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Meta-Analysis
. 2015 Mar 20;2015(3):CD010854.
doi: 10.1002/14651858.CD010854.pub2.

Add-back therapy with GnRH analogues for uterine fibroids

Rafael M Moroni  1 , Wellington P Martins, Rui A Ferriani, Carolina S Vieira, Carolina O Nastri, Francisco José Candido Dos Reis, Luiz Gustavo Brito
Affiliations
Meta-Analysis

Add-back therapy with GnRH analogues for uterine fibroids

Rafael M Moroni et al. Cochrane Database Syst Rev. .

Abstract

Background: Uterine fibroids (also known as leiomyomas) are the most common benign pelvic tumours among women. They may be asymptomatic, or may be associated with pelvic symptoms such as bleeding and pain. Medical treatment of this condition is limited and gonadotropin-releasing hormone (GnRH) analogues are the most effective agents. Long-term treatment with such agents, however, is restricted due to their adverse effects. The addition of other medications during treatment with GnRH analogues, a strategy known as add-back therapy, may limit these side effects. There is concern, however, that add-back therapy may also limit the efficacy of the GnRH analogues and that it may not be able to completely prevent their adverse effects.

Objectives: To assess the short-term (within 12 months) effectiveness and safety of add-back therapy for women using GnRH analogues for uterine fibroids associated with excessive uterine bleeding, pelvic pain, or urinary symptoms.

Search methods: We searched electronic databases including the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, CENTRAL, MEDLINE, PubMed, EMBASE, LILACS, CINAHL, PsycINFO; and electronic registries of ongoing trials including ClinicalTrials.gov, Current Controlled Trials, World Health Organization (WHO) International Clinical Trials Registry Platform. All searches were from database inception to 16 June 2014.

Selection criteria: Randomized controlled trials (RCTs) that included women with uterine fibroids experiencing irregular or intense uterine bleeding, cyclic or non-cyclic pelvic pain, or urinary symptoms, and that compared treatment with a GnRH analogue plus add-back therapy versus a GnRH analogue alone or combined with placebo were eligible for inclusion.

Data collection and analysis: Two authors independently reviewed the identified titles and abstracts for potentially eligible records. Two review authors reviewed eligible studies and independently extracted data. Two authors independently assessed the studies' risk of bias. They assessed the quality of the evidence using GRADE criteria.

