Delayed puberty
- Overview
- Theory
- Diagnosis
- Management
- Follow up
- Resources
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
constitutional delay
observation and monitoring
Patients need monitoring to assess for progression of pubertal signs and an increased height velocity.
Treatment is reserved for patients with severe delay or abnormalities of psychosocial adjustment.
short course of testosterone
Some boys have severe delay or abnormalities of psychosocial adjustment.
These patients may benefit from a short course of depot testosterone. The aim of low-dose testosterone is to activate puberty. Once activated, puberty often progresses spontaneously despite withdrawal of treatment.
Adverse effects associated with testosterone treatment include erythrocytosis, weight gain, and prostate hyperplasia.[1]Palmert MR, Dunkel L. Clinical practice. Delayed puberty. N Engl J Med. 2012 Feb 2;366(5):443-53. http://www.ncbi.nlm.nih.gov/pubmed/22296078?tool=bestpractice.com While these are rare, they should be monitored during treatment.
Treatment course: 3 to 6 months.
Primary options
testosterone cipionate: consult specialist for guidance on dose
OR
testosterone enantate: consult specialist for guidance on dose
observation and monitoring
Patients need monitoring to assess for progression of pubertal signs and an increased height velocity.
Treatment is reserved for patients with severe delay or abnormalities of psychosocial adjustment.
short course of oestrogen
Some girls have severe delay or abnormalities of psychosocial adjustment and may benefit from a short course of estradiol therapy.
Treatment course: 3 to 6 months.
Primary options
estradiol transdermal: consult specialist for guidance on dose
OR
estradiol: consult specialist for guidance on dose
organic (permanent) cause: boys
pubertal induction with testosterone or gonadotrophin therapy
Pubertal induction is carried out gradually, with a low starting dose of testosterone therapy that is increased until adult levels are reached. This can be achieved with intramuscular testosterone preparations administered every 4 weeks. The dose is gradually increased, as required by the patient, every 6 months once an adult dose is reached. A decreasing interval between injections (2-3 weekly) may be necessary if the patient becomes symptomatic of hypogonadism 2-3 weeks after each injection.
The serum levels of testosterone achieved through the intramuscular route are not physiological. Some boys report symptoms of irritability, aggression, and hypersexuality in the days following the injection. Other adverse effects associated with testosterone treatment include erythrocytosis, weight gain, and prostate hyperplasia.[1]Palmert MR, Dunkel L. Clinical practice. Delayed puberty. N Engl J Med. 2012 Feb 2;366(5):443-53. http://www.ncbi.nlm.nih.gov/pubmed/22296078?tool=bestpractice.com While these are rare, they should be monitored during treatment. Serum total testosterone levels should be checked 1 week after therapy to assess whether the doses are therapeutic.
In males with gonadotrophin deficiency, pubertal induction can alternatively be with gonadotrophin therapy.[55]Rohayem J, Hauffa BP, Zacharin M, et al. Testicular growth and spermatogenesis: new goals for pubertal hormone replacement in boys with hypogonadotropic hypogonadism? -a multicentre prospective study of hCG/rFSH treatment outcomes during adolescence. Clin Endocrinol (Oxf). 2017 Jan;86(1):75-87. http://www.ncbi.nlm.nih.gov/pubmed/27467188?tool=bestpractice.com As with testosterone, doses are increased gradually to induce puberty over 1 to 3 years. Combination therapy with recombinant follicle-stimulating hormone (rFSH) and human chorionic gonadotrophin (hCG) are most commonly used. Careful monitoring is required to target physiological serum concentrations of FSH and testosterone, and such regimes should be limited to experienced centres.[56]Dunkel L, Prasad R, Senniappan S, et al. Protocol for induction of puberty with gonadotropins in adolescent males with GnRH or gonadotropin deficiency pubertal induction with gonadotropins. Version 1.6. September 2021 [internet publication]. https://www.bsped.org.uk/media/1989/protocol-for-induction-of-puberty-with-gonadotropins-in-males-with-gnrh-or-gonadotropin-deficiency_bsped_website-002.pdf Consult your local protocols for guidance on dose regimens.
Primary options
testosterone cipionate: consult specialist for guidance on dose
OR
testosterone enantate: consult specialist for guidance on dose
organic (permanent) cause: girls
pubertal induction with oestrogen
Patients require gradually increasing doses of oestrogen treatment, with cyclic progesterone therapy introduced once adequate oestrogenisation has occurred or with breakthrough uterine bleeding. Puberty should not be induced using contraceptive pills or patches because the doses of oestrogen are too high and the androgenic progestogens impair optimal breast development.
