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Evaluation and Treatment of Hirsutism
 

Evaluation and Treatment of Hirsutism

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Hirsutism is a common endocrinological disorder in clinical practice. The causes vary from simple idiopathic hirsutism to most complicated malignant ovarian and adrenal tumors. Most common cause of ...

Hirsutism is a common endocrinological disorder in clinical practice. The causes vary from simple idiopathic hirsutism to most complicated malignant ovarian and adrenal tumors. Most common cause of hirsutism in endocrine clinic is due to a disorder known as PCOS (polycystic ovarian syndrome). Hirsutism poses embarrassment to the women. The purpose of this short review is to identify the common diseases associated with hirsutism, an approach to working through the differential diagnosis, investigations helping in diagnosis and the commonly available treatment modalities for the various forms of hirsutism. The review will provide the physician about the most efficient, cost effective and safe clinical approach to management of hirsutism.

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    Evaluation and Treatment of Hirsutism Evaluation and Treatment of Hirsutism Presentation Transcript

    • Evaluation and Treatment of Hirsutism.
    • Review Article Evaluation and treatment of hirsutism Kalpana Dash* Professor, Senior Consultant, Department of Endocrinology, Apollo Hospitals Bilaspur, Seepat Road, Lingiadih, Bilaspur 495006, India a r t i c l e i n f o Article history: Received 25 April 2013 Accepted 21 May 2013 Available online 14 June 2013 Keywords: Hirsutism Hyperandrogenism PCOS a b s t r a c t Hirsutism is a common endocrinological disorder in clinical practice. The causes vary from simple idiopathic hirsutism to most complicated malignant ovarian and adrenal tumors. Most common cause of hirsutism in endocrine clinic is due to a disorder known as PCOS (polycystic ovarian syndrome). Hirsutism poses embarrassment to the women. The pur- pose of this short review is to identify the common diseases associated with hirsutism, an approach to working through the differential diagnosis, investigations helping in diagnosis and the commonly available treatment modalities for the various forms of hirsutism. The review will provide the physician about the most efficient, cost effective and safe clinical approach to management of hirsutism. Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved. 1. Definition of hirsutism Hirsutism is defined as excessive male pattern terminal hair growth in women.1 It must be distinguished from hyper- trichosis which is excessive growth of vellus hair in androgen independent non-sexual areas, commonly found in familial back ground, metabolic diseases (anorexia nervosa, thyroid disorders) and certain medications (phenytoin, minoxidil & cyclosporine). The amount and location of the hair is commonly measured by FerrimaneGallwey2 scoring system which should score at least 8 (Fig. 1).3 Hirsutism can be defined by a total score of 8 or more by FerrimaneGallwey hirsutism scoring system. 2. Etiology of hirsutism Most common (80%) cause of hirsutism is polycystic ovary syndrome (PCOS).1,4 PCOS is a complex disorder comprising both hormonal and metabolic abnormalities. This diagnosis is typically made when there is unexplained chronic hyper- androgenism and oligo-anovulation. Other features associ- ated with PCOS are menstrual irregularity, polycystic ovaries, or central obesity, abnormal carbohydrate and lipid meta- bolism, acanthosis nigricans, or family history of type 2 dia- betes mellitus and infertility.5 Gonadotropin-dependent functional ovarian hyperandrogenism is the major source of the hyperandrogenemia in majority of PCOS cases.6 Insulin resistance is common in PCOS. Non-classic adrenal hyper- plasia is present in less than 5% of hyperandrogenic women in the general population. Androgen secreting tumors are present in about 0.2% of hyperandrogenic women, 50% of them are malignant.7 Hyperprolactinemia, Cushing’s syn- drome, acromegaly, and thyroid dysfunction must be considered as uncommon causes of hirsutism. Use of andro- gens or androgenic medications, such as anabolic steroids or danazol, or valproic acid should be ruled out while evaluation. Those women having hirsutism without hyperandrogenemia and normal menstrual cycle are known as idiopathic hirsutism. * Tel.: þ91 9630013474. E-mail address: drkdash@rediffmail.com. Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/apme a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 3 8 e1 4 5 0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved. http://dx.doi.org/10.1016/j.apme.2013.05.021
