Editing Testosterone (section)

=== Effects on physiological development ===
In general, [[androgens]] such as testosterone promote [[protein synthesis]] and thus growth of tissues with [[androgen receptors]].<ref name="pmid10821325">{{cite journal | vauthors = Sheffield-Moore M | title = Androgens and the control of skeletal muscle protein synthesis | journal = Annals of Medicine | volume = 32 | issue = 3 | pages = 181–186 | date = April 2000 | pmid = 10821325 | doi = 10.3109/07853890008998825 | s2cid = 32366484 }}</ref> Testosterone can be described as having [[anabolism|anabolic]] and androgenic ([[virilization|virilising]]) effects, though these categorical descriptions are somewhat arbitrary, as there is a great deal of mutual overlap between them.<ref name="pmid25905231">{{cite book | chapter = Androgen Physiology, Pharmacology and Abuse | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK279000/ | vauthors = Handelsman DJ | title = Endotext [Internet] | publisher = MDText.com, Inc | date = January 2013 | pmid = 25905231 | access-date = November 11, 2016 | archive-date = March 9, 2021 | archive-url = https://web.archive.org/web/20210309030923/https://www.ncbi.nlm.nih.gov/books/NBK279000/ | url-status = live }}</ref> The relative potency of these effects can depend on various factors and is a topic of ongoing research.<ref name="Ceponis-2017">{{cite book | chapter-url=https://link.springer.com/referenceworkentry/10.1007/978-3-319-29456-8_11-1 | doi=10.1007/978-3-319-29456-8_11-1 | chapter=Anabolic and Metabolic Effects of Testosterone and Other Androgens: Direct Effects and Role of Testosterone Metabolic Products | title=Thyroid Diseases | series=Endocrinology | date=2017 | last1=Čeponis | first1=Jonas | last2=Wang | first2=Christina | last3=Swerdloff | first3=Ronald S. | last4=Liu | first4=Peter Y. | pages=1–22 | isbn=978-3-319-29195-6 | access-date=April 6, 2024 | archive-date=April 7, 2024 | archive-url=https://web.archive.org/web/20240407084734/https://link.springer.com/referenceworkentry/10.1007/978-3-319-29456-8_11-1 | url-status=live }}</ref><ref name="pmid12017555">{{cite journal |vauthors=Kuhn CM |title=Anabolic steroids |journal=Recent Prog Horm Res |volume=57 |issue= |pages=411–34 |date=2002 |pmid=12017555 |doi=10.1210/rp.57.1.411 |url=|doi-access=free }}</ref> Testosterone can either directly exert effects on target tissues or be metabolized by 5α-reductase into dihydrotestosterone (DHT) or aromatized to estradiol (E2).<ref name="Ceponis-2017"/> Both testosterone and DHT bind to an androgen receptor; however, DHT has a stronger binding affinity than testosterone and may have more androgenic effect in certain tissues at lower levels.<ref name="Ceponis-2017"/>
* ''Anabolic effects'' include growth of [[muscle mass]] and strength, increased [[bone density]] and strength, and stimulation of linear growth and [[bone maturation]].
* ''Androgenic effects'' include [[Developmental biology|maturation]] of the [[sex organs]], particularly the [[Human penis|penis]], and the formation of the [[scrotum]] in the fetus, and after birth (usually at [[puberty]]) a deepening of the [[human voice|voice]], growth of [[facial hair]] (such as the [[beard]]) and [[axillary hair|axillary (underarm) hair]]. Many of these fall into the category of male [[secondary sex characteristics]].

Testosterone effects can also be classified by the age of usual occurrence. For [[postnatal]] effects in both males and females, these are mostly dependent on the levels and duration of circulating [[#Free testosterone|free testosterone]].<ref>{{Cite book |vauthors=Sfetcu N |url=https://books.google.com/books?id=8jF-AwAAQBAJ&dq=Testosterone+effects+can+also+be+classified+by+the+age+of+usual+occurrence.+For+postnatal+effects+in+both+males+and+females%2C+these+are+mostly+dependent+on+the+levels+and+duration+of+circulating+free+testosterone&pg=PA1081 |title=Health & Drugs: Disease, Prescription & Medication |date=2014-05-02 |publisher=Nicolae Sfetcu |language=en |access-date=November 21, 2022 |archive-date=November 18, 2023 |archive-url=https://web.archive.org/web/20231118175431/https://books.google.com/books?id=8jF-AwAAQBAJ&dq=Testosterone+effects+can+also+be+classified+by+the+age+of+usual+occurrence.+For+postnatal+effects+in+both+males+and+females%2C+these+are+mostly+dependent+on+the+levels+and+duration+of+circulating+free+testosterone&pg=PA1081 |url-status=live }}</ref>

==== Before birth ====
Effects before birth are divided into two categories, classified in relation to the stages of development.

