What are the treatment options for a 29-year-old female with elevated free testosterone levels?

Elevated Free Testosterone in a 29-Year-Old Female

The most critical first step is to confirm the elevation with repeat morning testing (8-10 AM) of total testosterone, free testosterone by equilibrium dialysis, and SHBG, then immediately investigate for androgen-secreting tumors if levels are markedly elevated (>2-3 SD above normal), as these require urgent surgical intervention. 1, 2

Immediate Diagnostic Workup

Confirm the Diagnosis

• Repeat morning (8-10 AM) total testosterone and obtain free testosterone by equilibrium dialysis (not analog immunoassay, which is unreliable) along with SHBG levels 1, 3
• Calculated free testosterone (cFT) and free androgen index (FAI) are superior to measured analog free testosterone for detecting hyperandrogenemia in women and correlate better with clinical manifestations 3
• Free testosterone elevation is the hallmark of hyperandrogenism—50% of hirsute women have normal total testosterone but elevated free testosterone 4

Essential Hormone Panel

• Measure LH and FSH to distinguish ovarian versus adrenal sources and assess for polycystic ovary syndrome (PCOS) 1, 5
• Obtain DHEAS to evaluate adrenal androgen contribution 3
• Measure prolactin as hyperprolactinemia can coexist with hyperandrogenism 1
• Consider DHT measurement if available, as it reflects peripheral testosterone conversion 2

Critical Red Flags Requiring Urgent Evaluation

• If total testosterone is >150-200 ng/dL (>2-3 SD above normal for women), immediately obtain pelvic ultrasound to rule out androgen-secreting ovarian tumor 2
• Ovarian steroid-cell tumors can produce extremely high testosterone without virilization signs due to selective tissue response 2
• Rapid onset of symptoms or very high levels mandate imaging even without virilization 2

Imaging Studies

When to Image

• Pelvic ultrasonography is essential for all women with confirmed hyperandrogenism to evaluate for polycystic ovaries or ovarian tumors 1
• Obtain immediately if testosterone levels are markedly elevated (>150-200 ng/dL) 2
• MRI may be needed if ultrasound is inconclusive and tumor is suspected 2

Dexamethasone Suppression Testing

• Perform dexamethasone suppression test (typically 0.5 mg every 6 hours for 4 days) to distinguish adrenal from ovarian sources 4, 5
• Measure free testosterone before and after dexamethasone administration 5
• Failure to suppress indicates ovarian source (PCOS or tumor); suppression to normal suggests adrenal source 4, 5
• This is the most sensitive single method for detecting PCOS in young women 5

Treatment Approach Based on Etiology

If PCOS is Diagnosed (Most Common)

• Combined oral contraceptives are first-line for suppressing ovarian androgen production 4
• Dexamethasone alone normalizes free testosterone in 47% of hirsute women with adrenal contribution 4
• Addition of oral contraceptives (historically Enovid-E, now modern combined OCPs) normalizes free testosterone in the remaining 53% 4

If Ovarian Tumor is Found

• Surgical resection is curative—testosterone normalizes within 24 hours post-operatively and menstruation typically resumes within one month 2
• Ovarian steroid-cell tumors are malignant in 25-43% of cases, making prompt surgical intervention critical 2

If Adrenal Source

• Low-dose dexamethasone or other glucocorticoid therapy may be appropriate 4

Monitoring Parameters

• Assess cardiovascular risk factors (dyslipidemia, hypertension, diabetes) as hyperandrogenism increases metabolic risk 1
• Measure hemoglobin/hematocrit at baseline 1
• Monitor free testosterone levels 2-3 months after treatment initiation to assess efficacy 1
• Regular follow-up of hormone levels to ensure treatment adequacy 1

Critical Pitfalls to Avoid

• Do not rely on analog immunoassay methods for free testosterone—they are unreliable and should be replaced by equilibrium dialysis or calculated values 1, 3, 6
• Do not dismiss very high testosterone levels without virilization signs as laboratory error without proper extraction procedures and imaging, as selective tissue response can occur 2
• Do not assume normal total testosterone excludes hyperandrogenism—free testosterone is elevated in 50% of hirsute women with normal total testosterone 4
• Laboratory interference should be suspected if clinical picture doesn't match; diethyl ether extraction can help clarify 2