    • 3. Causes of hirsutism 1. Ovarian: B Polycystic ovarian syndrome (PCOS) e 80% B Hyperthecosis (a severe PCOS variant) B Ovarian tumor. 2. Adrenal: B Nonclassical adrenal hyperplasia e 4.3% B Cushing’s syndrome B Glucocorticoid resistance B Adrenal tumor e 0.2%. 3. Specific conditions associated with pregnancy: B Luteoma pregnancy B Hyperreactio luteinalis B Aromatase deficiency in fetus. 4. Others: B Idiopathic hirsutism (ovulatory cycle with normal plasma testosterone) e 7.6% B Idiopathic hyperandrogenism (patients who do not fall into any category) e 15.5% B Medications e danazol, testosterone, phenytoin, minox- idil, anabolic steroids, diazoxide, valproate B Hyperprolactinemia, hypothyroidism, growth hormone excess, insulin resistance. 4. Clinical approach & diagnosis of hirsutism Hirsutism is a clinical diagnosis. Therapeutic approach to patient with hirsutism needs accurate diagnosis of underlying abnormalities in androgen production and metabolism. The diagnosis of hirsutism depends on clinical history and phys- ical examination. The age of onset of hirsutism, area of dis- tribution and the rate of progression should be determined. Simple hirsutism should be differentiated from virilization which is a more severe form of androgen excess signifying higher rates of plasma testosterone production. This is iden- tified by the presence of temporal balding, deepening of voice, decreased breast size, increased muscularity, presence of clitoromegaly and loss of female body contours. Before going for a major work-up for hirsutism or virilization, never forget to rule out use of exogenous androgen or other medications causing androgen excess and hirsutism. All old papers should be thoroughly checked to look for these medications. Androgen excess at the time of puberty is most commonly due to PCOS or nonclassical adrenal hyperplasia. Patients with PCOS present with menstrual irregularity (amenorrhea, oli- gomenorrhea and DUB), hirsutism, infertility. Oligomenor- rhea is missing 3e4 cycles in a year or cycle lengths more than 35 days. It is the most common form of chronic anovulation Fig. 1 e FerrimaneGallwey hirsutism scoring system: Each of the nine body areas most sensitive to androgen is assigned a score from 0 (no hair) to 4 (frankly virile), and these separate scores are summed to provide a hormonal hirsutism score. R. Hatch et al: Am J Obstet Gynecol 140:815e830, 1981.3 a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 3 8 e1 4 5 139
    • with androgen excess. PCOS is also associated with increased metabolic and cardiovascular risk factors. Most important features that should never be overlooked include onset, severity and rapidity with which hirsutism progress. Rapidly progressive severe androgen excess implies androgen secreting tumors until proved otherwise. DHEAS needs to be done if adrenal cortical adenoma or carcinomas are suspected. Plasma DHEAS levels more than 800e1000 ug/ dl suggests adrenal cortical adenoma or carcinoma. In such situation, CT scan or magnetic resonance imaging (MRI) of the adrenal glands is done. Ovarian tumors are rare and small. Adrenal tumors are small, more indolent are very rare.8 Ad- renal tumors secrete androgens alone in 16%, 64% androgens and cortisol and 16% androgens, cortisol and estrogens. Ad- enocarcinomas are large and secrete other hormones in addition to testosterone, usually glucocorticoids and some- times estrogens. The treatment is surgical. If adrenal and ovarian tumors are excluded, medications causing hirsutism should be ruled out. If plasma testosterone level remains between 50 and 200 ng/dl, consider nonclassic adrenal hy- perplasia in younger women and ovarian hyperthecosis (se- vere variant of PCOS) having high hirsutism score presenting during pubertal period. CAH rarely produce plasma testos- terone levels greater than 200 ng/dl. In these patients, the search should focus on adrenal tumors in the form of ade- noma or adenocarcinoma. Patients with plasma testosterone between 50 and 200 ng/dl could be due to nonclassic adrenal hyperplasia or due to insulin resistance. These patients can present as premature pubarche or peripubertal hirsutism, acne or amenorrhea. Such cases account for 2e3% of hirsutism in total population. The diagnostic test is the standard cortrosyn stimulation test using plasma 17-hydroxyprogesterone. Values greater than 1000 ng/dl are considered to be diagnostic. Once diagnosis of nonclassic adrenal hyperplasia is done, an effective and se- lective therapy is available with a good result. Patients having insulin resistance, usually have a history of significant weight gain and signs of insulin resistance such as acanthosis nig- ricans and glucose intolerance. Biochemical abnormalities include hypercholesterolemia and hypertriglyceridemia. Many of these patients will have polycystic ovaries. The underlying cause of this disorder is weight gain leading