Hirsutism

1. See Also
   1. Hyperandrogenism
   2. Hyperandrogenism Causes
   3. Medication Causes of Hirsutism
   4. Hypertrichosis
   5. Hirsutism Management
2. Definition
   1. Increased sexual Hair Growth
   2. 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
3. Pathophysiology
   1. See Hair Growth
   2. Vellus Hair
      1. Small, straight, fair hairs
   3. Terminal Hair
      1. Large, curly, dark hair
      2. Develop from Vellus Hair in sex-specific regions in response to androgens
   4. Hyperandrogenism in women results in Terminal Hair development from Vellus Hairs
4. 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
5. 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 and Acanthosis Nigricans
      4. Central Obesity
   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
6. 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 leads to diagnosis at Puberty
   2. Androgen-secreting tumors - Adrenal or ovarian (0.2% of cases)
      1. Consider for rapid onset Hirsutism, virilization or palpable abdominal or pelvic mass
      2. Androgen levels will be significantly above normal range
   3. Acromegaly
   4. Cushing Syndrome
   5. Hyperprolactinemia
   6. Hypothyroidism
7. 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)
8. 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
9. 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
10. 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. Avoid Dehydroepiandrosterone sulfate level (DHEAS) for screening
          1. Mild elevations are common and non-diagnostic with a normal Testerosterone level
    2. 17-Hydroxyprogesterone level
       1. Obtain corticotropin stimulation test (ACTH Stimulation Test) if 17-Hydroxyprogesterone >200 ng/dl
    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
11. 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
12. 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)
13. Differential Diagnosis
    1. Hypertrichosis
14. Management: Hair Removal
    1. See Hair Removal Techniques
15. Management: Anti-androgen management
    1. Hirsutism related to excess androgen from Anovulation
    2. Management 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 bid to tid
          1. Category D medication in pregnancy
       3. Eflornithine (Vaniqa) 13.9% cream
          1. FDA approved only for unwanted facial hair
    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 5 mg qd
             1. Category X medication in pregnancy
             2. Hepatotoxicity risk
       4. Glucocorticoid: Dexamethasone 0.5 mg PO qHS
          1. 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 qMonth 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. Dose 400 mg orally daily
16. References
    1. Hansen (1997) Female Patient 22:11-18
    2. Bode (2012) Am Fam Physician 85(4): 373-80
    3. Gilchrist (1995) Am Fam Physician 52(6):1837-44
    4. Hunter (2003) Am Fam Physician 67:2565-72
    5. Kalve (1996) Am Fam Physician 54(1):117-24
    6. Koulouri (2008) Clin Endocrinol 68(5): 800-5
    7. Leung (1993) Int J Dermatol 32:773-7
    8. Rosenfield (2005) 353(24): 2578-88
    9. Shenenberger (2002) Am Fam Physician 66(10):1907-14