Effects on physiological development In general,
androgens such as testosterone promote
protein synthesis and thus growth of tissues with
androgen receptors. Testosterone can be described as having
anabolic and androgenic (
virilising) effects, though these categorical descriptions are somewhat arbitrary, as there is a great deal of mutual overlap between them. The relative potency of these effects can depend on various factors and is a topic of ongoing research. Testosterone can either directly exert effects on target tissues or be metabolized by 5α-reductase into dihydrotestosterone (DHT) or aromatized to estradiol (E2).
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,
phallic urethra,
scrotal thinning and
rugation, and
phallic enlargement; although the role of testosterone is far smaller than that of
dihydrotestosterone. There is also development of the
prostate gland and
seminal vesicles. During the second trimester, androgen level is associated with
sex formation. Specifically, testosterone, along with anti-Müllerian hormone (AMH) promote growth of the Wolffian duct and degeneration of the Müllerian duct respectively. 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. 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.
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. The function of this rise in humans is unknown. It has been theorized that brain
masculinization is occurring since no significant changes have been identified in other parts of the body. The male brain is masculinized by the aromatization of testosterone into
estradiol,
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,
pubarche (appearance of
pubic hair),
axillary hair (armpit hair),
growth spurt, accelerated
bone maturation, and
facial hair.
Pubertal 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 in the
blood. The effects include: • Growth of
spermatogenic tissue in testicles, male
fertility,
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. • 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
fat in face decreases. • Pubic hair extends to thighs and up toward
umbilicus, development of
facial hair (
sideburns,
beard,
moustache), loss of scalp hair (androgenetic alopecia), increase in
chest hair, periareolar hair,
perianal hair,
leg hair,
armpit hair.
Adult Testosterone is necessary for normal
sperm development. It activates genes in
Sertoli cells, which promote differentiation of
spermatogonia. It regulates acute
hypothalamic–pituitary–adrenal axis (HPA axis) response under dominance challenge. Androgens including testosterone enhance muscle growth. Testosterone also regulates the population of
thromboxane A2 receptors on
megakaryocytes and
platelets and hence platelet aggregation in humans. 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. The brain is also affected by this sexual differentiation; There are some
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.
Health effects Testosterone does not appear to increase the risk of developing
prostate cancer. In people who have undergone testosterone deprivation therapy, testosterone increases beyond the castrate level have been shown to increase the rate of spread of an existing prostate cancer. Conflicting results have been obtained concerning the importance of
testosterone in maintaining cardiovascular health. Nevertheless, maintaining normal testosterone levels in elderly men has been shown to improve many parameters that are thought to reduce cardiovascular disease risk, such as increased lean body mass, decreased visceral fat mass, decreased total cholesterol, and improved glycemic control. High androgen levels are associated with
menstrual cycle irregularities in both clinical populations and healthy women. There also can be effects in unusual hair growth,
acne, weight gain, infertility, and sometimes even scalp hair loss. These effects are seen largely in women with polycystic ovary syndrome (
PCOS). For women with PCOS, hormones like
birth control pills can be used to help lessen the effects of this increased level of testosterone. Attention, memory, and spatial ability are key cognitive functions affected by testosterone in humans. Preliminary evidence suggests that low testosterone levels may be a risk factor for cognitive decline and possibly for
dementia of the Alzheimer's type, a key argument in
life extension medicine for the use of testosterone in anti-aging therapies. Much of the literature, however, suggests a curvilinear or even quadratic relationship between spatial performance and circulating testosterone, where both hypo- and hypersecretion (deficient- and excessive-secretion) of circulating androgens have negative effects on cognition.
Immune system and inflammation Testosterone deficiency is associated with an increased risk of
metabolic syndrome,
cardiovascular disease and
mortality, which are also sequelae of chronic
inflammation. Testosterone plasma concentration inversely correlates to multiple
biomarkers of inflammation including
CRP,
interleukin 1 beta,
interleukin 6,
TNF alpha and
endotoxin concentration, as well as
leukocyte count.
Medical use Testosterone is used as a medication for the treatment of
male hypogonadism,
gender dysphoria, and certain types of
breast cancer. This is known as
hormone replacement therapy (HRT) or testosterone replacement therapy (TRT), which maintains serum testosterone levels in the normal range.
Decline of testosterone production with age has led to interest in
androgen replacement therapy. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful. Testosterone is included in the
World Health Organization's list of essential medicines, which are the most important medications needed in a basic
health system. It is available as a
generic medication.), and behavioral changes. Current clinical guidelines recommend comprehensive baseline evaluation including complete blood count, lipid panel, prostate-specific antigen, and cardiovascular risk assessment before initiating testosterone replacement therapy. Regular monitoring during treatment typically includes hematocrit levels every 3-6 months to prevent polycythemia, along with PSA monitoring in men over 40.
