Testosterone: Wikis

  
  
  

Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.

Encyclopedia

From Wikipedia, the free encyclopedia

Testosterone
Systematic (IUPAC) name
(8R,9S,10R,13S,14S,17S)- 17-hydroxy-10,13-dimethyl- 1,2,6,7,8,9,11,12,14,15,16,17- dodecahydrocyclopenta[a]phenanthren-3-one
Identifiers
CAS number 58-22-0
57-85-2 (propionate ester)
ATC code G03BA03
PubChem 6013
ChemSpider 5791
Chemical data
Formula C19H28O2 
Mol. mass 288.42
SMILES eMolecules & PubChem
Physical data
Melt. point 155–156 °C (311–313 °F)
Spec. rot +110,2°
SEC Combust −11080 kJ/mol
Pharmacokinetic data
Bioavailability low (due to extensive first pass metabolism)
Metabolism Liver, Testis and Prostate
Half life 2-4 hours
Excretion Urine (90%), feces (6%)
Therapeutic considerations
Pregnancy cat. X (USA), Teratogenic effects
Legal status Schedule III (USA)
Schedule IV (Canada)
Routes Intramuscular injection, transdermal (cream, gel, or patch), sub-'Q' pellet
 Yes check.svgY(what is this?)  (verify)

Testosterone is a steroid hormone from the androgen group. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands. It is the principal male sex hormone and an anabolic steroid. Testosterone is evolutionarily conserved through most vertebrates, although fish make a slightly different form called 11-ketotestosterone.[1]

In men, testosterone plays a key role in the development of male reproductive tissues such as the testis and prostate as well as promoting secondary sexual characteristics such as increased muscle and bone mass and hair growth.[2] In addition, testosterone is essential for health and well-being[3] as well as preventing osteoporosis.[4]

On average, an adult human male body produces about ten times more testosterone than an adult human female body, but females are, from a behavioral perspective (rather than from an anatomical or biological perspective), more sensitive to the hormone.[5] However, the overall ranges for male and female are very wide, such that the ranges actually overlap at the low end and high end respectively.

Contents

Physiological effects

In general, androgens promote protein synthesis and growth of those tissues with androgen receptors. Testosterone effects can be classified as virilizing and anabolic, although the distinction is somewhat artificial, as many of the effects can be considered both. Testosterone is anabolic, meaning it builds up bone and muscle mass.

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.

Prenatal

Most of the prenatal androgen effects occur between 7 and 12 weeks of gestation.

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 4–6 months of age.[7][8] The function of this rise in humans is unknown. It has been speculated that "brain masculinization" is occurring since no significant changes have been identified in other parts of the body.[9][citation needed] Surprisingly, the male brain is masculinized by testosterone being aromatized into estrogen, which crosses the blood-brain barrier and enters the male brain, whereas female fetuses have alpha-fetoprotein which binds up the estrogen so that female brains are not affected.[10]

Pre-peripubertal

Pre- Peripubertal effects are the first visible effects of rising androgen levels at the end of childhood, occurring in both boys and girls.

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.

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 decrease in the later decades of adult life.

  • Libido and clitoral engorgement/penile erection frequency
  • Regulates acute HPA response under dominance challenge[12]
  • Mental and physical energy
  • Maintenance of muscle trophism
  • The most recent and reliable studies have shown that testosterone does not cause or produce deleterious effects on 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.[13][14][15]
  • Recent studies have shown conflicting results concerning the importance of testosterone in maintaining cardiovascular health.[16][17] Nevertheless, maintaining normal testosterone levels in elderly men has been shown to improve many parameters which are thought to reduce cardiovascular disease, risk such as increased lean body mass, decreased visceral fat mass, decreased total cholesterol, and glycemic control.[18]
  • Under dominance challenge, may play a role in the regulation of the fight-or-flight response[19]

Testosterone regulates the population of thromboxane A2 receptors on megakaryocytes and platelets and hence platelet aggregation in humans[20][21]

Reference ranges for blood tests, showing adult male testosterone levels in light blue at center-left.

Testosterone is necessary for normal sperm development. It activates genes in Sertoli cells, which promote differentiation of spermatogonia.

  • Studies show that falling in love decreases men's testosterone levels while increasing women's testosterone levels. It is speculated that these changes in testosterone result in the temporary reduction of differences in behavior between the sexes.[22]
  • Recent studies suggest that testosterone level plays a major role in risk taking during financial decisions.[23][24]
  • Fatherhood also decreases testosterone levels in men, suggesting that the resulting emotional and behavioral changes promote paternal care.[25]

In animals (grouse and sand lizards), higher testosterone levels have been linked to a reduced immune system activity. Testosterone seems to have become part of the honest signaling system between potential mates in the course of evolution.[26][27]

Brain

As testosterone affects the entire body (often by enlarging; men have bigger hearts, lungs, liver, etc.), the brain is also affected by this "sexual" advancement;[6] the enzyme aromatase converts testosterone into estradiol that is responsible for masculinization of the brain in a male fetus.[citation needed]

There are some differences in a male and female brain (the result of different testosterone levels), one of them being size: the male human brain is, on average, larger; however, females have more dendritic connections between brain cells[citation needed]. This means that the effect of testosterone is a greater overall brain volume, but a decreased connection between the hemispheres.[28]

A study conducted in 1996 found no immediate short term effects on mood or behavior from the administration of supraphysiologic doses of testosterone for 10 weeks on 43 healthy men.[11] Another study found a correlation between testosterone and risk tolerance in career choice among women.[29]

Literature suggests that 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,[30][31] 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,[32] where both hypo- and hypersecretion of circulating androgens have negative effects on cognition and cognitively-modulated aggressivity, as detailed above.

