Causes of High Total Testosterone Levels
The primary causes of high total testosterone levels include congenital adrenal hyperplasia, anabolic steroid use, androgen-secreting tumors, polycystic ovarian syndrome in women, resistance training, and elevated sex hormone-binding globulin (SHBG) levels.
Primary Pathological Causes
Congenital Adrenal Hyperplasia (CAH)
- Results from enzymatic defects in adrenal steroid biosynthesis, most commonly 21-hydroxylase deficiency
- Leads to excessive production of adrenal androgens including testosterone
- High ACTH levels (>200 pg/mL) are predictive of inadequate hormonal treatment and presence of testicular adrenal rest tumors in CAH patients 1
- Peripheral conversion of adrenal androstenedione to testosterone accounts for 76% of plasma testosterone in prepubertal females and 36% in males with CAH 2
Androgen-Secreting Tumors
- Testicular tumors in men
- Adrenal tumors in both men and women
- Ovarian tumors in women
- These tumors autonomously produce androgens, bypassing normal regulatory mechanisms
Exogenous Testosterone/Anabolic Steroid Use
- Commonly seen in athletes and bodybuilders seeking to increase muscle mass and strength 3
- Suppresses natural testosterone production through negative feedback
- Can be detected through specialized testing methods including immunoassays, liquid chromatography tandem mass-spectrometry, and electrochemical methods 4
Physiological and Secondary Causes
Elevated SHBG Levels
- SHBG binds to testosterone, increasing total testosterone while free testosterone remains normal 5
- Common causes of elevated SHBG include:
- Liver disease
- Hyperthyroidism
- Estrogen therapy
- Aging
- HIV infection
- Calculate free testosterone index (total testosterone/SHBG ratio) to assess true androgenic status 6
Resistance Exercise and Training
- Acute heavy resistance exercise can elevate testosterone levels, particularly in men 3
- The response is determined by exercise program variables, sex, and age
- Testosterone increases are typically transient and return to baseline within hours
Polycystic Ovarian Syndrome (PCOS)
- Most common cause of elevated androgens in women
- Diagnosis requires 2 of 3 criteria: androgen excess, ovulatory dysfunction, or polycystic ovaries 6
- Differential diagnosis includes thyroid disease, prolactin excess, and non-classical CAH
Evaluation Approach
Laboratory Assessment
- Confirm elevated total testosterone with repeat morning measurement (8-10 AM)
- Measure free testosterone using reliable assay (equilibrium dialysis preferred)
- Measure SHBG levels to calculate free testosterone index (total testosterone/SHBG ratio)
- If free testosterone is also elevated:
- Measure LH/FSH to distinguish primary from secondary causes
- Consider adrenal function tests (ACTH, 17-hydroxyprogesterone) if CAH is suspected
- Thyroid function tests to rule out hyperthyroidism
Clinical Assessment
- Evaluate for clinical signs of androgen excess:
- In men: acne, oily skin, increased muscle mass, aggressive behavior
- In women: hirsutism, acne, androgenetic alopecia, menstrual irregularities, infertility
- Screen for medication use and anabolic steroid abuse
- Assess for symptoms of underlying conditions (liver disease, thyroid disorders)
Management Considerations
- If elevated total testosterone is due to high SHBG with normal free testosterone, no specific treatment is required 5
- For underlying conditions:
- Monitor testosterone levels after treating underlying conditions
Common Pitfalls to Avoid
- Relying solely on total testosterone without measuring free testosterone and SHBG
- Failing to identify underlying conditions that alter SHBG levels
- Not considering time of day when measuring testosterone (morning samples are standard)
- Overlooking exogenous testosterone use in athletes or bodybuilders
Understanding the specific cause of elevated total testosterone is essential for appropriate management and to prevent potential complications related to androgen excess.