Editing Delayed puberty (section)

==Management==
The goals of short-term hormone therapy are to induce the beginning of sexual development and induce a growth spurt, but it should be limited to children with severe distress or anxiety secondary to their delayed puberty.<ref name=":1" /><ref name=":0" /> Bone age must be monitored frequently to prevent precocious closure of the bone plates, thereby stunting growth.<ref name=":0" />

=== Constitutional and physiologic delay ===
If a child is healthy with a constitutional delay of growth and puberty, reassurance and prediction based on the bone age can be provided.<ref name=":7" /><ref name=":8" /> No other intervention is usually necessary, but repeat evaluation by measuring serum testosterone or estrogen is recommended.<ref name=":1" /><ref name=":11" /><ref name=":0" /> Furthermore, the diagnosis of [[hypogonadism]] can be excluded once the adolescent has started puberty by age 16–18.<ref name=":11" /><ref name=":9" />

Boys over 14 years of age whose growth is severely stunted or are experiencing severe distress secondary to their lack of puberty can be started on [[testosterone]] to increase their height.<ref name=":7" /> Testosterone treatment can also be used to stimulate sexual development, but it can close bone plates prematurely stopping growth altogether if not carefully administered.<ref name=":6">{{Cite book|title=Brody's human pharmacology : molecular to clinical| first=Lynn|last=Wecker | name-list-style = vanc |date=2010|publisher=Elsevier Mosby|isbn=9780323053747|oclc=804133604}}</ref><ref name=":0" /> Another therapeutic option is the use of [[aromatase inhibitor]]s to inhibit the conversion of androgens to estrogens as estrogens are responsible for stopping bone growth plate development and thus growth.<ref name=":7" /> However, due to side effects, therapy with testosterone alone is most often used.<ref name=":7" /> Overall, neither growth hormone nor aromatase inhibitors are recommended for constitutional delay to increase growth.<ref name=":8" /><ref>{{cite journal | vauthors = Wit JM, Oostdijk W | title = Novel approaches to short stature therapy | journal = Best Practice & Research. Clinical Endocrinology & Metabolism | volume = 29 | issue = 3 | pages = 353–66 | date = June 2015 | pmid = 26051296 | doi = 10.1016/j.beem.2015.01.003 | series = Hormone replacement strategies in paediatric and adolescent endocrine disorders }}</ref>

Girls can be started on [[estrogen]] with the same goals as their male counterparts.<ref name=":7" />

Overall, studies have shown no significant difference in final adult height between adolescents treated with sex steroids and those who were only observed with no treatment.<ref name=":02">{{cite journal | vauthors = Zhu J, Chan YM | title = Adult Consequences of Self-Limited Delayed Puberty | journal = Pediatrics | volume = 139 | issue = 6 | pages = e20163177 | date = June 2017 | pmid = 28562264 | doi = 10.1542/peds.2016-3177 | pmc = 8579478 | s2cid = 41944095 }}</ref>

=== Malnutrition or chronic disease ===
If the delay is due to systemic disease or [[malnutrition]], the therapeutic intervention is likely to focus direction on those conditions. In patients with [[coeliac disease]], an early diagnosis and the establishment of a [[gluten-free diet]] prevents long-term complications and allows restoration of normal maturation.<ref name="Mearin2015" /><ref name="LevyBernstein2014" /> Thyroid hormone therapy will be necessary in the case of hypothyroidism.<ref name=":0" />

=== Primary failure of the ovaries or testes (hypergonadotropic hypogonadism) ===
Whereas children with constitutional delay will have normal levels of sex hormones post-puberty, gonadotropin deficiency or hypogonadism may require lifelong sex steroid replacement.<ref name=":1" />

In girls with [[primary ovarian failure]], [[estrogen]] should be started when puberty is supposed to start.<ref name=":0" /> [[Progestin]]s are usually added after there is acceptable breast development, about 12 to 24 months after starting estrogen, as starting treatment with progestin too early can negatively affect breast growth.<ref name=":0" /> After acceptable breast growth, administering [[estrogen]] and [[progestin]] in a cyclical manner can help establish regular menses once puberty is started.<ref name=":6" /><ref name=":9" /> The goal is to complete sexual maturation over 2 to 3 years.<ref name=":0" /> Once sexual maturation has been achieved, a trial period with no hormonal therapy can determine whether or not the child will require life-long treatment.<ref name=":1" /> Girls with congenital GnRH deficiency require enough sex hormone supplementation to maintain body levels in the expected pubertal levels necessary to induce ovulation, especially when fertility is a concern.<ref name=":0" />

Males with primary failure of the testes will be on lifelong [[testosterone]].<ref name=":14" />

Pulsatile GnRH, weekly multi-LH, or hCG and FSH can be used to induce fertility in adulthood for both males and females.<ref name=":7" /><ref name=":9" />

