Although hirsutism is broadly defined as excessive hairiness, the common clinical use of the term refers to women with excess growth of terminal hair in a male pattern. In this sense, hirsutism is one of the most common endocrine disorders, affecting approximately 10% of women in the United States. In these women, the hairiness implies the presence of abnormal androgen action, which may represent a serious or, more likely, a nonserious medical problem. Regardless of the etiology, hirsutism can produce mental trauma and emotional anguish.[1] Even mild cases of hirsutism may be viewed by the patient and others as a presumptive loss of femininity. In more severe cases, hirsutism can be a serious cosmetic problem. The major objectives in the management of hirsutism are to rule out a serious underlying medical condition and to devise a plan of treatment.[2, 3]
Idiopathic hirsutism in an elderly woman is shown in the photo below.
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Idiopathic hirsutism in an elderly woman.
Workup
Approximately 50% of women with even minimal hirsutism have excessive androgen. Laboratory studies in hirsutism serve both to confirm the clinical impression of hyperandrogenism and to identify the source of excess androgens, either adrenal or ovarian.
The most important assay is the level of serum testosterone, the major circulating androgen. If the total serum testosterone level is normal, measure the free serum level because hyperandrogenism (and insulin resistance, if present) decreases sex steroid-binding globulin, such that the unbound, biologically active testosterone moiety may be elevated even if the total level is unremarkable.
If indicated based on the findings from the clinical evaluation and laboratory testing, perform ovarian ultrasonography and adrenal computed tomography (CT) scanning or magnetic resonance imaging (MRI) to evaluate for either ovarian or adrenal sources of androgen production.
Management
The treatment of hirsutism begins with a careful explanation about the cause of the problem and reassurance that the patient is not losing her femininity. Then, direct intervention, if possible, is instituted for the underlying disorder. If hirsutism persists (or the patient has idiopathic hirsutism), other cosmetic or systemic treatment may be necessary. In some cases, cosmetic measures may be sufficient. In others, the slow progress of systemic therapy may necessitate more immediate cosmetic treatment. The most effective strategy is to combine systemic therapy, which has a slow onset of effectiveness, with mechanical depilation (shaving, plucking, waxing, depilatory creams) or light-based (laser or pulsed-light) hair removal.
Systemic therapies directed at hirsutism can be divided into those that decrease ovarian or adrenal androgen production and those that inhibit androgen action in the skin. The systemic therapies include glucocorticoids, oral contraceptives (OCs), spironolactone, flutamide, finasteride, cyproterone acetate (not available in the United States), and insulin sensitizers (metformin and rosiglitazone).
Laser therapy has been shown not only to reduce unwanted hair but also to improve depression and anxiety in women with hirsutism. In many patients, hirsutism can be controlled just with laser, without using any drugs.
Hormones and the intrinsic characteristics of the hair follicle determine the quality of hair growth. Vellus hairs are fine, lightly pigmented hairs that cover most of the body before puberty. Pubertal androgens promote the conversion of these vellus hairs to coarser, pigmented terminal hairs. The level and duration of exposure to androgens, the local 5-alpha-reductase activity, and the intrinsic sensitivity of the hair follicle to androgen action determine the extent of conversion from vellus to terminal hair. However, some terminal hair growth is androgen-independent (eg, scalp, eyebrows, lashes).[4]
The development of terminal hair or reversion back to a vellus pattern may not be immediately evident because of the characteristics of the hair cycle. This cycle has 2 phases that include active hair growth (anagen phase) and a resting period (telogen phase), which follows the anagen phase. During the resting period, the hair shaft separates from the dermal papillae at the follicle base, and no further growth takes place. Eventually, growth restarts and the new hair shaft formed by the reactivated papillae pushes the old hair out. The cycle may take months to years to complete, and this causes a delay in hair growth response to changes in the androgen milieu.
Dihydrotestosterone is the androgen that acts on the hair follicle to produce terminal hair. This hormone is derived from both the bloodstream and local conversion of a precursor, testosterone. The local production of dihydrotestosterone is determined by 5-alpha-reductase activity in the skin. Differences in the activity of this enzyme may explain why women with the same plasma levels of testosterone can have different degrees of hirsutism.
Hirsutism affects approximately 10% of women in the United States.
International
The prevalence rates of hirsutism in northern Europe are similar to those in the United States; in other places, rates are not known with certainty.
Mortality/Morbidity
The mortality and morbidity of hirsutism are determined by the underlying cause. Most women with idiopathic hirsutism have no associated mortality or morbidity. On the other extreme, a small number of women may have malignant disease with a grave prognosis.