to insulin resis- tance.9 Half of the isolated mild hirsutism (FerrimaneGallwey hirsutism score 8e15) may be unrelated to hyper- androgenemia. In the remainder of cases of mild hirsutism and in most cases of more severe hirsutism, plasma total and free testosterone levels are elevated.10e12 Women with idio- pathic hirsutism have normal ovulatory cycles and normal Evaluation of hirsutism History taking & clinical examination of Hirsutism Drug Use PCOS: Menstrual irregularity or infertility, acne, seborrhea, balding, central obesity, acanthosis nigricans Others: Cortisol excess, idiopathic hirsutism, hyperprolactinemia, growth hormone excess, thyroid dysfunction Neoplasm Risks: Sudden onset, rapid progression, virilization, abdominal or pelvic mass Hirsutism mild Score (8-15) Hirsutism > moderate (score > 15) Discontinue if possible Trial of cosmetic, dermatological, or oral contraceptive therapy Imaging & Endocrine work-up Testosterone blood level in early AM Testosterone Normal Testosterone Elevated with signs of virilization Course stable or improving Idiopathic hirsutism, PCOS & endocrinopathies Hyperandrogenemia Trial of cosmetic, dermatological, or oral contraceptive, antiandrogens, metformin History or signs suggestive of non classic adrenal hyperplasia Hyperthe cosis: severe PCOS variant Step 1 Step 2 Intermediate Testosterone Level PCOS, CAH, Idiopathic, drugs, other causes of hirsutism Surgery a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 3 8 e1 4 5140
    • plasmatestosterone levels. No furthertestingis required in this group. Flow chart given below provides an approach to the work- up for hyperandrogenism on the basis of degree of hirsutism, most common identifiable cause of hirsutism that is PCOS, virilizing disorders, androgenic medications, and other endocrinopathies. Given below is a flow chart of clinical approach to hirsutism. Mild to moderate hirsutism (FerrimaneGallwey score 8e15) without other evidence of virilization and menses are regular, testing for hyperandrogenemia may be omitted. Moderate to severe hirsutism (with a score of more than 15), assessment of androgens are must. Rapid onset and progression of hirsutism or progression despite therapy or evidence of virilization (clit- oromegaly, muscularity, frontal balding, deepening of voice) suggest the likelihood of androgen secreting tumor. Some- times such type of patients presenting with hirsutism and ambiguous genitalia, points to the virilizing forms of congen- ital adrenal hyperplasia. There are three virilizing forms: 21- hydroxylase deficiency, 11-hydroxylase deficiency, and 3-b hydroxysteroid dehydrogenase deficiency. 21-hydroxylase deficiency is by far the most common. It is easily diagnosed by AM plasma 17-hydroxyprogesterone or ACTH challenge test as earlier described.13 Serum 17-hydroxyprogesterone in excess of 1000 ng/dl confirms the diagnosis. 11-Hydroxylase deficiency, seen in less than 5e10% of cases, is usually associ- ated with hypertension. However, the laboratory criteria for the diagnosis of 11-hydroxylase deficiency and 3-b hydrox- ysteroid dehydrogenase deficiency are not well established. Measurement of the 11-deoxycortisol/cortisol ratio and the 17- hydroxypregnenolone/17-hydroxyprogesterone ratios are the most commonly applied criteria.14 Patients with abnormal external genitalia who do not have CAH should be referred to a medical genetics clinic. 5. Laboratory test for differential diagnosis of androgen excess 1. Initial testing: B Pregnancy test, in case of amenorrhea B Total testosterone, Prolactin, TSH, FSH. 2. Further testing depending on clinical presentation: B 17-Hydroxyprogesterone (8AM) B 17-Hydroxyprogesterone 60 min after IV ACTH (cortrosyn) B Cortisol (8AM) after 1 mg dexamethasone at midnight B DHEAS B Androstenedione. 3. Imaging of ovaries & adrenal gland: trans-vaginal ultraso- nography to detect an ovarian neoplasm or a polycystic ovary. Adrenal imaging by abdominal USG, CT scan/MRI. The most useful initial test to evaluate androgen excess is serum total testosterone. Plasma testosterone should remain normal in all ovulatory cycles and remain elevated in all anovulatory cycles. If all the above tests turn out to be negative, then the symptoms suggestive of an anovulatory cycle or other symptoms like oligomenorrhea, infertility and hirsutism which fulfills the criteria of PCOS along with raised testosterone level makes a diagnosis of PCOS.15e17 If androgen levels are high, further work-up required to determine the source of androgen which includes assessment of serum androstenedione; computed tomography of abdomen to exclude adrenal tumor; dynamic testing of the response to ACTH to exclude nonclassic adrenal hyperplasia and dexamethasone suppression test to exclude Cushing’s syndrome. When testing for elevated androgen levels, early morning plasma total testosterone level should be considered as the initial test. If the plasma total testosterone is normal in the presence of hyperandrogenism or hirsutism, measure an early morning free testosterone. In patients with high likelihood of congenital adrenal hy- perplasia [positive family history, certain high-risk ethnic group such as Ashkenazi Jews (prevalence 1 in 27)] and His- panics (1 in 40), and Slavics (1 in 50), measurement of an early morning follicular phase 17-hydroxyprogesterone is done, if elevated confirms the diagnosis. If not elevated can go for ACTH stimulated plasma 17-hydroxyprogesterone level. 