Testosterone is the most abundant male sex hormone (androgen) circulating in the body. It is mainly formed in the testes although androgens from the adrenal glands can also be converted into testosterone. This hormone is essential for the development of the male sex organs in the fetal stage and subsides a few months after birth. Throughout childhood boys have almost no testosterone secretion until the Leydig cells of the testes becomes active again and starts producing large amounts of the hormone. This accounts for the further development of primary sexual characteristics and the appearance of secondary sexual characteristics in males.
What is hypogonadism?
Male hypogonadism is the underactivity of the gonads (testes) which leads to a deficiency of the hormone testosterone. Without testosterone, the development of the genitalia and secondary sexual characteristics is impaired. The effect depends on when the testosterone deficiency occurs.
- Fetal onset. If hypogonadism occurs in the fetal stage and there is a failure of the testes to produce and secrete testosterone, the fetus will develop female organs. Despite the genetic difference between the genders, the lack of testosterone in fetal development will automatically have this effect.
- Childhood onset. If hypogonadism occurs before puberty, then the boy or man will continue to have underdeveloped genitalia and not develop the secondary sexual characteristics like the gruff voice, facial and body hair and larger muscle bulk. These adults will also grow taller and be less muscular. Essentially puberty is delayed but pathological causes should be differentiated from a constitutional delay in puberty (‘slow clock’).
- Adult onset. If hypogonadism occurs after puberty, then some of the primary and secondary male sexual characteristics regress partially or completely. The size of the genitals diminish slightly but not to the childhood size, loss of chest or body hair, musculature and a slight change in voice quality.
Testosterone Secretion in Males
The testicular production and secretion of testosterone is regulated by luteinizing hormone (LH) and follicle stimulating hormone (FSH). LH stimulates testosterone secretion while FSH plays more of a role in tissue development within the testes. Both LH and FSH are released from the anterior pitiutary (pituitary gland) in response to gonadotropin-releasing hormone (GnRH). If GnRH levels are low, then less LH and FSH are secreted which leads to low testosterone levels.
The cortex of the adrenal glands also produces androgens (male hormones) – dehydroepiandrosterone (DHEA) and androstenedione (andro) – which can be converted into testosterone. The quantity quantity of adrenal androgens in comparison to the testes is so small that it cannot compensate for the low hormone levels.
Types of Hypogonadism
Hypogonadism may be primary or secondary.
Primary hypogonadism is where the deficiency in testosterone lies with pathology in the testes. The gonadotropins, hormones that stimulate testosterone secretion, are raised in an attempt to ‘force’ testosterone secretion. Therefore primary hypogonadism is known as hypergonadotropic hypogonadism.
With secondary hypogonadism, the pathology leading to testosterone deficiency lies with the pituitary and/or hypothalamus. The gonadotropin levels are low and this does not stimulate testosterone secretions despite the testes being intact. This is known as hypogonadotropic hypogonadism.
There are certain mixed types of hypogonadism due to features of both primary and secondary hypogonadism.
Causes of Hypogonadism
Primary / Hypergonadotropic Hypogonadism
These causes directly affect the gonads (testes) and temporarily or permanently disrupts its ability to produce and secrete testosterone.
- Trauma or surgery to the testes
- Chemotherapy and/or radiation therapy
- Autoimmune diseases that target the testes
- Infections – mumps (orchitis), tuberculosis
- Hemochromatosis (iron overload)
- Genetic/congenital disorders
- Anorchidism – failure of testes to develop
- Cryptorchidism – undescended testes
- Steroid synthesis defects – tesosterone and other androgens are steroid hormones
- Klinefelter’s syndrome (47XXY, male phenotype)
- Turner’s syndrome (45XO, female phenotype)
Secondary / Hypogonadotropic Hypogonadism
These causes affect the hypothalamus and/or pituitary gland thereby disrupting the regulatory mechanisms that control testosterone secretion by the testes.
- Tumors – benign or malignant
- Granulomatous diseases
- Severe chronic diseases
- Endocrine diseases
- Cushing syndrome
- Hyperprolactinemia (high prolactin levels)
- Gonadotropin hormone deficiency (Kallmann syndrome) or hormone defect
- Anorexia nervosa
- Excessive physical exercise
The causes below affect both the testes and pituitary-hypothalamus axis simultaneously.
- Excessive alcohol intake (alcoholism)
- Liver failure
- Kidney failure
- Medication – corticosteroids
Signs and Symptoms
- Complete testosterone deficiency – female genitalia will develop
- Partial testosterone deficiency – underdeveloped male genitalia and hypospadias
- Lack of secondary sexual characteristics (gruff voice, chest and body hair, large muscle mass)
- Taller and thinner
- Regressions of sexual characteristics (partially or completely)
- Decrease in genitalia size
- Loss of chest and body hair
- Loss of muscle bulk
- Erectile dysfunction
- Loss of libido