=== Genetic or acquired defect of the hormonal pathway of puberty (hypogonadotropic hypogonadism) ===
Boys aged >12 years old with [[hypogonadotropic hypogonadism]] are most often treated with short-term testosterone while males with testicular failure will be on life-long [[testosterone]].<ref name=":7" /><ref name=":10">{{cite journal | vauthors = Watson S, Fuqua JS, Lee PA | title = Treatment of hypogonadism in males | journal = Pediatric Endocrinology Reviews | volume = 11 | pages = 230–9 | date = February 2014 | issue = Suppl 2 | pmid = 24683947 }}</ref><ref name="legato">{{cite book | veditors = Legato MJ | editor-link = Marianne Legato | date = 2004 | title = Principles of Gender-Specific Medicine | volume = 1–2 | isbn = 978-0-12-440905-7 | page = 22 | last1 = Legato | first1 = Marianne J. | last2 = Bilezikian | first2 = John P. | publisher = Elsevier Science }}</ref> Choice of formulation (topical vs injection) is dependent on the child's and family's preference as well as on how well they tolerate side effects.<ref name=":10" /> Although testosterone therapy alone will result in the start of puberty, to increase fertility potential, they may need pulsatile GnRH or hCG with rFSH.<ref name=":7" /><ref name=":10" /> hCG can be used by itself in boys with spontaneous onset of puberty from non-permanent forms of [[hypogonadotropic hypogonadism]] and rFSH can be added in cases of low sperm count after 6 to 12 months of treatment.<ref name=":7" />

If puberty has not started after 1 year of treatment, then permanent [[hypogonadotropic hypogonadism]] should be considered.<ref name=":7" />

Girls with hypogonadotropic hypogonadism are started on the same sex steroid therapy as their counterparts with a constitutional delay, however doses are gradually increased to reach full adult replacement levels.<ref name=":7" /> Dosage of estrogen is titrated based on the woman's ability to have withdrawal bleeds and to maintain appropriate bone density.<ref name=":7" /> Induction of fertility must also be done through pulsatile GnRH.<ref name=":7" />

=== Others ===
[[Growth hormone]] is another option that has been described, however it should only be used in proven growth hormone deficiency<ref>{{cite journal | vauthors = Heinrichs C, Bourguignon JP | title = Treatment of delayed puberty and hypogonadism in girls | journal = Hormone Research | volume = 36 | issue = 3–4 | pages = 147–52 | year = 1991 | pmid = 1818011 | doi = 10.1159/000182149 | hdl = 2268/260267 | hdl-access = free }}</ref><ref name="pmid12970282">{{cite journal | vauthors = Massa G, Heinrichs C, Verlinde S, Thomas M, Bourguignon JP, Craen M, François I, Du Caju M, Maes M, De Schepper J | title = Late or delayed induced or spontaneous puberty in girls with Turner syndrome treated with growth hormone does not affect final height | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 9 | pages = 4168–74 | date = September 2003 | pmid = 12970282 | doi = 10.1210/jc.2002-022040 | hdl = 2268/257143 | hdl-access = free }}</ref> such as [[idiopathic short stature]].<ref name=":7" /> Children with a constitutional delay have not been shown to benefit from growth hormone therapy.<ref name=":7" /> Although serum growth hormone levels are low in constitutional delay of puberty, they increase after treatment with sex hormones and in those cases, growth hormone is not suggested to accelerate growth.<ref name=":0" />

Subnormal [[vitamin A]] intake is one of the etiological factors in delayed pubertal maturation. Supplementation of both vitamin A and [[iron]] to normal constitutionally delayed children with subnormal vitamin A intake is as efficacious as hormonal therapy in the induction of growth and puberty.<ref>{{cite journal | vauthors = Zadik Z, Sinai T, Zung A, Reifen R | title = Vitamin A and iron supplementation is as efficient as hormonal therapy in constitutionally delayed children | journal = Clinical Endocrinology | volume = 60 | issue = 6 | pages = 682–7 | date = June 2004 | pmid = 15163330 | doi = 10.1111/j.1365-2265.2004.02034.x | s2cid = 27016335 }}</ref>

More therapies are being developed to target the more discreet modulators of the [[HPG axis]] including [[kisspeptin]] and [[neurokinin B]].<ref>{{cite book | vauthors = Newton CL, Anderson RC, Millar RP | title = Advanced Therapies in Pediatric Endocrinology and Diabetology | chapter = Therapeutic Neuroendocrine Agonist and Antagonist Analogs of Hypothalamic Neuropeptides as Modulators of the Hypothalamic-Pituitary-Gonadal Axis | language = en | journal = Endocrine Development | volume = 30 | pages = 106–29 | date = 2016 | pmid = 26684214 | doi = 10.1159/000439337 | isbn = 978-3-318-05636-5 }}</ref><ref>{{cite journal | vauthors = Wei C, Crowne EC | title = Recent advances in the understanding and management of delayed puberty | journal = Archives of Disease in Childhood | volume = 101 | issue = 5 | pages = 481–8 | date = May 2016 | pmid = 26353794 | doi = 10.1136/archdischild-2014-307963 | s2cid = 5372175 }}</ref>

In cases of severe delayed puberty secondary to [[hypogonadism]], evaluation by a psychologist or psychiatrist, as well as counseling and a supportive environment are an important supplemental therapy for the child.<ref name=":1" /><ref name="pmid25735941">{{cite book | vauthors = Berenbaum SA, Beltz AM, Corley R | title = The importance of puberty for adolescent development: conceptualization and measurement | journal = Advances in Child Development and Behavior | volume = 48 | pages = 53–92 | date = 2015 | pmid = 25735941 | doi = 10.1016/bs.acdb.2014.11.002 | isbn = 9780128021781 }}</ref> Transition from pediatric to adult care is also vital as many children are lost during transition of care.<ref name=":8" />