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| Name | Class |
|---|---|
| Foundation for Paediatric Research, Finland | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Testosterone | Active Comparator | ~1mg/kg every 4 weeks for 6 months |
|
| Letrozole | Active Comparator | 2.5mg daily for 6 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Testosterone | Drug | 1mg/kg every 4 weeks for 6 months |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| testicular volume | Testes will be measured with a ruler to the nearest millimeter and volume will be calculated at 0, 6, and 12 mo | one year |
| clinical and biochemical measures of pubertal progression | Activity of the hypothalamic-pituitary-gonadal axis, evaluated by
| one year |
| Measure | Description | Time Frame |
|---|---|---|
| Bone health | Several endpoints related to bone health | one year |
| Psychosocial well-being | Psycho-social well-being will assessed with questionnaires. |
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Inclusion Criteria:
as above, but serum testosterone 1 nM or more with normal DHEAS level, even if the mean testicular volume is less than 2.5 ml OR
as above, but tanner stage G2 and testosterone level less than 3 nM
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Taneli Raivio, MD, PhD | Helsinki University Central Hospital | Principal Investigator |
| Matti Hero, MD, PhD | Helsinki University Central Hospital | Study Director |
| Tero Varimo, MD, PhD | Helsinki University Central Hospital | Study Chair |
| Päivi Miettinen, MD, PhD | Helsinki University Central Hospital | Study Chair |
| Jorma Toppari, MD, PhD | University of Turku | Study Chair |
| Hanna Huopio, MD, PhD | Kuopio University Central Hospital | Study Chair |
| Sirpa Tenhola, MD, PhD | Kymeenlaakso Central Hospital | Study Chair |
| Raimo Voutilainen, MD, PhD | Kuopio University Central Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Helsinki University Central Hospital | Helsinki | 00029 | Finland | |||
| Kotka Central Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42299320 | Derived | 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. | |
| 40796279 | Derived |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Feb 23, 2022 | |
| Reset | Apr 25, 2022 | |
| Release | May 4, 2022 | |
| Reset | Feb 2, 2023 | |
| Release | Feb 27, 2023 | |
| Reset | Dec 4, 2023 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Feb 23, 2022 | Apr 25, 2022 | |||
| May 4, 2022 |
| ID | Term |
|---|---|
| D013739 | Testosterone |
| D000077289 | Letrozole |
| ID | Term |
|---|---|
| D000737 | Androstenols |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 |
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| Letrozole | Drug | 2.5mg daily for 6 months. Safety criteria: if testosterone level is above 30nM at 3 months, the dosage is reduced to 2.5mg every other day |
|
|
| one year |
| Puberty-related metabolical and clinical changes | Biochemical and metabolical changes will be compared btw testosterone and letrozole treatment groups. | one year |
| Kotka |
| Finland |
| Kuopio University Central Hospital | Kuopio | 70211 | Finland |
| Turku University Central Hospital | Turku | 20521 | Finland |
| 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. |
| 36518253 | Derived | 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. |
| 34596269 | Derived | 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. |
| 31958337 | Derived | 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. |
| 30612946 | Derived | 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. |
| Feb 2, 2023 |
| Feb 27, 2023 | Dec 4, 2023 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045165 | Testosterone Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |