Editing Hirsutism (section)

== Causes ==
{{See also|Hyperandrogenism#Causes}}

The causes of hirsutism can be divided into endocrine imbalances and non-endocrine etiologies. It is important to begin by first determining the distribution of [[body hair]] growth. If hair growth follows a male distribution, it could indicate the presence of increased androgens or hyperandrogenism. However, there are other hormones not related to androgens that can lead to hirsutism. A detailed history is taken by a provider in search of possible causes for hyperandrogenism or other non-endocrine-related causes. If the distribution of hair growth occurs throughout the body, this is referred to as [[hypertrichosis]], not hirsutism.<ref>{{Cite journal |last=Sachdeva |first=Silonie |title=Hirsutism: Evaluation and treatment |date=2010 |journal=Indian Journal of Dermatology |volume=55 |issue=1 |pages=3–7 |doi=10.4103/0019-5154.60342 |issn=0019-5154 |pmc=2856356 |pmid=20418968 |doi-access=free }}</ref>

=== Endocrine causes ===
Endocrine causes of hirsutism include:

* [[Ovarian cyst]]s such as in [[polycystic ovary syndrome]] (PCOS), the most common cause in women.<ref name="pmid18844715">{{cite journal |vauthors=Somani N, Harrison S, Bergfeld WF |title=The clinical evaluation of hirsutism |journal=Dermatol Ther |volume=21 |issue=5 |pages=376–91 |year=2008 |pmid=18844715 |doi=10.1111/j.1529-8019.2008.00219.x |s2cid=34029116 }}</ref> 
* [[Adrenal tumor|Adrenal gland tumor]]s, [[adrenocortical adenoma]]s, and [[adrenocortical carcinoma]], as well as [[adrenal hyperplasia]] due to [[pituitary adenoma]]s (as in [[Cushing's syndrome|Cushing's disease]]).<ref name="pmid21623779" />
* [[Inborn errors of steroid metabolism]] such as in [[congenital adrenal hyperplasia]], most commonly caused by [[congenital adrenal hyperplasia due to 21-hydroxylase deficiency|21-hydroxylase deficiency]].<ref name="pmid21623779">{{cite journal |vauthors=Unluhizarci K, Kaltsas G, Kelestimur F |title= Non polycystic ovary syndrome-related endocrine disorders associated with hirsutism |journal= Eur J Clin Invest |volume=42 |issue=1 |pages=86–94 |year=2012 |pmid=21623779 |doi= 10.1111/j.1365-2362.2011.02550.x |s2cid= 23701817 }}</ref>
* [[Acromegaly]] and [[gigantism]] ([[growth hormone]] and IGF-1 excess), usually due to [[pituitary tumor]]s.<ref name="pmid21623779" />

=== Non-endocrine causes ===
Causes of hirsutism not related to hyperandrogenism include:

