From the Guidelines
Elevated testosterone levels should be evaluated using total testosterone (TT), free testosterone (FT), and free androgen index (FAI) as first-line laboratory tests, with liquid chromatography-tandem mass spectrometry (LC-MS/MS) being the preferred method for assessing biochemical hyperandrogenism. This approach is supported by a recent systematic review and diagnostic meta-analysis published in 2025 in Human Reproduction Update 1. The evaluation of elevated testosterone should begin with confirming the elevation through repeat morning testing, as levels fluctuate throughout the day. Initial workup includes comprehensive history and physical examination focusing on symptoms like hirsutism, acne, menstrual irregularities in women, or infertility and gynecomastia in men.
Key Laboratory Tests
- Total testosterone (TT)
- Free testosterone (FT)
- Free androgen index (FAI)
- SHBG
- LH
- FSH
- Prolactin
- DHEAS
- 17-hydroxyprogesterone If these initial tests are not elevated but clinical suspicion is high, health professionals could consider measuring androstenedione (A4) and DHEAS, noting their poorer specificity, as recommended by the 2023 International PCOS Guidelines informed by the study 1.
Diagnostic Considerations
- Polycystic ovary syndrome (PCOS) is the most common cause in women, requiring ultrasound evaluation
- Congenital adrenal hyperplasia
- Androgen-secreting tumors
- Cushing's syndrome
- Exogenous testosterone use For suspected adrenal or ovarian tumors, imaging studies like CT or MRI are indicated. Treatment depends on the underlying cause - for PCOS, combined oral contraceptives are first-line therapy, often combined with metformin. Spironolactone can help manage hirsutism. For tumors, surgical intervention is typically required. Elevated testosterone requires thorough evaluation as it can indicate serious underlying conditions and cause significant symptoms affecting quality of life, morbidity, and mortality.
From the Research
Evaluation of Elevated Testosterone
- Elevated testosterone levels can be an indicator of hyperandrogenism, a common endocrine disorder in women of reproductive age, with a prevalence of 5-10% 2.
- The diagnosis of hyperandrogenism is complex and presents a challenge for both physicians and clinical investigators, with clinical manifestations including hirsutism, acne, androgenic alopecia, and virilization 2.
- Total testosterone assay is recommended as the first-line approach for investigating hyperandrogenism, with radioimmunological assay being the recommended method pending wider experience with mass spectrometry 3.
Investigation and Diagnosis
- Where testosterone levels are twice the upper limit of normal, it is recommended that DHEAS assay be performed to help diagnose the underlying cause of hyperandrogenism 3.
- A DHEAS level over 600 mg/dl indicates a diagnosis of androgen-secreting adrenal cortical adenoma, while a normal DHEAS level may indicate ovarian hyperthecosis or an androgen-secreting ovarian tumour 3.
- A thorough history and focused clinical examination are extremely helpful in the diagnostic evaluation of patients with suspected hyperandrogenism, with clinical symptoms such as hirsutism, acne, and androgenic alopecia being common indicators of the condition 2.
Treatment and Management
- Metformin therapy has been shown to result in a significant decrease in total testosterone levels and fasting blood sugar in women with polycystic ovarian syndrome (PCOS), leading to an improvement in clinical manifestations of hyperandrogenism 4.
- The effect of metformin on subjects with elevated DHEAS levels is different to that on individuals with normal DHEAS levels, with significant improvements in menstrual cycle length, BMI, and testosterone and DHEAS levels observed in the latter group 4.
Long-term Consequences
- Testicular cancer survivors are at risk of premature hormonal aging, with longitudinal alterations in testosterone, luteinizing hormone, and follicle-stimulating hormone levels observed in a population-based sample of long-term survivors 5.
- The risk of higher luteinizing hormone and lower testosterone levels is significantly increased for testicular cancer survivors treated with radiotherapy or chemotherapy, with cumulative platinum dose associated with risk of higher luteinizing hormone levels 5.