What is hirsutism?

Hirsutism can be defined as “excessive male pattern of hair growth in females”. The hairs may be coarse. Hirsutism affects approximately 10% of women. In general hirsutism is a variation of normal hair growth pattern, but sometimes it indicates serious underlying pathology. Hirsutism is essentially a female disease and hirsutism in men occurs very rarely if ever. Hirsutism in men can be diagnosed if excess hair growth occurs in abdomen, upper back, lower back, pelvis and thighs.

Why and how hirsutism occurs?

The hormones which are responsible for hirsutism are androgens. The main androgens which are involved in causation of hirsutism are testosterone, androstenedione, and dehydroepiandrosterone (DHEA) and sulfated form of dehydroepiandrosterone (DHEAS). Testosterone is the most important circulating androgen and it is also the penultimate androgen which mediate excess male pattern of hair growth in females to cause hirsutism. Testosterone is gets converted to more potent form, dihydrotestosterone (DHT) by enzyme 5-alpha reductase, which has 2 isoenzymes (type1 and type2). Type1 5-alpha reductase is found in sebaceous glands and type2 if found in prostate gland and in hair follicles. Dihydrotestosterone have higher affinity for androgen receptor and also it gets dissociated from androgen receptor more slowly.

What are the hirsutism causes?

The exact hirsutism causes may not be found in most of the cases of hirsutism and this type of hirsutism can be called “idiopathic hirsutism” or hirsutism due to unknown cause. But the common hirsutism causes include polycystic ovarian syndrome (PCOS) or can be called PCOS hirsutism, congenital adrenal hyperplasia (CAH) etc. The known causes of hirsutism are:

• Gonadal hyperandrogenism like polycystic ovarian syndrome, insulin resistance syndrome, tumor in ovary (benign or malignant), functional ovarian hyperandrogenism, steroidogenic blocks of ovaries etc.
• Adrenal hyperandrogenism like functional adrenal hyperandrogenism, CAH (congenital adrenal hyperplasia, which may be classic or nonclassic), initiation of secretion of adrenal hormones prematurely, abnormal cortisol metabolism or action, adrenal tumors (benign or malignant) etc. are also included among hirsutism causes.
• Hirsutism causes also include other hormonal disorders like Cushing’s syndrome, acromegaly (excess growth hormone secretion in adults cause acromegaly), hyperprolactinemia (excess secretion of prolactin). Androgen overproduction related to pregnancy (like thecoma of pregnancy and hyperreactio luteinalis) can cause hirsutism. Overproduction of androgen peripherally due to obesity or unknown cause can also cause hirsutism.
• The drugs which can cause hirsutism as side effect are androgens, minoxidil, phenytoin, cyclosporine, diazoxide etc. Oral contraceptive pills containing androgenic progestins can cause hirsutism.
• True hermaphroditism (presence of ovary and testis in same individual) can also cause hirsutism.

Growth & Differentiation of hair follicles:

To understand the clinical presentation of hirsutism; and hirsutism in general, it is important to know and understand how the growth and differentiation of hair follicles occurs in humans.

Hairs are of two types, namely (1) vellus hair, which is fine, soft and non-pigmented (light colored) and (2) terminal hair, which is long, coarse, and pigmented or dark colored. The number of hair follicles are fixed in a human being and do not change in lifetime, but the type of hairs may change, generally from vellus to terminal type in response to various factors and most common factor is androgen.

Androgens are essential for terminal types of hair and also for development of sebaceous glands. Androgens cause transformation of a vellus hair into a terminal hair and also a vellus hair follicle into a sebaceous gland while keeping the hair vellus type.

Hair growth occurs in three phases namely (1) anagen or the growth phase, (2) catagen or the involution phase and (3) telogen or the resting phase. Hormones play an important role in hair growth cycles in some parts of the body and have no action on certain parts of the body, e.g. hormones like androgens have no effect on the growth cycle of eyelashes, eyebrows and vellus hairs. Whereas in nine androgen sensitive areas of the body androgen play an important role in hair growth cycle, especially in pubic area which is sensitive to minimal level of androgens. In compare to pubic area, growth of hairs on face (upper lip and chin), chest, upper abdomen, and back requires much higher levels of androgens and this is the reason of characteristic pattern typically seen in men only. So androgen excess in women leads to increased hair growth in androgen sensitive areas (nine areas depending on the level of androgen) and loss of scalp hairs. Loss of scalp hair occurs in women with androgen excess due to shortening of anagen or the growth phase of hair growth cycle by androgens.

The correlation of androgen excess and the quantity of hair growth in women is only modest at the most as seen practically. This is because hair growth also depends on the local factors playing at the hair follicle as well as sensitivity of hair follicles to androgens. Genetic and ethnic factors also play its important role in the quantity of hair growth. But the fact is, most of the hirsute women have androgen excess.

What are the hirsutism symptoms?

