Pharmacokinetics in children

An adult PK model was allometrically scaled for boys aged 12-18 years (30–60 kg) to simulate subcutaneous and intramuscular testosterone dosing (12.5–100 mg, weekly, every other week or monthly). The final population PK model fixed-effect parameter estimates for subcutaneous and intramuscular testosterone enanthate in adolescents are:  

Cl, central clearance; IM, intramuscular; SC, subcutaneous; TE, testosterone enanthate [Vogiatzi 2023]

A clinical trial compared testosterone enanthate (Testoviron depot 75 mg IM every month, n=12) and testosterone undecanoate (Nebido 250 mg IM every 3 months, n=14) for pubertal induction in boys (14-16 years) with delayed puberty. Both testosterone enanthate and testosterone undecanoate achieved physiological testosterone levels and similar pubertal progression [Österbrand 2023]. 

A prospective study investigated four boys (12.7–17.1 years) using oral testosterone undecanoate 40 mg daily with constitutional delayed puberty and/or short stature. Tmax, peak and mean total testosterone were investigated. The study confirmed the inter- and intraindividual variability of the timing of the peak testosterone concentration in adolescent boys [Butler 1992]. 

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

In prepubertal boys, the following have been reported: premature sexual maturation, enlargement of the penis, more frequent erections and premature closure of the epiphyseal plates. 

Transdermal therapy 
Across studies, transdermal testosterone was generally well tolerated. Liver enzyme levels tended to improve or normalize during treatment [Contreras 2017]. In another study there were some cases that displayed a derangement in liver function. The specific formulation was not reported [Lucas-Herald 2018].  
Application site reactions were uncommon, and acne occurred in 14% of patients, which is expected in this population due to pubertal changes. The most frequently reported AEs were cough (27.6%), acne (13.8%) and headache (13.8%) [Rogol 2014].  
 
Intramuscular therapy 
Side effects are limited, with two cases of painful spontaneous erections among 148 patients; psychological satisfaction was reported in all treated individuals compared to 40% of controls [Soliman 1995]. In another study eight boys (100%) experienced erections and nocturnal emissions during therapy, which persisted after discontinuation [de Lange 1979]. In another cohort study, five boys (2.7%) developed adverse effects: two receiving 125 mg testosterone enanthate experienced severe low-flow priapism requiring intervention; one boy with 50 mg testosterone enanthate had self-limiting priapism and testicular pain; and two others with 50 mg testosterone enanthate reported testicular pain. No adverse effects occurred at 250 mg testosterone enanthate [Albrecht 2018]. 
 
Oral therapy 
In one study transient suppression of LH and FSH occurred in some patients, however this was not associated with adverse clinical outcomes [Lawaetz 2015]. In another study liver enzymes remained stable in patients, though authors caution about occasional short-lived androgen peaks after 40 mg testosterone undecanoate reported elsewhere [Gregory 1992]. 
 

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

The use of androgens in prepubescent boys should be carefully monitored in order to prevent premature closing of the epiphyseal discs or premature sexual maturation [SmPC Testosteron].

The indication growth reduction has been removed of the paediatric formulary in 2026. High-dose testosterone therapy has no significant reduction on final height in constitutionally tall boys. While long-term fertility outcomes appear reassuring, persistent hormonal changes, including elevated FSH and lower serum testosterone, suggest possible subtle effects on reproductive health. These findings underpin the current recommendation to avoid high-dose testosterone for growth suppression due to the balance of modest to no efficacy and potential long-term risks. [Tellingen 2023; de Waal 1995; Hendriks 2010] 

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

• GENITO URINARY SYSTEM AND SEX HORMONES
• SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM

ANDROGENEN

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

References

1. G. Bocca et al., Werkboek Kinderendocrinologie: Hoofdstuk 38. Kleine lengte/trage groei door familiaire late puberteit/trage rijping - Therapeutisch beleid , www.nvk.nl, 16-02-2023, https://nvk.medonline.nl/kinderendocrinologie/kleine-lengte-trage-groei-door-familiaire-late-puberteit-trage-rijping/
2. G. Bocca et al., Werkboek Kinderendocrinologie: Hoofdstuk 38. Kleine lengte/trage groei door familiaire late puberteit/trage rijping - Therapeutisch beleid, www.nvk.nl, 16-02-2023, https://nvk.medonline.nl/kinderendocrinologie/kleine-lengte-trage-groei-door-familiaire-late-puberteit-trage-rijping/
3. Albrecht A, et al., Short-term adverse effects of testosterone used for priming in prepubertal boys before growth hormone stimulation test, Pediatr Endocrinol Metab., 2018, 31(1), 21-24
4. Müller G, et al., Priming with testosterone enhances stimulated growth hormone secretion in boys with delayed puberty, Pediatr Endocrinol Metab., 2004, 17(1), 77-83
5. Ahmed S, et al., Randomized, crossover comparison study of the short-term effect of oral testosterone undecanoate and intramuscular testosterone depot on linear growth and serum bone alkaline phosphatase, Pediatr Endocrinol Metab., 2004, 147(7), 941-50
6. de Waal W, et al., High dose testosterone therapy for reduction of final height in constitutionally tall boys: does it influence testicular function in adulthood?, Clin Endocrinol., 1995, 43(1), 87-95
7. Vogiatzi MG, et al., Allometric Scaling of Testosterone Enanthate Pharmacokinetics to Adolescent Hypogonadal Males (IM and SC Administration), Endocr Soc., 2023, 7(6), 1-11
8. Hendriks AE, et al., Fatherhood in tall men treated with high-dose sex steroids during adolescence, Clin Endocrinol Metab., 2010, 95(12), 5233-40
9. Molina S, et al., Is testosterone and estrogen priming prior to clonidine useful in the evaluation of the growth hormone status of short peripubertal children?, Pediatr Endocrinol Metab., 2008, 21(3), 257-66
10. de Lange W, et al., The effect of short-term testosterone treatment in boys with delayed puberty, Acta Endocrinol., 1979, 91(1), 177-83
11. Soliman AT, et al., Testosterone treatment in adolescent boys with constitutional delay of growth and development, Metabolism., 1995, 44(8), 1013-5
12. Lucas-Herald AK, et al., Single-Centre Experience of Testosterone Therapy for Boys with Hypogonadism, Hormone research in paediatrics., 2018, 90(2), 123-27
13. Jenapharm GmbH & Co. KG, SmPC Testoviron Depot 250 mg/ml 09-2020
14. Österbrand M, et al., Pharmacological treatment for pubertal progression in boys with delayed or slow progression of puberty: A small-scale randomized study with testosterone enanthate and testosterone undecanoate treatment, Front Endocrinol., 2023, 14, 1158219
15. Gönç EM, et al., Final heights of boys with normal growth hormone responses to provocative tests following priming, Pediatr Endocrinol Metab., 2008, 21(10), 963-71
16. Contreras M, et al., Transdermal testosterone gel for induction and continuation of puberty in adolescent boys with hepatic dysfunction, Pediatr Endocrinol Metab., 2017, 30(1), 105-09
17. Rogol A, et al, A multicenter, open-label, observational study of testosterone gel (1%) in the treatment of adolescent boys with klinefelter syndrome or anorchia, Adolesc Health., 2014, 54(1), 20-5
18. Sas, T., & Vlaardingerbroek, H., Overview of treatment options for induction of puberty and pubertas tarda - Expert Opinion, Dutch Paediatric Association, 02-2025, ttps://www.nvk.nl/kennisdocument/overzicht-behandelmogelijkheden-inductie-van-puberteit-en-pubertas-tarda/
19. Chioma L, et al, Use of testosterone gel compared to intramuscular formulation for puberty induction in males with constitutional delay of growth and puberty: a preliminary study, Journal of endocrinological investigation., 2018, 41(2), 259-63
20. Albanese A, et al., Oral treatment for constitutional delay of growth and puberty in boys: a randomised trial of an anabolic steroid or testosterone undecanoate, Arch Dis Child., 1994, 71(4), 315-7
21. Butler G, et al., Oral testosterone undecanoate in the management of delayed puberty in boys: pharmacokinetics and effects on sexual maturation and growth, Clin Endocrinol Metab., 1992, 75(1), 37-44
22. Lawaetz JG, et al., Evaluation of 451 Danish boys with delayed puberty: diagnostic use of a new puberty nomogram and effects of oral testosterone therapy, Clin Endocrinol Metab., 2015, 100(4), 1376-85
23. Gregory JW, et al., Effects of oral testosterone undecanoate on growth, body composition, strength and energy expenditure of adolescent boys, Clinical Endocrinol., 1992, 37(3), 207-13
24. Gönç EM, et al., Comparison of stimulated growth hormone levels in primed versus unprimed provocative tests. Effect of various testosterone doses on growth hormone levels, Horm Res., 2001, 56(1-2), 32-7

Changes

Therapeutic Drug Monitoring

Overdose