Contrary to what has been postulated in outdated studies and by certain sections of the media, aggressive behaviour is not typically seen in hypogonadal men who have their testosterone replaced adequately to the eugonadal/normal range. In fact, aggressive behaviour has been associated with hypogonadism and low testosterone levels and it would seem as though supraphysiological and low levels of testosterone and hypogonadism cause mood disorders and aggressive behaviour, with eugondal/normal testosterone levels being important for mental well-being. Testosterone depletion is a normal consequence of aging in men. One consequence of this is an increased risk for the development of Alzheimer’s Disease.[33][34]

Biochemistry

Biosynthesis

Human steroidogenesis, showing testosterone near bottom.

Like other steroid hormones, testosterone is derived from cholesterol (see figure to the right).[35] The first step in the biosynthesis involves the cleavage of the sidechain of cholesterol by CYP11A, a mitochondrial cytochrome P450 oxidase with the loss of six carbon atoms to give pregnenolone. In the next step, two additional carbon atoms are removed by the CYP17A enzyme in the endoplasmic reticulum to yield a variety of C19 steroids.[36] In addition, the 3-hydroxyl group is oxidized by 3-β-HSD to produce androstenedione. In the final and rate limiting step, the C-17 keto group androstenedione is reduced by 17-β hydroxysteroid dehydrogenase to yield testosterone.

The largest amounts of testosterone (>95%) are produced by the testes in men.[2] It is also synthesized in far smaller quantities in women by the thecal cells of the ovaries, by the placenta, as well as by the zona reticularis of the adrenal cortex in both sexes. In the testes, testosterone is produced by the Leydig cells.[37] The male generative glands also contain Sertoli cells which require testosterone for spermatogenesis. Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific plasma protein, sex hormone binding globulin (SHBG).

Regulation

In males, testosterone is primarily synthesized in Leydig cells. The number of Leydig cells in turn is regulated by luteinizing hormone (LH) and follicle stimulating hormone (FSH). In addition, the amount of testosterone produced by existing Leydig cells is under the control of LH which regulates the expression of 17-β hydroxysteroid dehydrogenase.[38]

Environmental factors affecting testosterone levels include:

  • Loss of status or dominance in men.[19]
  • Implicit power motivation predicts an increased testosterone release in men.[39]
  • Aging reduces testosterone release.[40]
  • Hypogonadism
  • Sleep (REM dream) increases nocturnal testosterone levels.[41]
  • Resistance training increases testosterone levels,[42] however, in older men, that increase can be avoided by protein ingestion.[43]
  • Zinc deficiency lowers testosterone levels[44] but over supplementation has no effect on serum testosterone.[45]
  • Licorice. The active ingredient in licorice root, glycyrrhizinic acid has been linked to small, clinically non-significant decreases in testosterone levels.[46] In contrast, a more recent study found that licorice administration produced a substantial testosterone decrease in a small, female-only sample.[47]

Metabolism

Approximately 7% of testosterone is reduced to 5α-dihydrotestosterone (DHT) by the cytochrome P450 enzyme 5α-reductase,[48] an enzyme highly expressed in male accessory sex organs and hair follicles.[2] Approximately 0.3% of testosterone is converted into estradiol by aromatase (CYP19A1)[49] an enzyme expressed in the brain, liver, and adipose tissues.[2]

DHT is a more potent form of testosterone while estradiol has completely different activities (feminization) compared to testosterone (masculinization). Finally testosterone and DHT may be deactivated or cleared by enzymes that hydroxylate at the 6, 7, 15 or 16 positions.[50]

Mechanism of action

The effects of testosterone in humans and other vertebrates occur by way of two main mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors.[51][52]

Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5-alpha reductase. DHT binds to the same androgen receptor even more strongly than T, so that its androgenic potency is about 5 times that of T.[53] The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects. It is important to note that if there is a 5-alpha reductase deficiency, the body (of a human) will continue growing into a female with testicles.

Androgen receptors occur in many different vertebrate body system tissues, and both males and females respond similarly to similar levels. Greatly differing amounts of testosterone prenatally, at puberty, and throughout life account for a share of biological differences between males and females.

The bones and the brain are two important tissues in humans where the primary effect of testosterone is by way of aromatization to estradiol. In the bones, estradiol accelerates maturation of cartilage into bone, leading to closure of the epiphyses and conclusion of growth. In the central nervous system, testosterone is aromatized to estradiol. Estradiol rather than testosterone serves as the most important feedback signal to the hypothalamus (especially affecting LH secretion). In many mammals, prenatal or perinatal "masculinization" of the sexually dimorphic areas of the brain by estradiol derived from testosterone programs later male sexual behavior.

The human hormone testosterone is produced in greater amounts by males, and less by females. The human hormone estrogen is produced in greater amounts by females, and less by males. Testosterone causes the appearance of masculine traits (i.e., deepening voice, pubic and facial hairs, muscular build, etc.) Like men, women rely on testosterone to maintain libido, bone density and muscle mass throughout their lives. In men, inappropriately high levels of estrogens lower testosterone, decrease muscle mass, stunt growth in teenagers, introduce gynecomastia, increase feminine characteristics, and decrease susceptibility to prostate cancer, reduces libido and causes erectile dysfunction and can cause excessive sweating and hot flushes. However, an appropriate amount of estrogens is required in the male in order to ensure well-being, bone density, libido, erectile function, etc.

Therapeutic use

Routes of administration

There are many routes of administration for testosterone. Forms of testosterone for human administration currently available include injectable (such as testosterone cypionate or testosterone enanthate in oil), oral,[54] buccal,[55] transdermal skin patches, and transdermal creams or gels.[56]

In the pipeline are "roll on" methods and nasal sprays.

Indications

The original and primary use of testosterone is for the treatment of males who have too little or no natural endogenous testosterone production—males with hypogonadism. Appropriate use for this purpose is legitimate hormone replacement therapy (testosterone replacement therapy [TRT]), which maintains serum testosterone levels in the normal range.

However, over the years, as with every hormone, testosterone or other anabolic steroids has also been given for many other conditions and purposes besides replacement, with variable success but higher rates of side effects or problems. Examples include infertility, lack of libido or erectile dysfunction, osteoporosis, penile enlargement, height growth, bone marrow stimulation and reversal of anemia, and even appetite stimulation. By the late 1940s testosterone was being touted as an anti-aging wonder drug (e.g., see Paul de Kruif's The Male Hormone).[57] Decline of testosterone production with age has led to interest in androgen replacement therapy.[58]

Testosterone strongly reduces insulin resistance, therefore it can be used as anti-diabetes mellitus drug.

To take advantage of its virilizing effects, testosterone is often administered to transsexual men as part of the hormone replacement therapy, with a "target level" of the normal male testosterone level. Like-wise, transsexual women are sometimes prescribed anti-androgens to decrease the level of testosterone in the body and allow for the effects of estrogen to develop.

Testosterone patches are effective at treating low libido in post-menopausal women.[59] Low libido may also occur as a symptom or outcome of hormonal contraceptive use. Women may also use testosterone therapies to treat or prevent loss of bone density, muscle mass and to treat certain kinds of depression and low energy state. Women on testosterone therapies may experience an increase in weight without an increase in body fat due to changes in bone and muscle density. Most undesired effects of testosterone therapy in women may be controlled by hair-reduction strategies, acne prevention, etc. There is a theoretical risk that testosterone therapy may increase the risk of breast or gynaecological cancers, and further research is needed to define any such risks more clearly.[59]

Hormone replacement therapy

Testosterone levels decline gradually with age in human beings. The clinical significance of this decrease is debated (see andropause). There is disagreement about when to treat aging men with testosterone replacement therapy. The American Society of Andrology's position is that:[60]

"... testosterone replacement therapy in aging men is indicated when both clinical symptoms and signs suggestive of androgen deficiency and decreased testosterone levels are present."

The American Association of Clinical Endocrinologists says:[61]

"Hypogonadism is defined as a free testosterone level that is below the lower limit of normal for young adult control subjects. Previously, age-related decreases in free testosterone were once accepted as normal. Currently, they are not considered normal. Patients with low-normal to subnormal range testosterone levels warrant a clinical trial of testosterone."

There isn't total agreement on the threshold of testosterone value below which a man would be considered hypogonadal. (Currently there are no standards as to when to treat women.) Testosterone can be measured as "free" (that is, bioavailable and unbound) or more commonly, "total" (including the percentage which is chemically bound and unavailable). In the United States, male total testosterone levels below 300 ng/dL from a morning serum sample are generally considered low.[62] However these numbers are typically not age-adjusted, but based on an average of a test group which includes elderly males with low testosterone levels.[citation needed] Therefore a value of 300 ng/dL might be normal for a 65-year-old male, but not normal for a 30-year-old.[citation needed] Identification of inadequate testosterone in an aging male by symptoms alone can be difficult. The signs and symptoms are non-specific, and might be confused with normal aging characteristics, such as loss of muscle mass and bone density, decreased physical endurance, decreased memory ability[citation needed], and loss of libido.

Replacement therapy can take the form of injectable depots, transdermal patches and gels, subcutaneous pellets, and oral therapy. Adverse effects of testosterone supplementation include minor side effects such as acne and oily skin, and more significant complications such as increased hematocrit which can require venipuncture in order to treat, exacerbation of sleep apnea and acceleration of pre-existing prostate cancer growth in individuals who have undergone androgen deprivation. Exogenous testosterone also causes suppression of spermatogenesis and can lead to infertility.[63] It is recommended that physicians screen for prostate cancer with a digital rectal exam and PSA (prostate specific antigen) level before starting therapy, and monitor hematocrit and PSA levels closely during therapy.

Benefits

Appropriate testosterone therapy can prevent or reduce the likelihood of osteoporosis, type 2 diabetes, cardio-vascular disease (CVD), obesity, depression and anxiety and the statistical risk of early mortality. Low testosterone also brings with it an increased risk for the development of Alzheimer’s Disease.[33][34]

A small trial in 2005 showed mixed results.[64]

Large scale trials to assess the efficiency and long-term safety of testosterone are still lacking.[65]

Adverse effects

Exogenous testosterone supplementation comes with a number of health risks. Fluoxymesterone and methyltestosterone are synthetic derivatives of testosterone. In 2006 it was reported that women taking Estratest, a combination pill including estrogen and methyltestosterone, were at considerably heightened risk of breast cancer.[citation needed] That said methyltestosterone and Fluoxymesterone are no longer prescribed by physicians given their poor safety record, and testosterone replacement in men does have a very good safety record as evidenced by over sixty years of medical use in hypogonadal men.