6. Treatment of hirsutism Women with hirsutism seek treatment for reduction of hair growth, acne, regularizing menstrual cycle and infertility. PCOS patients are prone to develop metabolic abnormalities like diabetes, hypertension and hyperlipedemia. Hence, pa- tients are increasingly seeking advice for the treatment of the above metabolic abnormalities. Treatments include life style modification, mechanical removal of hair in the form of depilation, waxing, shaving, topical anti androgen, systemic antiandrogens (spironolactone, flutamide), OCPs and GnRH agonists. Experts have often made treatment recommenda- tions based on the severity of hirsutism using Ferri- maneGallwey scores (mild, score 8e15, or severe, score >15), this approach has several limitations: 1) Majority of clinicians are unfamiliar with calculating FerrimaneGallwey scores; 2) Most women use cosmetic measures before their first medical consultation and continue to use them during pharmaco- therapy, making it impossible to accurately determine a Fer- rimaneGallwey score. Therapeutic choice also depends on (a) patient preferences for pregnancy or treating hirsutism or menstrual irregularity (b) the extent of hirsutism (c) accessi- bility and affordability. (d) Fertility status (e) age of patient. General treatment of androgen excess is to prevent abnormal hair growth and virilization. This approach is followed in PCOS, idiopathic hirsutism and nonclassic adrenal hyperpla- sia. PCOS is often treated with a combination therapy of OCPs and antiandrogen (spironolactone) so as to suppress ovarian and peripheral androgen respectively. Treatment of androgen excess in nonclassic adrenal hyperplasia includes combina- tion of OCPs, antiandrogen (spironolactone) and a glucocorti- coid. GnRH analog has been used for treating ovarian hyperthecosis. Apart from these basic treatments, specific treatments like surgical intervention for ovarian and adrenal tumors and Cushing’s disease are followed separately. There are 3 types of therapeutic options for hirsutism:  Pharmacological therapy  Direct hair removal methods.  Cosmetic therapy. a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 3 8 e1 4 5 141
    • 7. Pharmacological treatments 7.1. Monotherapy 7.1.1. Oral contraceptives (OCP) OCP are the first line drug to be used in hirsutism. Oral con- traceptive agents contain either 30 or 35 mcg of ethinyl estradiol in combination with a progestin or cyproterone acetate (CPA) or drospirenone. Later two molecules are structurally unrelated to testosterone and function as androgen receptor antagonists. Most of these progestins are derived from testosterone and exhibit mild degrees of androgenicity.18 OCPS decrease circulating androgens19 in PCOS and synergize the effect of anti androgens. This also stimulates hepatic production of SHGB, reduction in adrenal androgen secretion, and also blocks the binding of androgens to their receptors. OCPs also provide the additional benefits control of bleeding and contraception. OCPs are given 21 days (d 5e25) in a month starting from day 5 of menstrual cycle. Women, who do not want to conceive, can use either oral contraceptives (OCPs) or antiandrogens in combination with OCP. 7.1.2. Antiandrogens Antiandrogen drugs have teratogenic potential. Hence it is recommended not to use antiandrogen as first line mono- therapy unless adequate contraception is used. Commonly used antiandrogens are spironolactone, cyproterone acetate (CPA), drospirenone, finasteride and flutamide. Spironolactone is the most commonly used aldosterone antagonist having dose-dependent competitive inhibition of androgen receptor as well as inhibition of 5a-reductase activ- ity.20 It is most effective for androgen excess in PCOS and idio- pathichirsutism.Inmostclinicalstudiesdoseofspironolactone varies from 50 to 400 mg/day.21 However most effective dose is generally accepted as 100 mg/day in divided doses. Because of the dangers of antiandrogens for fetal genital development, it is recommended that spironolactone be given only in combina- tion with an oral contraceptive agent.22 Spironolactone is generally well tolerated but sometimes associated with men- strual