Androgen Replacement in Women

Aka: Androgen Replacement in Women, Testosterone Replacement in Women, DHEA-S Replacement in Women, Dehydroepiandrosterone-Sulfate Replacement in Women, Hypoandrogenism

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II. Background

  1. Androgen Replacement in Women is controversial
  2. Androgen deficiency difficult to diagnose via labs
  3. Androgen may have significant adverse effects

III. Precautions

  1. No Testosterone products are FDA approved for Libido
  2. Long-term safety is a concern
    1. Risk of Breast Cancer and heart disease

IV. Indications

  1. NAMS position statement (September 2005)
    1. Only indicated in low desire in postmenopausal women
  2. Clinical uses that have been used
    1. Ovarian Failure or Oophorectomy
      1. Menopause
      2. Premature Ovarian Failure
      3. Perimenopause
    2. Neuropsychiatric changes in women ages 30 to 50 years
      1. Testosterone Deficiency
        1. Decreased Libido, sexual desire and orgasm
      2. Hippocampus changes and DHEA-S Decrease
        1. Decreased concentration and memory

V. Contraindications

  1. Pregnancy or Lactation
  2. Hyperandrogenism
  3. Androgen-dependent tumor
  4. Breast Cancer history

VI. Advantages: Overall benefits of androgen supplementation

  1. Increases Bone Mineral Density
  2. Enhances libido and sexual satisfaction
  3. Improves sense of well-being
  4. Appears to improve concentration and memory

VII. Adverse Effects

  1. Liver abnormalities (associated with oral androgens)
    1. Liver tumors
    2. Cholestatic Jaundice
  2. Iatrogenic Hyperandrogenism
    1. Irreversible effects
      1. Alopecia (Male patterned baldness)
      2. Voice deepening
      3. Clitoromegaly
    2. Reversible effects
      1. Acne Vulgaris and oily skin
      2. Hirsutism (facial hair)
      3. Adverse effect on lipid profile
        1. Increases LDL Cholesterol
        2. Decreases HDL Cholesterol

VIII. Causes: Secondary Causes of Hypoandrogenism

  1. Hypopituitarism
  2. Secondary Hypogonadism
    1. Premature Ovarian Failure
    2. Oophorectomy
  3. Secondary Adrenal Insufficiency
  4. Medications lowering androgen levels
    1. Estrogen Replacement or Oral Contraceptives
    2. Gonadotropin-Releasing Hormone Agonists
    3. Glucocorticoids
    4. Chemotherapy or Radiation Therapy

IX. Protocol: NAMS Position Statement (September 2005)

  1. Administer lowest dose for shortest duration
    1. Start with 6 month trial
    2. Continue only if clinically improved symptoms
    3. Safety data does not exist for use longer than 24 months in women
  2. FDA approved in women for oral and IM Testosterone
    1. Transdermal is preferred route, but not FDA approved
  3. Testosterone monitoring only for high Testosterone dose
  4. Dosing in women is much lower than that used in men

X. Labs

  1. Free Testosterone
    1. Not associated with low sexual desire
    2. Total Testosterone is not useful
    3. DHEA is more sensitive, but not specific
    4. Davis (2005) JAMA 294:91-6 [PubMed]
  2. Serum Hormone-binding globulin

XI. Preparations: Testosterone Replacement

  1. No commercial standard formulations exist in U.S. that supply recommended dose of 300 mcg/day
  2. Transdermal Testosterone ointment 2%
    1. Compounded 2% Testosterone propionate in petrolatum
    2. Apply small dab 2-3 times per day
      1. Apply to labia or hairless skin
  3. Methyl-Testosterone or EstraTest
    1. Risk of Hyperlipidemia and hepatic toxicity
    2. Testosterone patch 300 ug/day
  4. Testosterone enanthate-Estradiol
    1. Given 1 ml IM every 4 weeks
  5. Testosterone implant (pellet)
    1. Requires Transdermal Estrogen instead of oral
    2. Highly effective

XII. Preparations: Dehydroepiandrosterone-Sulfate (DHEA-S) Replacement

  1. May be used in combination with Testosterone
  2. Improves memory and concentration
  3. Excessive DHEA: Polycystic Ovary Syndrome
  4. Dosing U.S. Pharmaceutical DHEA
    1. DHEA 12.5 mg raises Serum DHEA-S 100-150 mg
    2. Post-Menopause Dose: 12.5 mg PO qd
    3. Post-Oophorectomy: 25 mg PO qd
    4. Target Serum DHEA-S: 80 to 370 ug/dl

XIII. Management: Monitoring

  1. History and examination (inc. Breast) every 6 months
  2. Annual labs
    1. Lipid profile
    2. Complete Blood Count
    3. Mammogram
    4. Endometrial Ultrasound

XIV. References

  1. Shuer (2001) CMEA Medicine Lecture, San Diego
  2. Guzick (2000) N Engl J Med 343:730-1 [PubMed]
  3. Margo (2006) Am Fam Physician 73(9):1591-603 [PubMed]
  4. Miller (2001) J Clin Endocrinol Metab 86:2395-401 [PubMed]
  5. Petering (2017) Am Fam Physician 96(7): 441-9 [PubMed]
  6. Shifren (2000) N Engl J Med 343:682-8 [PubMed]

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