Testosterone
Testosterone is the primary male sex hormone and androgen in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testicles and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass, and the growth of body hair. It is associated with increased aggression, sex drive, dominance, courtship display, and a wide range of behavioral characteristics. In addition, testosterone in both sexes is involved in health and well-being, where it has a significant effect on overall mood, cognition, social and sexual behavior, metabolism and energy output, the cardiovascular system, and in the prevention of osteoporosis. Insufficient levels of testosterone in men may lead to abnormalities including frailty, accumulation of adipose fat tissue within the body, anxiety and depression, sexual performance issues, and bone loss.
Excessive levels of testosterone in men may be associated with hyperandrogenism, higher risk of heart failure, increased mortality in men with prostate cancer, and male pattern baldness.
Testosterone is a steroid hormone from the androstane class containing a ketone and a hydroxyl group at positions three and seventeen respectively. It is biosynthesized in several steps from cholesterol and is converted in the liver to inactive metabolites. It exerts its action through binding to and activation of the androgen receptor. In humans and most other vertebrates, testosterone is secreted primarily by the testicles of males and, to a lesser extent, the ovaries of females. On average, in adult males, levels of testosterone are about seven to eight times as great as in adult females. As the metabolism of testosterone in males is more pronounced, the daily production is about 20 times greater in men. Females are also more sensitive to the hormone.
In addition to its role as a natural hormone, testosterone is used as a medication to treat hypogonadism and breast cancer. Since testosterone levels decrease as men age, testosterone is sometimes used in older men to counteract this deficiency. It is also used illicitly to enhance physique and performance, for instance in athletes. The World Anti-Doping Agency lists it as S1 Anabolic agent substance "prohibited at all times".
Regarding aggression, testosterone does not create aggression in an individual, but amplifies aggressive behaviors and responses that are already learned by the individual, increasing sensitivity to social triggers rather than inventing violence.
Biological effects
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 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 or aromatized to estradiol. 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.- 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 maturation of the sex organs, particularly the penis, and the formation of the scrotum in the fetus, and after birth a deepening of the voice, growth of facial hair and axillary hair. Many of these fall into the category of male secondary sex characteristics.
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 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, 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.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, axillary hair, growth spurt, accelerated bone maturation, and facial hair.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, loss of scalp hair, increase in chest hair, periareolar hair, perianal hair, leg hair, armpit hair.
Adult
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; 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 disorders of androgen formation or androgen receptor function, to be associated with functional androgen receptors.
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. 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 of circulating androgens have negative effects on cognition.