One adverse effect that many men complain of is that of the development of gynecomastia (breasts),[citation needed] but this is something that can be prevented by appropriate choice and dosing of medication, and, in required cases, the use of ancillary medications that help lower SHBG or estradiol. Another side-effect is having difficulty urinating.[citation needed]

Athletic use

Testosterone may be administered to an athlete in order to improve performance, and is considered to be a form of doping in most sports. There are several application methods for testosterone, including intramuscular injections, transdermal gels and patches, and implantable pellets.

Anabolic steroids (including testosterone) have also been taken to enhance muscle development, strength, or endurance. They do so directly by increasing the muscles' protein synthesis. As a result, muscle fibers become larger and repair faster than the average person's. After a series of scandals and publicity in the 1980s (such as Ben Johnson's improved performance at the 1988 Summer Olympics), prohibitions of anabolic steroid use were renewed or strengthened by many sports organizations. Testosterone and other anabolic steroids were designated a "controlled substance" by the United States Congress in 1990, with the Anabolic Steroid Control Act.[66] The levels of testosterone abused in sport greatly exceed the quantities of the steroid that are prescribed for medical use in hypogonadism.[citation needed] It is the supraphysiological doses and ultra high levels of testosterone that bring with it many undesirable effects and potential long term adverse health effects.[citation needed] Coupled with the nature of cheating in sport, this is seen as being a seriously problematic issue in modern sport, particularly given the lengths to which athletes and professional laboratories go to in trying to conceal such abuse from sports regulators. Steroid abuse once again came into the spotlight recently as a result of the Chris Benoit double murder-suicide in 2007, and the media frenzy surrounding it - however, there has been no evidence indicating steroid use as a contributing factor.

Synthetic analogs

A number of synthetic analogs of testosterone have been developed with improved bioavailability and metabolic half life relative to testosterone. Many of these analogs have an alkyl group introduced at the C-17 position in order to prevent conjugation and hence improve oral bioavailability. These are the so-called “17-aa” (17-alkyl androgen) family of androgens such as fluoxymesterone and methyltestosterone.

Related drugs

Some drugs specifically target testosterone as a way of treating certain conditions. For example, finasteride inhibits the conversion of testosterone into dihydrotestosterone (DHT), a metabolite which is more potent than testosterone. By lowering the levels of dihydrotestosterone, finasteride may be used for various conditions associated with androgens, such as benign prostatic hyperplasia (BPH) and androgenetic alopecia (male-pattern baldness). That said, there are many men who have complained of long lasting or permanent adverse effects resulting from the use of finasteride, and Dr Eugene Shippen has spoken for many years of finasteride causing a difficult to treat form of hypogonadism in some men.

History

A testicular action was linked to circulating blood fractions – now understood to be a family of androgenic hormones – in the early work on castration and testicular transplantation in fowl by Arnold Adolph Berthold (1803–1861).[67] Research on the action of testosterone received a brief boost in 1889, when the Harvard professor Charles-Édouard Brown-Séquard (1817–1894), then in Paris, self-injected subcutaneously a “rejuvenating elixir” consisting of an extract of dog and guinea pig testicle. He reported in The Lancet that his vigor and feeling of well-being were markedly restored but, predictably, the effects were transient[68] (and likely based on a placebo effect), and Brown-Séquard’s hopes for the compound were dashed. Suffering the ridicule of his colleagues, his work on the mechanisms and effects of androgens in human beings was abandoned by Brown-Séquard and succeeding generations of biochemists for nearly 40 years.

The trail remained cold until the University of Chicago’s Professor of Physiologic Chemistry, Fred C. Koch, established easy access to a large source of bovine testicles—the Chicago stockyards—and to students willing to endure the ceaseless toil of extracting their isolates. In 1927, Koch and his student, Lemuel McGee, derived 20 mg of a substance from a supply of 40 pounds of bovine testicles that, when administered to castrated roosters, pigs and rats, remasculinized them.[69] The group of Ernst Laqueur at the University of Amsterdam purified testosterone from bovine testicles in a similar manner in 1934, but isolation of the hormone from animal tissues in amounts permitting serious study in humans was not feasible until three European pharmaceutical giants—Schering (Berlin, Germany), Organon (Oss, Netherlands) and Ciba (Basel, Switzerland)—began full-scale steroid research and development programs in the 1930’s.

The Organon group in the Netherlands were the first to isolate the hormone, identified in a May 1935 paper "On Crystalline Male Hormone from Testicles (Testosterone)".[70] They named the hormone testosterone, from the stems of testicle and sterol, and the suffix of ketone. The structure was worked out by Schering’s Adolf Butenandt.[71]

The chemical synthesis of testosterone was achieved in August that year, when Butenandt and G. Hanisch published a paper describing "A Method for Preparing Testosterone from Cholesterol." Only a week later, the Ciba group in Zurich, Leopold Ruzicka (1887–1976) and A. Wettstein, announced a patent application in a paper "On the Artificial Preparation of the Testicular Hormone Testosterone (Androsten-3-one-17-ol)." These independent partial syntheses of testosterone from a cholesterol base earned both Butenandt and Ruzicka the joint 1939 Nobel Prize in Chemistry.[72][73] Testosterone was identified as 17β-hydroxyandrost-4-en-3-one (C19H28O2), a solid polycyclic alcohol with a hydroxyl group at the 17th carbon atom. This also made it obvious that additional modifications on the synthesized testosterone could be made, i.e., esterification and alkylation.

