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Hirsutism | |
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Specialty | Dermatology, endocrinology |
Treatment | Birth control pills, antiandrogens, insulin sensitizers [1] |
Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin hirsutus meaning "hairy". [2] It usually refers to a male pattern of hair growth in a female that may be a sign of a more serious medical condition, [3] especially if it develops well after puberty. [4] Cultural stigma against hirsutism can cause much psychological distress and social difficulty. [5] Discrimination based on facial hirsutism often leads to the avoidance of social situations and to symptoms of anxiety and depression. [6]
Hirsutism is usually the result of an underlying endocrine imbalance, which may be adrenal, ovarian, or central. [7] It can be caused by increased levels of androgen hormones. The amount and location of the hair is measured by a Ferriman–Gallwey score. It is different from hypertrichosis, which is excessive hair growth anywhere on the body. [3]
Treatments may include certain birth control pills, antiandrogens, or insulin sensitizers. [1]
Hirsutism affects between 5 and 15% of women across all ethnic backgrounds. [8] Depending on the definition and the underlying data, approximately 40% of women have some degree of facial hair. [9] About 10 to 15% of cases of hirsutism are idiopathic with no known cause. [10]
The causes of hirsutism can be divided into endocrine imbalances and non-endocrine etiologies. It is important to begin by first determining the distribution of body hair growth. If hair growth follows a male distribution, it could indicate the presence of increased androgens or hyperandrogenism. However, there are other hormones not related to androgens that can lead to hirsutism. A detailed history is taken by a provider in search of possible causes for hyperandrogenism or other non-endocrine-related causes. If the distribution of hair growth occurs throughout the body, this is referred to as hypertrichosis, not hirsutism. [11]
Endocrine causes of hirsutism include:
Causes of hirsutism not related to hyperandrogenism include:
Hormonal causes: [14] | Description: | Clinical cues: |
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Polycystic ovary syndrome | PCOS is a condition characterized by excess androgens that can lead to hirsutism, irregular periods, and even infertility. The excess androgens can lead to disruptions in normal body hormones in the hypothalamic-pituitary-gonadal axis leading to these symptoms. [21] With PCOS, hair may grow on the face (like on the upper lip, chin, or jawline), chest, stomach, and back. [22] | Characterized by having two of three Rotterdam criteria:
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Cushing's syndrome | Cushing syndrome occurs when there is an endogenous or exogenous elevated levels of cortisol. One cause of endogenous Cushing syndrome is an adrenocorticotrophic hormone-secreting pituitary adenoma that is responsible for high secretion of not just cortisol but also androgens from the pituitary gland. [24] | Cushing syndrome has an apparent symptoms including: Hirsutism weight gain, extra fat build up around the face, abdominal striae, and irregular menstruation. [24] |
Congenital adrenal hyperplasia | CAH can be attributed to several enzymatic deficiencies but the most common is 21-beta-hydroxylase. In CAH, a missing enzyme responsible for normal cortisol synthesis creates a build-up of androgen precursors. This precursor gets shunted to the androgen synthesis pathway leading to increased levels of androgen. Classical CAH is discovered at birth due to increased androgens during development causing ambitious genitalia. Meanwhile, non-classical CAH is found in puberty presenting as anovulation. [19] | Can present similar to PCOS in non-classical CAH. Increase levels of 17-hydroxyprogesterone. [14] [19] |
Androgen-secreting tumors | Tumors in the adrenal glands or in the ovaries leading to increase levels of androgens. [19] | Rapid progression and virilization symptoms. [14] |
Other less common hormonal causes: | Acromegaly: Elevated levels of insulin-like growth factor-1. [18] Hyperthyroidism or hypothyroidism: Elevated or decreased levels of thyroid hormones. [18] Hyperprolactinemia: Elevated levels of prolactin. [18] | Each of these have their own distinct presentation. [19] |
Hirsutism is a clinical diagnosis of excessive androgenic, terminal hair growth. [25] A complete physical evaluation should be done prior to initiating more extensive studies, the examiner should differentiate between widespread body hair increase and male pattern virilization. [15] One method of evaluating hirsutism is the Ferriman-Gallwey Score which gives a score based on the amount and location of hair growth. [26] The Ferriman-Gallwey Score has various cutoffs due to variable expressivity of hair growth based on ethnic background. [27] [28]
