Hyperandrogenism
| Hyperandrogenism | |
|---|---|
| Other names | Androgen excess |
| Frequency | 5% in reproductive age women[2] |
Hyperandrogenism is a
Treatment depends on the underlying cause.
The earliest known description of the condition is attributed to Hippocrates.[5][6]
In 2011, the
Signs and symptoms
Hyperandrogenism affects 5–10% of women of reproductive age.
- Hirsutism (male-pattern hair growth)
- Alopecia (balding)
- Masculine appearance
- Hidradenitis suppurativa
- Polycystic ovarian syndrome
- Oligomenorrhea (menstrual irregularities)
- Acne
- Obesity
- Infertility
- Deepening of voice
- Oily skin
- Seborrhea(skin inflammation)
- Libido (increased sex drive)
- Type 2 diabetes
Women
Hyperandrogenism, especially high levels of testosterone, can cause serious adverse effects if left untreated. High
Hyperandrogenism has also been observed to increase
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.[15] 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.[16] Many of the same signs and symptoms that are seen in women, such as alopecia and acne, may also be found in men.[17] Enlargement of the prostate may also occur.[17]
Causes
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
Elevated insulin leads to lower production of
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.[26][27] Studies have shown benefits for vitamin D supplementation in women with vitamin D deficiency and PCOS.[28]
Hyperinsulinemia can increase the production of androgens in the ovaries.[29] One context in which this occurs is HAIR-AN syndrome, a rare subtype of PCOS.[30][31]
Hyperthecosis and hyperinsulinemia
Obesity can play a role in insulin resistance.[34] It makes thecal cells more responsive to luteinizing hormone.[34] Therefore, obesity increases ovarian androgen production.[34] Additionally, obesity elevates inflammatory adipokines which leads to not only adipogenesis, but also heightened insulin resistance.[34]
Cushing's syndrome
Cushing's syndrome develops as a result of long-term exposure to the hormone cortisol.[35][36] Cushing's syndrome can either be exogenous or endogenous, depending on whether it is caused by an external or internal source, respectively.[37] 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.[38] Cushing's syndrome can cause androgen excess and hence the signs and symptoms of hyperandrogenism.[33]
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.[39] Heightened androgen levels can also affect the ovaries, which can lead to infertility as well as chronic anovulation.[39]
Since CAH consists of multiple disorders, the signs, symptoms and severity of hyperandrogenism may stem from a variety of specific mutations.[40] Genotyping is therefore critical to verify diagnoses and to establish prognostic factors for individuals.[41] Genotyping is also crucial for people seeking to use genetic counselling as an aid to family planning.[41]
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.[42]
Tumors
Adrenocortical carcinoma and tumors
Adrenocortical carcinoma occurs rarely; the average incidence rate is estimated to be 1–2 cases per million annually.
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 hyperandrogenism.[46]
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.[47]
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.[48]
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.[49] 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.[50]
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.[51]
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.
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.[55]
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.[56] However, no androgen elevations were found in the umbilical cord blood of children born to mothers with PCOS.[57]
Diagnosis
Diagnosing hyperandrogenism can be complex due to the wide variety and severity of signs and symptoms that may present.[58] It is most often diagnosed by checking for signs of hirsutism according to a standardized method that scores the range of excess hair growth.[11][12]
Girls may show symptoms of hyperandrogenism early in life, but physicians become more concerned when the patient is in her late teens or older.[12]
Checking medical history and a physical examination of symptoms are used for an initial diagnosis.[12] Patient history assessed includes age at thelarche, adrenarche, and menarche; patterns of menstruation; obesity; reproductive history; and the start and advancement of hyperandrogenism symptoms.[12] Patterns of menstruation are examined since irregular patterns may accompany hyperandrogenism.[11] Other conditions that may present alongside hirsutism that can contribute to diagnosis include androgenic alopecia and acne.[58] If hyperandrogenism is severe, virilization may occur.[58]
Family history is also assessed for occurrences of hyperandrogenism symptoms or obesity in other family members.[12]
Laboratory tests can measure
Prevention
Since risk factors are not known and vary among individuals with hyperandrogenism, there is no sure method to prevent the condition.[59] Accordingly, more long-term studies are needed to find a cause of the condition before a sufficient method of prevention can be established.[59]
Despite this, there are a few things that can help avoid long-term medical issues related to hyperandrogenism and
Treatment
There is no definitive treatment for hyperandrogenism as it varies with the underlying condition that causes it. As a hormonal symptom of PCOS, menopause, and other endocrine conditions, it is primarily treated as a symptom of these conditions. Drugs may be considered only in women who do not plan on becoming pregnant in the near future.
Hyperandrogenism is often managed symptomatically.
Supplementation can also contribute to the managing the symptomatic effects of hyperandrogenism. In a meta-analysis, high-dose vitamin D supplements given to women with vitamin D deficiency due to PCOS improved glucose levels, insulin sensitivity, and cholesterol levels, as well as lowering testosterone, sex hormone-binding globulin, and the free androgen index, all of which are associated with hyperandrogenism.[68] Vitamin D supplementation in women with vitamin D deficiency but without PCOS did not show the same results.[28]
Targeting insulin resistance and obesity
Lifestyle modifications are the first-line treatment for PCOS.[69] They help improve body composition, insulin resistance, and hyperandrogenism. However, it is unclear whether they help improve mood, quality of life, and reproductive outcomes.[70] A meta-analysis study in 2017 showed that bariatric surgery in women with severe obesity and PCOS decreased levels of total and free testosterone and helped correct hirsutism and menstrual dysfunction.[71]
Insulin resistance in women with PCOS is typically treated with insulin-sensitizer drugs such as metformin. Metformin can help to decrease weight and androgen levels.[72] When combined with lifestyle modifications (changes in diet and exercise), it has been linked with lower body mass index and a reduction in menstrual problems.[72] However, the use of metformin in women with PCOS should only be considered in patients with impaired glucose tolerance.[73]
Society and culture
Because androgen excess is manifested in noticeable physical features (such as hirsutism), social stigma may be associated with it.[citation needed]