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A. Definitions navigator

  1. Types of Hair
    1. Lanugo - fine pigmented hair on newborns
    2. Vellus - new hair, conversion to terminal hair controlled by androgens
    3. Terminal - coarse, dark hair seen in hirsutism (born with ~100,000 on the scalp)
    4. Club - fully keratinized, dead heair (final product of telogen stage)
  2. Hirsutism - excessive hair growth in androgen dependent areas in women
  3. Hypertrichosis - excessive hair growth (usually diffuse)
  4. Alopecia - hair loss
    1. Androgenic alopecia - baldness caused by miniaturization of susceptible follicles
    2. Alopecia areata - hair loss in patches believed to be autoimmune
    3. Permanent alopecia - caused by destruction of hair follicles

B. Phases of Hair Growth [1,7]navigator

  1. Anagen
    1. Growth stage of hair follicle
    2. Occupies most of the length of a full cycle
    3. Stimulated by FGF-7 and IGF-1
    4. FGF-5 also plays a role
    5. Normally occurs over 2-6 years
  2. Catagen
    1. Midstage of hair follicle, follows anagen
    2. Regression and involution of follicle
    3. Due to burst of programmed cell death (apoptosis)
    4. Requires 2-3 weeks
  3. Telogen
    1. Resting stage of hair follicle, follows catagen
    2. Club hair is final product and eventually falls out
    3. Requires 2-3 months

C. Modulators of Human Hair Growthnavigator

  1. Androgens
    1. Typically increase hair growth by shortening duration of anagen
    2. Enlarge hair follicle sizes during adolescence
    3. Testosterone - major effector as dihydrotestosterone (DHT)
    4. Weak Androgens: androstenedione, DHEA, DHEA-Sulfate
    5. Chronic exposure to DHT leads to typical pattern baldness
  2. Estrogens
    1. Prolong anagen stage
    2. Postpartum reduction in estrogen levels causes telogen effluvium
  3. Thyroxine
    1. High or low levels lead to increased telogen duration
    2. Hypothyroidism (such as myxedema) has increased hair, usually facial
    3. Hyperthyroidism (such as Graves Disease) has decreased hair growth
  4. Growth Hormone - acts synergistically with androgens during adolescence
  5. Prolactin - can induce hirsutism
  6. Drugs
    1. Anabolic steroids - same as androgens
    2. ß-adrenergic antagonists - can cause (rarely) telogen effluvium
    3. Cyclosporine - hypertrichosis
    4. Finasteride - prolongs anagen stage, converts vellus follicles to terminal follicles
    5. Minoxidil - induces and prolongs anagen stage, converts vellus to terminal follicles
    6. Phenytoin - hypertrichosis
    7. Retinoids - can cause premature onset of catagen stage, may cause telogen effluvium

D. Etiology of Hirsutismnavigator

  1. "Idiopathic"
    1. Apparent increase in 5-alpha reductase activity leads to increased DHT
    2. A number of these patients will have polycystic ovaries [3]
  2. Ovarian Dysfunction
    1. Chronic Anovulatory Syndrome (PCOS; see below)
    2. Insulin Resistance
    3. Ovarian Tumors
  3. PCOS [3]
    1. Triad of hirsuitism, obesity, and olig- or anovulation (galactorrhea may occur)
    2. Component of adrenal hyperandrogenism
    3. Symptoms similar to adrenal hyperplasia, adrenal tumors, gonadal tumors
    4. Serum levels of DHEA, DHEA Sulfate, and Testosterone should be obtained
    5. These levels will help rule out neoplastic causes of symptoms (see below)
    6. 40% of hirsute women with normal menstruation have polycystic ovaries on ultrasound [10]
    7. Many of these hirsute women have metabolic abnormalities typical of PCOS [10]
  4. Drug Induced
    1. Androgens - Danazol, DHEA, testosterone
    2. Anabolic Steroids
    3. Minoxidil
    4. Glucocroticoids
    5. Progesterone
    6. Cyclosporine
    7. Dilantin
    8. Diazoxide
  5. Adrenal Disease
    1. Cushing's Syndrome - ~75% have hirsutism (24hr free cortisol >100mg)
    2. Adrenal Hyperplasia
    3. Congenital Adrenal Hyperplasia
    4. Adrenal neoplasm - particularly with highly elevated DHEA levels
    5. 3ß-Hydroxysteroid Dehydrogenase - hirsutism, acne, amenorrhea
  6. Abnormal Gonadal Development
    1. XY female
    2. Turner Syndrome (X0)
  7. HAIR-AN Syndrome []
    1. Hyperandrogenism
    2. Insulin resistance
    3. Acanthosis nigricans
    4. Rare disorder in women
    5. Antiandrogen therapy, weight loss, and normalizing glycemia are used
  8. Stromal Hyperthecosis

E. Evaluationnavigator

  1. Onset
    1. Slow development is usual
    2. Rapid development is concerning for tumor associated hirsutism
  2. Ethnic Origin
  3. Acne, Oily Skin
  4. Signs of Virilization (Androgen Excess)
    1. Consider Adrenal or Ovarian Tumors
    2. Loss of female body habitus
    3. Muscle mass increased
    4. Increased libido
    5. Clitoromegaly
  5. Menstrual Irregularities - many patients with PCOS
  6. Galactorrhea - PCOS (~20%), prolactin secreting tumors

