Review Hirsutism Joshua C. Berkowitz, BA; Adeel Kahtri, MD; Rao N. Saladi, MD; Dovid Herskowitz, BA; Joshua L. Fox, MD Hirsutism is defined as the development of a malelike pattern of excess hair especially in women. Hirsut- ism often results from raised androgen levels in the body and may indicate the existence of a serious underlying endocrine condition, such as polycystic ovary syndrome (PCOS). Treatment of hirsutism may require both medical and cosmetic actions. Medical therapy aims to counteract any suspected hormonal imbalance and can include administration of oral contraceptives and antiandrogens. Cosmetic treat- ment directly addresses excess hair and seeks to either remove the hair or diminish its appearance. Cos- metic options range from conventional methods, such as shaving and waxing, to modern techniques, such as laserCOS photoepilation. DERM irsutism refers to the growth of coarse that occurs despite normal androgen levels and normal terminal hair in females that follows a ovulatory function. malelike pattern, most commonly in the To comprehend the underlying mechanism of hirsut- upper lip area, beard area, abdomen, or ism, it is necessary to understand the physiology of hair chest. The amount of hair that is consid- growth. There are 2 types of hair: fine, nonpigmented Hered Donormal is subjective. In someNot cultures, women are vellus hairCopy and coarse, pigmented terminal hair. Both of disturbed by even a small amount of excess hair, while these hair types originate from the same pilosebaceous in other cultures, larger amounts may be tolerated and unit in the skin. Development of terminal hair mainly considered normal. The perception of excess hair has an is dependent on stimulation of the pilosebaceous unit associated psychosocial stigma that affects the lives of by androgens. Overstimulation of pilosebaceous units afflicted women considerably.1,2 leads to growth of terminal hair in atypical areas of the body, which causes hirsutism. Some important factors ETIOLOGY AND PATHOPHYSIOLOGY that influence the follicle stimulation process are: the There is a wide variety of conditions that can cause quantity of androgens secreted by the adrenal glands hirsutism. Most of these conditions are associated with and the ovaries; the amount of free androgens circu- raised levels of androgens in the body, which often stem lating in the blood; the metabolic clearance rate; and from a dysfunction in the ovulatory process. Idiopathic the degree of sensitivity of hair follicles to androgens. hirsutism, on the other hand, refers to hair growth Peripheral conversion of testosterone to dihydrotestos- terone mediated by 5a-reductase, particularly type 1 From New Age Skin Research Foundation, Fresh Meadows, isoform3,4 and the metabolism of dihydrotestosterone by New York. Dr. Fox also is from Advanced Dermatology, 3a-hydroxysteroid dehydrogenase,5,6 plays a major role PC, Fresh Meadows. in determining the degree of sensitivity of hair follicles The authors report no conflict of interest in relation to to androgens (Figure). Activity of 5a-reductase mainly this article. is controlled by androgen levels, but studies have shown Correspondence: Joshua L. Fox, MD, President, New Age Skin that insulinlike growth factor 1,7 transforming growth Research Foundation, 58-47 188th St, Fresh Meadows, New York factor-b, epidermal growth factor, and inhibin and 11365 ([email protected]). activin8 also regulate its activity. VOL. 23 NO. 12 • DECEMBER 2010 • Cosmetic Dermatology® www.cosderm.com 549 Copyright Cosmetic Dermatology 2010. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Hirsutism norgestimate or norethindrone. Progestins with antiandro- genic activity such as cyproterone acetate and drospirenone Thin Vellus Hair Testosterone also can be used in combination with ethynyl estradiol.12,13 Antiandrogens—This category includes cyproterone 5␣-reductase acetate, spironolactone, and flutamide, which inhibit the Dihydrotestosterone binding of androgens to the peripheral androgen receptors. Flutamide, unlike cyproterone acetate or spironolactone, is 3␣-hydroxysteroid a nonsteroidal drug. Antiandrogens may be used alone or as dehydrogenase an adjunct to contraceptives. Recent data, however, suggest 5␣-androstane-3␣-17␤-diol that antiandrogens do not provide substantial benefits.14 Thick Terminal Hair Androgens and the terminalization of hair follicles. Table 1 Hirsutism may be considered a clinical presentation of Causes of Hirsutism many different conditions rather than a specific disease entity unto itself. Hirsutism is associated with condi- tions such as polycystic ovary syndrome (PCOS), ovar- Idiopathic hirsutism ian neoplasm, congenital adrenal