The partial synthesis in the 1930s of abundant, potent testosterone esters permitted the characterization of the hormone’s effects, so that Kochakian and Murlin (1936) were able to show that testosterone raised nitrogen retention (a mechanism central to anabolism) in the dog, after which Allan Kenyon’s group[74] was able to demonstrate both anabolic and androgenic effects of testosterone propionate in eunuchoidal men, boys, and women. The period of the early 1930s to the 1950s has been called "The Golden Age of Steroid Chemistry",[75] and work during this period progressed quickly. Research in this golden age proved that this newly synthesized compound—testosterone—or rather family of compounds (for many derivatives were developed from 1940 to 1960), was a potent multiplier of muscle, strength, and wellbeing.[57]

See also

References

  1. ^ Nelson, Randy F. (2005). An introduction to behavioral endocrinology. Sunderland, Mass: Sinauer Associates. pp. 143. ISBN 0-87893-617-3. 
  2. ^ a b c d Mooradian AD, Morley JE, Korenman SG (February 1987). "Biological actions of androgens". Endocr. Rev. 8 (1): 1–28. doi:10.1210/edrv-8-1-1. PMID 3549275. 
  3. ^ Bassil N, Alkaade S, Morley JE (June 2009). "The benefits and risks of testosterone replacement therapy: a review". Ther Clin Risk Manag 5 (3): 427–48. PMID 19707253. 
  4. ^ Tuck SP, Francis RM (2009). "Testosterone, bone and osteoporosis". Front Horm Res 37: 123–32. doi:10.1159/000176049. PMID 19011293. 
  5. ^ Dabbs M, Dabbs JM (2000). Heroes, rogues, and lovers: testosterone and behavior. New York: McGraw-Hill. ISBN 0-07-135739-4. 
  6. ^ a b Swaab DF, Garcia-Falgueras A (2009). "Sexual differentiation of the human brain in relation to gender identity and sexual orientation". Funct. Neurol. 24 (1): 17–28. PMID 19403051. 
  7. ^ Forest MG, Cathiard AM, Bertrand JA (July 1973). "Evidence of testicular activity in early infancy". J. Clin. Endocrinol. Metab. 37 (1): 148–51. doi:10.1210/jcem-37-1-148. PMID 4715291. 
  8. ^ Corbier P, Edwards DA, Roffi J (1992). "The neonatal testosterone surge: a comparative study". Arch Int Physiol Biochim Biophys 100 (2): 127–31. doi:10.3109/13813459209035274. PMID 1379488. 
  9. ^ Dakin CL, Wilson CA, Kalló I, Coen CW, Davies DC (May 2008). "Neonatal stimulation of 5-HT(2) receptors reduces androgen receptor expression in the rat anteroventral periventricular nucleus and sexually dimorphic preoptic area". Eur. J. Neurosci. 27 (9): 2473–80. doi:10.1111/j.1460-9568.2008.06216.x. PMID 18445234. 
  10. ^ http://homepage.psy.utexas.edu/homepage/class/psy308/Humm/ReviewofSexualDifferentiation
  11. ^ a b Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R (July 1996). "The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men". N. Engl. J. Med. 335 (1): 1–7. doi:10.1056/NEJM199607043350101. PMID 8637535. 
  12. ^ Mehta PH, Jones AC, Josephs RA (June 2008). "The social endocrinology of dominance: basal testosterone predicts cortisol changes and behavior following victory and defeat". J Pers Soc Psychol 94 (6): 1078–93. doi:10.1037/0022-3514.94.6.1078. PMID 18505319. http://homepage.psy.utexas.edu/homepage/faculty/josephs/pdf_documents/index.cfm.pdf. 
  13. ^ Morgentaler A, Schulman C (2009). "Testosterone and prostate safety". Front Horm Res 37: 197–203. doi:10.1159/000176054. PMID 19011298. 
  14. ^ Rhoden, E.L., M.A. Averbeck, and P.E. Teloken (2008). "Androgen replacement in men undergoing treatment for prostate cancer". J Sex Med 5 (9): 2202–8. 
  15. ^ Morgentaler, A. and A.M. Traish (2009). "Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth". Eur Urol 55 (2): 310–20. 
  16. ^ Haddad RM, Kennedy CC, Caples SM, Tracz MJ, Boloña ER, Sideras K, Uraga MV, Erwin PJ, Montori VM (January 2007). "Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials". Mayo Clin. Proc. 82 (1): 29–39. doi:10.4065/82.1.29. PMID 17285783. 
  17. ^ Jones TH, Saad F (April 2009). "The effects of testosterone on risk factors for, and the mediators of, the atherosclerotic process". Atherosclerosis. doi:10.1016/j.atherosclerosis.2009.04.016. PMID 19464009. 
  18. ^ Stanworth RD, Jones TH (2008). "Testosterone for the aging male; current evidence and recommended practice". Clin Interv Aging 3 (1): 25–44. PMID 18488876. 