F. Laboratory Evaluation [4]navigator

  1. Total Testosterone
    1. <200ng/dL implies PCOS, idiopathic, Congenital Adrenal Hyperplasia
    2. >200ng/dL should lead to radiographic evaluation for neoplasm
  2. DHEA-Sulfate
    1. Good marker for polycystic ovary / chronic anovulatory syndromes (PCOS)
    2. DHEA-S >700µg/dL highly suggestive of adrenal neoplasm
  3. 17-Hydroxy-Progesterone Levels (elevated in 21ß-hydroxylase deficiency)
  4. Prolactin Levels - elevated in some cases of PCOS, leads to galactorrhea
  5. Ovarian ultrasonography may be useful in patients with hirsutism [3,10]
  6. Metabolic Abnormalities [10]
    1. Evaluation for insulin resistance should be considered
    2. Fasting insulin levels may be elevated (most sensitive)
    3. Hemoglobin A1c or fructosamine for glucose intolerance
    4. Total, LDL, and HDL cholesterol levels
  7. Summary Laboratory Evaluation of Hirsutism [5]
    Summary Laboratory Evaluation of Hirsutism
    Entity / Test:CortisolTestostDHEALHFSHProlactin17-OHP
    CAHN/DN/UN/UNNNU
    PCOSNUU/NUD/NU/NN
    IdiopathicNNNNNNN
    ExogenousNNNNNNN
    TumorU/NUUNNNN
    N=normal D=Down U=Up Testost=Testosterone 17-OHP=17-hydroxygprogesterone

G. Therapy navigator

  1. Depends on cause of hirsutism
  2. Hormonal treatments require 9-12 months for full effect
    1. Oral contraptive pills (OCP)
    2. Antiandrogens
    3. Glucocorticoids
    4. Gonadotropin releasing hormone (GnRH) agonists
  3. OCP
    1. Ethyinyl estradiol (EE) + progestin including:
    2. EE 30µg + drospirenone (Yasmin®)
    3. EE 35µg _ norgestimate (Ortho-Cyclen®)
    4. EE 50µg + ethynodiol diacetate (Demulen 1-50®)
  4. Antiandrogens
    1. Spironolactone
    2. Cyproterone acetate
    3. Flutamide
  5. Spironolactone (Aldactone®)
    1. Aldosterone antagonist with anti-androgen activities
    2. Must monitor serum potassium and bicarbonate levels (suggest monthly)
    3. May increase frequency of menses, which can be blocked with oral contraceptives
    4. Dose is 25-50mg po bid to tid
    5. May take up to 6 months to work
  6. Flutamide (Drogenil®, Eulexin®)
    1. Pure anti-androgen, non-steroidal non-competitive antagonist
    2. For severe hirsutism
    3. Dose is 125-250mg po bid
    4. Hepatotoxicity concern, monitor liver functions
    5. Causes male pseudohermaphroditism in fetus (must use contraception)
  7. Cyproterone Acetate (Cyprostat®)
    1. Competitive (steroidal) inhibitor of androgen receptor
    2. Moderate or severe hirsutism
    3. Induction: 50-100mg qhs days 5-15 first month
    4. Maintenance: 5mg qhs days 5-15 each month
  8. Leuprolide Acetate
    1. GnRH agonist given as depot suspension (Lupron® depot)
    2. Dose 7.5mg monthly intramuscular, with 25-50µg transdermal estradiol
    3. Monitor and prevent osteoporosis (reduced with estrogen replacement)
  9. Prednisone
    1. Glucocorticoid, suppresses adrenal function
    2. Use in CAH
    3. Dose is 5-7.5mg po qhs
  10. Eflornithine (Vaniqa®) [8]
    1. alpha-difluoromethylornithine, irreversible inhibitor of ornithine decarboxylase (ODC)
    2. ODC required for polyamine production which is needed for normal cell cycle
    3. Eflornithine (Vaniqa®) is a 13.9% cream for twice daily application (8 hours apart)
    4. Treated area shoujld not be washed for at least 4 hours
    5. May apply cosmetics and sunscreen over treated areas after cream has dried
    6. Effects within 8 weeks of starting drug, but effects wear-off 8 weeks after cessation
    7. Stinging, burning, and tingling may occur in some patients after starting agent
    8. Effective contraception should be used in all persons using eflornithine
  11. Congenital Adrenal Hyperplasia (CAH) [5,11]
    1. Combination therapy now being used
    2. Testolactone
    3. Hydrocortisone or Prednisone - suppresses excess androgens
  12. Physical Methods [6]
    1. Electrolysis
    2. Laser hair removal - more effective, less painful than electrolysis
    3. High intensity pulsed light - may be as effective as laser methods

References navigator

  1. Rosenfield RL. 2005. NEJM. 353(24):2578 abstract
  2. Paus R and Cotsarelis G. 1999. NEJM. 341(7):491 abstract
  3. Franks S. 1995. NEJM. 333(13):853 abstract
  4. Gilchrist VJ and Hecht BR. 1995. Am Fam Phys. 52(6):1837 abstract
  5. Merke DP and Cutler GB Jr. 1997. JAMA. 277(13):1073 abstract
  6. Laser Hair Removal. 1999. Med Let. 41(1058):68 abstract
  7. Price VH. 1999. NEJM. 341(13):964 abstract
  8. Eflornithine. 2000. Med Let. 42(1089):96 abstract
  9. Elmer KB and George RM. 2001. Am Fam Phys. 63(12):2385 abstract
  10. Carmina E and Lobo RA. 2001. Am J Med. 111(8):602 abstract
  11. Speiser PW and White PC. 2003. NEJM. 349(8):776 abstract