While<unk>  in women can be caused by external factors, it can also appear spontaneously. Polycystic ovary syndrome Ultrasound of a polycystic ovary. Each of the dark circles represents a fluid-filled cyst. 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 cause of this condition is unknown. Speculations include genetic predisposition; however, the gene or genes responsible for this remain unidentified. The condition may<unk> ve 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<unk> . 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<unk> d 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<unk> ve 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<unk> IR-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<unk> ve 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 hHormone. 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 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). 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<unk> ir 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<unk> . Congenital adrenal hyperplasia Congenital adrenal hyperplasia (CAH) 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<unk>  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<unk> ir, 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<unk> ir, enlargement of the penis, and rapid musculoskeletal growth. 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<unk> , the possibility must be considered within this population. In one study, more than<unk> lf of tumor-affected patients<unk> d elevated levels of the androgens androstenedione, dehydroepiandrosterone sulfate, and testosterone. The elevation of androgens caused by adrenocortical carcinomas often causes patients to develop Cushing's syndrome, primary aldosteronism, and<unk> . The molecular basis of the disease<unk> s yet to be elucidated. Adenoma of the adrenal gland Adrenal adenomas are benign tumors of the adrenal gland. In most cases, the tumors display no symptoms and require no treatment. In rare cases, however, some adrenal adenomas may become activated. When activated, the adenoma begins to produce hormones in much larger quantities than what the adrenal glands would normally produce, leading to health complications including primary aldosteronism and<unk> . 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<unk>  in people with Krukenberg tumors. Menopause The end of ovulation and the beginning of menopause can result in<unk> . 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<unk> . 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<unk> . 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<unk>  include anabolic steroids, synthetic progestins, and antiepileptics; however, many other drugs may also cause<unk> . This can<unk> ppen 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<unk>  through mechanisms that remain unclear. For example, the molecular basis by which valproate induces<unk>  and polycystic ovary syndrome<unk> s yet to be determined. However, one study showed that women taking valproic acid<unk> d higher testosterone levels and incidences of<unk>  compared to women who were not taking valproic acid. Heredity<unk>  can appear as a symptom of many different genetic and medical conditions.
Hyperandrogenism
Hypergonadotropic hypogonadism
Hypogonadotropic hypogonadism
Hypergonadotropic hypergonadism
Late-onset hypogonadism
Delayed puberty
Premature thelarche
Constitutional growth delay