A study by Comim et al suggested that premenopausal hirsutism and/or oligomenorrhea are risk factors for postmenopausal fractures, especially in the humerus and lower leg. The study included 1057 postmenopausal women aged over 55 years.[5] However, another study, by Rubin et al, suggested that PCOS reduces fracture risk, although the report dealt with a younger group of patients than did the Comim study and indicated that the risk reduction was greater in women who were under age 30 years when diagnosed.[6]
Race
Ethnic origin significantly affects terminal hair growth in healthy women. Northern, fair-skinned Europeans have the least amount of terminal hair, whereas southern European, dark-skinned Mediterranean women have the greatest amount of terminal hair.
The difference in the racial patterns of normal terminal hair growth may be related to genetic differences of 5-alpha-reductase activity in the skin.
A study by Engmann et al reported that among patients with polycystic ovary syndrome (PCOS), aged 18-40 years, the prevalence of hirsutism was significantly greater in Hispanic women than in non-Hispanic white patients (93.8% vs 86.8%, respectively).[7]
A retrospective study by Afifi et al also found hirsutism in women with PCOS to be linked to ethnicity, as well as to Fitzpatrick skin type. Hirsutism in PCOS was most prevalent, and the modified Ferriman-Gallwey (mFG) hirsutism score was highest, in women of Hispanic, Middle Eastern, African American, and South Asian ethnicity. Moreover, a greater prevalence of hirsutism, along with an increased tendency toward truncal hirsutism, was noted with higher Fitzpatrick skin types. The investigators also determined that mFG scores in the truncal region and extremities tended to be higher in women of Middle Eastern and Hispanic ethnicity, while the score for the face was greater in African American and Hispanic patients. The least amount of hirsutism was found in women of Caucasian, Ashkenazi Jewish, East/Southeast Asian, and Native American ethnicity.[8]
With the exception of congenital adrenal hyperplasia (CAH), the actual prevalence of diseases that cause hyperandrogenism and hirsutism has not been shown to differ among persons of different races.
Sex
As a medical problem, hirsutism predominates in women.
Although hirsutism can occur in men, it is more difficult to recognize because of the wide variability of healthy male terminal hair growth.
Hirsutism in prepubertal children occurs equally between sexes, is usually a sign of precocious puberty, and may signify a serious underlying disease.
This discussion focuses on adult women.
Age
The age of onset of hirsutism depends on the etiology. Most forms of nonneoplastic hirsutism become evident around puberty. This includes polycystic ovary syndrome (PCOS), CAH, and idiopathic hirsutism.
Hirsutism and acne are shown in the image below.
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The photograph depicts hirsutism in a young woman with polycystic ovary syndrome. Note the acne lesions and excessive hair on her face and neck.
Hirsutism may also develop after weight gain and cessation of the use of oral contraceptives (OCs) in young women. Normally, terminal hair growth becomes apparent after adrenarche and accelerates after puberty. Terminal hair continues to develop gradually in healthy women until after menopause, when loss of ovarian androgen leads to a loss of hair. Rapidly worsening hirsutism, especially in older women, should raise the suspicion of an androgen-secreting tumor.
Hirsutism requires a careful and systematic clinical evaluation coupled with a rational approach to treatment. Throughout this process, the patient must understand that, although diagnostic testing can be time consuming (and even inconclusive), it is sometimes essential for the determination of an effective intervention. In other cases, counseling and education may be all that is needed.
For the patient who desires treatment, a wide variety of pharmacologic strategies are available. Informing the patient that current systemic therapy is imperfect is important. Furthermore, none of the drugs used to treat hirsutism has FDA approval for such use. Initiate therapy only in patients who give informed consent after a complete explanation of the potential benefits and risks of a particular treatment and alternative approaches.
An accurate history of the patient's onset of hirsutism and developmental milestones can be helpful in the etiologic diagnosis.
Age of onset
Idiopathic hirsutism and the other less-serious causes of hirsutism usually begin at puberty.
Conversely, hirsutism that occurs in middle-aged or older women should suggest an adrenal or ovarian tumor.
Family history: A patient with a family history of hirsutism is consistent with congenital adrenal hyperplasia (CAH); however, idiopathic hirsutism and polycystic ovary syndrome (PCOS) can also be familial. See presentation in the image below.
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The photograph depicts familial hirsutism in a Pakistani woman.
Hirsutism severity and rate of progression
The history of a benign form of hirsutism is usually characterized by pubertal onset with slow progression over many years. This is often true of hirsutism with PCOS.
When a history of rapid severe hirsutism or other signs of virilization are obtained, an androgen-secreting tumor is a possibility.
Adrenarche and puberty
Because the development of pubic hair depends on adrenal androgens, early development points toward CAH.
In contrast, ovarian hyperandrogenism is associated with normal adrenarche and delayed menarche or irregular menses.
The most important goal in the clinical evaluation of a patient with hirsutism is to rule out significant underlying disease. To do this, seek to understand the cause of hyperandrogenism, if this is present.