Main results: Fourteen RCTs were included in the review. Data were extracted from 12 studies (622 women). The primary outcome was quality of life (QoL).Add-back therapy with medroxyprogesterone (MPA): no studies reported QoL or uterine bleeding. There was no evidence of effect in relation to bone mass (standardized mean difference (SMD) 0.38, 95% confidence interval (CI) -0.62 to 1.38, 1 study, 16 women, P = 0.45, low quality evidence) and MPA was associated with a larger uterine volume (mean difference (MD) 342.19 cm(3), 95% CI 77.58 to 606.80, 2 studies, 32 women, I(2) = 0%, low quality evidence).Tibolone: this was associated with a higher QoL but the estimate was imprecise and the effect could be clinically insignificant, small or large (SMD 0.47, 95% CI 0.09 to 0.85, 1 study, 110 women, P = 0.02, low quality evidence). It was also associated with a decreased loss of bone mass, which could be insignificant, small or moderate (SMD 0.36, 95% CI 0.03 to 0.7, 3 studies, 160 women, I(2) = 7%, moderate quality evidence). Tibolone may, however, have been associated with larger uterine volumes (MD 23.89 cm(3), 95% CI= 8.13 to 39.66, 6 studies, 365 women, I(2) = 0%, moderate quality evidence) and more uterine bleeding (results were not combined but three studies demonstrated greater bleeding with tibolone while two other studies demonstrated no bleeding in either group). Four studies (268 women; not pooled owing to extreme heterogeneity) reported a large benefit on vasomotor symptoms in the tibolone group.Raloxifene: there was no evidence of an effect on QoL (SMD 0.11, 95% CI -0.57 to 0.34, 1 study, 74 women, P = 0.62, low quality evidence), while there was a beneficial impact on bone mass (SMD 1.01, 95% CI 0.57 to 1.45, 1 study, 91 women, P < 0.00001, low quality evidence). There was no clear evidence of effect on uterine volume (MD 27.1 cm(3), 95% CI -17.94 to 72.14, 1 study, 91 women, P = 0.24, low quality evidence), uterine bleeding or severity of vasomotor symptoms (MD 0.2 hot flushes/day, 95% CI -0.34 to 0.74, 1 study, 91 women, P = 0.46, low quality evidence).Estriol: no studies reported QoL, uterine size, uterine bleeding or vasomotor symptoms. Add-back with estriol may have led to decreased loss of bone mass, from results of a single study (SMD 3.93, 95% CI 1.7 to 6.16, 1 study, 12 women, P = 0.0005, low quality evidence).Ipriflavone: no studies reported QoL, uterine size or uterine bleeding. Iproflavone was associated with decreased loss of bone mass in a single study (SMD 2.71, 95% CI 2.14 to 3.27, 1 study, 95 women, P < 0.00001, low quality evidence); there was no evidence of an effect on the rate of vasomotor symptoms (RR 0.67, 95% Cl 0.44 to 1.02, 1 study, 95 women, P = 0.06, low quality evidence).Conjugated estrogens: no studies reported QoL, uterine size, uterine bleeding or vasomotor symptoms. One study suggested that adding conjugated estrogens to GnRH analogues resulted in a larger decrease in uterine volume in the placebo group (MD 105.2 cm(3), 95% CI 27.65 to 182.75, 1 study, 27 women, P = 0.008, very low quality evidence).Nine of 12 studies were at high risk of bias in at least one domain, most commonly lack of blinding. All studies followed participants for a maximum of six months. This short-term follow-up is usually insufficient to observe any significant effect of the treatment on bone health (such as the occurrence of fractures), limiting the findings.

