While hyperandrogenism in women can be caused by external factors, it can also appear spontaneously.
Polycystic ovary syndrome Polycystic ovary syndrome (PCOS) 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 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. 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 (SHBG), 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 Hyperthecosis 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. 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). 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 (
hirsutism), 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. Heightened androgen levels can also affect the ovaries, which can lead to infertility as well as chronic anovulation. 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.
Tumors Adrenocortical carcinoma and tumors Adrenocortical carcinoma occurs rarely; the average incidence rate is estimated to be 1–2 cases per million annually. The disease involves the formation of
cancerous cells within the
cortex of one or both of the
adrenal glands. Although these tumors are identified in fewer than two percent of patients diagnosed with hyperandrogenism, the possibility must be considered within this population. In one study, more than half of tumor-affected patients had elevated levels of the androgens
androstenedione,
dehydroepiandrosterone sulfate, and testosterone. The molecular basis of the disease has yet to be elucidated.
Arrhenoblastoma Arrhenoblastoma is an uncommon tumor of the ovary. It is composed of sterol cells, Leydig cells, or some combination of the two. The tumor can produce male or female hormones and may cause masculinization. In a prepubescent child, a tumor may cause precocious puberty. Malignant arrhenoblastoma accounts for 30% of cases of arrhenoblastoma, the other 70% being largely benign and curable with surgery.
Hilar cell tumor A hilar cell tumor is an androgen-producing ovarian tumor that is most commonly found in older women and often leads to the development of male sex characteristics. The tumor tends to occur around the region of the ovary where the blood vessels enter the organ, known as the
hilum. This type of tumor tends to be small in size and in most cases can be entirely removed and its symptoms reversed through surgery.
Krukenberg tumor A
Krukenberg tumor is a quickly developing malignant tumor found in one or both ovaries. In most cases, the tumor primarily originates from tissues in the stomach, pancreas, gallbladder, colon, or breast. It colonized the ovary by spreading through the
peritoneal cavity. These tumors cause virilization. Increased androgen production due to elevations in human chorionic gonadotropin is hypothesized as the main cause of hyperandrogenism in women with Krukenberg tumors.
Menopause The end of
ovulation and the beginning of
menopause can result in hyperandrogenism. During this transition, the body stops releasing estrogen at a faster rate than it stops releasing androgens. In some cases, the difference between the lower estrogen levels and higher androgen levels can produce hyperandrogenism. A decrease in sex hormone levels while the free androgen index increases can also contribute to this process.
Drugs Many drugs can provoke symptoms of hyperandrogenism. These symptoms include, but are not limited to hirsutism, acne, dermatitis, androgenic alopecia, irregularities in menstruation, clitoral hypertrophy, and the deepening of the voice. Drugs most frequently implicated in hyperandrogenism include anabolic steroids, synthetic progestins, and antiepileptics; however, many other drugs may also cause hyperandrogenism. This can happen through one of five mechanisms: the direct introduction of androgens to the body, the binding of the drug to androgen receptors (as is the case with anabolic-androgenic steroids), a reduction of sex hormone-binding globulin plasma concentration that leads to an increase in free testosterone, interference with the
hypothalamic–pituitary–ovarian (HPO) axis, or an increase in the release of adrenal androgens. Certain drugs cause hyperandrogenism through mechanisms that remain unclear. For example, the molecular basis by which
valproate induces hyperandrogenism and polycystic ovary syndrome has yet to be determined.
Heredity Hyperandrogenism can appear as a symptom of many different genetic and medical conditions. Some of the conditions with hyperandrogenic symptoms, including PCOS, may sometimes be hereditary. Additionally, it is thought that
epigenetics may contribute to the pathogenesis of polycystic ovary syndrome. One potential cause of PCOS is maternal hyperandrogenism, whereby hormonal irregularities in the mother can affect the development of the child during gestation, resulting in the passing of polycystic ovary syndrome from mother to child. However, no androgen elevations were found in the umbilical cord blood of children born to mothers with PCOS. == Diagnosis ==