The preferred preparations are either transdermal or oral estradiol in the smallest available dose. Transdermal delivery avoids first-pass effects on the liver.[57]Ankarberg-Lindgren C, Elfving M, Wikland KA, et al. Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls. J Clin Endocrinol Metab. 2001 Jul;86(7):3039-44. https://academic.oup.com/jcem/article/86/7/3039/2848398?login=false http://www.ncbi.nlm.nih.gov/pubmed/11443165?tool=bestpractice.com
Primary options
estradiol transdermal: consult specialist for guidance on dose
OR
estradiol: consult specialist for guidance on dose
cyclic progesterone after breakthrough bleeding or adequate oestrogenisation
Treatment recommended for ALL patients in selected patient group
Progesterone is added to oestrogen therapy after a suitable duration of unopposed oestrogen (usually 2-3 years) or if more than one episode of significant breakthrough bleeding occurs, to promote endometrial shedding. Many different formulations are available; consult your local drug formulary for more information.
chronic illness or malnutrition
treatment of underlying abnormality
Malnutrition, eating disorders, chronic heart disease, moderate to severe asthma, cystic fibrosis, coeliac disease, inflammatory bowel disease (Crohn's disease and ulcerative colitis), inflammatory disorders (e.g., juvenile idiopathic arthritis), chronic renal failure, any chronic malignancy, and poorly controlled diabetes mellitus can all cause temporary delay in puberty.
Treatment of the underlying cause may resolve the pubertal delay, with subsequent spontaneous pubertal progression.
short course of testosterone
Some boys have abnormalities of psychosocial adjustment and may benefit from a short (3- to 6-month) course of depot testosterone. The aim of low-dose testosterone is to activate puberty. Once activated, puberty progresses spontaneously despite withdrawal of treatment.
Adverse effects associated with testosterone treatment include erythrocytosis, weight gain, and prostate hyperplasia.[1]Palmert MR, Dunkel L. Clinical practice. Delayed puberty. N Engl J Med. 2012 Feb 2;366(5):443-53. http://www.ncbi.nlm.nih.gov/pubmed/22296078?tool=bestpractice.com While these are rare, they should be monitored during treatment.
Treatment course: 3 to 6 months.
Primary options
testosterone cipionate: consult specialist for guidance on dose
OR
testosterone enantate: consult specialist for guidance on dose
treatment of underlying abnormality
Malnutrition, eating disorders, chronic heart disease, moderate to severe asthma, cystic fibrosis, coeliac disease, inflammatory bowel disease (Crohn's disease and ulcerative colitis), inflammatory disorders (e.g., juvenile idiopathic arthritis), chronic renal failure, any chronic malignancy, and poorly controlled diabetes mellitus can all cause temporary delay in puberty.
Treatment of the underlying cause may resolve the pubertal delay, with subsequent spontaneous pubertal progression.
short course of oestrogen
Some girls have abnormalities of psychosocial adjustment and may benefit from a short course of estradiol therapy.
Treatment course: 3 to 6 months.
Primary options
estradiol transdermal: consult specialist for guidance on dose
OR
estradiol: consult specialist for guidance on dose
persistent hypogonadism post-puberty
testosterone supplementation
Those with confirmed hypogonadism post-puberty need lifelong testosterone supplementation. Options include intramuscular, oral, topical, or transdermal testosterone. Many formulations are available; consult your local drug formulary for more information.
Local skin irritation is the main adverse effect of transdermal preparations and is more frequent with the patches compared with the gel preparation. Showering and swimming should be avoided for 4 hours after gel application. Some patients who do not tolerate these preparations and have severe local skin irritation may be considered for intramuscular testosterone.
Adverse effects associated with testosterone treatment include erythrocytosis, weight gain, and prostate hyperplasia.[1]Palmert MR, Dunkel L. Clinical practice. Delayed puberty. N Engl J Med. 2012 Feb 2;366(5):443-53. http://www.ncbi.nlm.nih.gov/pubmed/22296078?tool=bestpractice.com While these are rare, they should be monitored during treatment.
testicular implants
Additional treatment recommended for SOME patients in selected patient group
Males with anorchidism can be counselled for testicular prosthesis. This does not restore fertility and is done for cosmetic and/or psychological concerns. The procedure is done in the latter stages of puberty, when scrotal growth is optimum, so that the procedure does not need to be revised.
ovarian hormone supplementation
All women with confirmed hypogonadism post-puberty need lifelong hormone-replacement therapy (HRT) after induction of puberty. HRT should continue until about 50 years of age. This can be achieved with transdermal estradiol along with micronised progesterone, or a combination of transdermal estradiol and other progesterone preparations. Another option is to replace transdermal oestrogen with oral estradiol. Many formulations are available; consult your local drug formulary for more information.
Inadequate or a lack of oestrogen treatment is associated with an increased risk of long-term complications such as osteoporosis.
breast implants
Additional treatment recommended for SOME patients in selected patient group
Girls who do not achieve adequate breast development with oestrogen treatment may require breast implants. The procedure is offered for cosmetic and psychological reasons and done at the end of or latter stages of puberty.
Choose a patient group to see our recommendations
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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