The first period occurs between 4 and 6 weeks of the gestation. Examples include genital virilisation such as midline fusion, [[Primordial phallus|phallic]] [[urethra]], [[scrotum|scrotal]] thinning and [[rugae|rugation]], and [[Primordial phallus|phallic]] enlargement; although the role of testosterone is far smaller than that of [[dihydrotestosterone]]. There is also development of the [[prostate]] gland and [[seminal vesicle]]s.{{citation needed|date=May 2022}}

During the second trimester, androgen level is associated with [[sex]] formation.<ref name="pmid19403051">{{cite journal | vauthors = Swaab DF, Garcia-Falgueras A | title = Sexual differentiation of the human brain in relation to gender identity and sexual orientation | journal = Functional Neurology | volume = 24 | issue = 1 | pages = 17–28 | year = 2009 | pmid = 19403051 }}</ref> Specifically, testosterone, along with anti-Müllerian hormone (AMH) promote growth of the Wolffian duct and degeneration of the Müllerian duct respectively.<ref>{{cite journal | vauthors = Xu HY, Zhang HX, Xiao Z, Qiao J, Li R | title = Regulation of anti-Müllerian hormone (AMH) in males and the associations of serum AMH with the disorders of male fertility | journal = Asian Journal of Andrology | volume = 21 | issue = 2 | pages = 109–114 | date = 2019 | pmid = 30381580 | pmc = 6413543 | doi = 10.4103/aja.aja_83_18 | doi-access = free }}</ref> This period affects the femininization or masculinization of the fetus and can be a better predictor of feminine or masculine behaviours such as sex typed behaviour than an adult's own levels. Prenatal androgens apparently influence interests and engagement in gendered activities and have moderate effects on spatial abilities.<ref>{{cite journal | vauthors = Berenbaum SA | title = Beyond Pink and Blue: The Complexity of Early Androgen Effects on Gender Development | journal = Child Development Perspectives | volume = 12 | issue = 1 | pages = 58–64 | date = March 2018 | pmid = 29736184 | pmc = 5935256 | doi = 10.1111/cdep.12261 }}</ref> Among women with [[congenital adrenal hyperplasia]], a male-typical play in childhood correlated with reduced satisfaction with the female gender and reduced heterosexual interest in adulthood.<ref>{{cite journal | vauthors = Hines M, Brook C, Conway GS | s2cid = 33519930 | title = Androgen and psychosexual development: core gender identity, sexual orientation and recalled childhood gender role behavior in women and men with congenital adrenal hyperplasia (CAH) | journal = Journal of Sex Research | volume = 41 | issue = 1 | pages = 75–81 | date = February 2004 | pmid = 15216426 | doi = 10.1080/00224490409552215 }}</ref>

