Jeanette Tinggaard1, Rikke Beck Jensen2, Karin Sundberg3, Niels Birkebæk4, Peter Christiansen1, Annie Ellermann5, Kirsten Holm6, Eva Mosfeldt Jeppesen7, Britta Kremke8, Pawel Marcinski9, Carsten Pedersen10, Nina Saurbrey7, Ebbe Thisted11, Katharina M Main1, Anders Juul1. 1. Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 2. Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: rikke.beck@dadlnet.dk. 3. Department of Fetal Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 4. Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark. 5. Department of Pediatrics, Holbæk Hospital, Holbæk, Denmark. 6. Department of Pediatrics, Nordsjællands Hospital, Hillerød, Denmark. 7. Department of Pediatrics, Herlev Hospital, Herlev, Denmark. 8. Department of Pediatrics, Randers Hospital, Randers, Denmark. 9. Department of Pediatrics, Vendsyssel Hospital Hjørring, Hjørring, Denmark. 10. Department of Pediatrics, Kolding Hospital, Kolding, Denmark. 11. Department of Pediatrics, Sønderborg Hospital, Sønderborg, Denmark.
Abstract
OBJECTIVE: To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. DESIGN: A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. SETTING: Not applicable. PATIENT(S): A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). INTERVENTION(S): One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated). MAIN OUTCOME MEASURE(S): Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. RESULT(S): Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. CONCLUSION(S): GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. CLINICAL TRIAL REGISTRATION NUMBER: EudraCT 2005-001507-19.
RCT Entities:
OBJECTIVE: To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. DESIGN: A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. SETTING: Not applicable. PATIENT(S): A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). INTERVENTION(S): One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated). MAIN OUTCOME MEASURE(S): Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. RESULT(S): Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. CONCLUSION(S): GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. CLINICAL TRIAL REGISTRATION NUMBER: EudraCT 2005-001507-19.
Authors: Robson Chacon Castoldi; Guilherme Akio Tamura Ozaki; Thiago Alves Garcia; Ines Cristina Giometti; Tatiana Emy Koike; Regina Celi Trindade Camargo; João Domingos Augusto Dos Santos Pereira; Carlos José Leopoldo Constantino; Mário Jefferson Quirino Louzada; José Carlos Silva Camargo Filho; William Dias Belangero Journal: Lasers Med Sci Date: 2019-06-15 Impact factor: 3.161