Editing Precocious puberty (section)

== Treatment ==
One possible treatment is with [[anastrozole]]. GnRH agonists, including [[histrelin]], [[triptorelin]], or [[leuprorelin]], are other possible treatments. Non-continuous use{{clarify|date=May 2022}} of GnRH agonists stimulates the pituitary gland to release [[follicle stimulating hormone]] (FSH) and [[luteinizing hormone]] (LH).{{why|date=May 2022}}<ref name=nejm_PP>{{cite journal|last=[[Florence Comite]]|author2=Cutler, Gordon B. |author3=Rivier, Jean |author4=Vale, Wylie W. |author5=Loriaux, D. Lynn |author6= Crowley, William F. |title=Short-Term Treatment of Idiopathic Precocious Puberty with a Long-Acting Analogue of Luteinizing Hormone-Releasing Hormone|journal=New England Journal of Medicine|date=24 December 1981|volume=305|issue=26|pages=1546–1550|doi=10.1056/NEJM198112243052602|pmid=6458765}}</ref>  Triptorelin depot is widely used to treat central precocious puberty (CPP) in children.<ref>{{Cite journal |last1=Bertelloni |first1=Silvano |last2=Mucaria |first2=Cristina |last3=Baroncelli |first3=Giampiero I. |last4=Peroni |first4=Diego |date=July 2018 |title=Triptorelin depot for the treatment of children 2 years and older with central precocious puberty |url=https://pubmed.ncbi.nlm.nih.gov/29957076/ |journal=Expert Review of Clinical Pharmacology |volume=11 |issue=7 |pages=659–667 |doi=10.1080/17512433.2018.1494569 |issn=1751-2441 |pmid=29957076}}</ref>

Puberty blockers work by stabilizing puberty symptoms, decreasing growth velocity, and slowing skeletal maturation.<ref>{{cite journal | vauthors = Latronico AC, Brito VN, Carel JC | title = Causes, diagnosis, and treatment of central precocious puberty | journal = The Lancet. Diabetes & Endocrinology | volume = 4 | issue = 3 | pages = 265–274 | date = March 2016 | pmid = 26852255 | doi = 10.1016/S2213-8587(15)00380-0 }}</ref> The outcomes of treatment are assessed in terms of height, reproduction, metabolic, and psychosocial measures. The most pronounced effects on height have been seen in children experiencing the onset of puberty before 6 years of age; however there is variability in height outcomes across studies which can be attributed to varying study designs, time of symptom presentation, and time of treatment termination.<ref>{{cite journal | vauthors = Fuqua JS | title = Treatment and outcomes of precocious puberty: an update | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 98 | issue = 6 | pages = 2198–2207 | date = June 2013 | pmid = 23515450 | doi = 10.1210/jc.2013-1024 }}</ref> A study investigating the effects of puberty blockers on reproductive health showed no significant difference in the number of irregular menstrual cycles, pregnancies, or pregnancy outcomes between women who received treatment for precocious puberty and those who opted out of treatment.<ref>{{cite journal | vauthors = Magiakou MA, Manousaki D, Papadaki M, Hadjidakis D, Levidou G, Vakaki M, Papaefstathiou A, Lalioti N, Kanaka-Gantenbein C, Piaditis G, Chrousos GP, Dacou-Voutetakis C | title = The efficacy and safety of gonadotropin-releasing hormone analog treatment in childhood and adolescence: a single center, long-term follow-up study | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 95 | issue = 1 | pages = 109–117 | date = January 2010 | pmid = 19897682 | doi = 10.1210/jc.2009-0793 | doi-access = free }}</ref> Individuals with precocious puberty, early adrenarche, and early normal puberty show less stress after treatment compared to individuals without preexisting developmental conditions.<ref>{{cite journal | vauthors = Menk TA, Inácio M, Macedo DB, Bessa DS, Latronico AC, Mendonca BB, Brito VN | title = Assessment of stress levels in girls with central precocious puberty before and during long-acting gonadotropin-releasing hormone agonist treatment: a pilot study | journal = Journal of Pediatric Endocrinology & Metabolism | volume = 30 | issue = 6 | pages = 657–662 | date = May 2017 | pmid = 28599388 | doi = 10.1515/jpem-2016-0425 }}</ref>

Blockers are also used in the treatment of central precocious puberty resulting from conditions like hypothalamic hamartomas or congenital adrenal hyperplasia, where early onset of puberty is a symptom. Additionally, puberty blockers can be prescribed for children with severe forms of idiopathic short stature, allowing for more time for growth before the closure of growth plates.<ref>{{cite journal | vauthors = Carel JC, Léger J | title = Clinical practice. Precocious puberty | journal = The New England Journal of Medicine | volume = 358 | issue = 22 | pages = 2366–2377 | date = May 2008 | pmid = 18509122 | doi = 10.1056/NEJMcp0800459 }}</ref>

