Hirsutism is defined as excessive hair growth in various body areas commonly known as “androgen-dependent” sites. Androgens are a group of hormones present in both the male and female, but the levels are much higher in the male (ie. testosterone). Androgen dependent body sites refer to body areas where males have more hair, including the upper and lower back, lower abdomen, thighs and legs, between breasts, chin and the face. It is well known that there is a cultural bias regarding what is normal hair growth. In some parts of the world such as the Mediterranean, excessive hair can be observed in healthy women on the chin, sideburns and above the upper lip.
Severe form of hirsutism is called virilization. Virilization presents with deepening of the voice, male type balding, changes in body habitus and enlargement of the clitoris. Virilization is due to excessive amount of androgen production and generally related to tumors releasing androgenic hormones (adrenal hyperplasia, androgen producing tumors of the ovary and the adrenal gland).
Hair follicle is the invagination of the skin with cells at its base that produce keratin proteins which compose the thread of hair. Cells called melanocytes produce the pigment for the skin as well as the hair follicle. Approximately 4-5 million hair follicles are present in the body other than genitalia, palms and soles, and their regulation is significantly dependent on androgenic hormones in the body.
Androgenic hormones include dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS) and testosterone (T). Testosterone is converted to dehydrotestosterone (DHT) in the hair follicle by the enzyme 5-alpha reductase. DHT is the most potent androgenic hormone involved in hair growth and distribution. Some women may have normal circulating T levels, but the activity and levels of DHT may be increased resulting in increased hair growth.
Clinical evaluation of hirsutism should be initiated by taking a detailed history and physical examination. Often times additional symptoms such as menstrual irregularities, infertility, milky discharge from the breasts (galactorrhea) and thyroid disease related signs can be identified. Certain drugs can result in excessive hair growth, especially some steroids that have androgenic activity. In some cases, it may be difficult to differentiate normal and excessive hair growth based on cultural background.
Causes of Hirsutism:
Polycystic ovary syndrome (PCOS) is the most common ovarian cause of hirsutism. The syndrome presents with irregular ovulation and thus irregular menstrual cycles, increased hair growth or presence of acne, and in some cases polycystic appearing ovaries (small growing follicles - not true cysts). Most cases of PCOS women are either overweight or obese and therefore have increased insulin levels, insulin resistance or diabetes. Insulin has a close association with androgenic hormone production in PCOS patients. Elevated levels of insulin are generally co-existent with elevated levels or activity of androgenic hormones, which result in increased hair growth.
Congenital adrenal hyperplasia is the most common adrenal cause of hirsutism, although this is a rare clinical entity in an adult. The deficiency of the enzyme called 21-hydroxylase results in shifting of hormone production from 17-hydroxyprogesterone to the androgenic pathway. In severe cases, hirsutism is apparent at puberty and diagnosis is based on exclusion of other causes. It can also present in mild form in later reproductive years as well.
Another rare disease called Cushing’s syndrome can also result in hirsutism, although other signs and symptoms are common and include high blood pressure, diabetes, muscle weakness, fatigue, red stretch marks and obesity. Specific and advanced hormone testing is indicated in such clinical presentations to rule out Cushing syndrome from hirsutism.
In some cases, there is no identifiable cause or association with another disorder and such cases are labeled as idiopathic hirsutism. Androgen levels (i.e. testosterone) can be within the normal range in patients with hirsutism and are not diagnostic in most cases, because DHT hormone is the key hormone that acts on the hair follicle and is not routinely measured outside of advanced laboratories.
Diagnosis and Treatment of Hirsutism:
It is important to exclude all causes of androgen access especially if there is virilization because the cause may be due to a tumor. In almost all cases of excessive androgen production related to tumor growth, clinical signs require advanced testing to identify the tumor. In other cases of hirsutism, PCOS is the most likely associated hormone disorder and both can be treated at the same time.
The choice of treatment depends on patient’s age, desire for pregnancy or contraception and co-existing metabolic disorders such as insulin resistance. In most cases, visible effects of hirsutism such as undesired facial and body hair are the most disturbing to the patient.
Birth control pills (BCP - oral contraceptives) are one of the most commonly used agents in hirsutism treatment. BCP contain estrogen and progesterone hormones and reduce the production of androgens from the ovaries. Estrogen component of BCP also increases a protein called sex-hormone binding globulin (SHBG) in the blood, which attaches to the free testosterone hormone and decreases the free form of testosterone that exerts the biological activity. There are many formulations of BCPs, but three brands are approved by the FDA for the treatment of acne: Orthotricyclen, Yaz, and Estrostep. Although these are the only FDA approved formulations, it is common practice to use any BCP for hirsutism treatment and expect similar results.
Anti-androgenic agents include spironolactone, finasteride and flutamide. Spironolactone is an antihypertensive agent with diuretic effects that also has anti-androgenic properties. It interferes with androgen production at the level of the adrenal gland and also competes for the potent androgen called DHT at the level of its receptor. The more spironolactone binds to the androgen receptor, the less DHT binding occurs and less hair growth. Spironolactone is a potassium sparing diuretic and elevated levels of potassium do not occur with normal kidney function. The drug is generally well tolerated; side effects include irregular menstrual bleeding and breast tenderness. In most cases, BCP are used concomitantly and such side effects are rare.
Finasteride is a 5-alpha reductase inhibitor and blocks the production of DHT from testosterone. Testosterone levels are generally not changed and the side effects are rare. Hair growth is less stimulated with finasteride use because the most potent androgen DHT is produced in lower quantities.
Flutamide acts as an anti-androgen at the level of the androgen receptor. It can result in urine color turning green and can be toxic to the liver; therefore its use is limited. If the drug is used for hirsutism treatment, a low initial dose should be used with monitoring of liver function.
Eflornithine (Vaniqa) is an enzyme blocker (ornithine decarboxylase) that has an important role in the development of the hair follicle. Its use has been limited to the face initially, but now it is commonly used in other body areas as well. The side effects are burning and tingling of the skin, but the drug is generally well tolerated. Once the drug is discontinued beneficial effects are diminished within 8 weeks, which is also the case with other agents.
Mechanical hair removal should be combined with hormonal or non-hormonal treatments and can include shaving, bleaching, using depilating agents, electrolysis and laser hair removal. Laser hair removal has been one of the most popular methods recently with high success rates.