Hirsutism symptoms include excess hair growth which generally starts in 2^nd or 3^rd decades of life and progress slowly but steadily. If hirsutism symptoms develop suddenly and progress rapidly, it generally indicate a tumor that secrete androgen and in case of androgen secreting tumor, generally virilization is also present.

Menstrual history is important. Generally irregular menstruation from the time of first onset of menstruation (menarche) indicates an ovarian hirsutism cause rather than adrenal androgen excess. Other symptoms associated with hirsutism can also indicate the possible causes e.g. presence of galactorrhea may be due to hyperprolactinemia and rarely due to hypothyroidism. Hirsutism associated with Cushing's syndrome generally presents with centripetal weight gain, high blood pressure, striae, easy bruising etc. (all of these are symptoms of Cushing's syndrome).

Clinical/physical examination in hirsutism:

Clinical examination in case of hirsutism should include calculation of BMI, along with measurement of height and weight. A BMI of more than 25 is considered as overweight and a BMI of more than 30 in females is associated with hirsutism. Routine clinical assessments like blood pressure etc. should also be done.

How to assess hirsutism clinically?

Assessment of severity of hirsutism is important for diagnosis as well as for treatment of hirsutism. The most commonly used is the modified scale of Ferriman and Gallwey, which takes into account the presence of hair in nine (9) androgen sensitive sites of human body (females) namely upper lip (mustache in males), chin (beard), chest, upper arms, abdomen, upper back, lower back, pelvis and thighs. This nine androgen sensitive sites are graded from 0 (zero) to 4, where 0 (zero) indicate absence of hair and 4 indicated presence of most dense hair (or very large number of hairs). All nine grades are added and a hirsutism score given. A hirsutism score above 8 (eight) suggests hirsutism (excess androgen-mediated hair growth) and the higher the hirsutism score the severe is hirsutism. According to modified scale of Ferriman and Gallwey approximately 95% of Western women (Caucasian) have less than hirsutism score 8. It is common to have some hair in these nine androgen sensitive areas, as score of 6 or 7 will have some hair which is normal. If hirsutism score is more than 8, the diagnosis should be assessed further by hormonal evaluation.

How common is hirsutism?

Genetics and ethnic factors play an important role in occurrence of hirsutism. Hirsutism affects approximately 10% of the women, but the incidence varies in different races, e.g. the incidence is much less among Native Americans and Asians, especially among Mongoloid race women, in compare to Caucasian women. People of Mediterranean descent are genetically more hirsute than other races. Generally fair people, especially blondes are less hirsute than dark colored people.

What investigations can be (are) done in hirsutism?

The laboratory investigations which can be done for diagnosis as well as for guiding management of hirsutism are plasma levels of testosterone, sulfated form of dehydroepiandrosterone (DHEA), and free or unbound (to sex-hormone binding globulin) testosterone. Free testosterone is converted to dihydrotestosterone (DHT) which than binds to androgen receptors (main step in causation of hirsutism).

Plasma testosterone level of more than 3.5 ng/ml (nano-gram per milliliter) indicates virilizing tumor (possibly in ovary or adrenal gland) and plasma testosterone level of more than 2 ng/ml (>7 nmol/liter) is suggestive of such tumors. A plasma level of sulfated form of dehydroepiandrosterone (DHEAS) of more than 7000 mcg/liter (>18.5 micromol/liter) is suggestive of adrenal tumor.

Computed tomography (CT) or magnetic resonance imaging (MRI) is used for localizing the adrenal tumors and ultrasonography is done for localizing ovarian tumor, if testosterone, DHEAS etc. is suggestive.

Polycystic ovarian syndrome is one of the commonest causes of androgen excess, which can be diagnosed easily with ultrasound.

To differentiate ovarian and adrenal cause of androgen excess, dexamethasone androgen-suppression test is done, as glucocorticoids like dexamethasone suppress excess androgens from adrenal gland, but can not suppress ovarian production of androgens. Dexamethasone androgen-suppression test is done by administering dexamethasone 0.5 mg orally every 6 h for 4 days. A blood sample is taken before administering dexamethasone to check androgen level (unbound testosterone). A normal level of unbound testosterone after administration of dexamethasone suggests adrenal source, whereas incomplete suppression of unbound testosterone (more than normal unbound testosterone) suggests ovarian source.

How hirsutism is treated?

Hirsutism treatment can be done by pharmacological or non pharmacological (mechanical removal of hairs) means. Treatment can not cause cure of hirsutism, it can only improve symptoms of hirsutism. As a general rule non pharmacological hirsutism treatment should be tried first either alone or in combination with pharmacological hirsutism treatment.