  19. ^ a b Mehta PH, Josephs RA (December 2006). "Testosterone change after losing predicts the decision to compete again". Horm Behav 50 (5): 684–92. doi:10.1016/j.yhbeh.2006.07.001. PMID 16928375. 
  20. ^ Ajayi AA, Halushka PV (May 2005). "Castration reduces platelet thromboxane A2 receptor density and aggregability". QJM 98 (5): 349–56. doi:10.1093/qjmed/hci054. PMID 15820970. 
  21. ^ Ajayi AA, Mathur R, Halushka PV (June 1995). "Testosterone increases human platelet thromboxane A2 receptor density and aggregation responses". Circulation 91 (11): 2742–7. PMID 7758179. 
  22. ^ Marazziti D, Canale D. 2004.Hormonal changes when falling in love. Psychoneuroendocrinology 29(7): 931-936.
  23. ^ Sapienza P, Zingales L, Maestripieri D (September 2009). "Gender differences in financial risk aversion and career choices are affected by testosterone". Proc. Natl. Acad. Sci. U.S.A. 106 (36): 15268–73. doi:10.1073/pnas.0907352106. PMID 19706398. 
  24. ^ Apicella CL, Dreber A, Campbell B, Gray PB, Hoffman M, Little AC (November 2008). "Testosterone and financial risk preferences". Evolution and Human Behavior 29 (6): 384–390. doi:10.1016/j.evolhumbehav.2008.07.001. 
  25. ^ Berg SJ, Wynne-Edwards KE. 2001. Changes in testosterone, cortisol, and estradiol levels in men becoming fathers. Mayo Clinic Proceedings 76(1): 582-592.
  26. ^ Braude S, Tang-Martinezb Z, Taylor GT (March 1999). "Stress, testosterone, and the immunoredistribution hypothesis". Behavioral Ecology 10 (3): 345–350. doi:10.1093/beheco/10.3.345. http://beheco.oxfordjournals.org/cgi/content/full/10/3/345. 
  27. ^ Olsson M, Wapstra E, Madsen T, Silverin B (November 2000). "Testosterone, ticks and travels: a test of the immunocompetence-handicap hypothesis in free-ranging male sand lizards". Proc. Biol. Sci. 267 (1459): 2339–43. doi:10.1098/rspb.2000.1289. PMID 11413653. 
  28. ^ Turnbull O, Solms M (2002). The brain and the inner world: an introduction to the neuroscience of subjective experience. London: Karnac. ISBN 1-85575-982-9. 
  29. ^ http://www.npr.org/templates/story/story.php?storyId=112334459
  30. ^ Hogervorst E, Bandelow S, Combrinck M, Smith AD (2004). "Low free testosterone is an independent risk factor for Alzheimer's disease". Exp. Gerontol. 39 (11-12): 1633–9. doi:10.1016/j.exger.2004.06.019. PMID 15582279. 
  31. ^ Moffat SD, Zonderman AB, Metter EJ, Kawas C, Blackman MR, Harman SM, Resnick SM (January 2004). "Free testosterone and risk for Alzheimer disease in older men". Neurology 62 (2): 188–93. PMID 14745052. 
  32. ^ Moffat SD, Hampson E (April 1996). "A curvilinear relationship between testosterone and spatial cognition in humans: possible influence of hand preference". Psychoneuroendocrinology 21 (3): 323–37. doi:10.1016/0306-4530(95)00051-8. PMID 8817730. 
  33. ^ a b Pike CJ, Rosario ER, Nguyen TV (April 2006). "Androgens, aging, and Alzheimer's disease". Endocrine 29 (2): 233–41. doi:10.1385/ENDO:29:2:233. PMID 16785599. 
  34. ^ a b Rosario ER, Chang L, Stanczyk FZ, Pike CJ (September 2004). "Age-related testosterone depletion and the development of Alzheimer disease". JAMA 292 (12): 1431–2. doi:10.1001/jama.292.12.1431-b (inactive 2009-07-18). PMID 15383512. 
  35. ^ Waterman MR, Keeney DS (1992). "Genes involved in androgen biosynthesis and the male phenotype". Horm. Res. 38 (5-6): 217–21. doi:10.1159/000182546. PMID 1307739. 
  36. ^ Zuber MX, Simpson ER, Waterman MR (December 1986). "Expression of bovine 17 alpha-hydroxylase cytochrome P-450 cDNA in nonsteroidogenic (COS 1) cells". Science 234 (4781): 1258–61. PMID 3535074. 
  37. ^ Brooks RV (November 1975). "Androgens". Clin Endocrinol Metab 4 (3): 503–20. PMID 58744. 
  38. ^ Payne AH, O'Shaughnessy P (1996). "Structure, function, and regulation of steroidogenic enzymes in the Leydig cell". in Payne AH, Hardy MP, Russell LD. Leydig Cell. Vienna [Il]: Cache River Press. pp. 260-285. ISBN 0-9627422-7-9. 
  39. ^ Schultheiss OC, Campbell KL, McClelland DC (December 1999). "Implicit power motivation moderates men's testosterone responses to imagined and real dominance success". Horm Behav 36 (3): 234–41. doi:10.1006/hbeh.1999.1542. PMID 10603287. 
  40. ^ Liu PY, Pincus SM, Takahashi PY, Roebuck PD, Iranmanesh A, Keenan DM, Veldhuis JD (January 2006). "Aging attenuates both the regularity and joint synchrony of LH and testosterone secretion in normal men: analyses via a model of graded GnRH receptor blockade". Am. J. Physiol. Endocrinol. Metab. 290 (1): E34–E41. doi:10.1152/ajpendo.00227.2005. PMID 16339924. 
