Evaluation and Treatment of Women with Hirsutism MELISSA H. HUNTER, M.D., and PETER J. CAREK, M.D. Medical University of South Carolina, Charleston, South Carolina Hirsutism is a common disorder, often resulting from conditions that are not life- threatening. It may signal more serious clinical pathology, and clinical evaluation should differentiate benign causes from tumors or other conditions such as polycystic ovary syndrome, late-onset adrenal hyperplasia, and Cushing’s syndrome. Laboratory testing should be based on the patient’s history and physical findings, but screening for levels of serum testosterone and 17␣-hydroxyprogesterone is sufficient in most cases. Women with irregular menses and hirsutism should be screened for thyroid dys- function and prolactin disorders. Pharmacologic and/or nonpharmacologic treatments may be used. Advances in laser hair removal methods and topical hair growth retar- dants offer new options. The use of insulin-sensitizing agents may be useful in women with polycystic ovary syndrome. (Am Fam Physician 2003;67:2565-72. Copyright 2003 American Academy of Family Physicians.)
growth varies widely among women, and dis-
tinguishing normal variations of hair growth
from hypertrichosis and true hirsutism is
for “Practical Therapeu-tics.” This article is onein a series coordinatedby the Department of
der affecting up to 8 percentof women.1 It often resultsfrom conditions that are not
chronic anovulation. Hirsutism is defined as
androgen-sensitive pilosebaceous units.3,4
the presence of excessive terminal hair in
While 60 to 80 percent of women with hir-
sutism have increased levels of circulating
body.2 The disorder is a sign of increased
androgens, degrees of hirsutism correlate
editor of the series isWilliam J. Hueston, M.D.
poorly with androgen levels.5 The ovary is the
increased circulating levels of androgens
major source of increased levels of testos-
(endogenous or exogenous) or increased sen-
terone in women who have hirsutism.6 Dehy-
sitivity of hair follicles to normal levels of cir-
androgen that arises almost exclusively from
the adrenal gland but is an uncommon cause
serious pathology, and clinical evaluation
of hirsutism. Nearly all circulating testos-
terone is bound to sex hormone binding glob-
tumors or other conditions that require spe-
ulin (SHBG) and albumin, with free testos-
cific treatment. Most women who seek treat-
terone being the most biologically active form.
ment for hirsutism do so for cosmetic rea-
When elevated insulin levels are present,
sons, because excess body hair outside of
SHBG levels decrease while free testosterone
cultural norms can be very distressing. Hair
Hypertrichosis is defined as a diffuse in-
crease in vellus hair growth and is not andro-gen dependent. Hypertrichosis may be con-
Hirsutism is a sign of increased androgen action on hair
genital (e.g., Hurler’s syndrome, trisomy 18
follicles, from increased circulating levels of androgens or
syndrome, or fetal alcohol syndrome) or asso-
increased sensitivity of hair follicles to normal levels of
ciated with hypothyroidism, porphyrias, epi-
dermolysis bullosa, anorexia nervosa, malnu-trition, or dermatomyositis. It also may occur
TABLE 1 Medications That May Cause Hirsutism and/or Hypertrichosis Hirsutism Hypertrichosis
after severe head injury, be present at sites of skin trauma,
Causes of Hirsutism
When evaluating hirsutism, it is important to remember
that it is only one sign of hyperandrogenism. Other abnor-
malities associated with excessive levels of androgen are
listed in Table 2.6,8 Increased androgen effect that results inhirsutism can be familial, idiopathic, or caused by excess
Information from Leung AK, Robson WL. Hirsutism. Int J Derma-
androgen secretion by the ovary (e.g., tumors, polycystic
ovary syndrome [PCOS]), excess secretion of androgensby adrenal glands (e.g., congenital adrenal hyperplasia[CAH], Cushing’s syndrome, tumor), or exogenous phar-macologic sources of androgens. Table 38 outlines consid-eration for these causes, along with laboratory findings.
