What causes elevated total and free testosterone levels in a post-hysterectomy (surgical removal of the uterus) 60-year-old female?

Causes of Elevated Testosterone in a Post-Hysterectomy 60-Year-Old Female

Elevated total and free testosterone in a 60-year-old female who has had a hysterectomy is most likely due to an androgen-secreting tumor, particularly ovarian stromal hyperplasia or an adrenal adenoma, which requires immediate evaluation to rule out malignancy.

Diagnostic Approach

Initial Laboratory Evaluation

• Confirm elevated testosterone levels with repeat testing
• Measure additional hormones:
  • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) 1
  • Sex hormone-binding globulin (SHBG) 1
  • Dehydroepiandrosterone sulfate (DHEAS) 2
  • Androstenedione 2
  • Estradiol 1
  • Prolactin (if LH/FSH are low or low-normal) 1
  • Inhibin B 2

Most Common Causes in Post-Hysterectomy Women

1. Ovarian sources (if ovaries were preserved):

   • Ovarian stromal hyperplasia/hyperthecosis 2, 3
   • Ovarian androgen-secreting tumors (0.5% of all ovarian tumors) 2
   • Lipid cell tumors 4
   • Hilar cell hyperplasia 5

2. Adrenal sources:

   • Adrenal adenomas 5
   • Adrenal carcinomas (less common than ovarian tumors) 2

3. Other causes:

   • Ectopic testosterone-producing tissue (residual ovarian tissue or from primitive mesenchymal cells) 5
   • Exogenous testosterone or anabolic steroid use 6
   • Undiagnosed polycystic ovary syndrome worsening after menopause 2
   • Congenital adrenal hyperplasia 2
   • Cushing syndrome 2

Imaging Studies

• MRI of adrenal glands and pelvis (if ovaries were preserved) 2
• CT scan of abdomen and pelvis if MRI is not available
• Transvaginal ultrasound (if ovaries were preserved)

Special Diagnostic Tests

• Overnight dexamethasone suppression test to differentiate adrenal from ovarian sources 3
• ACTH stimulation test if adrenal source is suspected 5
• GnRH agonist test (nafarelin) if gonadotropin-responsive tissue is suspected 5

Management Considerations

For Ovarian Source (if ovaries were preserved):

• Bilateral oophorectomy is recommended for confirmed ovarian hyperplasia or tumors 3
• Post-surgical follow-up with testosterone levels to confirm resolution

For Adrenal Source:

• Laparoscopic adrenalectomy for confirmed adrenal adenomas 5
• Referral to oncology for suspected adrenal carcinoma

For Unidentified Source:

• GnRH agonist/analogues or antagonists may be effective for unidentified sources 2
• Medical management with anti-androgens may be considered for patients unfit for surgery

Important Considerations

• Elevated testosterone in postmenopausal women increases risk for hypercholesterolemia, insulin resistance, hypertension, and cardiac disease 2
• Peripheral aromatization of excess androgens may increase estrogen levels, raising endometrial cancer risk if uterus is intact 3
• Persistent elevation after initial treatment warrants further investigation for additional or ectopic sources 5

Follow-up

• Monitor testosterone levels post-treatment to confirm resolution
• Assess for improvement in clinical symptoms (hirsutism, alopecia, etc.)
• Consider hormone replacement therapy after definitive treatment if indicated 6

Remember that elevated testosterone in a postmenopausal woman, especially with clinical manifestations of hyperandrogenism, should never be considered normal and requires thorough evaluation to exclude potentially serious underlying causes.