Hyperandrogenism
Hyperandrogenism is a medical condition characterized by high levels of androgens. It is more common in women than men. Symptoms of hyperandrogenism may include acne, seborrhea, hair loss on the scalp, increased body or facial hair, and infrequent or absent menstruation. Complications may include high blood cholesterol and diabetes. It occurs in approximately 5% of women of reproductive age.
Polycystic ovary syndrome accounts for about 70% of hyperandrogenism cases. Other causes include Congenital adrenal hyperplasia, insulin resistance, hyperprolactinemia, Cushing's disease, certain types of cancers, and certain medications. Diagnosis often involves blood tests for testosterone, 17-hydroxyprogesterone, and prolactin, as well as a pelvic ultrasound.
Treatment depends on the underlying cause. Symptoms of hyperandrogenism can be treated with birth control pills or antiandrogens, such as cyproterone acetate or spironolactone. Other measures may include hair removal techniques.
The earliest known description of the condition is attributed to Hippocrates.
In 2011, the International Association of Athletics Federations and IOC released statements restricting the eligibility of female athletes with high testosterone, whether through hyperandrogenism or as a result of a difference in sex development. These regulations were referred to by both bodies as hyperandrogenism regulations and have led to athletes with DSDs being described as having hyperandrogenism. They were revised in 2019 to focus more specifically on DSDs.
Signs and symptoms
Hyperandrogenism affects 5–10% of women of reproductive age. Hyperandrogenism can affect both men and women but is more noticeable in women since elevated levels of androgens in women may facilitate virilization. Because hyperandrogenism is characterized by elevated male sex hormone levels, symptoms of hyperandrogenism in men are often negligible. Hyperandrogenism in women is typically diagnosed in late adolescence with a medical evaluation. The medical evaluation usually consists of a pelvic exam, observation of external symptoms, and a blood test measuring androgen levels. Symptoms may include the following:Women
Hyperandrogenism, especially high levels of testosterone, can cause serious adverse effects if left untreated. High testosterone levels are associated with other health conditions such as obesity, hypertension, amenorrhea, and ovulatory dysfunction, which can lead to infertility. Prominent signs of hyperandrogenism are hirsutism, adult acne, deepening of the voice, and alopecia.Hyperandrogenism has also been observed to increase insulin tolerance, which can lead to type two diabetes and dyslipidemia, such as high cholesterol. These effects may have psychological impacts, sometimes leading to social anxiety and depression, especially in adolescent girls and young women. Paired with obesity and hirsutism, it can cause the individual to have low self-esteem.
Men
Administration of high-dose testosterone in men over a course of weeks can cause an increase in aggression and hypomanic symptoms, though these were seen in only a minority of subjects. Acute high-dose anabolic-androgenic steroid administration in males attenuates endogenous sex hormone production and affects the thyroid hormone axis. Effects on mood and aggression observed during high-dose anabolic-androgenic steroid administration may occur secondarily to hormonal changes. Many of the same signs and symptoms that are seen in women, such as alopecia and acne, may also be found in men, as well as possible differences in metabolic health outcomes. Enlargement of the prostate may also occur.Causes
While hyperandrogenism in women can be caused by external factors, it can also appear spontaneously.Polycystic ovary syndrome
Polycystic ovary syndrome is an endocrine disorder characterized by an excess of androgens produced by the ovaries. It is estimated that approximately 90% of women with PCOS demonstrate hypersecretion of these hormones. The cause of this condition is unknown. Speculations include genetic predisposition; however, the gene or genes responsible for this remain unidentified. The condition may have a hereditary basis. Other possible causes include elevated insulin production. Most cases of PCOS involve insulin resistance. It is thought that adipose tissue dysfunction plays a role in the insulin resistance seen in PCOS. Insulin can induce excess testosterone secretion from the ovaries. A complication associated with polycystic ovary syndrome is high cholesterol, which is treated with statins. In a meta-analysis, atorvastatin was shown to decrease androgen concentrations in people with hyperandrogenism.Elevated insulin leads to lower production of sex hormone binding globulin, a regulatory glycoprotein that suppresses the function of androgens. High blood levels of insulin also work in conjunction with ovarian sensitivity to insulin to cause hyperandrogenemia, the primary symptom of PCOS. Obese individuals may be more biologically inclined to PCOS due to markedly higher insulin. This hormonal imbalance can lead to chronic anovulation, in which the ovaries fail to release mature eggs. These cases of ovulatory dysfunction are linked to infertility and menstrual disturbances. A post hoc analysis from a randomized, placebo-controlled, multi-centre study carried out at 11 secondary care centres, as well as a longitudinal single-centre study on pregnant women in Norway, also determined that metformin had no effect on maternal androgens in pregnancies occurring in the setting of PCOS.
