Testosterone

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.

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

In addition, testosterone is essential for health and well-being] as well as preventing osteoporosis.

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. 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.

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.

• 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 the beard and axillary 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.

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.

• Adult-type body odour
• Increased oiliness of skin and hair, acne
• Pubarche (appearance of pubic hair)
• Axillary hair
• Growth spurt, accelerated bone maturation
• Hair on upper lip and sideburns.

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.

• Enlargement of sebaceous glands. This might cause acne.
• Phallic enlargement or clitoromegaly
• Increased libido and frequency of erection or clitoral engorgement
• Pubic hair extends to thighs and up toward umbilicus
• Facial hair (sideburns, beard, moustache)
• Loss of scalp hair (Androgenetic alopecia)
• Chest hair, periareolar hair, perianal hair
• Leg hair
• Axillary hair
• Subcutaneous fat in face decreases
• Increased muscle strength and mass
• Deepening of voice
• Increase in height
• Growth of the Adam’s apple
• Growth of spermatogenic tissue in testicles, male fertility
• Growth of jaw, brow, chin, nose, and remodeling of facial bone contours
• Shoulders become broader and rib cage expands
• Completion of bone maturation and termination of growth. This occurs indirectly via estradiol metabolites and hence more gradually in men than women.

Therapeutic use

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, buccal transdermal skin patches, and transdermal creams or gels.

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). Decline of testosterone production with age has led to interest in androgen replacement therapy.

Testosterone strongly reduces insulin resistance, therefore it can be used as anti diabetes agent.

Testosterone patches are effective at treating low libido in post-menopausal women. 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.

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:

“… 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:

“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. 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 Therefore a value of 300 ng/dL might be normal for a 65-year-old male, but not normal for a 30-year-old 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 abillity 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.[64] 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.

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