Excess androgens can be from either an exogenous or an endogenous source.
An exogenous source of androgens can usually be elicited by history findings; however, surreptitious androgen use has been reported in female athletes, especially those at a high level of competition.
Endogenous androgens originate from either the adrenal cortex or the ovary. Therefore, the evaluation of androgen excess can focus on disorders of these 2 glands. The principal possibilities are tumors of the ovary or the adrenal cortex, Cushing syndrome, CAH, and PCOS. Idiopathic hirsutism is the most common etiology, but it is a diagnosis of exclusion. Therefore, seek other causes first.
The initial task in the evaluation of hirsutism via the physical examination is to quantitate the disorder.[9] This task requires that terminal hair, which depends on androgen, be differentiated from vellus hair, which is androgen-independent.
Vellus hair is fine, soft, and lightly pigmented. An excess of vellus hair (hypertrichosis) is usually idiopathic, but may be associated with metabolic disorders (eg, hyperthyroidism, anorexia nervosa, porphyria) and with some medications (eg, phenytoin, diazoxide, minoxidil, glucocorticoids, cyclosporine, hexachlorobenzene).
By contrast, terminal hair is coarse, curly, and pigmented. Because small amounts of terminal hair are normal in women, quantitation is important.
The most widely accepted method of quantitation uses the Ferriman and Gallwey scale. However, use care because this method has significant interobserver variability. In this approach, hair growth is judged in each of 11 androgen-sensitive areas.
The grade for each area ranges from 0 (no terminal hair) to 4 (frankly virile).
The body areas used to grade hirsutism are (1) the upper lip, (2) chin, (3) chest, (4) leg, (5) thigh, (6) upper arm, (7) forearm, (8) upper back, (9) lower back, (10), upper abdomen, and (11) lower abdomen.
Areas such as the axilla and pubis are not included because terminal hair grows in these places at normal androgen levels in women.
The total score correlates roughly with the elevation of androgen levels. A woman with a score of 8 or higher is considered to have hirsutism. Most women who seek medical attention for the disorder have scores of 15 or higher. Normal scores have also been established for Turkey (up to 11) and Thailand (up to 3 on the modified Ferriman and Gallwey scale).
In women with moderate-to-severe hirsutism (score >15), seek additional signs of hyperandrogenism, including (1) temporal hair recession, (2) oily skin, (3) masculine voice, (4) well-developed musculature, (5) enlargement of the clitoris (>35 mm2 in surface area), (6) irregular menses, and (7) psychological changes (eg, heightened libido, aggressiveness).
The degree to which these clinical factors are present suggests the level of androgen overproduction and, thus, helps to determine the degree of concern for the presence of an underlying disease.
The extent of the evaluation for the cause of hirsutism is greater in women who have more severe clinical evidence of masculinization.
A thorough abdominal and pelvic examination is important in patients with hirsutism because more than half of androgen-secreting adrenal and ovarian tumors are palpable.
Examine the skin for acanthosis nigricans, a manifestation of insulin resistance.
Women with hirsutism are usually obese, with increased waist-hip ratios, and are thought to be at an increased risk for atherosclerosis and coronary heart disease. They also have increased bone mineral density scores at the hip and spine. These increases correlate with higher levels of serum free testosterone and estrogen.
Multiple diseases can cause hyperandrogenism and hirsutism. The etiologic forms of hirsutism include endocrine-related, idiopathic, medication-related, and miscellaneous. Endocrine-related causes include adrenocortical disorders and ovarian disorders.
Tumors, Cushing syndrome, and CAH are the adrenocortical causes. Tumors (malignant or benign) and PCOS are the ovarian causes of hirsutism.
Adrenal tumors
Adrenocortical tumors are almost always malignant in patients who present with hirsutism. These tumors are usually large and are associated with a very poor prognosis.
Cushing syndrome
In most instances, Cushing syndrome is caused by glucocorticoid therapy. Because pure glucocorticoids have no androgenic activity, the treatment rarely produces hirsutism. Instead, glucocorticoid therapy is one of the causes of hypertrichosis (see Physical), resulting in vellus hair growth, especially on the face. Thus, excess growth of terminal hair in a patient with the clinical stigmata of Cushing syndrome suggests that the syndrome has an endogenous origin, ie, a pituitary tumor that secretes adrenocorticotropin hormone (ACTH), an adrenal tumor that secretes both cortisol and androgens, or an ectopic tumor that secretes ACTH. The pituitary tumor is the most likely possibility. Cushing syndrome, as a cause of hirsutism, is diagnosed based on the presence of dexamethasone that fails to suppress both androgens and cortisol.
