Testosterone is the primary male sex hormone. Testosterone is an:
- Androgen (a male sex hormone that acts on androgen receptors)
- Steroid hormone
- Anabolic hormone (a building hormone)
Testosterone can be converted to dihydrotestosterone (DHT) in the tissues by the enzyme 5-alpha reductase, particularly in the liver, prostate and skin. DHT is a particularly potent androgen hormone (with stronger effects than testosterone).
Production
The Leydig cells in the testes produce more than 95% of the testosterone in males.
Testosterone is also produced in much smaller quantities by the:
- Adrenal cortex (the outer part of the adrenal glands)
- Ovaries in females
Cholesterol is the starting point for most steroid hormones. Cholesterol is converted through different precursor molecules, with the help of specific enzymes, to become a variety of steroid hormones:
- Testosterone
- Progesterone
- Oestrogen
- Cortisol
- Aldosterone
CLINICAL RELEVANCE
Congenital adrenal hyperplasia (CAH) is caused by a congenital deficiency of the 21-hydroxylase enzyme. 21-hydroxylase is the enzyme responsible for an essential step in the creation of aldosterone and cortisol. A deficiency of the 21-hydroxylase enzyme means that precursor molecules (17-hydroxyprogesterone and progesterone) cannot be converted to aldosterone or cortisol.
These precursors can become testosterone. The creation of testosterone does not involve 21-hydroxylase. The extra leftover precursors get converted to testosterone.
Congenital adrenal hyperplasia results in low aldosterone, low cortisol, and abnormally high testosterone. Low aldosterone and low cortisol lead to hyponatraemia (low sodium), dehydration, hyperkalaemia (high potassium), and hypoglycaemia. Due to the high testosterone, female patients often have vitalisation, meaning male characteristics, including ambiguous genitalia.
Function
Testosterone is responsible for the development of male characteristics. It promotes the development of the male reproductive system during fetal development.
During puberty, testosterone promotes further growth of the reproductive organs, the start of spermatogenesis and the development of male secondary sexual characteristics (e.g., facial hair, deep voice and increased muscle mass).
Testosterone has various ongoing actions in the body:
- Increases protein synthesis and muscle mass
- Increases bone density
- Reduces subcutaneous fat
- Increases libido (desire for sexual activity)
- Supports sexual function (e.g., erections)
- Controls hair patterns (e.g., facial hair)
- Influences behaviour, emotion, mood and energy (e.g., risk-taking and competitiveness)
Hypothalamic–Pituitary–Gonadal Axis
The hypothalamus and pituitary gland are located in the middle of the brain. The hypothalamus releases gonadotropin-releasing hormone (GnRH). GnRH stimulates the anterior pituitary to produce luteinising hormone (LH) and follicle-stimulating hormone (FSH).
Luteinising hormone stimulates the Leydig cells in the testes to produce testosterone. In women, LH stimulates the theca cells of the follicles to produce testosterone.
Sperm production (spermatogenesis) is supported and coordinated by the Sertoli cells in the testes. A combination of follicle-stimulating hormone and testosterone stimulate sperm production.
Testosterone goes off to the body tissues to carry out its effects. It also travels to the brain and has a suppressing effect on the hypothalamus and the pituitary (it provides negative feedback). The presence of testosterone suppresses the release of GnRH and LH. This helps keep the testosterone level within normal limits and relatively stable over time.
Małe Hypogonadism
Hypogonadism refers to a lack of sex hormones, specifically testosterone in males. It can be categorised into:
- Primary hypogonadism, caused by a problem with the testes
- Secondary hypogonadism, caused by a problem with the pituitary
- Tertiary hypogonadism, caused by a problem with the hypothalamus
In primary hypogonadism, where the testes fail to produce adequate testosterone, the lack of testosterone means a lack of negative feedback on the hypothalamus and pituitary, resulting in increased production of GnRH, LH and FSH. This may be referred to as hypergonadotropic hypogonadism, referring to raised gonadotropins (LH and FSH) and reduced gonad (testes) function. On a blood test, LH and FSH will be high, and testosterone will be low.
Causes of primary hypogonadism include:
- Klinefelter syndrome (XXY sex chromosomes)
- Testicular damage (e.g., chemotherapy, testicular torsion or trauma)
- Infection (e.g., mumps)
In secondary hypogonadism, the pituitary produces inadequate LH and FSH, which causes understimulation of the testes and underproduction of testosterone. This may be referred to as hypogonadotropic hypogonadism, which refers to reduced gonadotropins (LH and FSH) and reduced output of the gonads (testes). On a blood test, LH, FSH, and testosterone will all be low.
Causes of secondary hypogonadism include:
- Pituitary disorders (e.g., damage by radiotherapy or a tumour)
- Hyperprolactinemia (raised prolactin suppresses LH and FSH)
- Anabolic steroid use (adding exogenous androgens suppresses the production of GnRH, LH and FSH)
- Kallman syndrome (a genetic condition)
Testosterone levels naturally decline with age as the testicular function declines. This is sometimes referred to as the andropause (similar to the female menopause).