In the USA, since 1993, the [[Food and Drug Administration|US Food and Drug Administration (FDA)]] has supported the use of puberty blockers to treat precocious puberty.<ref>{{cite web |last=Benisek |first=Alexandra |title=What Are Puberty Blockers? |url=https://www.webmd.com/children/what-are-puberty-blockers |access-date=2024-08-01 |website=WebMD |language=en}}</ref> Currently under FDA regulation the use of puberty blockers is considered on-label for the treatment of central precocious puberty.<ref name="Lopez_2018">{{cite journal | vauthors = Lopez CM, Solomon D, Boulware SD, Christison-Lagay E | title = Trends in the "Off-Label" Use of GnRH Agonists Among Pediatric Patients in the United States | journal = Clinical Pediatrics | volume = 57 | issue = 12 | pages = 1432–1435 | date = October 2018 | pmid = 30003804 | doi = 10.1177/0009922818787260 }}</ref>]<ref name="apa.org">{{cite web |title=Proposed Talking Points to Oppose Gender-Affirming Care Criminalization Bills |url=https://www.apa.org/pi/lgbt/resources/policy/issues/gender-affirmative-care |website=apa.org |publisher=American Psychological Association |access-date=11 October 2022 |archive-url=https://web.archive.org/web/20210505180900/https://www.apa.org/pi/lgbt/resources/policy/issues/gender-affirmative-care |archive-date=5 May 2021 |language=en-US |url-status=dead}}</ref>

For years, the [[Food and Drug Administration|FDA]], [[Endocrine Society]], [[American Academy of Pediatrics|American Academy of Pediatrics(AAP)]] and many other pediatric associations have supported the use of [[Gonadotropin-releasing hormone modulator|Gonadotropin-releasing hormone analogs]][[Gonadotropin-releasing hormone agonist|(GnRHas)]] in central precocious puberty (CPP).<ref>{{cite journal | vauthors = Kletter GB, Klein KO, Wong YY | title = A pediatrician's guide to central precocious puberty | journal = Clinical Pediatrics | volume = 54 | issue = 5 | pages = 414–424 | date = May 2015 | pmid = 25022947 | doi = 10.1177/0009922814541807 }}</ref> 

In 2009, the Lawson Wilkins Pediatric Endocrine Society and European Society for Pediatric Endocrinology published a consensus statement highlighting the effectiveness of [[Gonadotropin-releasing hormone modulator|Gonadotropin-releasing hormone analogs]][[Gonadotropin-releasing hormone agonist|(GnRHas)]] in early onset central precocious puberty.<ref name="Carel_2009">{{cite journal | vauthors = Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR, Antoniazzi F, Berenbaum S, Bourguignon JP, Chrousos GP, Coste J, Deal S, de Vries L, Foster C, Heger S, Holland J, Jahnukainen K, Juul A, Kaplowitz P, Lahlou N, Lee MM, Lee P, Merke DP, Neely EK, Oostdijk W, Phillip M, Rosenfield RL, Shulman D, Styne D, Tauber M, Wit JM | title = Consensus statement on the use of gonadotropin-releasing hormone analogs in children | journal = Pediatrics | volume = 123 | issue = 4 | pages = e752–e762 | date = April 2009 | pmid = 19332438 | doi = 10.1542/peds.2008-1783 | url = http://orbi.ulg.ac.be/handle/2268/109500 }}</ref> They confirmed that the use of [[Gonadotropin-releasing hormone modulator|Gonadotropin-releasing hormone analogs]][[Gonadotropin-releasing hormone agonist|(GnRHas)]] has had a positive effect on increasing adult height.<ref name="Carel_2009" /><ref>{{cite journal | vauthors = Chen M, Eugster EA | title = Central Precocious Puberty: Update on Diagnosis and Treatment | journal = Paediatric Drugs | volume = 17 | issue = 4 | pages = 273–281 | date = August 2015 | pmid = 25911294 | pmc = 5870137 | doi = 10.1007/s40272-015-0130-8 }}</ref> However these Endocrine Societies believe additional research should be conducted before routinely suggesting [[Gonadotropin-releasing hormone agonist|GnRHAs]] for other conditions.<ref name="Carel_2009" /> There is still some uncertainty surrounding the effectiveness of [[Gonadotropin-releasing hormone agonist|GnRHas]]  when utilized for other conditions.

Overall, puberty blockers have demonstrated an excellent safety and efficacy profile in the treatment of precocious puberty. 

=== Side effects ===
The most common side effects reported include nonspecific headaches, hot flashes, and implant-related skin reactions.<ref>{{cite journal | vauthors = Lewis KA, Eugster EA | title = Experience with the once-yearly histrelin (GnRHa) subcutaneous implant in the treatment of central precocious puberty | language = English | journal = Drug Design, Development and Therapy | volume = 3 | pages = 1–5 | date = September 2009 | pmid = 19920916 | doi = 10.2147/DDDT.S3298 | doi-access = free | pmc = 2769233 }}</ref>

A systematic review of studies investigating the long-term effects of treating precocious puberty with GnRH agonists found that [[Bone density|bone mineral density]] decreases during treatment but normalizes afterward, with no lasting effects on [[peak bone mass]].<ref name="Soliman">{{cite journal |last1=Soliman |first1=Ashraf T. |last2=Alaaraj |first2=Nada |last3=De Sanctis |first3=Vincenzo |last4=Hamed |first4=Noor |last5=Alyafei |first5=Fawzia |last6=Ahmed |first6=Shayma |title=Long-term health consequences of central precocious/early puberty (CPP) and treatment with Gn-RH analogue: a short update: Long term consequences of precocious puberty |journal=Acta Biomedica: Atenei Parmensis |date=5 December 2023 |volume=94 |issue=6 |pages=e2023222 |doi=10.23750/abm.v94i6.15316 |pmid=38054666|pmc=10734238 }}</ref>