II. Definitions

  1. Hirsutism
    1. Increased Terminal Hair male-patterned growth in women
  2. Vellus Hair
    1. Small, straight, fair hairs
    2. Eyebrows and eyelashes growth are completely androgen independent
    3. Excessive vellus Hair Growth (Hypertrichosis), independent of androgens
  3. Terminal Hair
    1. Large, curly, dark hair
    2. Develop from Vellus Hair in sex-specific regions in response to androgens
    3. Terminal Hair growth is androgen dependent

III. Epidemiology

  1. Excessive upper lip hair in a third of women ages 14-45
  2. Unwanted chin and sideburn hair in 6-9% of women

IV. Pathophysiology

  1. See Hair Growth
  2. Hyperandrogenism in women results in Terminal Hair development
    1. Androgens stimulate facial Hair Growth (mustache, bear, sideburns)
    2. Androgens inhibit scalp Hair Growth and may result in Androgenic Alopecia
  3. Women develop male-type body hair distribution
    1. Face
      1. Mustache
      2. Beard
      3. Sideburns
    2. Body
      1. Chest
      2. Circum-areolar
      3. Linea alba
      4. Abdominal trigone
      5. Inner Thighs

V. Causes: Common

  1. See Hyperandrogenism Causes
  2. See Medication Causes of Hirsutism
  3. Polycystic Ovary Syndrome (72-82% of cases)
    1. Metrorrhagia and Infertility
    2. Hyperandrogenemia
    3. Insulin Resistance (>50% of PCOS patients)
    4. Acanthosis Nigricans
    5. Central Obesity
    6. Acne Vulgaris
  4. Idiopathic Hyperandrogenemia (6-15% of cases)
    1. Normal Menstrual Cycles
    2. Hyperandrogenemia without obvious cause
  5. Idiopathic Hirsutism (5-15% of cases)
    1. Normal androgen levels and no obvious cause of Hirsutism

VI. Causes: Uncommon or Rare

  1. Adrenal hyperplasia (2-4% of cases)
    1. Classic adrenal hyperplasia
      1. Ambiguous Genitalia leads to diagnosis at birth
    2. Non-classic adrenal hyperplasia
      1. Annovulation and Primary Amenorrhea leads to diagnosis at Puberty
      2. Higher Incidence in Ashkenazi Jews, Hispanics and Slavic people
  2. Androgen-Secreting tumors - Adrenal or ovarian (0.2% of cases, 50% are malignant)
    1. Consider for rapid onset Hirsutism, Virilization or palpable abdominal or pelvic mass
    2. Androgen levels will be significantly above normal range
  3. Acromegaly
    1. Enlarged hands and feet
    2. Enlarged nose and ears, frontal bossing and course facial features
  4. Cushing Syndrome
    1. Central Obesity
    2. Acne Vulgaris
    3. Hypertension
    4. Glucose Intolerance
    5. Moon facies
  5. Hyperprolactinemia
    1. Amenorrhea and Infertility
    2. Galactorrhea
  6. Hypothyroidism
    1. Cold intolerance
    2. Hair Loss
    3. Myxedema
    4. Dry Skin

VII. History

  1. See Ferriman-Gallway Scale
  2. Hirsutism onset
    1. Rapid onset?
    2. Pubertal onset?
  3. Gynecologic history
    1. Metrorrhagia
    2. Infertility
  4. Family History
    1. Hair Growth patterns in women family members (idiopathic Hirsutism)
  5. Hyperandrogenemia signs
    1. Acne Vulgaris
    2. Acanthosis Nigricans
  6. Virilization signs
    1. Deepening voice
    2. Increased Muscle mass
    3. Clitoromegaly
    4. Female body contour lost
  7. Other findings
    1. Striae (Cushing Syndrome)
    2. Galactorrhea (Hyperprolactinemia)

VIII. Signs

  1. Hirsutism
    1. See Ferriman-Gallway Scale
    2. Excessive Terminal Hairs in women in sex-specific regions (male distribution)
  2. Other signs of Hyperandrogenism
    1. See Hyperandrogenism
    2. Acne Vulgaris
    3. Alopecia

IX. Signs: Red Flags suggestive of adrenal hyperplasia or androgen Secreting tumor

  1. Onset of Hirsutism after Puberty
  2. Rapid progression of Virilization or Hirsutism
  3. Irregular Menses
  4. Exam suggesting Hyperandrogenism or Virilization
  5. Family History does not suggest familial cause

