Evaluation and Management of Elevated DHT with Normal Total Testosterone in Women
A woman with elevated dihydrotestosterone (DHT) and normal total testosterone should undergo measurement of free testosterone (calculated free androgen index or equilibrium dialysis), SHBG, androstenedione, and DHEAS to identify biochemical hyperandrogenism, as DHT elevation reflects increased peripheral 5α-reductase activity in target tissues rather than systemic androgen overproduction. 1
Understanding the Physiology
DHT is primarily a paracrine hormone formed locally in peripheral tissues (especially skin) through conversion of testosterone by 5α-reductase enzyme, not secreted directly by ovaries or adrenals. 2, 3
In women, approximately 70% of circulating DHT derives from peripheral conversion of androstenedione, with less than 20% coming from testosterone conversion. 3
Blood DHT levels do not reliably reflect total body DHT formation because DHT acts predominantly as a local tissue hormone rather than a circulating one. 2, 4
Women with cutaneous hyperandrogenism (hirsutism, acne, androgenic alopecia) may have increased 5α-reductase activity in skin without elevated systemic androgens—this represents localized enzyme hyperactivity, not generalized overproduction. 5
Diagnostic Algorithm
First-Line Testing (If Not Already Done)
Measure free testosterone using calculated free androgen index (FAI = total testosterone/SHBG × 100) or equilibrium dialysis, as these have sensitivity of 89% and specificity of 83% for detecting hyperandrogenism. 6
Measure SHBG, as low SHBG increases bioavailable testosterone even when total testosterone appears normal. 6
Total testosterone measured by LC-MS/MS in the morning (8-10 AM) remains essential despite being "normal," as timing and assay method affect accuracy. 6
Second-Line Testing (When Free Testosterone/FAI Normal)
Measure androstenedione (A4), which has 75% sensitivity and 71% specificity for hyperandrogenism and may be elevated when testosterone is not. 1, 6
Measure DHEAS to assess adrenal androgen contribution (sensitivity 75%, specificity 67%), using age-adjusted reference ranges as levels decline after age 30. 1, 6, 7
Check morning prolactin to exclude hyperprolactinemia (>20 µg/L warrants pituitary MRI). 8
Measure TSH to rule out thyroid dysfunction. 6
Metabolic Screening (Mandatory in All Cases)
Perform fasting glucose followed by 2-hour 75-gram oral glucose tolerance test, as PCOS carries high diabetes risk regardless of androgen pattern. 6
Obtain fasting lipid panel (total cholesterol, LDL, HDL, triglycerides). 6
Calculate glucose-to-insulin ratio if available (>4 suggests insulin resistance). 8
Imaging Studies
Obtain transvaginal pelvic ultrasound in early follicular phase to assess for polycystic ovarian morphology (>10 peripheral cysts 2-8 mm with thickened stroma). 8
Consider adrenal CT/MRI only if DHEAS is markedly elevated (>600 µg/dL or >3,800 ng/mL in women aged 20-29) or symptoms developed rapidly, suggesting androgen-secreting tumor. 7, 8
Differential Diagnosis by Likelihood
Most Common: PCOS with Peripheral Androgen Sensitivity
PCOS accounts for 95% of hyperandrogenism cases and affects 10-13% of women globally, often presenting with normal total testosterone but elevated free testosterone or isolated DHT elevation. 6
LH/FSH ratio >2 supports PCOS diagnosis, while mid-luteal progesterone <6 nmol/L confirms anovulation. 8
Isolated DHT elevation with normal systemic androgens suggests increased peripheral 5α-reductase activity in skin—a recognized PCOS variant. 1, 5
Less Common: Isolated Peripheral 5α-Reductase Hyperactivity
Some women have increased skin 5α-reductase enzyme activity without systemic androgen overproduction, causing hirsutism/acne despite normal laboratory values. 5
3α-androstanediol glucuronide (3α-diol G) is the best marker of peripheral DHT formation in skin, though not routinely available. 2
Rare: Non-Classic Congenital Adrenal Hyperplasia (NCAH)
Consider if DHEAS is elevated above age-specific thresholds (>3,800 ng/mL ages 20-29). 8
Confirm with morning 17-hydroxyprogesterone level; if elevated, perform ACTH stimulation test. 7
Management Strategy
When Free Testosterone/FAI or Other Androgens Are Elevated
Initiate combined oral contraceptives (COCs) as first-line therapy to regulate menstrual cycles and reduce androgen effects (hirsutism, acne). 6, 7
Add spironolactone 50-200 mg daily as anti-androgen therapy for persistent cutaneous symptoms despite COCs. 6
Prescribe metformin 1,500-2,000 mg daily if insulin resistance is documented (abnormal glucose tolerance test or glucose/insulin ratio). 7
When All Systemic Androgens Are Normal (Isolated DHT Elevation)
Consider finasteride 2.5-5 mg daily, a competitive 5α-reductase inhibitor that blocks peripheral conversion of testosterone to DHT in target tissues. 5
Finasteride is particularly effective for cutaneous hyperandrogenism (hirsutism, androgenic alopecia) when systemic androgens are normal but local DHT production is increased. 5
Alternatively, use spironolactone 100-200 mg daily as an androgen receptor blocker, which remains effective regardless of DHT source. 5
Implement lifestyle modifications including weight loss if BMI >25, as this improves insulin sensitivity and reduces androgen production. 7
Monitoring and Follow-Up
Repeat DHT, free testosterone, and SHBG every 3-6 months initially, then annually once stable. 7, 8
Reassess clinical symptoms (hirsutism score, acne severity, menstrual regularity) at each visit. 7
Continue metabolic screening annually (fasting glucose, lipids) due to persistent cardiovascular and diabetes risk in PCOS. 6
Critical Pitfalls to Avoid
Do not dismiss normal total testosterone as excluding hyperandrogenism—up to 30% of PCOS cases have normal total testosterone but elevated free testosterone or FAI. 6
Do not measure DHT in isolation to diagnose or monitor hyperandrogenism, as blood levels poorly reflect tissue DHT formation and action. 2, 4
Do not use direct immunoassay methods for free testosterone in women—they are highly inaccurate at low female concentrations; always calculate FAI or use equilibrium dialysis. 6
Do not overlook metabolic screening (glucose tolerance test, lipids) even when focusing on androgen evaluation, as PCOS carries significant long-term metabolic risk. 6
Do not prescribe finasteride without reliable contraception, as it causes severe fetal abnormalities if pregnancy occurs. 5
Do not assume isolated polycystic ovaries on ultrasound (without hormonal abnormalities or symptoms) equals PCOS—this morphology occurs in 17-22% of normal women. 8