Obesity is linked with lower testosterone levels. Fat tissue contains an enzyme called aromatase, which converts testosterone into oestrogen. Increased fat tissue means increased aromatase and more testosterone being converted to oestrogen.
A lack of testosterone can cause features of:
- Reduced muscle mass and weakness
- Reduced bone density and osteoporosis
- Increased body fat
- Metabolic syndrome (dyslipidaemia, hypertension, obesity and diabetes)
- Reduced libido (desire for sexual activity)
- Erectile dysfunction
- Infertility
- Fatigue
- Depression
Androgen Insensitivity Syndrome
Androgen insensitivity syndrome is a condition where cells are unable to respond to androgen hormones due to a lack of androgen receptors. It is an X-linked recessive genetic condition caused by a mutation in the androgen receptor gene on the X chromosome. Extra androgens are converted into oestrogen, resulting in female secondary sexual characteristics. It was previously known as testicular feminisation syndrome.
Patients with androgen insensitivity syndrome are genetically male, with XY sex chromosomes. However, the absent response to testosterone and the conversion of additional androgens to oestrogen result in a female phenotype externally. Typical male sexual characteristics do not develop, and patients have normal female external genitalia and breast tissue.
Patients have testes in the abdomen or inguinal canal, and absence of a uterus, upper vagina, cervix, fallopian tubes and ovaries. The female internal organs do not develop because the testes produce anti-Müllerian hormone, which prevents males from developing an upper vagina, uterus, cervix and fallopian tubes.
Hyperandrogenism
There are several conditions that can lead to increased androgens (hyperandrogenism):
- Polycystic ovarian syndrome (involving multiple ovarian cysts, lack of ovulation and absent periods)
- Congenital adrenal hyperplasia (a genetic condition causing deficiency of the 21-hydroxylase enzyme)
- Androgen-secreting tumours of the ovaries or adrenal glands
- Anabolic steroid use (exogenous steroids)
Symptoms of hyperandrogenism are most notable in women, causing virilisation (male characteristics), facial hair (hirsutism), deepening of the voice, increased muscle mass and changes to the genitals.
Sex Hormone-Binding Globulin
Sex hormone-binding globulin (SHBG) is a carrier protein produced by the liver and found in the bloodstream. It binds to the sex hormones (testosterone, dihydrotestosterone and oestrogen). When testosterone is bound to SHBG, it is inactive, meaning it cannot exert its effects on the tissues. There is an inverse relationship between the SHBG level and the activity of testosterone. When there is more SHBG, there is less free testosterone, resulting in less androgen activity.
Low SHBG is found in female patients with polycystic ovarian syndrome, which leads to increased androgen activity, causing symptoms such as hirsutism (male-pattern facial hair) and acne.
Raised SHBG is found in older age, liver cirrhosis and hyperthyroidism and leads to reduced androgen activity.
Prostate Health
Androgens, particularly dihydrotestosterone (DHT), stimulate prostate cell growth. This can contribute to:
- Benign prostatic hyperplasia (growth of the prostate, causing urinary symptoms)
- Prostate cancer
Androgenetic Alopecia
Androgenetic alopecia refers to male pattern baldness. Androgenic refers to it being caused by androgens. Alopecia refers to hair loss. It is driven by the effects of dihydrotestosterone (DHT).
Certain individuals are more genetically predisposed to developing androgenetic alopecia. Multiple genes are responsible, and the condition is not inherited in a predictable fashion.
Dihydrotestosterone (DHT) causes the affected hair follicles to gradually shrink and eventually stop producing hairs. This effect occurs in a typical pattern, causing hair loss at the front, top and vertex (crown), where the hair follicles are particularly susceptible to DHT.
Medications
Testosterone replacement therapy (TRT) can be used to treat hypogonadism causing a low testosterone level. Testosterone can be administered as a long-acting intramuscular injection or a daily transdermal gel or tablet.
5-alpha reductase inhibitors (e.g., finasteride) block the enzyme 5-alpha reductase, which converts testosterone to dihydrotestosterone. They are used for treating benign prostatic hypertrophy and androgenetic alopecia.
Gonadotropin-releasing hormone (GnRH) agonists (e.g., goserelin and leuprorelin) shut down the production of sex hormones (testosterone in men and oestrogen in women). They initially stimulate the pituitary gland to produce a surge in FSH and LH, with a short-term increase in testosterone or oestrogen. However, this is followed by a longer period of desensitisation and down-regulation of FSH and LH from the pituitary, with a long-term drop in testosterone or oestrogen. They are used to treat many conditions, for example:
- Prostate cancer
- Breast cancer
- Endometriosis
Anti-androgen medications (e.g., bicalutamide and cyproterone acetate) work by blocking androgen receptors. They are primarily used to treat prostate cancer. Cyproterone acetate is found in certain contraceptive pills (combined with oestrogen) and can help treat acne and hirsutism.
Last updated August 2024
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