CAH
CAH is actually a family of defects in 1 of 5 enzymes that are responsible for the biosynthesis of cortisol. The resulting cortisol deficiency heightens the secretion of ACTH and thereby leads to adrenal cell proliferation. However, only 3 of these defects can produce hirsutism—21-hydroxylase (most frequent), 3β-hydroxysteroid dehydrogenase (less frequent), and 11-β-hydroxylase deficiency (least frequent).
If CAH is considered, an ACTH-stimulation test is indicated, which is a search for exaggerated quantities of the precursors of cortisol. The stimulation test is required because baseline elevation of these steroids may be in the reference range.
Hyperandrogenism in CAH can cause infertility, but dexamethasone therapy in this setting may induce ovulation. Two important reasons for the diagnosis of CAH are that specific therapy is available and genetic counseling may be necessary. Women with both CAH (21-hydroxylase deficiency) and Cushing syndrome. Have been described with particularly severe hirsutism.
Ovarian tumors
Ovarian tumors may be malignant, and the threat can be serious. Androgen-secreting ovarian tumors are a less-serious threat. The most common among them is arrhenoblastoma, which accounts for less than 1% of all ovarian tumors. In patients with this neoplasm, the serum testosterone level is always elevated, and most patients have amenorrhea and a palpable ovarian mass.
Gonadoblastomas
Gonadoblastomas usually develop in younger persons (aged 10-30 y) who are genetic males with female external genitalia. Nearly half of these tumors are malignant, and many are bilateral. Pelvic examination findings are abnormal because internal female genitalia are absent.
Lipoid cell tumors
Lipoid cell tumors are of 2 histologic types: adrenal-like cells (in younger patients) and hilar or Leydiglike cells (in older patients). These tumors are usually palpable but are seldom malignant. Ovarian tumors, which are even less frequently encountered, include dysgerminomas, Brenner tumors, and cystic granulosa-theca cell tumors.
PCOS
PCOS is the most common ovarian disorder associated with hirsutism. Although the cause of PCOS is not known, the etiology is speculated to be multifactorial. By definition, polycystic ovaries have 20 or more subcapsular follicles, which range from approximately 1-15 mm in diameter. The follicles are at various states of atresia, and hyperplasia of the theca interna, the anatomic source of ovarian androgens, is present. However, the basic abnormalities in PCOS are functional, rather than anatomic, in nature. In particular, levels of luteinizing hormone (LH) are tonically elevated (with LH levels higher than those of follicle-stimulating hormone [FSH]).
Many women with PCOS have insulin resistance, manifested by acanthosis nigricans and elevated plasma insulin levels. Increased insulin levels have been speculated to stimulate androgen production from the ovarian theca interna cells. An experiment in nature supports this hypothesis; women with PCOS who have a specific genetic mutation that lowers insulin resistance have lower hirsutism scores. In addition, the importance of insulin resistance is emphasized by the therapeutic effect of insulin-sensitizing medications (eg, metformin, thiazolidinediones), which restore normal ovarian androgen production and ovulation.[10]
PCOS usually begins at puberty. The incidence has been estimated to be approximately 5% among adolescent girls and adult women in the United States. As noted, the characteristic endocrine abnormality is an elevation in levels of plasma free testosterone that is not suppressed by dexamethasone; however, as many as 50% of patients also show abnormal adrenal androgen secretion.
A study by Villarroel et al indicated that in adolescent girls, hirsutism and oligomenorrhea (persistent menstrual cycles >45 days) have a strong association with the presence of biochemical hyperandrogenism and polycystic ovarian morphology and are therefore useful in the diagnosis of PCOS.[11]
A study by Turan et al indicated that in patients with PCOS, hyperandrogenism contributes to the elevation of hearing thresholds. Among the study’s subjects, the investigators found that increased free testosterone index values and hirsutism scores were associated with a greater extended high-frequency threshold.[12]
Idiopathic hirsutism
Idiopathic hirsutism is a diagnosis of exclusion.
The patient's hirsutism is not caused by well-defined abnormalities such as an androgen-secreting tumor or CAH.
The spectrum of clinical presentations ranges from normal menses and mild hirsutism to amenorrhea and signs of virilization, and testosterone levels range from normal to frankly elevated.
The hirsutism usually begins at puberty.
The disorder is often familial and may be associated with obesity and insulin resistance.
Some classification schemes distinguish patients with elevated adrenal androgen levels (dehydroepiandrosterone sulfate [DHEAS]); in these cases, the disorder is called idiopathic adrenal hyperandrogenism.
Some patients with idiopathic hirsutism have normal plasma androgen levels. As noted above, the underlying mechanism in these patients may be an increase in androgen sensitivity or in 5-alpha-reductase activity in the skin. Increased activity of the enzyme has been demonstrated based on skin biopsy findings and by a finding of elevated urinary levels of dihydrotestosterone metabolites; however, presently, tests for 5-alpha-reductase activity have been used only in research.
