GRADEpro GDT. Version accessed prior to 18 July 2017. Hamilton (ON): McMaster University (developed by Evidence Prime), 2015.
Gurusamy 2016
    1. Gurusamy KS, Vaughan J, Fraser IS, Best LMJ, Richards T. Medical therapies for uterine fibroids ‐ a systematic review and network meta‐analysis of randomised controlled trials. PloS One 2016;11(2):e0149631. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Jacoby 2010
    1. Jacoby VL, Fujimoto VY, Guidice LC, Kupperman M, Washington AE. Racial and ethnic disparities in benign gynecologic conditions and associated surgeries. American Journal of Obstetrics and Gynecology 2010;202(6):514‐21. - PMC - PubMed
Jirecek 2004
    1. Jirecek S, Lee A, Pavo I, Crans G, Eppel W, Wenzl R. Raloxifene prevents the growth of uterine leiomyomas in premenopausal women. Fertility and Sterility 2004;81(1):132‐6. - PubMed
Jourdain 1996
    1. Jourdain O, Descamps P, Abusada N, Ventrillon E, Dallay D, Lansac J, et al. Treatment of fibromas. European Journal of Obstetrics, Gynecology, and Reproductive Biology 1996;66(2):99‐107. - PubMed
Kamath 2014
    1. Kamath MS, Kalampokas EE, Kalampokas TE. Use of GnRH analogues preoperatively for hysteroscopic resection of submucous fibroids: a systematic review and metaanalysis. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2014;177:11‐8. - PubMed
Kongnyuy 2014
    1. Kongnyuy EJ, Wiysonge CS. Interventions to reduce haemorrhage during myomectomy for fibroids. Cochrane Database of Systematic Reviews 2014, Issue 8. [DOI: 10.1002/14651858.CD005355.pub5] - DOI - PMC - PubMed
Matta 1989
    1. Matta WHM, Shaw RW, Nye M. Long‐term follow‐up of patients with uterine fibroids after treatment with the LHRH agonist buserelin. British Journal of Obstetrics and Gynaecology 1989;96(2):200‐6. - PubMed
Merrill 2008
    1. Merrill RM. Hysterectomy surveillance in the United States, 1997 to 2005. Medical Science Monitor 2008;14(1):CR24‐31. - PubMed
Moroni 2015
    1. Moroni RM, Martins WP, Ferriani RA, Vieria CS, Nastri CO, Candido Dos Reis FJ, et al. Add‐back therapy with GnRH analogues for uterine fibroids. Cochrane Database of Systematic Reviews 2015, Issue 3. [DOI: 10.1002/14651858.CD010854.pub2] - DOI - PMC - PubMed
Nagy 2014
    1. Nagy B, Timar G, Józwiak‐Hagymásy J, Kovács G, Merész G, Vámossy I, et al. The cost effectiveness of ulipristal acetate tablets in treating patients with moderate to severe symptoms of uterine fibroids. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2014;175:75‐81. - PubMed
Parazzini 1998
    1. Parazzini F, Vercellini P, Giorgi O, Pesole A, Ricci E, Crosignani PG. Efficacy of preoperative medical treatment in facilitating hysteroscopic endometrial resection, myomectomy and metroplasty: literature review. Human Reproduction (Oxford, England) 1998;13(9):2592‐7. - PubMed
Patel 2014
    1. Patel A, Malik M, Britten J, Cox J, Catherino WH. Alternative therapies in management of leiomyomas. Fertility and Sterility 2014;102(3):649‐55. - PubMed
Perino 1993
    1. Perino A, Chianchiano N, Petronio M, Cittadini E. Role of leuprolide acetate depot in hysteroscopic surgery: a controlled study. Fertility and Sterility 1993;59:507‐10. - PubMed
Pérez Lopez 2014
    1. Pérez‐López FR, Ornat L, Ceausu I, Depypere H, Erel CT, Lambrinoudaki I, et al. EMAS position statement: management of uterine fibroids. Maturitas 2014;79(1):106‐16. - PubMed
Stovall 1989
    1. Stovall TG. Rationale for the short‐term use of luteinising hormone‐releasing hormone analogues in the treatment of uterine myomata. Hormone Research 1989;32(Suppl 1):134‐6. - PubMed
Stovall 1991
    1. Stovall TG, Ling FW, Henry LC, Woodruff MR. A randomized trial evaluating leuprolide acetate before hysterectomy as a treatment for leiomyomas. American Journal of Obstetrics and Gynecology 1991;164(6 Pt 1):1420‐5. - PubMed
Tamaya 1985
    1. Tamaya T, Fujimoto J, Okada H. Comparison of cellular levels of steroid receptors in uterine leiomyomas and myometrium. Acta Obstetricia et Gynaecologica Scandinavica 1985;64(4):307‐9. - PubMed
Wallach 1992
    1. Wallach EE. Myomectomy. In: Thompson JD, Rock JA editor(s). Te Linde's Operative Gynaecology. 7th Edition. Philadelphia: Lippincott, 1992:647‐62.
West 1992
    1. West CP, Lumsden MA, Baird DT. Goserelin (Zoladex) in the treatment of fibroids. British Journal of Obstetrics and Gynaecology 1992;99(Suppl 7):27‐30. - PubMed
Williams 2012
    1. Williams ARW, Bergeron C, Barlow DH, Ferenczy A. Endometrial morphology after treatment of uterine fibroids with the selective progesterone receptor modulator, ulipristal acetate. International Journal of Gynecological Pathology 2012;31(6):556‐69. - PubMed
Wilson 1980
    1. Wilson EA, Yang F, Rees ED. Estradiol and progesterone binding in uterine leiomyomata and in normal uterine tissue. Obstetrics and Gynecology 1980;55(1):20‐4. - PubMed
Yang 2011
    1. Yang JH, Chen MJ, Chen DC, Chen CL, Ho HN, Yang YS. Impact of submucous fibroid on the severity of anemia. Fertility and Sterility 2011;95(5):1769‐72. - PubMed
Zakiyah 2017
    1. Zakiyah N, Asselt ADI, Postma MJ. Ulipristal acetate for pre‐operative treatment of moderate‐to‐severe uterine fibroids in women of reproductive age in the Netherlands: cost minimisation analysis and budget impact analysis. Journal of Medical Economics 2017;20(3):280‐7. - PubMed
Zhang 2014
    1. Zhang Y, Sun L, Guo Y, Cheng J, Wang Y, Fan S, et al. The impact of preoperative gonadotropin‐releasing hormone agonist treatment on women with uterine fibroids: a metaanalysis. Obstetrical & Gynecological Survey 2014;69(2):100‐8. - PubMed

References to other published versions of this review

Lethaby 2000
    1. Lethaby A, Vollenhoven B, Sowter M. Pre‐operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database of Systematic Reviews 2000, Issue 1. [DOI: 10.1002/14651858.CD000547] - DOI - PubMed
Lethaby 2001
    1. Lethaby A, Vollenhoven B, Sowter M. Pre‐operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database of Systematic Reviews 2001, Issue 1. [DOI: 10.1002/14651858.CD000547] - DOI - PubMed

MeSH terms