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

We discuss how growth hormone treatment of girls born small for gestational age appeared to normalize ovarian morphology and function, while the long-term effects of growth hormone treatment on adult reproductive function remain unknown.


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

Volume 102, Issue 6, Pages 1733-1741



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.


A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA.


Not applicable.


A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS).


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.


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.


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.

Read the full text at: http://www.fertstert.org/article/S0015-0282(14)02166-9/fulltext