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

Testosterone is the primary male sex hormone and androgen in males.[4] 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.[5] 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.[6][7] 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,[8] 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.[9] It exerts its action through binding to and activation of the androgen receptor.[9] 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.[10] As the metabolism of testosterone in males is more pronounced, the daily production is about 20 times greater in men.[11][12] Females are also more sensitive to the hormone.[13][page needed]

In addition to its role as a natural hormone, testosterone is used as a medication to treat hypogonadism and breast cancer.[14] 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.[15] The World Anti-Doping Agency lists it as S1 Anabolic agent substance "prohibited at all times".[16]

Biological effects

Effects on physiological development

In general, androgens such as testosterone promote protein synthesis and thus growth of tissues with androgen receptors.[17] 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.[18] The relative potency of these effects can depend on various factors and is a topic of ongoing research.[19][20] Testosterone can either directly exert effects on target tissues or be metabolized by 5α-reductase into dihydrotestosterone (DHT) or aromatized to estradiol (E2).[19] 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.[19]

• 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 (usually at puberty) a deepening of the voice, growth of facial hair (such as the beard) and 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.[21]

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.[citation needed]

During the second trimester, androgen level is associated with sex formation.[22] Specifically, testosterone, along with anti-Müllerian hormone (AMH) promote growth of the Wolffian duct and degeneration of the Müllerian duct respectively.[23] 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.[24] 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.[25]

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.[26][27] 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.[28] The male brain is masculinized by the aromatization of testosterone into estradiol,[29] 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.[30]

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.[31]

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:[31][32]

• 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.[33]
• 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.