Authors' conclusions: There was low or moderate quality evidence that tibolone, raloxifene, estriol and ipriflavone help to preserve bone density and that MPA and tibolone may reduce vasomotor symptoms. Larger uterine volume was an adverse effect associated with some add-back therapies (MPA, tibolone and conjugated estrogens). For other comparisons, outcomes of interest were not reported or study findings were inconclusive.

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Conflict of interest statement

The authors declare no conflicts of interest.

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: 2 GnRH‐a + tibolone versus GnRH‐a ± placebo, outcome: 2.1 Quality of life.
5
5
Forest plot of comparison: 3 GnRH‐a + raloxifene versus GnRH‐a ± placebo, outcome: 3.1 Quality of life.
1.1
1.1. Analysis
Comparison 1 GnRH‐a + medroxyprogesterone acetate versus GnRH‐a ± placebo, Outcome 1 Bone Density.
1.2
1.2. Analysis
Comparison 1 GnRH‐a + medroxyprogesterone acetate versus GnRH‐a ± placebo, Outcome 2 Uterine Size.
1.3
1.3. Analysis
Comparison 1 GnRH‐a + medroxyprogesterone acetate versus GnRH‐a ± placebo, Outcome 3 Rate of Vasomotor Symptoms.
2.1
2.1. Analysis
Comparison 2 GnRH‐a + tibolone versus GnRH‐a ± placebo, Outcome 1 Quality of Life.
2.2
2.2. Analysis
Comparison 2 GnRH‐a + tibolone versus GnRH‐a ± placebo, Outcome 2 Bone Density.
2.3
2.3. Analysis
Comparison 2 GnRH‐a + tibolone versus GnRH‐a ± placebo, Outcome 3 Uterine Size.
2.4
2.4. Analysis
Comparison 2 GnRH‐a + tibolone versus GnRH‐a ± placebo, Outcome 4 Uterine Bleeding.
2.5
2.5. Analysis
Comparison 2 GnRH‐a + tibolone versus GnRH‐a ± placebo, Outcome 5 Severity of Vasomotor Symptoms.
2.6
2.6. Analysis
Comparison 2 GnRH‐a + tibolone versus GnRH‐a ± placebo, Outcome 6 Rate of Vasomotor Symptoms.
3.1
3.1. Analysis
Comparison 3 GnRH‐a + raloxifene versus GnRH‐a ± placebo, Outcome 1 Quality of Life.
3.2
3.2. Analysis
Comparison 3 GnRH‐a + raloxifene versus GnRH‐a ± placebo, Outcome 2 Bone Density.
3.3
3.3. Analysis
Comparison 3 GnRH‐a + raloxifene versus GnRH‐a ± placebo, Outcome 3 Uterine Size.
3.4
3.4. Analysis
Comparison 3 GnRH‐a + raloxifene versus GnRH‐a ± placebo, Outcome 4 Uterine Bleeding.
3.5
3.5. Analysis
Comparison 3 GnRH‐a + raloxifene versus GnRH‐a ± placebo, Outcome 5 Severity of Vasomotor Symptoms (No. of hot flashes per day).
4.1
4.1. Analysis
Comparison 4 GnRH‐a + estriol versus GnRH‐a ± placebo, Outcome 1 Bone Density.
5.1
5.1. Analysis
Comparison 5 GnRH‐a + ipriflavone versus GnRH‐a ± placebo, Outcome 1 Bone Density.
5.2
5.2. Analysis
Comparison 5 GnRH‐a + ipriflavone versus GnRH‐a ± placebo, Outcome 2 Rate of Vasomotor Symptoms.
6.1
6.1. Analysis
Comparison 6 GnRH‐a + conjugated estrogens versus GnRH‐a ± placebo, Outcome 1 Uterine s ize .
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Carr 1993 {published and unpublished data}
    1. Carr BR, Breslau NA, Peng N, Adams‐Huet B, Bradshaw KD, Steinkampf MP. Effect of gonadotropin‐releasing hormone agonist and medroxyprogesterone acetate on calcium metabolism: A prospective, randomized, double‐blind, placebo‐controlled, crossover trial. Fertility and Sterility 2003;80(5):1216‐23. - PubMed
    1. Carr BR, Marshburn PB, Weatherall PT, Bradshaw KD, Breslau NA, Byrd W, et al. An evaluation of the effect of gonadotropin‐releasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: A prospective, randomized, double blind, placebo‐ controlled, crossover trial. Journal of Clinical Endocrinology and Metabolism 1993;76(5):1217‐23. - PubMed
Daniels 2002 {published data only (unpublished sought but not used)}
    1. Daniels A, Pike M, Daniels J, Spicer D. Treatment with the GnRH agonist (GnRHa) deslorelin (D) and low‐dose add‐back estradiol (E2) is effective in reducing pain, bleeding and uterine volume(UV) while maintaining bone mineral density (BMD) in women with symptomatic uterine fibroids (UF). Fertility and Sterility 2002;78(3 Suppl 1):S65‐6.
DiLieto 2005 {published data only}
    1. Falco M, Staibano S, D'Armiento FP, Mascolo, M, Salvatore G, Busiello A, et al. 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):297‐303. - PubMed
    1. Falco M, Staibano S, Pollio F, Salvatore G, Pontillo M, Ciociola F, Mansueto G. Expression of proliferating cell nuclear antigen and bcl‐2 during a pseudomenopausal state induced by presurgical treatment of uterine leiomyomas with gonadotropin‐releasing hormone analogues plus tibolone. International Journal of Gynecological Pathology 2005;24(3):286‐91. - PubMed
