What are the causes and treatment options for elevated testosterone levels not caused by testosterone supplement use?

Causes and Treatment for Elevated Testosterone Not Due to Supplements

Elevated testosterone levels not caused by testosterone supplements require thorough endocrine evaluation to identify underlying causes, which commonly include polycystic ovary syndrome in women, adrenal or testicular tumors, congenital adrenal hyperplasia, or pituitary disorders, with treatment directed at the specific etiology.

Diagnostic Approach for Elevated Testosterone

Initial Evaluation

• Measure serum luteinizing hormone (LH) levels to help establish the etiology of testosterone abnormality 1
• Measure serum prolactin levels, particularly in patients with abnormal LH levels to screen for hyperprolactinemia 1
• Measure serum estradiol in patients who present with breast symptoms or gynecomastia 1
• Assess hemoglobin/hematocrit levels, as elevated testosterone can lead to erythrocytosis 1

Common Causes of Elevated Testosterone

In Men:

• Testicular tumors (Leydig cell tumors) 2
• Adrenal tumors or hyperplasia 2
• Congenital adrenal hyperplasia 2
• Androgen-secreting pituitary tumors 1
• Anabolic steroid use (not supplements but performance-enhancing drugs) 3
• Resistance to androgens with compensatory elevation of testosterone 2

In Women:

• Polycystic ovary syndrome (PCOS) - most common cause 4
• Adrenal tumors or hyperplasia 4
• Ovarian tumors (e.g., Sertoli-Leydig cell tumors) 4
• Congenital adrenal hyperplasia 4
• Cushing's syndrome 5

Treatment Approach

Treatment Based on Underlying Cause

• For tumors (adrenal, testicular, ovarian, pituitary):

  • Surgical removal of the tumor is the primary treatment 1
  • Follow-up monitoring of testosterone levels after surgery 1

• For polycystic ovary syndrome (PCOS):

  • Weight loss for overweight/obese patients 5
  • Oral contraceptives to reduce androgen production 4
  • Anti-androgenic medications (e.g., spironolactone) 4
  • Metformin for insulin resistance 5

• For congenital adrenal hyperplasia:

  • Glucocorticoid replacement therapy to suppress ACTH and reduce androgen production 2
  • Regular monitoring of hormone levels 6

• For functional causes:

  • Treatment of underlying conditions (obesity, diabetes, inflammatory diseases) 6
  • Lifestyle modifications including diet and exercise 6

Monitoring During Treatment

• Regular measurement of testosterone levels to assess treatment efficacy 1
• Monitor hemoglobin/hematocrit, as high testosterone can cause erythrocytosis 1
• In men, monitor PSA levels (if age >40) to screen for prostate abnormalities 1
• Assess for symptoms improvement (e.g., hirsutism, acne, menstrual irregularities in women; mood changes, sexual function in both sexes) 5, 4

Special Considerations

For Women

• Hyperandrogenic states can manifest as hirsutism, acne, and menstrual irregularities 5
• High testosterone levels may be associated with aggressive behavior and depression in some women 5
• Balance between estradiol and testosterone is important; imbalances can lead to various health issues 5

For Men

• Persistently elevated testosterone without supplementation warrants thorough investigation 2
• Elevated testosterone may sometimes paradoxically indicate relative hypoandrogenism with increased binding proteins 2
• Consider the impact on fertility when treating testosterone abnormalities 1

Clinical Pitfalls to Avoid

• Don't assume all testosterone elevations are beneficial: High testosterone can cause adverse effects including erythrocytosis, aggressive behavior, and metabolic disturbances 1, 5
• Don't overlook pituitary imaging: Men with significantly abnormal testosterone levels should undergo pituitary MRI regardless of prolactin levels, as non-secreting adenomas may be present 1
• Don't ignore fertility concerns: Treatment approaches should consider the patient's fertility goals, as some treatments may impair fertility 1
• Don't miss the underlying cause: Treating symptoms without addressing the root cause will lead to suboptimal outcomes 6
• Don't forget to repeat abnormal hormone tests: Hormone levels can fluctuate; confirmation of abnormal results is essential before initiating treatment 1