Constitutional Delay of Growth and Puberty: Towards Evidence-based Treatment

Summary

Boys with constitutional delay of growth and puberty (CDGP) should be offered evidence-based effective and safe treatment option. This study compares the effects of low-dose testosterone and aromatase inhibitor letrozole on pubertal progression. The hypothesis is that, in boys CDGP showing earliest signs of puberty, peroral letrozole (2.5 mg/d for 6 mo) induces faster biochemical and clinical progression of puberty as compared to low-dose intramuscular testosterone Rx (\~1mg/kg/mo for 6 mo). In addition, 10 or more boys who select watchful waiting instead of medication will provide background data on the natural progression of CDGP, and their data will not be used in primary statistical comparisons.

Timeline

Start

2013-10

Primary completion

2017-03-20

Completion

2018-02-05

Publications

• Raivio T, Tanner M, Vaaralahti K, Hero M, Miettinen PJ, Varimo T. Transient gonadotropin suppression by exogenous testosterone decreases INSL3 in early puberty in boys with constitutional delay of growth and puberty. J Endocr Soc. 2026 May 30;10(7):bvag123. doi: 10.1210/jendso/bvag123. eCollection 2026 Jul.
• Varimo T, Miettinen PJ, Huopio H, Rikkonen T, Voutilainen R, Tenhola S, Raivio T, Hero M. Impact of aromatase inhibition on bone mineral density and structure: a randomized controlled trial in boys with delayed puberty. Eur J Endocrinol. 2025 Jul 31;193(2):289-296. doi: 10.1093/ejendo/lvaf160.
• Kariola L, Varimo T, Huopio H, Tenhola S, Voutilainen R, Kosola S, Toppari J, Sintonen H, Miettinen PJ, Raivio T, Hero M. Health-related quality of life in boys with constitutional delay of growth and puberty. Front Endocrinol (Lausanne). 2022 Nov 25;13:1028828. doi: 10.3389/fendo.2022.1028828. eCollection 2022.
• Huttunen H, Varimo T, Huopio H, Voutilainen R, Tenhola S, Miettinen PJ, Raivio T, Hero M. Serum testosterone and oestradiol predict the growth response during puberty promoting treatment. Clin Endocrinol (Oxf). 2022 Feb;96(2):220-226. doi: 10.1111/cen.14605. Epub 2021 Oct 1.
• Kohva E, Varimo T, Huopio H, Tenhola S, Voutilainen R, Toppari J, Miettinen PJ, Vaaralahti K, Viinamaki J, Backman JT, Hero M, Raivio T. Anti-Mullerian hormone and letrozole levels in boys with constitutional delay of growth and puberty treated with letrozole or testosterone. Hum Reprod. 2020 Feb 29;35(2):257-264. doi: 10.1093/humrep/dez231.
• Varimo T, Huopio H, Kariola L, Tenhola S, Voutilainen R, Toppari J, Toiviainen-Salo S, Hamalainen E, Pulkkinen MA, Laaperi M, Tarkkanen A, Vaaralahti K, Miettinen PJ, Hero M, Raivio T. Letrozole versus testosterone for promotion of endogenous puberty in boys with constitutional delay of growth and puberty: a randomised controlled phase 3 trial. Lancet Child Adolesc Health. 2019 Feb;3(2):109-120. doi: 10.1016/S2352-4642(18)30377-8. Epub 2019 Jan 4.

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