Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age

Jeanette Tinggaard; Rikke Beck Jensen; Karin Sundberg; Niels Birkebæk; Peter Christiansen; Annie Ellermann; Kirsten Holm; Eva Mosfeldt Jeppesen; Britta Kremke; Pawel Marcinski; Carsten Pedersen; Nina Saurbrey; Ebbe Thisted; Katharina M Main; Anders Juul

doi:10.1016/j.fertnstert.2014.09.014

Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age

Jeanette Tinggaard, Rikke Beck Jensen, Karin Sundberg, Niels Birkebæk, Peter Christiansen, Annie Ellermann, Kirsten Holm, Eva Mosfeldt Jeppesen, Britta Kremke, Pawel Marcinski, Carsten Pedersen, Nina Saurbrey, Ebbe Thisted, Katharina M Main, Anders Juul

Department of Clinical Medicine

6 Citations (Scopus)

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.

Original language	English
Journal	Fertility and Sterility
Volume	102
Issue number	6
Pages (from-to)	1733-1741
Number of pages	9
ISSN	0015-0282
DOIs	https://doi.org/10.1016/j.fertnstert.2014.09.014
Publication status	Published - 1 Dec 2014

Keywords

Anti-Mullerian Hormone
Body Height
Child
Child, Preschool
Female
Human Growth Hormone
Humans
Infant, Small for Gestational Age
Insulin-Like Growth Factor I
Ovary
Reference Values
Sexual Maturation
Uterus

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10.1016/j.fertnstert.2014.09.014

http://www.fertstert.org/article/S0015028214021669/pdf

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Tinggaard, J., Jensen, R. B., Sundberg, K., Birkebæk, N., Christiansen, P., Ellermann, A., Holm, K., Jeppesen, E. M., Kremke, B., Marcinski, P., Pedersen, C., Saurbrey, N., Thisted, E., Main, K. M., & Juul, A. (2014). Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age. Fertility and Sterility, 102(6), 1733-1741. https://doi.org/10.1016/j.fertnstert.2014.09.014

Tinggaard, J, Jensen, RB, Sundberg, K, Birkebæk, N, Christiansen, P, Ellermann, A, Holm, K, Jeppesen, EM, Kremke, B, Marcinski, P, Pedersen, C, Saurbrey, N, Thisted, E, Main, KM & Juul, A 2014, 'Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age', Fertility and Sterility, vol. 102, no. 6, pp. 1733-1741. https://doi.org/10.1016/j.fertnstert.2014.09.014

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title = "Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age",

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-M{\"u}llerian 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.",

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author = "Jeanette Tinggaard and Jensen, {Rikke Beck} and Karin Sundberg and Niels Birkeb{\ae}k and Peter Christiansen and Annie Ellermann and Kirsten Holm and Jeppesen, {Eva Mosfeldt} and Britta Kremke and Pawel Marcinski and Carsten Pedersen and Nina Saurbrey and Ebbe Thisted and Main, {Katharina M} and Anders Juul",

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doi = "10.1016/j.fertnstert.2014.09.014",

language = "English",

volume = "102",

pages = "1733--1741",

journal = "Sexuality, Reproduction and Menopause",

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TY - JOUR

T1 - Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age

AU - Tinggaard, Jeanette

AU - Jensen, Rikke Beck

AU - Sundberg, Karin

AU - Birkebæk, Niels

AU - Christiansen, Peter

AU - Ellermann, Annie

AU - Holm, Kirsten

AU - Jeppesen, Eva Mosfeldt

AU - Kremke, Britta

AU - Marcinski, Pawel

AU - Pedersen, Carsten

AU - Saurbrey, Nina

AU - Thisted, Ebbe

AU - Main, Katharina M

AU - Juul, Anders

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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.

AB - 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.

KW - Anti-Mullerian Hormone

KW - Body Height

KW - Child

KW - Child, Preschool

KW - Female

KW - Human Growth Hormone

KW - Humans

KW - Infant, Small for Gestational Age

KW - Insulin-Like Growth Factor I

KW - Ovary

KW - Reference Values

KW - Sexual Maturation

KW - Uterus

U2 - 10.1016/j.fertnstert.2014.09.014

DO - 10.1016/j.fertnstert.2014.09.014

M3 - Journal article

C2 - 25439809

SN - 1546-2501

VL - 102

SP - 1733

EP - 1741

JO - Sexuality, Reproduction and Menopause

JF - Sexuality, Reproduction and Menopause

IS - 6

ER -

Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age

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Keywords

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