  41. ^ Andersen ML, Tufik S (October 2008). "The effects of testosterone on sleep and sleep-disordered breathing in men: its bidirectional interaction with erectile function". Sleep Med Rev 12 (5): 365–79. doi:10.1016/j.smrv.2007.12.003. PMID 18519168. http://www.sono.org.br/pdf/2008_Andersen_Sleep_Med_Rev.pdf. 
  42. ^ Marin DP, Figueira AJ Junior, Pinto LG. "One session of resistance training may increase serum testosterone and triiodetironine in young men". Medicine & Science in Sports & Exercise 38 (5): S285. 
  43. ^ Hulmi JJ, Ahtiainen JP, Selänne H, Volek JS, Häkkinen K, Kovanen V, Mero AA (May 2008). "Androgen receptors and testosterone in men--effects of protein ingestion, resistance exercise and fiber type". J. Steroid Biochem. Mol. Biol. 110 (1-2): 130–7. doi:10.1016/j.jsbmb.2008.03.030. PMID 18455389. 
  44. ^ Prasad AS, Mantzoros CS, Beck FW, Hess JW, Brewer GJ (May 1996). "Zinc status and serum testosterone levels of healthy adults". Nutrition 12 (5): 344–8. doi:10.1016/S0899-9007(96)80058-X. PMID 8875519. 
  45. ^ Koehler K, Parr MK, Geyer H, Mester J, Schänzer W (January 2009). "Serum testosterone and urinary excretion of steroid hormone metabolites after administration of a high-dose zinc supplement". Eur J Clin Nutr 63 (1): 65–70. doi:10.1038/sj.ejcn.1602899. PMID 17882141. 
  46. ^ Josephs RA, Guinn JS, Harper ML, Askari F (November 2001). "Liquorice consumption and salivary testosterone concentrations". Lancet 358 (9293): 1613–4. doi:10.1016/S0140-6736(01)06664-8. PMID 11716893. 
  47. ^ Armanini D, Mattarello MJ, Fiore C, Bonanni G, Scaroni C, Sartorato P, Palermo M (2004). "Licorice reduces serum testosterone in healthy women". Steroids 69 (11-12): 763–6. doi:10.1016/j.steroids.2004.09.005. PMID 15579328. 
  48. ^ Randall VA (April 1994). "Role of 5 alpha-reductase in health and disease". Baillieres Clin. Endocrinol. Metab. 8 (2): 405–31. doi:10.1016/S0950-351X(05)80259-9. PMID 8092979. 
  49. ^ Meinhardt U, Mullis PE (August 2002). "The essential role of the aromatase/p450arom". Semin. Reprod. Med. 20 (3): 277–84. doi:10.1055/s-2002-35374. PMID 12428207. 
  50. ^ Trager L (1977) (in German). Steroidhormone: Biosynthese, Stoffwechsel, Wirkung. Springer-Verlag. pp. 349. doi:0387080120. 
  51. ^ Hiipakka RA, Liao S (October 1998). "Molecular mechanism of androgen action". Trends Endocrinol. Metab. 9 (8): 317–24. doi:10.1016/S1043-2760(98)00081-2. PMID 18406296. 
  52. ^ McPhaul MJ, Young M (September 2001). "Complexities of androgen action". J. Am. Acad. Dermatol. 45 (3 Suppl): S87–94. doi:10.1067/mjd.2001.117429. PMID 11511858. 
  53. ^ Breiner M, Romalo G, Schweikert HU (August 1986). "Inhibition of androgen receptor binding by natural and synthetic steroids in cultured human genital skin fibroblasts". Klin. Wochenschr. 64 (16): 732–7. doi:10.1007/BF01734339. PMID 3762019. 
  54. ^ "Andriol". Food and Drug Administration. http://google2.fda.gov/search?client=FDA&site=FDA&oe=&lr=&proxystylesheet=FDA&output=xml_no_dtd&getfields=*&q=Andriol&as=GO. 
  55. ^ "Striant". Food and Drug Administration. http://google2.fda.gov/search?client=FDA&site=FDA&oe=&lr=&proxystylesheet=FDA&output=xml_no_dtd&getfields=*&q=Striant&as=GO. 
  56. ^ "Androgel" (PDF). Food and Drug Administration. http://www.fda.gov/medwatch/SAFETY/2003/03SEP_PI/AndroGel_PI.pdf.  and "Testim". Food and Drug Administration. http://google2.fda.gov/search?client=FDA&site=FDA&oe=&lr=&proxystylesheet=FDA&output=xml_no_dtd&getfields=*&q=Testim.&as=GO. 
  57. ^ a b de Kruif P (1945). The Male Hormone. New York: Harcourt, Brace. 
  58. ^ Myers JB, Meacham RB (2003). "Androgen replacement therapy in the aging male". Rev Urol 5 (4): 216–26. PMID 16985841. 
  59. ^ a b Davis SR, Moreau M, Kroll R, Bouchard C, Panay N, Gass M, Braunstein GD, Hirschberg AL, Rodenberg C, Pack S, Koch H, Moufarege A, Studd J (November 2008). "Testosterone for low libido in postmenopausal women not taking estrogen". N. Engl. J. Med. 359 (19): 2005–17. doi:10.1056/NEJMoa0707302. PMID 18987368. 
  60. ^ "Testosterone replacement therapy for male aging: ASA position statement". J. Androl. 27 (2): 133–4. 2006. PMID 16474019. 