Behavioural correlations Sexual arousal Testosterone levels follow a
circadian rhythm that peaks early each day, regardless of sexual activity. In women, correlations may exist between positive orgasm experience and testosterone levels. Studies have shown small or inconsistent correlations between testosterone levels and male orgasm experience, as well as sexual assertiveness in both sexes. Sexual arousal and
masturbation in women produce small increases in testosterone concentrations. The
plasma levels of various
steroids significantly increase after masturbation in men and the testosterone levels correlate to those levels.
Mammalian studies Studies conducted in rats have indicated that their degree of sexual arousal is sensitive to reductions in testosterone. When testosterone-deprived rats were given medium levels of testosterone, their sexual behaviours (copulation, partner preference, etc.) resumed, but not when given low amounts of the same hormone. Therefore, these mammals may provide a model for studying clinical populations among humans with sexual arousal deficits such as
hypoactive sexual desire disorder. Every mammalian species examined demonstrated a marked increase in a male's testosterone level upon encountering a female. The reflexive testosterone increases in male mice is related to the male's initial level of sexual arousal. In non-human primates, it may be that testosterone in puberty stimulates sexual arousal, which allows the primate to increasingly seek out sexual experiences with females and thus creates a sexual preference for females. Some research has also indicated that if testosterone is eliminated in an adult male human or other adult male primate's system, its sexual motivation decreases, but there is no corresponding decrease in ability to engage in sexual activity (mounting, ejaculating, etc.). This reaction engages penile reflexes (such as erection and ejaculation) that aid in sperm competition when more than one male is present in mating encounters, allowing for more production of successful sperm and a higher chance of reproduction.
Males In men, higher levels of testosterone are associated with periods of sexual activity. Men who watch a sexually explicit movie have an average increase of 35% in testosterone, peaking at 60–90 minutes after the end of the film, but no increase is seen in men who watch sexually neutral films. Men who watch sexually explicit films also report increased motivation and competitiveness, and decreased exhaustion. A link has also been found between relaxation following sexual arousal and testosterone levels.
Females Androgens may modulate the physiology of vaginal tissue and contribute to female genital sexual arousal. Women's level of testosterone is higher when measured pre-intercourse vs. pre-cuddling, as well as post-intercourse vs. post-cuddling. There is a time lag effect when testosterone is administered, on genital arousal in women. In addition, a continuous increase in vaginal sexual arousal may result in higher genital sensations and sexual appetitive behaviors. Testosterone may prove to be an effective treatment in
female sexual arousal disorders, and is available as a
dermal patch. There is no FDA-approved androgen preparation for the treatment of androgen insufficiency; however, it has been used as an
off-label use to treat low
libido and
sexual dysfunction in older women. Testosterone may be a treatment for postmenopausal women as long as they are effectively estrogenized. There has been speculation that these changes in testosterone result in the temporary reduction of differences in behavior between the sexes. or married, Marriage or commitment could cause a decrease in testosterone levels. Single men who have not had relationship experience have lower testosterone levels than single men with experience. It is suggested that these single men with prior experience are in a more competitive state than their non-experienced counterparts. Married men who engage in bond-maintenance activities such as spending the day with their spouse or child have no different testosterone levels compared to times when they do not engage in such activities. Collectively, these results suggest that the presence of competitive activities rather than bond-maintenance activities is more relevant to changes in testosterone levels. Men who produce more testosterone are more likely to engage in extramarital sex.
Fatherhood Fatherhood decreases testosterone levels in men, suggesting that the emotions and behaviour tied to paternal care decrease testosterone levels. In humans and other species that utilize
allomaternal care, paternal investment in offspring is beneficial to said offspring's survival because it allows the two parents to raise multiple children simultaneously. This increases the reproductive fitness of the parents because their offspring are more likely to survive and reproduce. Paternal care increases offspring survival due to increased access to higher quality food and reduced physical and immunological threats. This is particularly beneficial for humans since offspring are dependent on parents for extended periods of time and mothers have relatively short inter-birth intervals. While the extent of paternal care varies between cultures, higher investment in direct child care has been seen to be correlated with lower average testosterone levels as well as temporary fluctuations. For instance, fluctuation in testosterone levels when a child is in distress has been found to be indicative of fathering styles. If a father's testosterone levels decrease in response to hearing their baby cry, it is an indication of empathizing with the baby. This is associated with increased nurturing behavior and better outcomes for the infant.