Non pharmacological hirsutism treatment:

1. Bleaching
2. Removal of hairs from skin surface which is known as “depilatory” like shaving (although there is a general perception that shaving increases rate of hair growth and density, in reality it does not), chemical removal etc. Chemical removal of hairs from skin surface are used for treatment of mild hirsutism that affects only limited areas of skin surface, but they may cause irritation to the skin, especially in persons with allergy.
3. Removal of hairs including the roots of hairs which is known as “epilatory” and include plucking, waxing, electrolysis, and laser therapy. Removal of hairs with wax (waxing) can be painful or uncomfortable and it can not generally remove hairs permanently. Plucking can also be used for hirsutism treatment, as women commonly use to pluck eyebrows (hairs) for cosmetic purpose and they are familiar and used to it. Electrolysis of hairs most effective among all the above mentioned non pharmacological hirsutism treatment techniques and provide permanent removal of hairs, especially in the hands of experienced and skilled electrologist. Laser is also effective in removing hairs which removes hairs permanently in most of the patients of hirsutism or at least delays the hair regrowth. But the long term complications as well as effects of laser hair removal are still unknown.

Pharmacological hirsutism treatment:

The use of drugs for hirsutism treatment is mainly directed towards interruption of one or more steps in the synthesis of androgens as well as one or more steps in the action of androgens. But unfortunately even with pharmacological treatment the hair growth reduces only modestly after pharmacological hirsutism treatment and that too takes very long time (result becomes evident only 4-6 months after initiation of treatment) for the result to be seen.

The commonly used “combined oral contraceptive pill” which is combination of estrogen and progesterone is the first line hormone treatment for hirsutism and acne associated with hirsutism, generally done after cosmetic and dermatologic management or if cosmetic and dermatologic management treatment fails. The estrogen used in combined oral contraceptive pill is ethinyl estradiol, which suppress lutinizing hormone (LH) which in turn reduce production of androgens from ovaries. Reduced androgens also results in proportionate increase in SHBG (sex-hormone binding globulin), which helps in lowering unbound plasma testosterone (by binding to SHBG).

The progestational component of oral contraceptive pill should be selected which is non androgenic (because commonly used progestins like norgestrel and levonorgestrel have androgenic potential), like newer generation Norgestimate which is non androgenic. Drospirenone, which is spironolactone analogue with antimineralocorticoid and antiandrogenic activities, is the progestin of choice these days along with ethinyl estradiol (estrogen).

The combined oral contraceptive pill is contraindicated in women with thromboembolic disease and estrogen dependent cancers. Combined oral contraceptive pill also should not be used by smokers, women with migraine and high blood pressure.

If hirsutism is due to congenital adrenal hyperplasia (CAH) the treatment of choice is glucocorticoids in low doses, due to their better suppressive action on adrenals. But sometimes glucocorticoids can restore ovulatory functions. Dexamethasone (0.2–0.5 mg) or prednisone (5–10 mg) is commonly used at bedtime, which suppresses the nocturnal surge of ACTH (adrenocortico tropic hormone).

Cyproterone acetate (not available in the United States, but available in most other countries) is a classic anti androgen. Cyproterone is given on days 1–15 at the dose of 50–100 mg and ethinyl estradiol at the dose of 50 microgram is given on days 5–26 of the menstrual cycle. The common side effects are irregular uterine bleeding, nausea, weakness, headache, weight gain, and decreased libido and should be kept in mind. Cyproterone acetate acts by competitively inhibiting testosterone and dihydrotestosterone to androgen receptors. It also increase metabolism of testosterone by inducing liver enzyme.

Finesteride, a competitive inhibitor of 5-alpha reductase type 2 enzyme, has beneficial effects in hirsutism. The limited use and efficacy of finesteride is due to the presence of 5-alpha reductase type1 enzyme in pilosebaceous unit of hair follicle. Additional disadvantage of finesteride is impairment of sexual differentiation in a male fetus and pregnancy should be avoided during use of finesteride.

Flutamide is a non steroidal anti androgen which is used for treatment of hirsutism. But it can induce liver dysfunction and used rarely if ever.

Eflornithine cream (trade name Vaniqa) is approved (including USFDA) for treatment of extra unwanted facial hairs in women. But the long term effects (and side effects) of eflornithine is not known and yet to be established. Long term and excessive use of eflornithine can cause ski irritation.

Spironolactone is weak anti androgen and equally effective as cyproterone acetate in high dose of 100-200 mgs per day. Plasma potassium should be closely monitored while using large dose of spironolactone. Oral contraceptives should be used along with spironolactone to prevent pregnancy, as it may cause feminization of a male fetus.

Finally the choice of pharmacological hirsutism treatment should be tailored according to the need of the individual (woman suffering from hirsutism) and pharmacological treatment should always along with non pharmacological treatment. The patient should also be educated against unrealistic expectation and made to understand that no treatment will be able to cure hirsutism completely. The improvement of hirsutism (by any method of treatment) is approximately 20% (which also takes up to 9-12 months) although there is arrest of further progression.

Related Articles/sites/sources:

1. Carmina E: Antiandrogens for the treatment of hirsutism. Expert Opin Investig Drugs 11:357, 2002 [PMID: 11866665]