    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
Espejo 1999 {published data only (unpublished sought but not used)}
    1. Espejo M, Espejo A, Tomas F, Gallego A, Santonja J. Add‐back therapy of uterine fibroids with tibolone and goserelin. European Journal of Obstetrics, Gynecology, and Reproductive Biology 1999;86:S19.
Friedman 1988 {published data only}
    1. Friedman AJ, Barbieri RL, Doubilet PM, Fine C, Schiff I. A randomized, double‐blind trial of a gonadotropin releasing‐hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri. Fertility and Sterility 1988;49(3):404‐9. - PubMed
Gocmen 2002 {published data only (unpublished sought but not used)}
    1. Gocmen A, Hamdi Kara I, Karaca M. The effects of add‐back therapy with tibolone on myoma uteri. Clinical and Experimental Obstetrics and Gynecology 2002;29(3):222‐4. - PubMed
    1. Gocmen A, Kara IH, Karaca M. The effect of add‐back treatment with tibolone on patients with myoma uteri treated with triptorelin. Human Reproduction 1999;14(Suppl 1):273.
Morris 2008 {published and unpublished data}
    1. Morris EP. A placebo controlled, randomised, double blind study of tibolone as "add‐back therapy" in conjunction with a gonadotrophin‐releasing hormone analogue in the treatment of uterine fibroids. Thesis ‐ Doctor of Medicine ‐ University of London 2001.
    1. Morris EP, Rymer J, Robinson J, Fogelman I. Efficacy of tibolone as "add‐back therapy" in conjunction with a gonadotropin‐releasing hormone analogue in the treatment of uterine fibroids. Fertility and Sterility 2008;89(2):421‐8. - PubMed
Nakayama 1999 {published data only (unpublished sought but not used)}
    1. Nakayama H, Yano T, Sagara Y, Kikuchi A, Ando K, Wang Y, et al. Estriol add‐back therapy in the long‐acting gonadotropin‐releasing hormone agonist treatment of uterine leiomyomata. Gynecological Endocrinology 1999;13(6):382‐9. - PubMed
Palomba 1998 {published data only (unpublished sought but not used)}
    1. Palomba S, Affinito P, Tommaselli GA, Nappi C. A clinical trial of the effects of tibolone administered with gonadotropin‐releasing hormone analogues for the treatment of uterine leiomyomata. Fertility and Sterility 1998;70(1):111‐8. - PubMed
Palomba 2001 {published data only (unpublished sought but not used)}
    1. Palomba S, Pellicano M, 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
Palomba 2002 {published data only}
    1. Palomba S, Orio F Jr, Morelli M, Russo T, Pellicano M, Nappi C, et al. Raloxifene administration in women treated with gonadotropin‐releasing hormone agonist for uterine leiomyomas: effects on bone metabolism. Journal of Clinical Endocrinology and Metabolism 2002;87(10):4476‐81. - PubMed
    1. Palomba S, Orio F Jr, Russo T, Falbo A, Amati A, Zullo F. Gonadotropin‐releasing hormone agonist with or without raloxifene: effects on cognition, mood, and quality of life. Fertility and Sterility 2004;82(2):480‐2. - PubMed
    1. Palomba S, Russo T, Orio F Jr, Tauchmanova, L, Zupi E, Panici PLB, et al. Effectiveness of combined GnRH analogue plus raloxifene administration in the treatment of uterine leiomyomas: a prospective, randomized, single‐blind, placebo‐controlled clinical trial. Human Reproduction 2002;17(12):3213‐9. - PubMed
Palomba 2008 {published data only (unpublished sought but not used)}
    1. Palomba S, Orio F Jr, Falbo A, Oppedisano R, Tolino A, Zullo F. Tibolone reverses the cognitive effects caused by leuprolide acetate administration, improving mood and quality of life in patients with symptomatic uterine leiomyomas. Fertility and Sterility 2008;90(1):165‐73. - PubMed
Sherwin 1996 {published data only (unpublished sought but not used)}
    1. Sherwin BB, Tulandi T. 'Add‐back' estrogen reverses cognitive deficits induced by a gonadotropin‐releasing hormone agonist in women with leiomyomata uteri. Journal of Clinical Endocrinology and Metabolism 1996;81(7):2545‐9. - PubMed
Somekawa 2001 {published data only (unpublished sought but not used)}
    1. Somekawa Y, Chiguchi M, Ishibashi T, Wakana K, Aso T. Efficacy of ipriflavone in preventing adverse effects of leuprolide. Journal of Clinical Endocrinology and Metabolism 2001;86(7):3202‐6. - PubMed