irregularity unless an OCP is used concomitantly. It rarely can cause hyperkalemia, increased diuresis, postural hypo- tension and dizziness early in treatment. CPA (Cyproterone acetate) is used worldwide for the treatment of hirsutism and acne but is not available in the United States. CPA is a progestogenic compound with anti- androgen activity and acts by inhibiting the androgen receptor and 5a-reductase activity.23 It also suppresses serum gonad- otropin and androgen levels. There are evidence that CPA in combination with ethinyl estradiol can inhibit 5a-reductase activity in skin. In one systematic review, CPA (2 mg) with ethinyl estradiol was more effective than placebo but not better than any other antiandrogen.24 Because of its long half- life, CPA is usually administered in a reverse sequential way. Doses of ethinyl estradiol (20e50 mg/d) are given for 3 weeks (d 5e25) to assure normal menstrual cycle, and CPA is adminis- tered for the first 10 d (d 5e15) of the cycle. Doses of CPA are 50e100 mg/d, often prescribed until the maximal effect is obtained, and then lower doses (such as 5 mg/d) are prescribed for maintenance. CPA is also available as an oral contraceptive at lower daily doses of 2 mg CPA with 35 mg ethinyl estradiol. CPA is generally well tolerated, should be discontinued 6 months before planning for pregnancy to avoid its teratogenic effect. Drospirenone, a progestin used in several OCPs having weak antiandrogen effect. 3 mg of drospirenone (the dose used in OCPs) is roughly equivalent to 25 mg spironolactone and 1 mg CPA.25 A 12-month trial comparing oral contracep- tives containing either 3 mg drospirenone or 2 mg CPA showed similar reductions in hirsutism scores.26 Finasteride is 5a-reductase inhibitor & it reduces hirsutism scores by 30e60% and also reduces hair shaft diameter.27 It has been seen that 5 mg finasteride and 100 mg spi- ronolactone have equal efficacy.28 Most commonly used dose of finasteride is 5 mg/day, some data suggest that 7.5 mg is more effective.29 At a dose of 5 mg/day for 6 months period shows very good response without side effects. Flutamide is a pure antiandrogen that works by competi- tively inhibiting androgen receptors.30 Several studies show that flutamide is as effective as spironolactone (100 mg/d) and finasteride (5 mg/d) in the treatment of androgen-mediated hirsutism.31e37 Most frequently used dose is 500 mg/d. The major concern is, it causes hepatic toxicity in a dose-depen- dent manner and which is not trivial. Death and liver failure are reported.38e40 Hence lowest effective dose should be used and the patient should be monitored closely. 7.1.3. Glucocorticoids Glucocorticoids are used for women with hirsutism due to nonclassic adrenal hyperplasia who have a suboptimal response to OCPs and/or antiandrogens or cannot tolerate them, or are seeking ovulation induction. Women with hirsut- ism who do not have classic or nonclassic adrenal hyperplasia due to 21-hydroxylase deficiency (CYP21A2), glucocorticoid therapy should not be used. Women with severe forms of hyperandrogenemia, such as ovarian hyperthecosis or who have a suboptimal response to OCPs and antiandrogens, GnRH agonists is recommended. 7.1.4. GnRH agonists Consideration of GnRH agonist therapy is based on the assumption that hirsutism is at least in part gonadotropin- dependent. The action of chronic GnRH agonist therapy is to inhibit LH and to a lesser extent FSH secretion, thereby leading to a decline in ovarian function and consequently decreased ovarian androgen production. Data on the effect of GnRH ag- onists on hirsutism come almost exclusively from non- placebo-controlled trials, with only one RCT published.41 7.1.5. Combination therapy If hirsutism remains despite 6 or more months of mono- therapy with an oral contraceptive, antiandrogens are added to the therapy. 7.1.6. Treatment of insulin resistance Basic pathophysiology of PCOS is hyperinsulinemia and hyperandrogenemia. Reducing insulin levels pharmacologi- cally attenuates both hyperinsulinemia and hyper- androgenemia. Role of insulin sensitizers in treating a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 3 8 e1 4 5142
