Background: The flare-up effect of GnRH analogues may cause transient uterine bleeding in girls affected with idiopathic central precocious puberty (ICPP). Aims: To assess the incidence of endometrial bleeding and verify whether pretreatment with cyproterone acetate could counteract it. Methods: Fifty-four girls affected by ICPP were divided into 2 groups. The first group (30 girls) was treated with triptorelin (3.75 mg, i.m. injection) every 28 days. The second group (24 girls) was treated with cyproterone acetate and triptorelin: cyproterone acetate (50 mg/m2) was administered every day for 8 weeks, and triptorelin (3.75 mg) was commenced 4 weeks after starting the cyproterone, then the intramuscular injection of triptorelin was repeated every 28 days. Results: Eight of 54 girls (15%) had mild withdrawal bleeding. There were no differences in incidence between groups 1 and 2. Girls with pubertal uterus at pelvic ultrasound had a higher incidence of uterine bleeding than girls with infantile uterus (25 vs. 7%), but this difference was not significant. Conclusion: Co-administration of cyproterone acetate and GnRH analogues does not significantly decrease the incidence of uterine bleeding.

Keywords:
Precocious puberty, females, GnRH analogue, Cyproterone acetate, Flare-up effect
1.
Partsch CJ, Sippell WG: Treatment of central precocious puberty. Best Pract Res Clin Endocrinol Metab 2002;16:165–189.
2.
Carel JC, Blumberg J, Seymour C, Adamsbaum C, Lahlou N: Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty. Eur J Endocrinol 2006;154:119–124.
3.
Conn PM: The molecular basis of gonadotropin-releasing hormone action. Endocr Rev 1986;7:3–10.
4.
Yeshaya A, Kauschansky A, Orvieto R, Varsano I, Nussinovitch M, Ben-Rafael Z: Prolonged vaginal bleeding during central precocious puberty therapy with a long-acting gonadotropin-releasing hormone agonist. Acta Obstet Gynecol Scand 1998;77:327–329.
5.
Dattani MT, Hindmarsh PC: Normal and abnormal puberty; in Brook CGD, Clayton PE, Brown RS (eds): Clinical Pediatric Endocrinology. Malden, Blackwell, 2005, pp 183–210.
6.
Mul D, Hughes IA: The use of GnRH agonists in precocious puberty. Eur J Endocrinol 2008;159(suppl 1):S3–S8.
7.
Denmeade SR, Isaacs JT: Androgen deprivation strategies in the treatment of advanced prostate cancer; in Kufe DW, Pollock RE, Weichselbaum RR, Bast RC Jr, Gansler TS, Holland JF, Frei E III (eds): Cancer Medicine. Hamilton, BC Decker, 2003.
8.
McEwen BS: Endocrine effects on the brain and their relationship to behavior; in Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD (eds): Basic Neurochemistry. Molecular, Cellular and Medical Aspects. Philadelphia, Lippincott Williams & Wilkins, 1999.
9.
Lahlou N, Carel JC, Chaussain JL, Roger M: Pharmacokinetics and pharmacodynamics of GnRH agonists: clinical implications in pediatrics. J Pediatr Endocrinol Metab 2000;13(suppl 1):723–737.
10.
Garel L, Dubois J, Grignon A, Filiatrault D, Van Vliet G: US of the pediatric female pelvis: a clinical perspective. Radiographics 2001;21:1393–1407.
11.
Greulich WW, Pyle SI: Radiographic Atlas of Skeletal Development of the Hand and Wrist. Stanford, Stanford University Press, 1959.
12.
Comite F, Cutler GB Jr, Rivier J, Vale WW, Loriaux DL, Crowley WF Jr: Short-term treatment of idiopathic precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. A preliminary report. N Engl J Med 1981;305:1546–1550.
13.
Luder AS, Holland FJ, Costigan DC, Jenner MR, Wielgosz G, Fazekas AT: Intranasal and subcutaneous treatment of central precocious puberty in both sexes with a long-acting analog of luteinizing hormone-releasing hormone. J Clin Endocrinol Metab 1984;58:966–972.
14.
Chaussain JL, Roger M, Couprie C, Lahlou N, Canlorbe P: Treatment of precocious puberty with a long-acting preparation of D-Trp6-LHRH. Horm Res 1987;28:155–163.
15.
Carel JC, Lahlou N, Jaramillo O, Montauban V, Teinturier C, Colle M, Lucas C, Chaussain JL: Treatment of central precocious puberty by subcutaneous injections of leuprorelin 3-month depot (11.25 mg). J Clin Endocrinol Metab 2002;87:4111–4116.
16.
Mericq GM, Youlton RR, Willshaw ZM: Effectiveness of leuprolide acetate therapy every three months in central precocious puberty. Rev Med Child 2006;134:821–826.
17.
Liang Y, Wei H, Zhang J, Hou L, Luo X: Efficacy of subcutaneous administration of gonadotropin-releasing hormone agonist on idiopathic central precocious puberty. J Huazhong Univ Sci Technolog Med Sci 2006;26:558–561.
18.
Mahler C, Verhelst J, Denis L: Clinical pharmacokinetics of the antiandrogens and their efficacy in prostate cancer. Clin Pharmacokinet 1998;34:405–417.
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