What is the appropriate evaluation and management for an adult female with an elevated total testosterone level?

Elevated Testosterone in Adult Female: Evaluation and Management

A total testosterone of 95 ng/dL in an adult female is significantly elevated and requires immediate systematic evaluation to identify the underlying cause, with particular attention to androgen-secreting tumors, polycystic ovary syndrome, and exogenous androgen exposure.

Understanding the Clinical Context

The reported testosterone level of 95 ng/dL is markedly abnormal for a female. Research demonstrates that normal premenopausal women have testosterone levels ranging from 15-46 ng/dL (5th to 95th percentile), with most healthy women having levels below 40 ng/dL 1, 2. This patient's level of 95 ng/dL falls well above the normal female range but remains below the typical male range (which begins around 300 ng/dL) 3. Importantly, commercial laboratory reference ranges (often listed as 10-95 ng/dL) are inappropriately broad and fail to detect hyperandrogenemia in most affected women 2, 4.

Immediate Diagnostic Workup

Essential Hormonal Panel

• Measure serum LH and FSH immediately to differentiate between ovarian and adrenal sources of excess androgens 5

  • An LH/FSH ratio >2 suggests polycystic ovary syndrome 5
  • FSH >35 IU/L indicates ovarian failure 5

• Check serum prolactin levels because hyperprolactinemia can coexist with hyperandrogenism and requires different management 6, 7

  • Prolactin >20 µg/L warrants pituitary MRI to exclude prolactinoma 5

• Measure DHEA-S (dehydroepiandrosterone sulfate) to assess for adrenal androgen excess 5

  • DHEA-S >3,800 ng/mL (in women aged 20-29) suggests non-classic congenital adrenal hyperplasia 5
  • Androstenedione >10.0 nmol/L raises concern for adrenal or ovarian androgen-secreting tumor 5

• Obtain estradiol levels to characterize the complete hormonal profile 6

Metabolic Assessment

• Measure fasting glucose and insulin to calculate the glucose-to-insulin ratio 5

  • Ratio >4 or fasting glucose >7.8 mmol/L indicates insulin resistance commonly associated with PCOS 5

• Check mid-luteal phase progesterone (day 21 of cycle if regular) 5

  • Progesterone <6 nmol/L confirms anovulation 5

Critical Imaging Studies

• Obtain transvaginal pelvic ultrasound in the early follicular phase 5

  • More than 10 peripheral ovarian cysts (2-8 mm) with thickened stroma confirms polycystic ovaries 5
  • This finding, combined with hormonal abnormalities, supports PCOS diagnosis (affecting 4-6% of women) 5

• Order pituitary MRI with sellar cuts if prolactin is elevated or if LH is inappropriately low 6, 5

  • This excludes prolactinomas and other pituitary pathology 6

• Consider adrenal and ovarian imaging (CT or MRI) if DHEA-S or androstenedione are markedly elevated 5

  • Androgen-secreting tumors require urgent identification 5

Differential Diagnosis Framework

Most Likely Causes at This Testosterone Level

1. Polycystic Ovary Syndrome (PCOS) - most common cause of hyperandrogenism in reproductive-age women 5

   • Characterized by LH/FSH ratio >2, modestly elevated testosterone (typically 50-100 ng/dL), insulin resistance, and polycystic ovarian morphology 5, 2

2. Exogenous Androgen Exposure - must be explicitly ruled out 5

   • Direct questioning about testosterone therapy, anabolic steroids, or supplements containing androgens 5
   • Requires immediate discontinuation with gradual tapering to prevent withdrawal symptoms 5

3. Non-Classic Congenital Adrenal Hyperplasia - particularly if DHEA-S is markedly elevated 5

4. Androgen-Secreting Tumors - less common but critical to exclude 5

   • Ovarian or adrenal tumors typically produce testosterone levels >150-200 ng/dL but can present at lower levels 5

Management Strategy

If Exogenous Source Identified

• Discontinue all exogenous testosterone or anabolic steroids immediately with gradual tapering 5
• Monitor testosterone levels every 3-6 months initially, then annually once stable 5
• Recovery of normal hormonal function typically requires 6 months or longer 5

If Endogenous Hyperandrogenism Confirmed

• Refer to endocrinology for comprehensive management of underlying disorder 5
• Treatment depends on specific etiology identified through workup 5

Baseline Risk Assessment

• Check complete blood count to assess for polycythemia, as elevated testosterone can increase hematocrit 5, 7

  • Hematocrit >50% warrants investigation and potential intervention 5

• Obtain lipid profile because elevated testosterone increases atherosclerosis risk and causes adverse lipid changes 5

• Perform bone mineral density testing if chronic hormonal abnormalities are present 6

Fertility Considerations

• Conduct comprehensive fertility assessment before initiating any therapy that could further affect reproductive function 5
• Elevated testosterone suppresses normal ovulation in most cases 5
• Women with PCOS represent the leading cause of anovulatory infertility in young women 5

Monitoring and Follow-Up

• Regular laboratory monitoring including testosterone levels, complete blood count, and lipid profile to assess treatment effectiveness 5

• Cardiovascular risk assessment with blood pressure and lipid monitoring 5

• Evaluate for menstrual irregularities including oligomenorrhea (cycles >35 days) or amenorrhea (no bleeding >6 months) 5

Common Pitfalls to Avoid

• Do not rely on commercial laboratory reference ranges (typically 10-95 ng/dL), as these fail to detect hyperandrogenemia in most affected women 2, 4

  • The appropriate upper limit for normal women is approximately 28-46 ng/dL depending on age 2, 1

• Do not assume PCOS without confirming other diagnostic criteria, as isolated polycystic ovarian morphology occurs in 17-22% of otherwise normal women 5

• Do not delay imaging if androstenedione or DHEA-S are markedly elevated, as androgen-secreting tumors require urgent identification 5

• Always assess for exogenous androgen use through direct, non-judgmental questioning, as this is a common and reversible cause 5