    • hirsutism, in the absence of the menstrual or metabolic dis- turbances is controversial. Both metformin (a biguanide) and the thiazolidinediones (troglitazone and pioglitazone) have been used to reduce insulin levels. Metformin inhibits hepatic glucose production and thereby reduces plasma insulin con- centrations over time. The usual dose is 500 mg three times a day. Most studies show reduced levels of insulin in response to a glucose challenge, reduced weight, and reduced plasma testosterone levels. For all pharmacological therapies for hirsutism, at least 6 months of trial is taken before making any changes in dose, medication, or adding medication. 8. Direct hair removal methods Permanent methods of hair removal therapy are laser/pho- toepilation and electrolysis. Hair removal with laser devices and IPL sources is based on the principle of selective photo- thermolysis.42 The most commonly used lasers include alex- andrite, neodymiumeyttriumealuminumegarnet (Nd: YAG), and ruby lasers. Women undergoing photoepilation therapy requiring more rapid initial response, eflornithine cream during treatment may be added. Before undergoing hair removal therapy, pharmacologic therapy is done first to minimize hair regrowth. Electrolysis can be painful and time- consuming because it treats each hair individually. 9. Cosmetic measures (a) Depilation, removing hair shafts from the skin surface and epilation extracting hairs to above the bulb. Shaving sometimes can be used as a depilation method and chemical depilatory agents are also commonly used to dissolve the hair. However, most depilatories can cause dermatitis. (b) Epilation methods are plucking and waxing, are relatively safe and inexpensive, but cause some discomfort. This can cause scarring, folliculitis, and hyperpigmentation. (c) Bleaching can be used with products containing hydrogen peroxide and sulfates are a method for masking the pres- ence of undesired hair, particularly facial hair. Side effects include irritation, pruritus, and possible skin discoloration. (d) Topical treatment. Eflornithine is an irreversible inhibitor of ornithine decar- boxylase, an enzyme that catalyzes the rate-limiting step for follicular polyamine synthesis, which is necessary for hair growth. Eflornithine hydrochloride cream 13.9% (Vaniqa) is a topical preparation is approved in many countries for the treatment of unwanted facial hair in women. Eflornithine does not remove hair but acts to reduce the rate of hair growth. Open-label43e47 and randomized48 trials have shown that eflornithine reduces the growth and appearance of facial hair and helps to improve quality of life. Noticeable results take about 6e8 weeks, and once the cream is discontinued, hair returns to pretreatment levels after about 8 weeks. Side effects are itching and dry skin. 10. Conclusion Hirsutism is a common disorder in endocrine clinic during reproductive period. It requires proper investigation and diagnosis. Treatment plan depends on the etiology and severity of the disease. For all practical purposes physical removal of the hair by depilation or epilation and imple- menting life style modification in losing weight, are the mainstay of treatment for all forms of hirsutism. OCPs are the most common medical therapy used for hirsutism and are most effective when hyperandrogenism is of ovarian origin. Most common cause of hirsutism that is PCOS is often treated with combination of antiandrogens and OCPs. Antiandrogens (spironolactone) suppress extra ovarian action of androgens and OCPs suppresses ovarian sources of androgens. Which- ever drug is used, improvement in hirsutism scoring takes at least 6 months period because one hair cycle growth takes at least 3e6 month period. Cosmetic therapies for the terminal hairs should be done by mechanical/physical methods like epilation, depilation or electrolysis, diathermy, or laser treat- ment. All of them should be done at least 3 months after androgen suppression is achieved. Eflornithine is currently thought of as a replacement for shaving. However, the clinical effects of eflornithine require 8e12 weeks reaching maximum effect. The best approach is physical removal of hair and use of OCPs for at least 6e8 months before the decision to use an antiandrogen is made. However, if pregnancy is not a concern combining OCPs with spironolactone for treating androgen excess in PCOS has been seen to be very effective. Because of the danger of antiandrogen-induced abnor- malities of fetal genital development, antiandrogen treatment should only be given to women known to be infertile or use of OCPs must always precede antiandrogen treatment. Finally, if a patient does not respond to monotherapy, a combination of birth control pills with or without the addition of physical removal of hair, eflornithine, or antiandrogens should be used. In severe form of disease, addition of cyproterone ace- tate or finasteride helps. Weight loss programs have to be implemented because of many associated health benefits. Every effort should be made to treat these patients with an aggressive weight loss regimen because most common cause of hirsutism is PCOS and this is associated with many meta- bolic abnormalities in future. Conflicts of interest The author has none to declare. r e f e r e n c e s 1. Rosenfield RL. Clinical practice e hirsutism. N Engl J Med. 2005;353:2578e2588. 2. Ferriman D, Gallwey JD. 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