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Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age
Jeanette Tinggaard1, Rikke Beck Jensen1, Karin Sundberg2
1Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Insights
Growth hormone (GH) treatment significantly increased uterine and ovarian size in short, small-for-gestational-age (SGA) girls. Monitoring puberty and ovarian function is recommended due to potential alterations in development.
Area of Science:
- Pediatric Endocrinology
- Reproductive Medicine
- Growth Hormone Therapy
Background:
- Small-for-gestational-age (SGA) is associated with various health concerns.
- Growth hormone (GH) is used to treat short stature in children.
- The impact of GH on reproductive organ development in SGA girls requires further investigation.
Purpose of the Study:
- To evaluate the effects of GH treatment on ovarian and uterine morphology in short, prepubertal SGA girls.
- To assess changes in ovarian function and pubertal development during GH therapy.
Main Methods:
- A multinational, randomized controlled trial involving 18 Danish girls born SGA.
- One year of GH treatment followed by two years of randomized GH or IGF-I titration.
- Data collection included anthropometrics, reproductive hormones, and ultrasonographic examination over 36 months.
Main Results:
- Significant increases in uterine (64%) and ovarian (110%) volume observed during 3 years of GH treatment.
- Ovarian follicle visibility increased from 28% to 58% after one year of GH therapy.
- Anti-Müllerian hormone levels increased significantly, remaining within normal ranges; two girls experienced altered pubertal development or ovarian morphology.
Conclusions:
- GH treatment promotes significant growth of internal genitalia in SGA girls, maintaining normal size.
- Monitoring of pubertal development and ovarian function is crucial due to observed alterations in a subset of patients.
- Long-term reproductive outcomes following GH therapy in SGA girls remain to be determined.
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.
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