==== Early infancy ====
Early infancy androgen effects are the least understood.  In the first weeks of life for male infants, testosterone levels rise. The levels remain in a pubertal range for a few months, but usually reach the barely detectable levels of childhood by 4–7 months of age.<ref name="pmid4715291">{{cite journal | vauthors = Forest MG, Cathiard AM, Bertrand JA | title = Evidence of testicular activity in early infancy | journal = The Journal of Clinical Endocrinology & Metabolism| volume = 37 | issue = 1 | pages = 148–51 | date = July 1973 | pmid = 4715291 | doi = 10.1210/jcem-37-1-148 }}</ref><ref name="pmid1379488">{{cite journal | vauthors = Corbier P, Edwards DA, Roffi J | title = The neonatal testosterone surge: a comparative study | journal = Archives Internationales de Physiologie, de Biochimie et de Biophysique | volume = 100 | issue = 2 | pages = 127–31 | year = 1992 | pmid = 1379488 | doi = 10.3109/13813459209035274 }}</ref> The function of this rise in humans is unknown. It has been theorized that brain [[virilization|masculinization]] is occurring since no significant changes have been identified in other parts of the body.<ref name="pmid18445234">{{cite journal | vauthors = Dakin CL, Wilson CA, Kalló I, Coen CW, Davies DC | title = Neonatal stimulation of 5-HT(2) receptors reduces androgen receptor expression in the rat anteroventral periventricular nucleus and sexually dimorphic preoptic area | journal = The European Journal of Neuroscience | volume = 27 | issue = 9 | pages = 2473–80 | date = May 2008 | pmid = 18445234 | doi = 10.1111/j.1460-9568.2008.06216.x | s2cid = 23978105 }}</ref> The male brain is masculinized by the aromatization of testosterone into [[estradiol]],<ref name="HäggströmRichfield2014" /> which crosses the [[blood–brain barrier]] and enters the male brain, whereas female fetuses have [[α-fetoprotein]], which binds the estrogen so that female brains are not affected.<ref name="isbn0-495-60300-7">{{cite book | vauthors = Kalat JW | title = Biological psychology | publisher = Wadsworth, Cengage Learning | location = Belmont, Calif | year = 2009 | isbn = 978-0-495-60300-9 | chapter = Reproductive behaviors | chapter-url = https://books.google.com/books?id=ZlSbk5rUY60C&pg=PA321 | page = 321 | access-date = October 8, 2020 | archive-date = January 11, 2023 | archive-url = https://web.archive.org/web/20230111143031/https://books.google.com/books?id=ZlSbk5rUY60C&pg=PA321 | url-status = live }}</ref>

==== Before puberty ====
Before puberty, effects of rising androgen levels occur in both boys and girls. These include adult-type [[body odor]], increased oiliness of skin and hair, [[acne vulgaris|acne]], [[pubarche]] (appearance of [[pubic hair]]), [[axillary hair]] (armpit hair), [[growth spurt]], accelerated [[epiphysis|bone maturation]], and [[facial hair]].<ref name="pmid15815567">{{cite journal | vauthors = Pinyerd B, Zipf WB | title = Puberty-timing is everything! | journal = Journal of Pediatric Nursing | volume = 20 | issue = 2 | pages = 75–82 | year = 2005 | pmid = 15815567 | doi = 10.1016/j.pedn.2004.12.011 | s2cid = 28274693 }}</ref>

==== Pubertal ====
[[Puberty|Pubertal]] effects begin to occur when androgen has been higher than normal adult female levels for months or years. In males, these are usual late pubertal effects, and occur in women after prolonged periods of heightened levels of [[#Free testosterone|free testosterone]] in the [[blood]].  The effects include:<ref name="pmid15815567" /><ref name= "Ganong_2012">{{cite book | vauthors = Barrett KE, Ganong WF | title = Ganong's Review of Medical Physiology | publisher = TATA McGRAW Hill | isbn = 978-1-259-02753-6 | pages = 423–25 | edition = 24 | year = 2012 }}</ref>
* Growth of [[spermatogenic]] tissue in testicles, male [[fertility]], [[human penis|penis]] or [[clitoris]] enlargement, increased [[libido]] and frequency of [[erection]] or clitoral engorgement occurs.
* Growth of [[jaw]], brow, chin, and nose and remodeling of facial bone contours, in conjunction with [[human growth hormone]] occurs.<ref name="pmid20501658">{{cite journal | vauthors = Raggatt LJ, Partridge NC | title = Cellular and molecular mechanisms of bone remodeling | journal = The Journal of Biological Chemistry | volume = 285 | issue = 33 | pages = 25103–8 | year = 2010 | pmid = 20501658 | pmc = 2919071 | doi = 10.1074/jbc.R109.041087 | doi-access = free }}</ref>
* Completion of bone maturation and termination of growth. This occurs indirectly via [[estradiol]] [[metabolites]] and hence more gradually in men than women.
* Increased muscle strength and mass, shoulders become broader and rib cage expands, deepening of voice, growth of the [[Adam's apple]].
* Enlargement of [[sebaceous glands]]. This might cause acne, subcutaneous [[body fat|fat]] in face decreases.
* Pubic hair extends to thighs and up toward [[Navel|umbilicus]], development of [[facial hair]] ([[sideburns]], [[beard]], [[moustache]]), loss of scalp hair (androgenetic alopecia), increase in [[chest hair]], periareolar hair, [[perianal]] hair, [[leg hair]], [[Axillary hair|armpit hair]].