References to studies excluded from this review

Alfonso 1998 {published data only}
    1. Alfonso R, Giannelli L, Biase S, Trojano V. Bone mass changes in patients treated for 6 months with GnRH analogues associated with a low dose of ERT as 'add‐back' therapy. [Modificazioni della massa ossea in pazienti trattate per 6 mesi con GnRH analogo associato a HRT a basse dosi come terapia 'Add‐back']. Archivio di Ostetricia e Ginecologia 1998;7(1):13‐6.
Benagiano 1990 {published data only}
    1. Benagiano G, Morini A, Aleandri V, Piccinno F, Primiero FM, Abbondante G, Elkind Hirsch K. Sequential Gn‐RH superagonist and medroxyprogesterone acetate treatment of uterine leiomyomata. International Journal of Gynaecology & Obstetrics 1990;33(4):333‐43. - PubMed
Caird 1997 {published data only}
    1. Caird LE, West CP, Lumsden MA, Hannan WJ, Gow, SM. Medroxyprogesterone acetate with Zoladex for long‐term treatment of fibroids: Effects on bone density and patient acceptability. Human Reproduction 1997;12(3):436‐40. - PubMed
Friedman 1994 {published data only}
    1. Friedman AJ, Daly M, Juneau‐Norcross M, Gleason R, Rein MS, Leboff M. Long‐term medical therapy for leiomyomata uteri: a prospective, randomized study of leuprolide acetate depot plus either oestrogen—progestin or progestin ‘add‐back’ for 2 years. Human Reproduction 1994;9(9):1618‐25. - PubMed
Ishimaru 1995 {published data only}
    1. Ishimaru T, Samejima T, Masuzaki H. GnRHa and steroid add‐back therapy for uterine myoma. International Journal of Gynaecology and Obstetrics 1995;48(2):221. - PubMed
Ivanov 1998 {published data only}
    1. Ivanov S. The use of Ovestin to overcome the side effects of treatment with GnRH agonists (Zoladex) [Izpolzvane na Ovestin pri preodoliavane na stranichnite efekti ot lechenieto s GTPKh agonisti (Zoladeks)]. Akusherstvo i ginekologiia 1998;37(4):25‐6. - PubMed
Lindsay 1996 {published and unpublished data}
    1. Lindsay PC, Shaw RW, Bennink HJ, Kicovic P. The effect of add‐back treatment with tibolone (Livial) on patients treated with the gonadotropin‐releasing hormone agonist triptorelin (Decapeptyl). Fertility and Sterility 1996;65(2):342‐8. - PubMed
Maheux 1992 {published data only}
    1. Maheux R, Lemay A. Treatment of peri‐menopausal women: potential long‐term therapy with a depot GnRH agonist combined with hormonal replacement therapy. British Journal of Obstetrics and Gynaecology 1992;99 Suppl 7:13‐7. - PubMed
Mukherjee 1996 {published data only (unpublished sought but not used)}
    1. Mukherjee T, Barad D, Turk R, Freeman R. A randomized, placebo‐controlled study on the effect of cyclic intermittent etidronate therapy on the bone mineral density changes associated with six months of gonadotropin‐releasing hormone agonist treatment. American Journal of Obstetrics and Gynecology 1996;175(1):105‐9. - PubMed
Scialli 1995 {published data only}
    1. Scialli AR, Jestila KJ. Sustained benefits of leuprolide acetate with or without subsequent medroxyprogesterone acetate in the nonsurgical management of leiomyomata uteri. Fertility and Sterility 1995;64(2):313‐20. - PubMed
Somekawa 1999 {published data only}
    1. Somekawa Y, Chigughi M, Harada M, Ishibashi T. Use of vitamin K2 (menatetrenone) and 1,25‐dihydroxyvitamin D3 in the prevention of bone loss induced by leuprolide. Journal of Clinical Endocrinology and Metabolism 1999;84(8):2700‐4. - PubMed

References to studies awaiting assessment

Ingrassia 1994 {published data only}
    1. Ingrassia I, Calzolari S, Santoni S, Tondi M. Possible role of LH‐RH analog and oral contraceptive binding in the treatment of uterine leiomyoma. Giornale Italiano di Ostetricia e Ginecologia 1994;16(1):21‐3.
Opala 1997 {published data only}
    1. Opala T, Pawelczyk L. Bone mineral density evaluation in women treated with GnRH agonists for leiomyomata and receiving Mercilon "add‐back" therapy. Osteoporosis International 1997;7(2):not informed.