* Familial: Family history of hirsutism with normal androgen levels.<ref name=":3">{{Cite journal |last1=Radi |first1=Suhaib |last2=Tamilia |first2=Michael |date=2019-12-30 |title=Adrenocortical carcinoma: an ominous cause of hirsutism |journal=BMJ Case Reports |volume=12 |issue=12 |pages=e232547 |doi=10.1136/bcr-2019-232547 |issn=1757-790X |pmc=6954802 |pmid=31892624}}</ref>
* Drug-induced: medications were used before the onset of hirsutism. The recommendation is to stop the medication and replace it with another.<ref name=":0" />
** [[Minoxidil]]<ref name="pmid26903750">{{cite journal | vauthors = Chellini PR, Pirmez R, Raso P, Sodré CT | title = Generalized Hypertrichosis Induced by Topical Minoxidil in an Adult Woman | journal = Int J Trichology | volume = 7 | issue = 4 | pages = 182–3 | year = 2015 | pmid = 26903750 | pmc = 4738488 | doi = 10.4103/0974-7753.171587 | doi-access = free }}</ref><ref name="pmid12702063">{{cite journal | vauthors = Dawber RP, Rundegren J | title = Hypertrichosis in females applying minoxidil topical solution and in normal controls | journal = J Eur Acad Dermatol Venereol | volume = 17 | issue = 3 | pages = 271–5 | year = 2003 | pmid = 12702063 | doi = 10.1046/j.1468-3083.2003.00621.x| s2cid = 23329383 }}</ref> 
** [[Androgen]]s like [[testosterone]], [[anabolic steroid]]s, and [[androgen]]ic [[progestin]]s<ref name=":3" /><ref name=":0" />
* [[Valproic acid]] and [[methyldopa]]<ref name=":3" /><ref name=":0" />
* [[Pregnancy]]: Due to changes in hormone production<ref name=":6" />
* [[Idiopathic disease|Idiopathic]]: When no other cause can be attributed to an individual's hirsutism, the cause is considered idiopathic by exclusion.<ref name=":0" /> In these cases, [[menstrual cycles]] and levels of conventionally tested androgens (testosterone, [[androstenedione]], and [[dehydroepiandrosterone sulfate]]) are normal.<ref name=":4">{{Cite journal |last1=Bode |first1=David |last2=Seehusen |first2=Dean A. |last3=Baird |first3=Drew |date=2012-02-15 |title=Hirsutism in Women |url=https://www.aafp.org/pubs/afp/issues/2012/0215/p373.html |journal=American Family Physician |language=en-US |volume=85 |issue=4 |pages=373–380|pmid=22335316 }}</ref> Around 10 to 15% of women with hirsutism have idiopathic hirsutism.<ref name="pmid35292252">{{cite journal | vauthors = de Kroon RW, den Heijer M, Heijboer AC | title = Is idiopathic hirsutism idiopathic? | journal = Clin Chim Acta | volume = 531 | issue = | pages = 17–24 | date = June 2022 | pmid = 35292252 | doi = 10.1016/j.cca.2022.03.011 | s2cid = 247419684 | url = | doi-access = free }}</ref> Idiopathic hirsutism may be due to increased production of [[dihydrotestosterone]] (DHT) in hair follicles and hence may actually still be due to hyperandrogenism.<ref name="pmid35292252" /> It may be detectable by measurement of DHT or DHT metabolites.<ref name="pmid35292252" />
** Rice et al. 2016 propose that idiopathic hirsutism is caused by epigenetic inheritance of discordant epigenetic markers. It is testable with current technology.<ref>{{Cite journal |last1=Rice |first1=William R. |last2=Friberg |first2=Urban |last3=Gavrilets |first3=Sergey |date=2016 |title=Sexually antagonistic epigenetic marks that canalize sexually dimorphic development |url=http://volweb2.utk.edu/~gavrila/papers/mol_ecol_16.pdf |journal=Molecular Ecology |language=en |volume=25 |issue=8 |pages=1812–1822 |bibcode=2016MolEc..25.1812R |doi=10.1111/mec.13490 |issn=0962-1083 |pmid=26600375 |s2cid=71599}}</ref>

{| class="wikitable"
|+
! Hormonal causes:<ref name=":3" />
! Description: 
! Clinical cues:
|-
| [[Polycystic ovary syndrome]]
| PCOS is a condition characterized by excess androgens that can lead to hirsutism, irregular periods, and even infertility. The excess androgens can lead to disruptions in normal body hormones in the [[Hypothalamic–pituitary–gonadal axis|hypothalamic-pituitary-gonadal axis]] leading to these symptoms.<ref name="pmid31384717">{{cite journal |vauthors=Witchel SF, Oberfield SE, Peña AS |title=Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls |journal=J Endocr Soc |volume=3 |issue=8 |pages=1545–1573 |date=August 2019 |pmid=31384717 |pmc=6676075 |doi=10.1210/js.2019-00078}}</ref> With PCOS, hair may grow on the face (like on the upper lip, chin, or jawline), chest, stomach, and back.<ref>{{Cite web |author=Emma |date=November 4, 2024 |title=What Are the First Signs of PCOS in Teenagers? |url=https://pcosnest.com/what-are-the-first-signs-of-pcos-in-teenager/ |website=PCOS Nest}}</ref>
| Characterized by having two of three Rotterdam criteria:

* Oligomenorrhea (fewer than eight menses in a year)
* Clinical or biochemical evidence of hyperandrogenism 
* Polycystic ovaries on ultrasound
<ref>{{Cite journal |last1=Legro |first1=Richard S. |last2=Arslanian |first2=Silva A. |last3=Ehrmann |first3=David A. |last4=Hoeger |first4=Kathleen M. |last5=Murad |first5=M. Hassan |last6=Pasquali |first6=Renato |last7=Welt |first7=Corrine K. |date=December 2013 |title=Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline |journal=The Journal of Clinical Endocrinology & Metabolism |language=en |volume=98 |issue=12 |pages=4565–4592 |doi=10.1210/jc.2013-2350 |issn=0021-972X |pmc=5399492 |pmid=24151290}}</ref>
|-
| [[Cushing's syndrome]]
| Cushing syndrome occurs when there is an endogenous or exogenous elevated levels of cortisol. One cause of endogenous Cushing syndrome is an adrenocorticotrophic hormone-secreting pituitary adenoma that is responsible for high secretion of not just cortisol but also androgens from the pituitary gland.<ref name=":5">{{Cite journal |last1=Mihailidis |first1=John |last2=Dermesropian |first2=Racha |last3=Taxel |first3=Pamela |last4=Luthra |first4=Pooja |last5=Grant-Kels |first5=Jane M. |date=2015-06-04 |title=Endocrine evaluation of hirsutism |journal=International Journal of Women's Dermatology |volume=1 |issue=2 |pages=90–94 |doi=10.1016/j.ijwd.2015.04.003 |issn=2352-6475 |pmc=5418744 |pmid=28491965}}</ref>
| Cushing syndrome has an apparent symptoms including: Hirsutism weight gain, extra fat build up around the face, abdominal striae, and irregular menstruation.<ref name=":5" />
|-
| [[Congenital adrenal hyperplasia]]
| CAH can be attributed to several enzymatic deficiencies but the most common is [[Congenital adrenal hyperplasia due to 21-hydroxylase deficiency|21-beta-hydroxylase]]. In CAH, a missing enzyme responsible for normal cortisol synthesis creates a build-up of androgen precursors. This precursor gets shunted to the androgen synthesis pathway leading to increased levels of androgen. Classical CAH is discovered at birth due to increased androgens during development causing ambiguous genitalia. Meanwhile, non-classical CAH is found in puberty presenting as anovulation.<ref name=":4" />
| Can present similar to PCOS in non-classical CAH. Increase levels of 17-hydroxyprogesterone.<ref name=":3" /><ref name=":4" />
|-
| [[Androgen-secreting tumor]]s
| Tumors in the adrenal glands or in the ovaries leading to increase levels of androgens.<ref name=":4" />
| Rapid progression and [[virilization]] symptoms.<ref name=":3" />
|-
| Other less common hormonal causes: 
| [[Acromegaly]]: Elevated levels of [[insulin-like growth factor-1]].<ref name=":6">{{Citation |last1=Hafsi |first1=Wissem |title=Hirsutism |date=2022 |url=http://www.ncbi.nlm.nih.gov/books/NBK470417/ |work=StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29262139 |access-date=2022-09-15 |last2=Badri |first2=Talel}}</ref> [[Hyperthyroidism]] or [[hypothyroidism]]: Elevated or decreased levels of thyroid hormones.<ref name=":6" /> [[Hyperprolactinemia]]: Elevated levels of [[prolactin]].<ref name=":6" />
| Each of these have their own distinct presentation.<ref name=":4" />
|}