Androgen Deficiency

Androgen deficiency is a medical condition marked by inadequate androgenic activity in the body. It most often affects women and is also known as Female androgen insufficiency syndrome (FAIS), although it can occur in both genders. Androgenic activity is facilitated by androgens (a group of steroid hormones with different affinities for the androgen receptor) and depends on factors like the abundance, sensitivity, and function of androgen receptors. Androgen deficiency is linked to symptoms such as lack of energy and motivation, depression, reduced desire (libido), and in severe cases, changes in secondary sex characteristics.

Signs and symptoms

In males, symptoms include loss of libido, impotence, infertility, shrinkage of the testicles, penis, and prostate, decreased masculinization (e.g., reduced facial and body hair growth), low muscle mass, anxiety, depression, fatigue, vasomotor symptoms (hot flashes), insomnia, headaches, cardiomyopathy and osteoporosis. Additionally, symptoms of hyperestrogenism, such as gynecomastia and feminization, may also be present in males.

In males, a form of myopathy can arise from androgen deficiency, known as testosterone deficiency myopathy or (hypogonadotropic) hypogonadism with myopathy. Symptoms include elevated serum CK, symmetrical muscle wasting and muscle weakness (mainly proximal), a burning sensation in the feet at night, waddling gait, and impaired fasting glucose. EMG showed low volitional contraction of short duration polyphasic units. Muscle biopsy revealed signs of myonecrosis and regeneration, some fibre splitting, chronic inflammatory cells (macrophages) infiltrating degenerating fibres, and increased adipose and fibrous tissue (fibrosis). A predominance of type I (slow-twitch/oxidative) muscle fibres was observed, with some mixed atrophy of type II (fast-twitch/glycolytic) muscle fibres. Treatment involves hormone replacement therapy with testosterone.

In females, hypoandrogenism includes loss of libido, reduced body hair growth, depression, fatigue, vaginal vasocongestion (which may cause cramps), vasomotor symptoms (e.g., hot flashes and palpitations), insomnia, headaches, osteoporosis, and reduced muscle mass. Since estrogens are synthesized from androgens, symptoms of hypoestrogenism may appear in both sexes in cases of severe androgen deficiency.

Causes

Hypoandrogenism is primarily due to dysfunction, failure, or absence of the gonads (hypergonadotropic) or impairment of the hypothalamus or pituitary gland (hypogonadotropic). This can result from a variety of causes, including genetic conditions (e.g., GnRH/gonadotropin insensitivity and enzymatic defects of steroidogenesis), tumors, trauma, surgery, autoimmunity, radiation, infections, toxins, drugs, and others. It may also result from conditions such as androgen insensitivity syndrome or hyperestrogenism. Old age may also contribute to hypoandrogenism, as androgen levels decrease with age.

Diagnosis

Diagnosis of androgen deficiency in males is based on symptoms along with at least two testosterone measurements taken in the morning after fasting. Testing is generally not recommended for asymptomatic individuals. Androgen deficiency is not typically evaluated for diagnosis in healthy women.

Treatment

Treatment may involve hormone replacement therapy with androgens for those with symptoms. Treatment primarily enhances sexual function in males.

Gonadotropin-releasing hormone (GnRH)/GnRH agonists or gonadotropins may be administered in cases of hypogonadotropic hypoandrogenism. In 2015, the Food and Drug Administration (FDA) stated that neither the benefits nor the safety of testosterone have been confirmed for low testosterone levels due to aging. The FDA has required that testosterone product labels include warnings about the potential increased risk of heart attacks and strokes.