Motivation Testosterone levels play a major role in risk-taking during financial decisions. Higher testosterone levels in men reduce the risk of becoming or staying unemployed. Research has also found that heightened levels of testosterone and
cortisol are associated with an increased risk of impulsive and violent criminal behavior. On the other hand, elevated testosterone in men may increase their generosity, primarily to attract a potential mate.
Aggression and criminality Most studies support a link between adult criminality and testosterone. Nearly all studies of juvenile delinquency and testosterone are not significant. Most studies have found testosterone to be associated with behaviors or personality traits linked with
antisocial behavior and
alcoholism. Many studies have been undertaken on the relationship between more general aggressive behavior, and feelings, and testosterone. About half of studies have found a relationship and about half, no relationship. Studies have found that testosterone facilitates aggression by modulating
vasopressin receptors in the
hypothalamus. There are two theories on the role of testosterone in aggression and competition. The first is the
challenge hypothesis which states that testosterone would increase during puberty, thus facilitating reproductive and competitive behavior which would include aggression. Testosterone and other androgens have evolved to motivate men to pursue competition, even when doing so leads to risk. By doing so, individuals with masculinized brains are better able to survive and copulate with as many mates as possible. Studies have found higher pre-natal testosterone or lower digit ratio to be correlated with higher aggression. The rise in testosterone during competition predicted aggression in males, but not in females. In one experiment, subjects who interacted with handguns showed higher testosterone levels and aggression than those who interacted with toys. One study proposed that natural selection may have caused men to be more sensitive to situations in which their status is challenged, and that testosterone is the key factor that causes these situations to spark into aggression. Structural brain characteristics associated with testosterone levels have also been found to predict individuals' levels of aggression. The
Annals of the New York Academy of Sciences has found that the use of anabolic steroids (which increases testosterone) among teenagers is correlated with increased likelihood of using violence. One study found that administering testosterone increased verbal aggression in some participants. A few studies indicate that the testosterone derivative
estradiol might play an important role in male aggression. Estradiol is known to correlate with aggression in male mice. Moreover, the conversion of testosterone to estradiol regulates male aggression in
sparrows during breeding season. Rats who were given anabolic steroids that increase testosterone were also more physically aggressive to provocation as a result of "threat sensitivity". The relationship between testosterone and aggression may also function indirectly, as it has been proposed that testosterone does not amplify tendencies towards aggression, but rather amplifies whatever tendencies will allow an individual to maintain social status when challenged. In most animals, aggression is the means of maintaining social status. However, humans have multiple ways of obtaining status. This could explain why some studies find a link between testosterone and pro-social behaviour, if pro-social behaviour is rewarded with social status. Thus the link between testosterone and aggression and violence is due to these being rewarded with social status. The relationship may also be one of a "permissive effect" whereby testosterone does elevate aggression levels, but only in the sense of allowing average aggression levels to be maintained; chemically or physically castrating the individual will reduce aggression levels (though not eliminate them) but the individual only needs a small-level of pre-castration testosterone to have aggression levels to return to normal, which they will remain at even if additional testosterone is added. Testosterone may also simply exaggerate or amplify existing aggression; for example, chimpanzees who receive testosterone increases become more aggressive to chimps lower than them in the social hierarchy, but will still be submissive to chimps higher than them. Testosterone thus does not make the chimpanzee indiscriminately aggressive, but instead amplifies his pre-existing aggression towards lower-ranked chimps. In humans, testosterone appears more to promote status-seeking and social dominance than simply increasing physical aggression. When controlling for the effects of belief in having received testosterone, women who have received testosterone make fairer offers than women who have not received testosterone.
Fairness Testosterone might encourage fair behavior. For one study, subjects took part in a behavioral experiment where the distribution of a real amount of money was decided. The rules allowed both fair and unfair offers. The negotiating partner could subsequently accept or decline the offer. The fairer the offer, the less probable a refusal by the negotiating partner. If no agreement was reached, neither party earned anything. Test subjects with an artificially enhanced testosterone level generally made better, fairer offers than those who received placebos, thus reducing the risk of a rejection of their offer to a minimum. Two later studies have empirically confirmed these results. However men with high testosterone were significantly 27% less generous in an ultimatum game. This additional information could suggest, contrarily, that testosterone may encourage greed or selfishness. Fairer offers from test subjects with higher testosterone in the original study increase the likeliness of the offer being accepted by the negotiating partner, therefore decreasing the probability of both participants leaving without any money. ==Biological activity==