X. Diagnosis

XI. Labs: Evaluation of secondary cause (indicated for moderate to severe Hirsutism or red flags above)

  1. Total Testosterone
    1. Total Testosterone >200 ng/dl should prompt complete endocrine workup with Abdomen and Pelvis imaging
    2. Total Testosterone levels are also mildly elevated in Polycystic Ovary Syndrome
    3. Avoid Dehydroepiandrosterone sulfate level (DHEAS) for screening
      1. Mild elevations are common and non-diagnostic with a normal Testerosterone level
      2. Consider DHEAS level if adrenal androgen Secreting tumors (rare) are suspected
  2. 17-Hydroxyprogesterone level
    1. Obtain Corticotropin Stimulation Test (ACTH Stimulation Test) if 17-Hydroxyprogesterone >200 ng/dl
    2. Levels >1000 ng/dl suggest nonclassic Congenital Adrenal Hyperplasia or 21-hydroxylase deficiency
  3. Thyroid Stimulating Hormone
  4. Serum Prolactin level
    1. See Hyperprolactinemia for evaluation
    2. Consider MRI imaging of pituitary
  5. Consider urine free Cortisol level
    1. Indicated if Cushing Syndrome suspected

XII. Imaging (as indicated)

  1. Pelvic Ultrasound
    1. May demonstrate Polycystic Ovaries
  2. CT Abdomen and Pelvis
    1. Indicated for rapid Virilization and evaluation for adrenal or ovarian Secreting tumor
  3. MRI Brain (or CT Brain)
    1. Indicated for Hyperprolactinemia and evaluation of sella turcica

XIII. Evaluation

  1. Step 1: Initial
    1. History including Ferriman-Gallway Scale
    2. Exam including Thyroid exam, skin exam, Breast Exam and abdominal and pelvic exam
  2. Step 2: Consider evaluation for androgen Secreting tumor
    1. Indications
      1. Rapid onset Virilization or Hirsutism or abdominal/pelvic mass
      2. If not indicated, go to Step 3
    2. Tests
      1. See labs above
      2. See Imaging above
  3. Step 3: Moderate Hirsutism (Ferriman-Gallwey Score 8-15) or PCOS suspected
    1. If more mild Hirsutism, go to step 4
    2. Tests
      1. See labs above
  4. Step 4: Mild Hirsutism (Ferriman-Gallwey Score 8-15)
    1. Treat Hirsutism (see below)

XIV. Differential Diagnosis

XV. Management: Hair Removal

XVI. Management: Anti-androgen management

  1. Hirsutism related to excess androgen from Anovulation
  2. Mechanisms directed at reducing DHT and androgens
    1. Inhibit ovary and adrenal androgen secretion
    2. Alter Sex Hormone Binding Globulin (SHBG) binding
    3. Impair peripheral androgen precursor conversion
    4. Inhibit androgen action at target tissue
  3. General Measures
    1. Weight loss if Obesity present (lowers androgens)
    2. See Hair Removal Techniques
  4. Medications: First line
    1. Oral Contraceptives
      1. Lowers Serum LH: Decreases Testosterone production
      2. Increase Serum SHBG: Increases Testosterone binding
      3. Decreases Free Testosterone (unbound) levels
      4. Lowest Progestin Androgenic Activity
        1. Norgestimate (Ortho Tricyclen, Ortho Cyclen)
        2. Desogestrel (Ortho-Cept, Desogen)
        3. Norethindrone (Modicon)
        4. Ethynodiol (Demulen 1/35)
    2. Spironolactone 100 to 200 mg PO divided twice to three times daily
      1. Category D medication in pregnancy
      2. Accidental use in pregnancy risks Spontaneous Abortion or feminization of male fetus
    3. Eflornithine (Vaniqa) 13.9% cream applied twice daily
      1. FDA approved only for unwanted facial hair
      2. May be an adjunct to other hair removal methods, but effects are only temporary
  5. Medications: Second-Line for specific indications
    1. Metformin (Glucophage): Polycystic Ovary Syndrome
      1. Not indicated for Hirsutism without Polycystic Ovary Syndrome
  6. Medications: Third line due to potential toxicity
    1. Indicated only in severe, refractory cases
    2. Most of these agents are Teratogenic and require reliable Contraception
    3. Antiandrogen
      1. Flutamide (Eulexin) 250 mg bid to tid
        1. Endocrine Society discourages Flutamide use due to liver failure risk
      2. Finasteride 2.5 to 5 mg orally daily
        1. Category X medication in pregnancy (must use reliable Contraception)
        2. Hepatotoxicity risk
    4. Glucocorticoid
      1. Dexamethasone 0.5 mg orally at bedtime or Prednisone 5 mg orally twice daily
      2. May be indicated in non-classic Congenital Adrenal Hyperplasia
    5. GnRH Agonist: Leuprolide (Lupron Depot)
      1. Dose: 3.75 mg to 7.5 mg IM each Month for 6 months
      2. Depot dose: 11.25 mg q3 months
      3. Category X medication in pregnancy
      4. Causes menopausal symptoms (consider add-back Hormones)
    6. Ketoconazole
      1. Not recommended due to Ketoconazole hepatotoxicity

Images: Related links to external sites (from Bing)

Related Studies