==== Adult ====
Testosterone is necessary for normal [[sperm]] development. It activates genes in [[Sertoli cell]]s, which promote differentiation of [[spermatogonia]]. It regulates acute [[hypothalamic–pituitary–adrenal axis]] (HPA axis) response under dominance challenge.<ref name="pmid18505319">{{cite journal |vauthors=Mehta PH, Jones AC, Josephs RA |title=The social endocrinology of dominance: basal testosterone predicts cortisol changes and behavior following victory and defeat |journal=Journal of Personality and Social Psychology |volume=94 |issue=6 |pages=1078–1093 |date=Jun 2008 |pmid=18505319 |doi=10.1037/0022-3514.94.6.1078 |url=http://homepage.psy.utexas.edu/homepage/faculty/josephs/pdf_documents/index.cfm.pdf |archive-url=https://web.archive.org/web/20090419200557/http://homepage.psy.utexas.edu/homepage/faculty/josephs/pdf_documents/index.cfm.pdf |archive-date=April 19, 2009 |url-status=dead |citeseerx=10.1.1.336.2502}}</ref> Androgens including testosterone enhance muscle growth. Testosterone also regulates the population of [[Thromboxane A2|thromboxane A<sub>2</sub>]] receptors on [[megakaryocytes]] and [[platelets]] and hence platelet aggregation in humans.<ref name="pmid15820970">{{cite journal |vauthors=Ajayi AA, Halushka PV | title = Castration reduces platelet thromboxane A2 receptor density and aggregability |journal=QJM |volume=98 |issue=5 |pages=349–356 |date=May 2005 |pmid=15820970 |doi=10.1093/qjmed/hci054 |doi-access=free}}</ref><ref name="pmid7758179">{{cite journal |vauthors=Ajayi AA, Mathur R, Halushka PV |title=Testosterone increases human platelet thromboxane A2 receptor density and aggregation responses |journal=Circulation |volume=91 |issue=11 |pages=2742–2747 |date=Jun 1995 |pmid=7758179 |doi=10.1161/01.CIR.91.11.2742}}</ref>

Adult testosterone effects are more clearly demonstrable in males than in females, but are likely important to both sexes. Some of these effects may decline as testosterone levels might decrease in the later decades of adult life.<ref>{{cite journal | vauthors = Kelsey TW, Li LQ, Mitchell RT, Whelan A, Anderson RA, Wallace WH | title = A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years | journal = PLOS ONE | volume = 9 | issue = 10 | pages = e109346 | date = October 8, 2014 | pmid = 25295520 | pmc = 4190174 | doi = 10.1371/journal.pone.0109346 | bibcode = 2014PLoSO...9j9346K | doi-access = free }}</ref>

The brain is also affected by this sexual differentiation;<ref name="pmid19403051" /> the [[enzyme]] [[aromatase]] converts testosterone into [[estradiol]] that is responsible for [[masculinization]] of the brain in male mice. In humans, masculinization of the fetal brain appears, by observation of gender preference in patients with [[congenital disease|congenital]] disorders of androgen formation or androgen receptor function, to be associated with functional androgen receptors.<ref name="pmid11534997">{{cite journal |vauthors=Wilson JD |date=Sep 2001 |title=Androgens, androgen receptors, and male gender role behavior |department=Review |journal=Hormones and Behavior |volume=40 |issue=2 |pages=358–66 |doi=10.1006/hbeh.2001.1684 |pmid=11534997 |s2cid=20480423}}</ref>

There are some [[Neuroscience of sex differences|differences between a male and female brain]] that may be due to different testosterone levels, one of them being size: the male human brain is, on average, larger.<ref name="pmid17544382">{{cite journal |vauthors=Cosgrove KP, Mazure CM, Staley JK |date=Oct 2007 |title=Evolving knowledge of sex differences in brain structure, function, and chemistry |journal=Biological Psychiatry |volume=62 |issue=8 |pages=847–55 |doi=10.1016/j.biopsych.2007.03.001 |pmc=2711771 |pmid=17544382}}</ref>