hyperplasia, Cushing syndrome, adrenal neoplasm, obesity, hyperinsulinism, Ovarian causes hyperprolactinemia, excess growth hormone, and hypo- Polycystic ovaries thyroidism (Table 1). Hyperreactio luteinalis9,10 Ovarian tumors TREATMENT COS DERM Luteoma of pregnancy Hirsutism treatment options may be divided into 2 main categories: those that treat the underlying dis- Arrhenoblastomas order and androgenic dysfunction, and those that sim- Leydig cell tumors ply remove unwanted hair. The aspect of therapy that Hilar cell tumors addresses androgenic dysfunction mostly consists of Thecal cell tumors medical treatment, while procedures for hair removal Adrenal causes have evolved to include a wide spectrum of options Do Not CongenitalCopy adrenal hyperplasia ranging from conventional methods, such as shaving, to more modern processes, such as laser and intense Cushing syndrome pulsed light therapies. Adrenal neoplasm 3β-hydroxysteroid dehydrogenase Medical Therapy 11β-hydroxylase deficiency Pharmacologic therapy is aimed at either lowering the Hypothyroidism free androgen level or reducing the sensitivity of hair follicles to androgens. These aims can be accomplished Insulin resistance and hyperinsulinemia by drugs that suppress androgen secretion, androgen Anorexia nervosa receptor inhibitors, 5a-reductase inhibitors, or insulin Acromegaly sensitizers. Oral contraceptives suppress androgen pro- Porphyria duction and increase sex hormone–binding globulin, Hyperprolactinemia which effectively decreases free androgen quantities.11 Oral Contraceptives—Oral contraceptives suppress Drugs pituitary production of luteinizing and follicle-stimulating Oral contraceptives hormones, thereby reducing ovarian androgen output. Phenytoin Oral contraceptives are particularly useful in situations Minoxidil where hirsutism is caused by an overproduction of andro- Diazoxide gens by the ovaries, as in cases of PCOS. Oral contraceptive pills used for treating hirsutism contain ethynyl estradiol Anabolic steroids in combination with a nonandrogenic progestin such as 550 Cosmetic Dermatology® • DECEMBER 2010 • VOL. 23 NO. 12 www.cosderm.com Copyright Cosmetic Dermatology 2010. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Hirsutism a-Reductase Inhibitors—5a-Reductase type 2 is Removal of Unwanted Hair responsible for the conversion of testosterone to dihy- Removal of unwanted hair is a central aspect of hir- drotestosterone in peripheral tissues, including the hair sutism treatment. Although mild forms of hirsutism follicles found in the skin. Inhibitors of this enzyme, such may be controlled by the aforementioned medical as finasteride can be effective in treating hirsutism.15,16 procedures, severe forms of hirsutism usually require Insulin-Sensitizing Drugs—Hyperinsulinism and removal of terminalized hair follicles in addition to insulin resistance contribute substantially to the medical therapy. The different methods of hair removal hyperandrogenism associated with PCOS, which may include shaving, waxing, plucking, threading, depila- be the most common cause of hirsutism.17 Metformin, an tory creams, bleaching, eflornithine cream, electrolysis, insulin sensitizer, has come to be regarded as first-line lasers, and intense pulsed light–assisted hair removal. therapy for PCOS. Some studies have shown insu- Temporary Methods—Several of the hair removal lin sensitizers to be effective in treating hirsutism, methods are classified as temporary because their effects especially hirsutism associated with PCOS18,19; recent usually only last for a few days or weeks (Table 2). These analyses, however, have shown that insulin sensitizers methods do not impede the permanent growth of hair produce inconsistent results.20,21 and therefore must be repeated as hair reappears. Table 2 Temporary Methods of Hair Removal COSMechanism DERMAdvantages Disadvantages Shaving Manual or electric Easy and inexpensive Cuts may occur; effec- razor is used. Hair is tive only for a few days cut at or just below or weeks; hair regrowth the skin surface appears thicker Waxing Hot or cold wax Hair is removed at or Patient discomfort; Do is appliedNot and near the base;Copy effects may result in irrita- then ripped off usually last longer tion and scarring; an using a piece of than shaving experienced person paper or cloth is needed to perform the procedure Plucking Tweezers or twisted Hair is removed May cause discomfort and threading thread is used above the hair bulb and folliculitis Depilatory cream Usually contains Ease of application; Sulfur compounds calcium thioglycolate, can be used at home; may lead to irritation which breaks down quick results and pruritus; bad disulfide bonds in odor;