What causes high testosterone levels?

Causes of High Testosterone Levels

High testosterone levels can be caused by various conditions including polycystic ovary syndrome (PCOS), congenital adrenal hyperplasia (CAH), androgen-secreting tumors, and medication use, with the specific cause determining appropriate management strategies.

Primary Causes of High Testosterone

Physiological Causes

• Obesity and metabolic syndrome - Insulin resistance associated with obesity can stimulate ovarian androgen production 1
• Acromegaly - Excess growth hormone can lead to increased testosterone production 1
• Cushing's disease - Excess cortisol production can disrupt normal hormone balance and increase testosterone 1

Pathological Causes

• Polycystic Ovary Syndrome (PCOS) - The most common cause of hyperandrogenism in women, characterized by multiple ovarian cysts, menstrual irregularities, and elevated testosterone 2
• Congenital Adrenal Hyperplasia (CAH) - Both classical and non-classical forms can cause elevated testosterone due to enzyme deficiencies in adrenal steroid production 1
• Androgen-secreting tumors - Rare but serious cause of rapidly developing, severe hyperandrogenism with very high testosterone levels 2
• Adrenal disorders - Including adrenal hyperplasia and adrenal tumors 1

Medication-Induced Causes

• Anabolic androgenic steroids - Direct exogenous source of testosterone or testosterone-like compounds 1
• Growth hormone - Can increase testosterone production 1
• Testosterone replacement therapy - Direct source of exogenous testosterone 1
• Glucocorticoids - Can disrupt normal hormone balance 1

Secondary Causes

Endocrine System Disorders

• Hyperthyroidism - Can affect sex hormone binding globulin (SHBG) levels, leading to changes in free testosterone 1
• Insulin resistance/Type 2 diabetes - Associated with increased testosterone production, particularly in women 1
• Aromatase deficiency - Rare condition preventing conversion of testosterone to estradiol 1
• 5α-reductase deficiency - Affects testosterone metabolism 1

Other Factors

• Nonalcoholic fatty liver disease - Associated with elevated testosterone levels, particularly in women with PCOS 3
• Chromosomal abnormalities - Including 47 XYY syndrome and other genetic variations 1

Diagnostic Approach

Initial Assessment

• Measure total testosterone levels - Normal ranges differ significantly between men (8.8-30.9 nmol/L) and women (0.4-2.0 nmol/L) 4
• Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) - To determine if the cause is primary (testicular/ovarian) or secondary (pituitary/hypothalamic) 1
• Check for clinical signs - Hirsutism, acne, male-pattern baldness, menstrual irregularities in women 1

Further Testing

• Measure prolactin levels - Particularly in patients with low or low/normal LH levels 1
• Consider SHBG measurement - Changes in SHBG can affect total testosterone levels 1
• Measure estradiol - Particularly in patients with gynecomastia or breast symptoms 1
• Dexamethasone suppression test - To rule out adrenal causes of high testosterone 2

Special Considerations

In Women

• Extremely high testosterone levels (>4-5 times upper limit of normal) should prompt investigation for androgen-secreting tumors 2
• Moderate elevations are more typical of PCOS or non-classical CAH 4
• Recent onset of severe hyperandrogenism suggests a possible tumor rather than PCOS, which typically develops gradually after menarche 2

In Men

• Exogenous testosterone use is the most common cause of supraphysiologic testosterone levels 1
• Monitor for complications of high testosterone including erythrocytosis, which occurs in up to 44% of men receiving injectable testosterone 1

Management Considerations

• Identify and treat underlying cause rather than just addressing the elevated testosterone 1
• For PCOS, treatment may include lifestyle modifications, hormonal contraceptives, or anti-androgen medications 5
• For medication-induced elevations, consider dose adjustment or alternative treatments 1
• Monitor for complications of high testosterone including cardiovascular effects, erythrocytosis, and prostate issues in men 1