Idiopathic hirsutism is common9 and often familial. It is
Abnormalities Associated with Androgen Excess
a diagnosis of exclusion and thought to be related to dis-orders in peripheral androgen activity. Onset occurs
shortly after puberty with slow progression. Patients with
idiopathic hirsutism generally have normal menses and
normal levels of testosterone, 17␣-hydroxyprogesterone
PCOS affects approximately 6 percent of women of
Adapted with permission from Gilchrist VJ, Hecht BR. A practical
reproductive age,10 and is represented by chronic anovula-
approach to hirsutism. Am Fam Physician 1995;52:1837-46, with
tion and hyperandrogenemia, excluding other causes such
information from Speroff L, Glass RH, Kase NG, eds. Clinical gyne-cologic endocrinology and infertility. 6th ed. Baltimore: Lippincott
as adult-onset CAH, hyperprolactinemia, and androgen-
Williams & Wilkins, 1999:529-56.
secreting tumors.11 Patients often report menstrual irregu-larities, infertility, obesity, and symptoms associated withandrogen excess, and diagnosis usually is based on clinicalrather than laboratory findings. Up to 70 percent of pa-tients with PCOS have signs of hyperandrogenism.12
CAH is a spectrum of inherited disorders of adrenal
steroidogenesis, with decreased cortisol production result-
MELISSA H. HUNTER, M.D., is an associate professor in the Depart-ment of Family Medicine, Medical University of South Carolina College
ing in overproduction of androgenic steroids.13 Hirsutism,
of Medicine, Charleston. She received her medical degree from the
acne, menstrual disorders, and infertility may be present-
Medical University of South Carolina College of Medicine, and com-
ing symptoms during adolescence or adulthood.
pleted a residency in family medicine at McLeod Regional MedicalCenter, Florence, S.C. Dr. Hunter also completed a faculty develop-
Although rare, Cushing’s syndrome should be considered
ment fellowship at the University of North Carolina at Chapel Hill
in the differential diagnosis. It may be caused by increased
production of adrenocorticotropic hormone (ACTH) by the
PETER J. CAREK, M.D., is an associate professor in the Department of
pituitary, adrenal carcinoma/adenoma, or secretion of
Family Medicine, Medical University of South Carolina College of Med-
ectopic ACTH.14 Profound hirsutism is seen most commonly
icine. He received his medical degree from the Medical University ofSouth Carolina College of Medicine, where he also served a residency
in patients with macronodular hyperplasia, and clinical
in family medicine. Dr. Carek completed a sports medicine fellowship
signs of Cushing’s syndrome are usually quite apparent.14
and obtained a master’s degree in exercise physiology at the University
Hirsutism may result from use of exogenous pharmaco-
of Tennessee, Memphis, College of Medicine.
logic agents, including danazol (Danocrine), anabolic
Address correspondence to Melissa H. Hunter, M.D., University Family
steroids, and testosterone. Oral contraceptives (OCs) con-
Medicine, 9298 Medical Plaza Dr., N. Charleston, SC 29406 [e-mail:email@example.com]. Reprints are not available from the authors.
taining levonorgestrel, norethindrone, and norgestrel tend
TABLE 3 Causes of Hirsutism, Associated Laboratory Findings, and Recommended Additional Testing 17-OHP = 17␣-hydroxyprogesterone; LH = luteinizing hormone; FSH = follicle-stimulating hormone; DHEAS = dehydroepiandrosteronesulfate; ACTH = adrenocorticotropic hormone; CT = computed tomography.Adapted with permission from Gilchrist VJ, Hecht BR. A practical approach to hirsutism. Am Fam Physician 1995;52:1841.
to have stronger androgenic effects, while those with ethyn-
Androgen-secreting adrenal tumors are less common.
odiol diacetate, norgestimate, and desogestrel are less
Generally large at the time of diagnosis, these adrenal car-
androgenic.9 Medications that cause hyperprolactinemia
cinomas are associated with a poor prognosis.9
also may cause hirsutism (Table 1).7
Androgen-secreting tumors of the ovary or adrenal are
usually heralded by virilization (i.e., development of male
A thorough history and physical examination are essen-
characteristics in women) and rapid progression of hir-
tial to evaluate women with hirsutism to determine which
sutism and cessation of menses. Virilization occurs in less
patients need additional diagnostic testing. Family history
than 1 percent of patients with hirsutism (Table 4).8
is important; 50 percent of women with hirsutism have a
Arrhenoblastoma is the most common ovarian tumor.2,9
positive family history of the disorder.4 Key elements ofhistory and physical examination are noted in Table 5.6,8Methods the patient has used to treat hirsutism should be
noted, including hair removal methods, to provide some
Signs of Virilization
semiquantitative measure for evaluating severity and pro-gression of hair growth. Discussion of the psychosocial
effects of hirsutism as well as the patient’s infertility con-
Physical examination should distinguish normal
amounts of hair growth from hirsutism and hypertri-
chosis. Amounts, characteristics, and distribution of hair
growth should be noted. Standardized scoring systems for
evaluating hirsutism are limited by subjective variability
Information from Gilchrist VJ, Hecht BR. A practical approach to
and felt by some to be of little clinical use.6 Diagnosis often
hirsutism. Am Fam Physician 1995;52:1837-46.