Diagnosis of patients with even mild hirsutism should include assessment of ovulation and ovarian ultrasound, due to the high prevalence of polycystic ovary syndrome (PCOS), as well as 17α-hydroxyprogesterone (because of the possibility of finding non-classic 21-hydroxylase deficiency [29] ). People with hirsutism may present with an elevated serum dehydroepiandrosterone sulfate (DHEA-S) level, however, additional imaging is required to discriminate between malignant and benign etiologies of adrenal hyperandrogenism. [30] Levels greater than 700 μg/dL are indicative of adrenal gland dysfunction, particularly congenital adrenal hyperplasia due to 21-hydroxylase deficiency. However, PCOS and idiopathic hirsutism make up 90% of cases. [15]
Treatment of hirsutism is indicated when hair growth causes patient distress. The two main approaches to treatment are pharmacologic therapies targeting androgen production/action, and direct hair removal methods including electrolysis and photo-epilation. These may be used independently or in combination. [31]
Common medications consist of antiandrogens, insulin sensitizers, and oral contraceptive pills. All three types of therapy have demonstrated efficacy on their own, however insulin sensitizers are shown to be less effective than antiandrogens and oral contraceptive pills. [32] The therapies may be combined, as directed by a physician, in line with the patient's medical goals. Antiandrogens are drugs that block the effects of androgens like testosterone and dihydrotestosterone (DHT) in the body. [13] They are the most effective pharmacologic treatment for patient-important hirsutism, however they have teratogenic potential, and are therefore not recommended in people who are pregnant or desire pregnancy. Current data does not favor any one type of oral contraceptive over another. [32]
List of medications:
Polycystic ovary syndrome, or polycystic ovarian syndrome (PCOS), is the most common endocrine disorder in women of reproductive age. The syndrome is named after cysts which form on the ovaries of some women with this condition, though this is not a universal symptom, and not the underlying cause of the disorder.
Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.
The Ferriman–Gallwey score is a method of evaluating and quantifying hirsutism in women. The method was originally published in 1961 by D. Ferriman and J.D. Gallwey in the Journal of Clinical Endocrinology.
Anovulation is when the ovaries do not release an oocyte during a menstrual cycle. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause. Chronic anovulation is a common cause of infertility.
Spironolactone, sold under the brand name Aldactone among others, is a diuretic medication primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood pressure, and low blood potassium that does not improve with supplementation, early puberty in boys, acne and excessive hair growth in women. Spironolactone is taken by mouth.
Adrenarche is an early stage in sexual maturation that happens in some higher primates, typically peaks at around 20 years of age, and is involved in the development of pubic hair, body odor, skin oiliness, axillary hair, sexual attraction/sexual desire/increased libido and mild acne. During adrenarche the adrenal glands secrete increased levels of weak adrenal androgens, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione (A4), but without increased cortisol levels. Adrenarche is the result of the development of a new zone of the adrenal cortex, the zona reticularis. Adrenarche is a process related to puberty, but distinct from hypothalamic–pituitary–gonadal axis maturation and function.
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.
Bicalutamide, sold under the brand name Casodex among others, is an antiandrogen medication that is primarily used to treat prostate cancer. It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical removal of the testicles to treat metastatic prostate cancer (mPC). To a lesser extent, it is used at high doses for locally advanced prostate cancer (LAPC) as a monotherapy without castration. Bicalutamide was also previously used as monotherapy to treat localized prostate cancer (LPC), but authorization for this use was withdrawn following unfavorable trial findings. Besides prostate cancer, bicalutamide is limitedly used in the treatment of excessive hair growth and scalp hair loss in women, as a puberty blocker and component of feminizing hormone therapy for transgender girls and women, to treat gonadotropin-independent early puberty in boys, and to prevent overly long-lasting erections in men. It is taken by mouth.
Flutamide, sold under the brand name Eulexin among others, is a nonsteroidal antiandrogen (NSAA) which is used primarily to treat prostate cancer. It is also used in the treatment of androgen-dependent conditions like acne, excessive hair growth, and high androgen levels in women. It is taken by mouth, usually three times per day.
Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroepiandrosterone (DHEA) and circulates in far greater relative concentrations than DHEA. The steroid is hormonally inert and is instead an important neurosteroid and neurotrophin.