  61. ^ Guay AT, Spark RF, Bansal S, Cunningham GR, Goodman NF, Nankin HR, Petak SM, Perez JB (2003). "American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of male sexual dysfunction: a couple's problem--2003 update". Endocr Pract 9 (1): 77–95. PMID 12917096. http://www.aace.com/pub/pdf/guidelines/sexdysguid.pdf. 
  62. ^ Holt EH, Zieve D (2008-03-18). "Testosterone". MedlinePlus Medical Encyclopedia. U.S. National Library of Medicine. http://www.nlm.nih.gov/MEDLINEPLUS/ency/article/003707.htm. Retrieved 2009-07-17. 
  63. ^ "Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility". Lancet 336 (8721): 955–9. October 1990. doi:10.1016/0140-6736(90)92416-F. PMID 1977002. 
  64. ^ Emmelot-Vonk MH, Verhaar HJ, Nakhai Pour HR, Aleman A, Lock TM, Bosch JL, Grobbee DE, van der Schouw YT (January 2008). "Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial". JAMA 299 (1): 39–52. doi:10.1001/jama.2007.51. PMID 18167405. 
  65. ^ Cunningham GR (2008-06-25). "Testosterone treatment in aging men". EndocrineToday.com. http://www.endocrinetoday.com/view.aspx?rid=29171. Retrieved 2009-07-17. 
  66. ^ "Anabolic Steroid Control Act". United States Sentencing Commission. 1990. http://www.ussc.gov/USSCsteroidsreport-0306.pdf#search=%22Anabolic%20Steroid%20Control%20Act%20of%201990%22. 
  67. ^ Berthold AA (1849). "Transplantation der Hoden [Transplantation of testis]" (in German). Arch. Anat. Physiol. Wissensch. 16: 42–6. 
  68. ^ Brown-Sequard CE (1889). "The effects produced on man by subcutaneous injections of liquid obtained from the testicles of animals". Lancet 2: 105. doi:10.1016/S0140-6736(00)64118-1. 
  69. ^ Gallagher TF, Koch FC (November 1929). "The testicular horomone". J. Biol. Chem. 84 (2): 495–500. 
  70. ^ David KG., Dingemanse E, Freud J. Laqueur E (May 1935). "Über krystallinisches mannliches Hormon aus Hoden (Testosteron) wirksamer als aus harn oder aus Cholesterin bereitetes Androsteron [On crystalline male hormone from testicles (testosterone) effective as from urine or from cholesterol]" (in German). Hoppe Seylers Z Physiol Chem 233: 281. 
  71. ^ Butenandt A, Hanisch G (1935). "Umwandlung des Dehydroandrosterons in Androstendiol und Testosterone; ein Weg zur Darstellung des Testosterons aus Cholestrin [About Testosterone. Conversion of Dehydro-androsterons into androstendiol and testosterone; a way for the structure assignment of testosterone from cholestrol]" (in German). Hoppe Seylers Z Physiol Chem 237 (2): 89. doi:10.1097/00005392-200102000-00004. PMID 11176375. 
  72. ^ Hoberman JM, Yesalis CE (February 1995). "The history of synthetic testosterone". Sci. Am. 272 (2): 76–81. PMID 7817189. 
  73. ^ Freeman ER, Bloom DA, McGuire EJ (February 2001). "A brief history of testosterone". J. Urol. 165 (2): 371–3. doi:10.1097/00005392-200102000-00004. PMID 11176375. 
  74. ^ Kenyon AT, Knowlton K, Sandiford I, Koch FC, Lotwin,G (February 1940). "A comparative study of the metabolic effects of testosterone propionate in normal men and women and in eunuchoidism". Endocrinology 26 (1): 26–45. doi:10.1210/Endo-26-1-26. 
  75. ^ Schwarz S, Onken D, Schubert A (July 1999). "The steroid story of Jenapharm: from the late 1940s to the early 1970s". Steroids 64 (7): 439–45. doi:10.1016/S0039-128X(99)00003-3. PMID 10443899. http://www.ingentaconnect.com/content/els/0039128x/1999/00000064/00000007/art00003. 

External links


Simple English

[[File:|thumb|Molecular structure]] Testosterone is an androgen sex steroid hormone. A steroid hormone is one that is made from cholesterol. A sex hormone is one that regulates sexual changes in the body. An androgen is the male type of sex hormone.

The testicles of men make lots of testosterone. Ovaries and adrenal glands make testosterone too. But they make much less than the testicles do. So men have much higher testosterone levels than women.

Testosterone has two different kinds of effects. One effect is anabolic. This effect causes growth of muscle and bone. The other effect of testosterone is androgenic. These effects make the body look male. This includes the effects that boys have at puberty: growing a beard, making the penis and testicles bigger, and making the voice deeper.








Got something to say? Make a comment.
Your name
Your email address
Message