Approximately 50% of women with even minimal hirsutism have excessive androgen. Laboratory studies in hirsutism serve both to confirm the clinical impression of hyperandrogenism and to identify the source of excess androgens, either adrenal or ovarian. The workup described in the image below recommends 2 visits, a baseline evaluation followed by a 2-week dexamethasone treatment period. Specific discussion of the testing is below.
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Etiologic diagnosis of hirsutism.
See the list below:
Testosterone: The most important assay is the level of serum testosterone, the major circulating androgen. If the total serum testosterone level is normal, measure the free serum level because hyperandrogenism (and insulin resistance, if present) decreases sex steroid-binding globulin, such that the unbound, biologically active testosterone moiety may be elevated even if the total level is unremarkable. Extremely high testosterone levels are likely to be associated with adrenal or ovarian tumors, whereas idiopathic and benign etiologies result in very mild elevations. Indeed, in idiopathic hirsutism, the results from testing androgen levels are often normal. In some of these women, hirsutism is thought to be caused by increased skin sensitivity to androgen or by increased skin 5-alpha-reductase activity. This enzyme is located in the skin near the hair follicle, and it converts plasma testosterone to the androgen metabolite dihydrotestosterone.
Dehydroepiandrosterone sulfate (DHEAS): Because testosterone can originate in either the adrenal cortex or the ovary, an elevated testosterone level does not indicate the gland of origin. Accordingly, measurement of elevated plasma levels of DHEAS, an androgen synthesized almost exclusively by the adrenal cortex, can indicate excess adrenal function. Elevations in both testosterone and DHEAS suggest an adrenal origin, whereas an isolated testosterone elevation indicates an ovarian source.
Dexamethasone suppression (see the image above): Laboratory testing of testosterone (free or total) and DHEAS can be performed on the initial visit. At the same time, a diagnostic trial of dexamethasone therapy for 7-14 days can be initiated to help exclude adrenocorticotropin hormone (ACTH)–dependent hirsutism. When the patient returns, free testosterone, DHEAS, and plasma cortisol levels are measured. Dexamethasone-mediated suppression of androgens is observed in healthy women who do not have hirsutism and in those with congenital adrenal hyperplasia (CAH) and idiopathic hirsutism.
Adrenocorticotropin stimulation: An ACTH-stimulation test (250 mcg for 30 min) can help differentiate between CAH and idiopathic hirsutism because CAH produces abnormal findings (elevations in metabolic precursors of cortisol).
Hirsutism caused by CAH is due to 1 of 3 cortisol biosynthetic defects, ie, 21-hydroxylase deficiency, 3 3 β -hydroxysteroid dehydrogenase, or 11-β -hydroxylase deficiency.
Because 21-hydroxylase deficiency accounts for the vast majority of cases of CAH (approximately 90%), the discussion is focused on this diagnosis. Investigate possible 21-hydroxylase deficiency by measuring plasma 17-hydroxyprogesterone levels obtained between 0700 and 0900 hours. Values of less than 7 nmol/L exclude the diagnosis, and values of greater than 45 nmol/L (in women who are nongestational) confirm 21-hydroxylase deficiency. When basal values of 17-hydroxyprogesterone are between 7 and 45 nmol/L, an ACTH-stimulated concentration of greater than 45 nmol/L is also diagnostic.
Although elevated basal plasma 17-hydroxyprogesterone levels (as high as 17 nmol/L) may be present during the luteal phase of the menstrual cycle and in PCOS, ACTH-stimulated increments are blunted.
Cortisol suppression: Investigation of subnormal dexamethasone suppression of androgens can be guided by the patient’s cortisol level, without the need for an ACTH-stimulation test. PCOS and adrenal and ovarian tumors are associated with normal suppression of cortisol by dexamethasone, whereas cortisol levels in patients with Cushing syndrome are not suppressed.
Other laboratory tests include the following:
Serum prolactin or FSH: Women with hirsutism and amenorrhea of unknown cause should have a serum prolactin or FSH test to evaluate for either a prolactinoma or ovarian failure.
Diabetes screening: Women with hirsutism, PCOS, obesity, or acanthosis nigricans may have insulin resistance, and screening for diabetes and hyperlipidemia is warranted. Approximately 50% of these women have increased insulin levels and 5% have undiagnosed diabetes mellitus.
Prostate-specific antigen (PSA): Ultrasensitive assays can detect PSA in women and is a potential marker for androgen excess. Studies thus far, however, have not shown a good correlation with the change in androgen levels after treatment. Therefore, further studies are needed.[13]
If indicated based on the findings from the clinical evaluation and laboratory testing, perform ovarian ultrasonography and adrenal CT scanning or MRI to evaluate for either ovarian or adrenal sources of androgen production.