can be made on clinical assessment alone or by limited lab-oratory testing. Virilization should be noted (Table 4),8 and
TABLE 5 History and Physical Examination in the Evaluation of Hirsutism History Abdominal symptoms Family history Breast discharge Extent of hair growth
underlying ovarian and/or adrenal tumors and adult-onset
Menstrual, reproductive, and medication history
adrenal hyperplasia.2,6 For diagnostic purposes, serum levels
of testosterone and 17-OHP are usually sufficient.6 A diag-
nostic algorithm is provided in Figure 1.6,8
For patients with irregular menses, anovulation, PCOS,
late-onset adrenal hyperplasia, and idiopathic hirsutism,
prolactin levels and thyroid function tests may be consid-
Height, weight, blood pressure (may suggest condition of
ered to identify thyroid dysfunction and pituitary tumors.
androgen excess related to adrenal enzyme deficiencies)
Testing of glucose, testosterone, and 17-OHP levels should
Documentation of hair amount, distribution, and characteristics
be considered, along with careful breast examination to
Skin changes (i.e., acne, acanthosis nigricans)Galactorrhea
Abdominal and pelvic examination/palpation for masses
Hirsutism outside of the perimenarchal period, rapid
Physical features of Cushing’s syndrome (i.e., striae, acne,
progression of hirsutism, or signs of Cushing’s syndrome or
proximal muscle weakness, “moon” facies, central obesity)
virilization should indicate the possibility of an ovarian or
adrenal neoplasm. Diagnostic testing should examine levelsof serum testosterone, 17-OHP, and DHEAS. Levels of
Adapted with permission from Gilchrist VJ, Hecht BR. A practical
serum testosterone greater than 200 ng per dL (6.94 nmol
approach to hirsutism. Am Fam Physician 1995;52:1837-46, with
per L) and/or DHEAS greater than 700 ng per dL
information from Speroff L, Glass RH, Kase NG, eds. Clinical gyne-
(24.3 nmol per L) are strongly indicative of virilizing
cologic endocrinology and infertility. 6th ed. Baltimore: LippincottWilliams & Wilkins, 1999:529-56.
tumors.16 For patients with this degree of hormonal ele-vation or those whose history suggests a neoplasm, addi-tional diagnostic imaging, including abdominal com-puted tomography to assess the adrenals, should be
thorough abdominal and pelvic examinations should be
performed. Selective venous catheterization may be nec-
performed to exclude any masses. Acanthosis nigricans, a
essary whenever imaging has not identified a tumor but
marker for insulin resistance, also should be noted.15
Identification of serious underlying disorders is the pri-
mary purpose of laboratory testing and should be individ-
ualized. About 95 percent of these patients have PCOS or
Treatment options for patients who have hirsutism can
idiopathic hirsutism.3,4 History and physical examination
be divided into those measures targeting local manifesta-
can exclude most underlying disorders, and full hormonal
tions of hirsutism and pharmacologic therapy aimed at the
investigation is usually warranted only in those patients
underlying causes. Therapy that targets local manifestations
with rapid progression of hirsutism, abrupt symptom
includes physical methods of hair removal ranging from
shaving to laser therapy, topical treatment, and weight loss.
