ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume: 14 Issue: 2 Year: 2022
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Turkish Society for Pediatric Endocrinology and Diabetes
Efficacy and Safety of Letrozole in the Management of Constitutional Delay in Growth and Puberty: A Systematic Review and Meta-analysis [J Clin Res Pediatr Endocrinol]
J Clin Res Pediatr Endocrinol. 2022; 14(2): 131-144 | DOI: 10.4274/jcrpe.galenos.2021.2021.0169

Efficacy and Safety of Letrozole in the Management of Constitutional Delay in Growth and Puberty: A Systematic Review and Meta-analysis

Deep Dutta1, Rajiv Singla2, Vineet Surana3, Meha Sharma4
1CEDAR Superspeciality Clinics, Department of Endocrinology, New Delhi, India
2Kalpavriksh Superspeciality Healthcare, Department of Endocrinology, New Delhi, India
3Manipal Hospitals, Department of Endocrinology, New Delhi, India
4CEDAR Superspeciality Clinics, Department of Rheumatology, New Delhi, India

No meta-analysis is available which has analysed the role of letrozole in constitutional delay in growth and puberty (CDGP). Electronic databases were searched for randomized controlled trials (RCTs) involving children with CDGP receiving letrozole. Primary outcomes were changes in predicted adult height (PAH) and pubertal progression. Secondary outcomes were alterations in bone age (BA), hormonal markers of puberty, bone mineral density and side-effects. One hundred-thirty articles were reviewed, from which seven RCTs which fulfilled all criteria were analysed. Letrozole was superior to placebo [mean difference (MD) 4.63 cm (95% confidence interval (CI): 3.90-5.36); p<0.01; I2=0%] but not testosterone [MD: 2.21 cm (95% CI: -1.71-6.16); p=0.27; I2=98%] with regards to improvement in PAH after 12-months use. Letrozole was superior to both placebo [MD: 4.80 mL (95% CI: 0.57-9.03); p=0.03] and testosterone [MD: 3.36 mL (95% CI: 0.58-6.75); p=0.02; I2=0%] with regards to improvement in testicular volume after 12-months use. Letrozole tended to be superior to testosterone [MD: -0.84 years (95% CI: 2.83-8.18); p=0.06; I2=0%] with regards to slowing in BA progression after 12-months use. Serum luteinizing hormone, follicle stimulating hormone, testosterone and inhibin-B were significantly higher after 6-months letrozole use compared to active as well as passive controls. No increased occurrence of adverse events, including spinal deformities, were noted with letrozole. Letrozole is safe and effective for improving height and pubertal outcomes in CDGP, and is better than testosterone with regards to improvement in testicular volume and may be better at delaying bone-age progression.

Keywords: Letrozole, meta-analysis, safety, constitutional delay in growth and puberty, short stature

Deep Dutta, Rajiv Singla, Vineet Surana, Meha Sharma. Efficacy and Safety of Letrozole in the Management of Constitutional Delay in Growth and Puberty: A Systematic Review and Meta-analysis. J Clin Res Pediatr Endocrinol. 2022; 14(2): 131-144

Corresponding Author: Deep Dutta, India
Manuscript Language: English
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