Additional references

Borgfeldt 2000
    1. Borgfeldt C, Andolf E. Transvaginal ultrasonographic findings in the uterus and the endometrium: low prevalence of leiomyoma in a random sample of women age 25–40 years. Acta Obstetricia et Gynecologica Scandinavica 2000;79(3):202‐7. - PubMed
Bozzini 2004
    1. Bozzini N, Messina ML, Borsari R, Hilário SG, Pinotti JA. Comparative study of different dosages of goserelin in size reduction of myomatous uteri. The Journal of the American Association of Gynecologic Laparoscopists 2004;11:462‐3. - PubMed
Cheung 2011
    1. Cheung W, Borawski D. Lower tract urinary symptoms in patients with uterine myomas. International Urogynecology Journal and Pelvic Floor Dysfunction 2011;22 Suppl 2:1309‐10.
Cohen 1988
    1. Cohen J. Statistical Power Analysis for the Behavioral Sciences. Hillsdale, NJ: Erlbaum Associates, 1988.
Costantini 1990
    1. Costantini S, Anserini P, Valenzano M, Remorgida V, Venturini PL, Cecco L. Luteinizing hormone‐releasing hormone analogue therapy of uterine fibroid: analysis of results obtained with buserelin administered intranasally and goserelin administered subcutaneously as a monthly depot. European Journal of Obstetrics, Gynecology, and Reproductive Biology 1990;37(1):63‐9. - PubMed
Day Baird 2003
    1. Day Baird D, 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;188:100‐7. - PubMed
Flake 2002
    1. Flake GP, Andersen J, Dixon D. Etiology and pathogenesis of uterine leiomyomas: a review. Environmental Health Perspectives 2003;111(8):1037‐54. - PMC - PubMed
Friedman 1987
    1. Friedman AJ, Barbieri RL, Benacerraf BR, Schiff I. Treatment of leiomyomata with intranasal or subcutaneous leuprolide, a gonadotropin‐releasing hormone agonist. Fertility and Sterility 1987;48(4):560‐4. - PubMed
Friedman 1991
    1. Friedman AJ, Hoffman DI, Comite F, Browneller RW, Miller JD. Treatment of leiomyomata uteri with leuprolide acetate depot: A double‐blind, placebo‐controlled, multicenter study. Obstetrics and Gynecology 1991;77(5):720‐5. - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Higham 1990
    1. Higham JM, O'Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. British Journal of Obstetrics and Gynaecology 1990;97(8):734‐9. - PubMed
Islam 2013
    1. Islam MS, Protic O, Giannubilo SR, Toti P, Tranquilli AL, Petraglia F, et al. Uterine leiomyoma: available medical treatments and new possible therapeutic options. Journal of Clinical Endocrinology and Metabolism 2013;98(3):921‐34. - PubMed
Lethaby 2011
    1. Lethaby A, Vollenhoven B. Fibroids (uterine myomatosis, leiomyomas). Clinical Evidence (Online) 2011;pii:0814.
Lippman 2003
    1. Lippman SA, Warner M, Samuels S, Olive D, Vercellini P, Eskenazi B. Uterine fibroids and gynecologic pain symptoms in a population‐based study. Fertility and Sterility 2003;80:1488‐94. - PubMed
Lumsden 1998
    1. Lumsden MA, Wallace EM. Clinical presentation of uterine fibroids. Baillière's Clinical Obstetrics and Gynaecology 1998;12(2):177‐95. - PubMed
Palomba 1999
    1. Palomba S, Affinito P, Carlo C, Bifulco G, Nappi C. Long term administration of tibolone plus gonadotropin‐releasing hormone agonist for the treatment of uterine leiomyomas: effectiveness and effects on vasomotor symptoms, bone mass and lipid profiles. Fertility and Sterility 1999;72(5):889‐95. - PubMed
Palomba 2004
    1. Palomba S, Orio F Jr, Russo T, Falbo A, Cascella T, Doldo P, et al. Long‐term effectiveness and safety of GnRH agonist plus raloxifene administration in women with uterine leiomyomas.. Human Reproduction 2004;19(6):1308‐14. - PubMed
Perry 1996
    1. Perry CM, Brogden RN. Goserelin. Drugs 1996;51(2):319‐46. - PubMed
Sankaran 2008
    1. Sankaran S, Manyonda I. Medical management of fibroids. Best Practice & Research. Clinical Obstetrics & Gynaecology 2008;22(4):655‐76. - PubMed
Schlaff 1989
    1. Schlaff WD, Zerhouni EA, Huth JA, Chen J, Damewood MD, Rock JA. A placebo‐controlled trial of a depot gonadotropin‐releasing hormone analogue (leuprolide) in the treatment of uterine leiomyomata. Obstetrics and Gynecology 1989;74(6):856‐62. - PubMed
Shaw 1972
    1. Shaw ST Jr, Aaronson DE, Moyer DL. Quantitation of menstrual blood loss—further evaluation of the alkaline hematin method. Contraception 1972;5(6):497‐513. - PubMed
Sunkara 2010
    1. Sunkara SK, Khairy M, El‐Toukhy T, Khalaf Y, Coomarasamy A. The effect of intramural fibroids without uterine cavity involvement on the outcome of IVF treatment: a systematic review and meta‐analysis. Human Reproduction 2010;25(2):418‐29. - PubMed
Wegienka 2003
    1. Wegienka G, Baird DD, Hertz‐Picciotto I, Harlow SD, Steege JF, Hill MC. Self‐reported heavy bleeding associated with uterine leiomyomata. Obstetrics and Gynecology 2003;101:431‐7. - PubMed
Williams 1990
    1. Williams IA, Shaw RW. Effect of nafarelin on uterine fibroids measured by ultrasound and magnetic resonance imaging. European Journal of Obstetrics, Gynecology, and Reproductive Biology 1990;34:111‐7. - PubMed

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