In patients with hirsutism of peripubertal onset and
slow progression, regular menses, otherwise normal phys-
ical examination, and no virilization, the likelihood of an
For patients with mild hirsutism, local measures such as
underlying neoplasm is small. Whether laboratory investi-
shaving, bleaching, depilatories, and electrolysis may suf-
gation in these patients is warranted is controversial; how-
fice. Shaving is the easiest and safest method, but is often
ever, some experts recommend routine testing to exclude
unacceptable to patients. Bleaching products are oftenineffective for dark hair growth, and skin irritation mayoccur. Chemical depilatories produce results similar toshaving, but skin irritation is common. Electrolysis is one
Identification of serious underlying disorders is
of the most effective and permanent methods of hair
the primary purpose of laboratory testing for
removal, and may be an adjunct to hormonal treatment.18
However, electrolysis is costly and time consuming, andlargely has been supplanted by use of laser techniques. Hirsutism Evaluation of Hirsutism
FIGURE 1. Algorithm showing the evaluation of hirsutism. (ACTH = adrenocorticotropic hormone; CAH = congenitaladrenal hyperplasia; DHEAS = dehydroepiandrosterone sulfate; PCOS = polycystic ovary syndrome; 17-OHP = 17␣-hydroxy-progesterone)
Information from Gilchrist VJ, Hecht BR. A practical approach to hirsutism. Am Fam Physician 1995;52:1837-46, and Speroff L, Glass RH,Kase NG, eds. Clinical gynecologic endocrinology and infertility. 6th ed. Baltimore: Lippincott Williams & Wilkins, 1999:529-56.
that all preparations are comparable in efficacy.24 These
Laser hair removal methods work best on dark
agents increase the level of SHBG and therefore decreaseovarian androgen production while decreasing the risk of
hair growth, although post-treatment hyperpig-
endometrial hyperplasia often seen in anovulatory
Antiandrogens may be combined with OCs for the treat-
ment of hirsutism. Up to 75 percent of women report clini-
The need for rapid methods of hair removal has led to
cal improvement with combination therapy,27 but data have
the development of laser therapy for hirsutism. Several dif-
shown that combined therapy is not significantly better than
ferent lasers exist, including ruby, alexandrite, pulsed
single agents alone. Patients who use antiandrogens alone
diode, and Q-switched yttrium-aluminum-garnet (YAG)
may experience irregular uterine bleeding and ovulation.6
lasers. Pulsed diode lasers are generally less expensive and
The most commonly used antiandrogens are spironolac-
more reliable than other laser sources for hair removal.19
tone (Aldactone) and flutamide (Eulexin). However, no
Q-switched YAG lasers work well in patients with darker
antiandrogens are approved by the U.S. Food and Drug
skin; however, these lasers are ineffective for long-term hair
Administration for the treatment of hirsutism. Spi-
removal.20 Most patients experience a two- to six-month
ronolactone is most commonly used because of its safety,
growth delay after a single treatment, and some have per-
availability, and low cost. Flutamide has been shown to be as
manent hair removal after multiple treatments. Laser ther-
effective as spironolactone; however, hepatic function must
apy works best on dark hair, although post-treatment
be monitored.28 Finally, finasteride (Proscar), a competitive
inhibitor of 5␣-reductase, has been shown to be effective in
Weight loss should be encouraged for obese patients,
treating hirsutism with relatively few side effects.29 Response
because this increases SHBG levels and decreases insulin
to antiandrogens is slow and may take up to 18 months.
resistance and the levels of serum androgens and luteiniz-
Duration of therapy is unclear, but treatment cessation gen-
ing hormones. Women who are overweight, hyperandro-
erally is followed by recurrent hair growth.
genic, or hyperinsulinemic should be counseled regarding
Gonadotropin-releasing hormone (Gn-RH) analogs
future risk of diabetes mellitus and cardiovascular disease.6
such as leuprolide (Lupron) should be reserved for use inwomen who do not respond to combination hormonal
therapy or those who cannot tolerate OCs. Gn-RH analogs
Pharmacologic treatment for hirsutism should be aimed
should be used cautiously with particular attention to pos-
at blocking androgen action at hair follicles or suppression
sible long-term consequences (e.g., hot flushes, bone de-
of androgen production (Table 6). Response to pharmaco-
logic agents is slow, occurring over many months. When
For patients whose terminal hair growth does not
medical therapy is unacceptable to patients, combining
decrease significantly, treatment with insulin-sensitizing
local measures with medical therapy may be appropriate.
agents may be useful. Metformin (Glucophage) has been
Eflornithine (Vaniqa) topical cream has been shown to
shown to improve insulin sensitivity and decrease testos-
slow rates of terminal hair growth significantly in up to
terone levels in patients with PCOS.30 Clinical manifesta-
32 percent of patients and can be used adjunctively with
tions of hyperandrogenism have shown improvement after
usual methods of hair removal.21,22 Once use of eflor-
metformin therapy.31,32 A three-month therapeutic trial of
nithine is discontinued, hair growth usually returns to pre-
metformin to assess efficacy may be useful.