One systemic review suggested that polymorphisms in the vitamin D receptor gene are associated with the prognosis of polycystic ovary syndrome, though this is based on small sample sizes and is debated. Studies have shown benefits for vitamin D supplementation in women with vitamin D deficiency and PCOS.
Hyperinsulinemia can increase the production of androgens in the ovaries. One context in which this occurs is HAIR-AN syndrome, a rare subtype of PCOS.
Hyperthecosis and hyperinsulinemia
occurs when the cells of the ovarian stroma transition from interstitial cells, located between other cells, into luteinized theca cells. Theca cells are located in the ovarian follicles and become luteinized when the ovarian follicle bursts and a new corpus luteum is formed. The dispersal of luteinized theca cells throughout the ovarian stroma—in contrast to their distribution in PCOS, in which luteinized theca cells occur around cystic follicles only—causes women with hyperthecosis to have higher testosterone levels and virilization than women with PCOS. Elevated insulin is also characteristic of hyperthecosis. Hyperthecosis most commonly develops in postmenopausal women and is linked to acne, hirsutism, growth of the clitoris, baldness, and voice deepening.Obesity can play a role in insulin resistance. It makes thecal cells more responsive to luteinizing hormone. Therefore, obesity increases ovarian androgen production. Additionally, obesity elevates inflammatory adipokines which leads to not only adipogenesis, but also heightened insulin resistance.
Cushing's syndrome
develops as a result of long-term exposure to the hormone cortisol. Cushing's syndrome can either be exogenous or endogenous, depending on whether it is caused by an external or internal source, respectively. The intake of glucocorticoids, a type of corticosteroid, is a common cause for the development of exogenous Cushing's syndrome. Endogenous Cushing's syndrome can occur when the body produces excess cortisol. This occurs when the hypothalamus of the brain signals to the pituitary gland with excess corticotropin-releasing hormone, which in turn secretes adrenocorticotropin hormone. ACTH then causes the adrenal glands to release cortisol into the blood. Signs of Cushing's syndrome include muscle weakness, easy bruising, weight gain, male-pattern hair growth, coloured stretch marks, and an excessively reddish complexion in the face. Cushing's syndrome can cause androgen excess and hence the signs and symptoms of hyperandrogenism.Congenital adrenal hyperplasia
describes a group of autosomal recessive disorders that cause a lack of an enzyme necessary for the production of cortisol and/or aldosterone, steroid hormones produced by the adrenal cortex. Most cases of CAH are due to 21-hydroxylase deficiencies. The heightened androgen levels seen in congenital adrenal hyperplasia affect the hypothalamic–pituitary–gonadal axis. Heightened androgen levels can also affect the ovaries, which can lead to infertility as well as chronic anovulation.Since CAH consists of multiple disorders, the signs, symptoms and severity of hyperandrogenism may stem from a variety of specific mutations. Genotyping is therefore critical to verify diagnoses and to establish prognostic factors for individuals. Genotyping is also crucial for people seeking to use genetic counselling as an aid to family planning.
In women, CAH causes ambiguous genitals at birth and excessive pubic hair, enlargement of the clitoris, and hirsutism in adolescence. Although CAH causes rapid growth in childhood, adult women with CAH are shorter than average due to early puberty and closure of the growth plates in the long bones. Symptoms in males include early showings of pubic hair, enlargement of the penis, and rapid musculoskeletal growth.