The treatment of hirsutism begins with a careful explanation about the cause of the problem and reassurance that the patient is not losing her femininity. Then, direct intervention, if possible, is instituted for the underlying disorder. If hirsutism persists (or the patient has idiopathic hirsutism), other cosmetic or systemic treatment may be necessary. In some cases, cosmetic measures may be sufficient. In others, the slow progress of systemic therapy may necessitate more immediate cosmetic treatment. The most effective strategy is to combine systemic therapy, which has a slow onset of effectiveness, with mechanical depilation (shaving, plucking, waxing, depilatory creams) or light-based (laser or pulsed-light) hair removal.
Hirsutism requires a careful and systematic clinical evaluation coupled with a rational approach to treatment. Throughout this process, the patient must understand that, although diagnostic testing can be time consuming (and even inconclusive), it is sometimes essential for determining an effective intervention. In other cases, counseling and education may be all that is needed. For the patient who desires treatment, a wide variety of pharmacologic strategies are available. Informing the patient that current systemic therapy is imperfect is important. Furthermore, none of the drugs used to treat hirsutism have US Food and Drug Administration (FDA) approval for such use. Initiate therapy only in patients who give informed consent after a complete explanation of the potential benefits and risks of a particular treatment and alternative approaches.
Systemic therapies directed at hirsutism can be divided into those that decrease ovarian or adrenal androgen production and those that inhibit androgen action in the skin. The systemic therapies include glucocorticoids, oral contraceptives (OCs), spironolactone, flutamide, finasteride, cyproterone acetate (not available in the United States), and insulin sensitizers (metformin and rosiglitazone).
Glucocorticoids: Glucocorticoids (dexamethasone or prednisone), which suppress adrenocorticotropin hormone (ACTH)–dependent adrenal androgen synthesis, have been used with variable success in women with adrenal hirsutism, as in congenital adrenal hyperplasia (CAH) or idiopathic adrenal hyperandrogenism. Usually, 0.5-1 mg of dexamethasone at bedtime is sufficient to suppress ACTH and adrenal androgen production. Unfortunately, some patients gain weight and develop cushingoid features, even with this small of a dose. Further investigations may establish that lower doses (perhaps 0.25 mg) can be effective without adverse effects.
OCs: The drugs most widely used to suppress ovarian androgen production are OCs. They are probably the first choice for young women with hirsutism who do not want to become pregnant.
OCs are inexpensive and promote regular uterine bleeding. In addition, OCs can be used in combination with one of the antiandrogens or other forms of therapy. On the other hand, do not use OCs in women with a history of migraines, known or possible thrombotic disease, or breast or uterine cancer.
Moreover, for several reasons, OCs have a significant failure rate in patients with hirsutism. Low-dose OCs and progestin-only minipills fail to suppress ovulation in as many as 50% of women. Ovarian function continues at a variable rate, and ovarian androgens continue to be produced. Second, the progestins in OCs are attenuated derivatives of testosterone and have variable degrees of androgenic activity in women. The degree depends on the type of progestin and, more importantly, on individual susceptibility.
Spironolactone: Spironolactone, in daily doses of 50-200 mg, blocks androgen receptors. Spironolactone also decreases testosterone production, making it additionally effective for hirsutism. Spironolactone is especially useful in a patient with hypertension or edema because the drug is a mild diuretic.
Sexually active women taking spironolactone should ensure that contraceptive measures are adequate. In some cases, spironolactone can be combined with an OC for added effect on the hirsutism.
With current systemic therapies for hirsutism, 6 months to a year of therapy is usually required before results are noticeable. Even then, only approximately one half to three quarters of patients show improvement. The problem may lie partially in the nature of the hair follicle, which persists for 6 months to a year even after androgen levels have been normalized. Ineffectiveness may also be due to the inability of treatment to completely normalize elevated tissue dihydrotestosterone levels. Newer therapies directed at inhibition of 5-alpha-reductase or blockade of the androgen receptor may improve the ability to treat patients.
Finasteride: Finasteride is a 5-alpha-reductase inhibitor approved for the treatment of benign prostatic hyperplasia. No adverse effects have been reported in women, and the efficacy is similar to that of spironolactone. In at least one study, finasteride was added to spironolactone, demonstrating an additive reduction in hirsutism scores. The main concern with finasteride, however, is the risk of ambiguous genitalia in male fetuses exposed to the enzyme inhibitor during the first trimester. Therefore, use this drug only in women who are postmenopausal with no chance of becoming pregnant.
Flutamide: Flutamide, an example of the newer therapies, is a potent nonsteroidal selective antiandrogen without progestational, estrogenic, corticoid, or antigonadotropin activity. Preliminary data indicate that it is effective as therapy for hirsutism (and also acne); however, flutamide is expensive and has caused fatal hepatitis.