An androgen-dependent condition, disease, disorder, or syndrome, is a medical condition that is, in part or full, dependent on, or is sensitive to, the presence of androgenic activity in the body.
Aromatase deficiency is a rare condition characterized by extremely low levels or complete absence of the enzyme aromatase activity in the body. It is an autosomal recessive disease resulting from various mutations of gene CYP19 (P450arom) which can lead to ambiguous genitalia and delayed puberty in females, continued linear growth into adulthood and osteoporosis in males and virilization in pregnant mothers. As of 2020, fewer than 15 cases have been identified in genetically male individuals and at least 30 cases in genetically female individuals.
Hyperthecosis, or ovarian hyperthecosis, is hyperplasia of the theca interna of the ovary. Hyperthecosis occurs when an area of luteinization occurs along with stromal hyperplasia. The luteinized cells produce androgens, which may lead to hirsutism and virilization in affected women.
Cyproterone acetate (CPA), sold alone under the brand name Androcur or with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the treatment of androgen-dependent conditions such as acne, excessive body hair growth, early puberty, and prostate cancer, as a component of feminizing hormone therapy for transgender individuals, and in birth control pills. It is formulated and used both alone and in combination with an estrogen. CPA is taken by mouth one to three times per day.
Benorterone, also known by its developmental code name SKF-7690 and as 17α-methyl-B-nortestosterone, is a steroidal antiandrogen which was studied for potential medical use but was never marketed. It was the first known antiandrogen to be studied in humans. It is taken by mouth or by application to skin.
A nonsteroidal antiandrogen (NSAA) is an antiandrogen with a nonsteroidal chemical structure. They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the effects of androgens like testosterone and dihydrotestosterone (DHT). NSAAs are used in the treatment of androgen-dependent conditions in men and women. They are the converse of steroidal antiandrogens (SAAs), which are antiandrogens that are steroids and are structurally related to testosterone.
The HAIR-AN syndrome is a rare subtype of polycystic ovary syndrome (PCOS) characterized by hyperandrogenism (HA), insulin resistance (IR) and acanthosis nigricans (AN). The symptoms of the HAIR-AN syndrome are largely due to severe insulin resistance, which can be secondary to blocking antibodies against the insulin receptor or genetically absent/reduced insulin receptor number/function. Insulin resistance leads to hyperinsulinemia which, in turn, leads to an excess production of androgen hormones by the ovaries. High levels of androgen hormones (hyperandrogenism) in females causes excessive hair growth, acne and irregular menstruation. Patients with both underlying mechanisms of insulin resistance may have more severe hyperandrogenism. Insulin resistance is also associated with diabetes, heart disease and excessive darkening of the skin
The medical uses of bicalutamide, a nonsteroidal antiandrogen (NSAA), include the treatment of androgen-dependent conditions and hormone therapy to block the effects of androgens. Indications for bicalutamide include the treatment of prostate cancer in men, skin and hair conditions such as acne, seborrhea, hirsutism, and pattern hair loss in women, high testosterone levels in women, hormone therapy in transgender women, as a puberty blocker to prevent puberty in transgender girls and to treat early puberty in boys, and the treatment of long-lasting erections in men. It may also have some value in the treatment of paraphilias and hypersexuality in men.
Comparison of the nonsteroidal antiandrogen (NSAA) bicalutamide with other antiandrogens reveals differences between the medications in terms of efficacy, tolerability, safety, and other parameters. Relative to the other first-generation NSAAs, flutamide and nilutamide, bicalutamide shows improved potency, efficacy, tolerability, and safety, and has largely replaced these medications in clinical practice. Compared to the second-generation NSAAs, enzalutamide and apalutamide, bicalutamide has inferior potency and efficacy but similar tolerability and safety and a lower propensity for drug interactions.
Ethinylestradiol/cyproterone acetate (EE/CPA), also known as co-cyprindiol and sold under the brand names Diane and Diane-35 among others, is a combination of ethinylestradiol (EE), an estrogen, and cyproterone acetate (CPA), a progestin and antiandrogen, which is used as a birth control pill to prevent pregnancy in women. It is also used to treat androgen-dependent conditions in women such as acne, seborrhea, excessive facial/body hair growth, scalp hair loss, and high androgen levels associated with ovaries with cysts. The medication is taken by mouth once daily for 21 days, followed by a 7-day free interval.
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