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


  • Deep Dutta
  • Rajiv Singla
  • Vineet Surana
  • Meha Sharma

Received Date: 01.07.2021 Accepted Date: 02.09.2021 J Clin Res Pediatr Endocrinol 0;0(0):0-0 [e-Pub] PMID: 34477355


No meta-analysis is available which has analysed role of letrozole in constitutional delay in growth and puberty (CDGP).


Electronic databases were searched for RCTs involving children with CDGP receiving letrozole. Primary outcome were changes in predicted adult height (PAH) and pubertal progression. Secondary outcomes were alterations in bone age, hormonal markers of puberty, bone mineral density and side-effects.


One hundred-thirty articles were reviewed, from which 7 RCTs which fulfilled all criteria were analysed. Letrozole was superior to placebo [mean difference (MD) 4.63cm (95% CI: 3.90 – 5.36); P<0.01; I2=0%] but not testosterone [MD 2.21cm (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 4.80ml (95% CI: 0.57 – 9.03); P=0.03] and testosterone [MD 3.36ml (95% CI: 0.58 – 6.75); P=0.02; I2=0%] with regards to improvement in testicular volume after 12-months use. Letrozole was superior to testosterone [MD -0.84 years (95% CI: 2.83 – 8.18); P=0.06; I2=0%] with regards to slowing in bone age progression after 12-months use, which approached statistical significance. Serum LH, FSH, 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, 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 delaying bone-age progression.

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