Unluhizarci et al investigated the effectiveness of combining finasteride with flutamide for the treatment of hirsutism.[14] Of the 44 women in the study, 14 patients received finasteride (5 mg/d), 16 women received flutamide (125 mg/d), and 14 women received a combination of finasteride and flutamide (5 mg/d and 125 mg/d, respectively).
The authors found that after 12 months of treatment, the hirsutism score for patients receiving combination therapy had been reduced by 49%, compared with 45% for the group receiving flutamide alone, and 32% for patients receiving only finasteride. They therefore concluded that a combination of finasteride and flutamide is approximately as effective as flutamide alone in the treatment of hirsutism and that both of these alternatives are more effective than the administration of finasteride by itself.
Cyproterone acetate has been effective in the treatment of hirsutism. When added to ethinyl estradiol, it is as effective as flutamide in the treatment of hirsutism. Cyproterone is not available in the United States.
Insulin sensitizers: Both metformin and rosiglitazone improve insulin resistance and have been shown to be effective in lowering androgen levels and in treating hirsutism.
Sibutramine (withdrawn from US market October 8, 2010[15] ): Weight loss with this anorectic agent improves hirsutism scores, androgen levels, and cardiovascular risk factors in women with polycystic ovary syndrome (PCOS).
Cosmetic measures for hirsutism and their disadvantages are as follows:
Hydrogen peroxide bleaching is not suitable for severe hirsutism.
Plucking can cause skin irritation, folliculitis, and scarring.
Waxing can cause skin irritation, folliculitis, and scarring. The wax used has a low melting point.
Shaving may be psychologically unacceptable.
Chemical depilatories can cause skin irritation.
Electrolysis can be painful, and short-wave diathermy can cause scarring.
Laser therapy has been shown not only to reduce unwanted hair but also to improve depression and anxiety in women with hirsutism. In many patients, hirsutism can be controlled just with laser, without using any drugs. A study by Shrimal et al reported that idiopathic facial hirsutism can be more effectively treated with a long-pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (1064 nm) than with intense pulsed light (IPL)–755 nm. After six sessions, 14 of the 15 women who underwent laser therapy (93.3%) experienced hair reduction of more than 75%, compared with three of the 18 patients treated with IPL (16.7%). Moreover, erythema, perifollicular edema, and hyperpigmentation occurred in 26.7%, 13.3%, and 13.3% of the laser group, respectively, compared with 50.0%, 16.7%, and 38.9% of the IPL patients, respectively.[16]
In 2018, the Endocrine Society released an update to their 2008 guidelines on the evaluation and treatment of hirsutism in premenopausal women.[17, 18]
The guidelines suggest testing for elevated androgen levels in all women with an abnormal hirsutism score. However, they recommend against testing for elevated androgen levels in eumenorrheic women with unwanted local hair growth (ie, in the absence of an abnormal hirsutism score) because of the low likelihood of identifying a medical disorder that would change management or outcome.[17, 18]
For most women with patient-important hirsutism despite cosmetic measures (shaving, plucking, waxing), the Endocrine Society recommends starting with pharmacologic therapy and adding direct hair removal methods (electrolysis, photoepilation) for those who desire additional cosmetic benefit. For women with mild hirsutism and no evidence of an endocrine disorder, either pharmacologic therapy or direct hair removal methods are suggested.[17, 18]
For pharmacologic therapy, oral combined estrogen-progestin contraceptives are suggested for the majority of women, with the addition of an antiandrogen agent after 6 months if the response is suboptimal. The guidelines recommend against antiandrogen monotherapy unless adequate contraception is used. In addition, they recommend against using insulin-lowering drugs solely for treating hirsutism.[17, 18]
For women who choose hair removal therapy, the guidelines suggest photoepilation for those whose unwanted hair is auburn, brown, or black and electrolysis for those with white or blonde hair.[17, 18]
For women of color who choose photoepilation treatment, the Endocrine Society suggests using a long-wavelength, long pulse-duration light source such as Nd:YAG or diode laser delivered with appropriate skin cooling. The guidelines also recommend that clinicians warn Mediterranean and Middle Eastern women with facial hirsutism about the increased risk of developing paradoxical hypertrichosis (PH) with photoepilation therapy and suggest using topical treatment or electrolysis over photoepilation for these patients.[17, 18]
The most effective strategy for treating hirsutism is to combine systemic therapy, which has a slow onset of effectiveness, with mechanical depilation (shaving, plucking, waxing, depilatory creams).
Systemic therapies directed at hirsutism can be divided into those that decrease ovarian or adrenal androgen production and those that inhibit androgen action in the skin.