Increased androgen production from nonspecific hyper-
For women with idiopathic hirsutism, PCOS, or late-
secretion or adult-onset adrenal hyperplasia responds to
onset CAH, appropriate treatment decisions depend on
glucocorticoid suppression with dexamethasone.33 Adrenal
each patient’s desires and childbearing plans. Women who
androgen secretion is more sensitive to dexamethasone
do not wish to become pregnant should use low-dose OCs.
than is cortisol secretion.33 Generally, glucocorticoid ther-
OCs containing less androgenic progestins, such as norges-
apy in patients with uncomplicated adrenal hyperplasia
timate, gestodene (not available in the United States), and
results in normal menstrual cycles and improvement in hir-
desogestrel, seem to be the best choice, but some maintain
sutism or acne.34 Combined therapy with Gn-RH analogs,
TABLE 6 Medications Commonly Used in the Treatment of Hirsutism
heparin, potassium supplements, potassium sparing diuretics.
Hot flushes, decreased bone Pregnancy category X. Use with
Skin adverse effects include Pregnancy category C
FDA approval for reduction No significant drug interaction
(rare with mortality nearly Resumption of ovulation may
function before starting,and monitor. GI = gastrointestinal; FDA = U.S. Food and Drug Administration; NSAIDs = nonsteroidal anti-inflammatory drugs; ACE = angiotensin-converting enzyme; Gn-RH = gonadotropin-releasing hormone; IM = intramuscular; HT = hormone therapy; PCOS = polycystic ovary syndrome.
*—For more detailed information, consult the package insert provided by the manufacturer of each drug. †—Estimated cost to the pharmacies (rounded to the nearest dollar) based on average wholesale prices in Red book, Montvale, N.J.: Medical Economics Data,2002. Cost to the patient will be higher, depending on prescription filling fee. Hirsutism
OCs, and antiandrogens may be more effective in severe
17. Surrey ES, de Ziegler D, Gambone JC, Judd HL. Preoperative local-
cases. Because of side effects, long-term use of glucocorti-
ization of androgen-secreting tumors: clinical, endocrinologic, andradiologic evaluation of ten patients. Am J Obstet Gynecol
coids should be limited to patients with infertility or unre-
sponsiveness to other antiandrogen therapy.3
18. Hatasaka HH, Wentz AC. Hirsutism: facts and folklore. Part II:
Ketoconazole (Nizoral), an antifungal agent, has proved
management options. Female Patient 1991;16:73-81.
19. Dierickx CC. Hair removal by lasers and intense pulsed light
effective in the treatment of hirsutism. Severe side effects,
sources. Semin Cutan Med Surg 2000;19:267-75.
including alopecia, dry skin, abdominal pain, and hepatotox-
20. Dierickx CC, Alora MB, Dover JS. A clinical overview of hair removal
icity, can occur, and use should be reserved for patients with
using lasers and light sources. Dermatol Clin 1999;17:357-66.
21. Hickman JG, Huber F, Palmisano M. Human dermal safety studies
severe hirsutism that has not responded to other therapeutic
with eflornithine HCl 13.9% cream (Vaniqa), a novel treatment for
options.35 Liver function testing should be performed before
excessive facial hair. Curr Med Res Opin 2001;16:235-44.
and at periodic intervals during prolonged treatment.
22. Eflornithine cream for facial hair reduction. Med Lett Drugs Ther
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The authors indicate that they do not have any conflicts of inter-
O, et al. Ketoconazole therapy for women with acne and/or hir-
est. Sources of funding: none reported.
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Le Olimpiadi del Viagra Sembra, dalle analisi dei controlli antidoping effettuati alle Olimpiadi di Pechino, che moltissimi atleti (uomini e donne) facciano uso di Viagra : il farmaco che è stato scoperto e messo in commercio nel 1992 ed è consigliato per aiutare le persone anziane (uomini) ad essere ancora attivi sessualmente, cioè ad avere erezioni ancora efficienti con le benefiche c
SEIS ANÁLISIS es un libro que trata del desarrollo personal que incorpora la reencarnación, pero que no se basa en las antiguas religiones como, por ejemplo, el Budismo, sino en una concepción occidental de la misma que adquiere cada vez mayor aceptación. Una concepción individual que encuentra acogida en la propia intuición de las personas. El libro dilucida algunos de los factores que t