OCs inhibit ovarian androgen production and are probably the first choice for young women with hirsutism who do not want to become pregnant. OCs are inexpensive, and they promote regular uterine bleeding. OCs can be used in combination with antiandrogens or other agents. They have a significant failure rate in hirsutism for several reasons. Low-dose OCs and progestin-only minipills fail to suppress ovulation in as many as 50% of women. Ovarian function continues at a variable rate, and ovarian androgens continue to be produced. Second, the progestins in OCs are attenuated derivatives of testosterone and have variable degrees of androgenic activity in women. The degree depends on the type of progestin and, more importantly, on individual susceptibility.
Glucocorticoids are used to inhibit adrenal androgens. These agents have antiinflammatory properties and cause profound and varied metabolic effects. Glucocorticoids suppress ACTH-dependent adrenal androgen synthesis. These agents are used with variable success in women with adrenal hirsutism, CAH, and idiopathic adrenal hyperandrogenism.
Clinical Context:
Specific inhibitor of the intracellular enzyme that converts testosterone into the androgen 5-α -dihydrotestosterone. Efficacy in hirsutism is similar to that of spironolactone. To be used only in postmenopausal women with no chance of becoming pregnant.
These agents are indicated for treatment of benign prostatic hyperplasia and male pattern baldness. An unlabeled use is for the treatment of female hirsutism.
What is hirsutism?What is the workup for hirsutism?How is hirsutism treated?What is the pathophysiology of hirsutism?How common is hirsutism in the US?What is the international prevalence of hirsutism?What is the mortality and morbidity of hirsutism?What is the epidemiology of hirsutism by race?Is hirsutism more common in men or women?What is the age of onset of hirsutism?What is the prognosis of hirsutism?What education should be provided to patients with hirsutism?What is the clinical history of patients with hirsutism?What are the indications of hyperandrogenism in hirsutism?How are vellus hair and terminal hair differentiated in the evaluation of hirsutism?What is the method of quantitation in the evaluation of hirsutism?What are other physical findings in the evaluation of hirsutism?What is the role of gonadoblastoma in the development of hirsutism?What causes hirsutism?What is the role of adrenal tumors in hirsutism?What is the relationship between Cushing syndrome and hirsutism?What is the role of congenital adrenal hyperplasia (CAH) in the development of hirsutism?What is the role of ovarian tumors in the development of hirsutism?What is the role of lipoid cell tumors in the development of hirsutism?What is the relationship between polycystic ovary syndrome (PCOS) and hirsutism?What are the diagnostic criteria for idiopathic hirsutism?What are the differential diagnoses for Hirsutism?What is the role of lab studies in the workup of hirsutism?Which lab studies are indicated in the workup of hirsutism?Which imaging studies are indicated in the workup of hirsutism?What is the medical treatment for hirsutism?Which systemic therapies are indicated in the treatment of hirsutism?What is the role of glucocorticoids in the treatment of hirsutism?What is the role of oral contraceptives (OCs) in the treatment of hirsutism?What is the role of spironolactone in the treatment of hirsutism?What is the role of finasteride in the treatment of hirsutism?What is the role of flutamide in the treatment of hirsutism?What is the role of cyproterone acetate in the treatment of hirsutism?What is the role of insulin sensitizers in the treatment of hirsutism?What is the role of sibutramine in the treatment of hirsutism?What are the cosmetic measures for the treatment of hirsutism?What are the Endocrine Society treatment guidelines for hirsutism?What is the most effective strategy for treating hirsutism?Which medications in the drug class 5 alpha-reductase inhibitors are used in the treatment of Hirsutism?Which medications in the drug class Aldosterone Antagonists, Selective are used in the treatment of Hirsutism?Which medications in the drug class Glucocorticoids are used in the treatment of Hirsutism?Which medications in the drug class Oral contraceptives are used in the treatment of Hirsutism?
George T Griffing, MD, Professor Emeritus of Medicine, St Louis University School of Medicine
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Steven R Feldman, MD, PhD, Professor, Departments of Dermatology, Pathology and Public Health Sciences, and Molecular Medicine and Translational Science, Wake Forest Baptist Health; Director, Center for Dermatology Research, Director of Industry Relations, Department of Dermatology, Wake Forest University School of Medicine
Disclosure: Received honoraria from Amgen for consulting; Received honoraria from Abbvie for consulting; Received honoraria from Galderma for speaking and teaching; Received consulting fee from Lilly for consulting; Received ownership interest from www.DrScore.com for management position; Received ownership interest from Causa Reseasrch for management position; Received grant/research funds from Janssen for consulting; Received honoraria from Pfizer for speaking and teaching; Received consulting fee from No.
Chief Editor
Michel E Rivlin, MD, Former Professor, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Arash Taheri, MD, Research Fellow, Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine
FDA News Release. Abbott Laboratories agrees to withdraw its obesity drug Meridia. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm228812.htm. Accessed: October 8, 2010.
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