From the Guidelines
Elevated testosterone levels can be caused by several conditions, including polycystic ovary syndrome (PCOS) in women, congenital adrenal hyperplasia, androgen-secreting tumors of the ovaries or adrenal glands, and anabolic steroid use. Management of elevated testosterone levels depends on the underlying cause and typically involves medication and lifestyle modifications. For PCOS, treatment often includes combined oral contraceptives like ethinyl estradiol with drospirenone (Yaz, Yasmin) or cyproterone acetate, which reduce testosterone production 1. Anti-androgens such as spironolactone (50-200 mg daily in divided doses) or finasteride (5 mg daily) may be prescribed to block testosterone effects. Metformin (500-2000 mg daily) can improve insulin sensitivity, indirectly lowering testosterone levels. For adrenal causes, corticosteroids like dexamethasone (0.25-0.5 mg at bedtime) may be used. Tumors typically require surgical removal. Lifestyle modifications including weight loss, regular exercise, and a low-glycemic diet can help reduce testosterone levels naturally. Regular monitoring of hormone levels is essential during treatment, and patients should be aware that some medications may take 3-6 months to show full effects. Side effects vary by medication but may include fatigue, electrolyte disturbances with spironolactone, or gastrointestinal issues with metformin. These treatments work by either reducing testosterone production, blocking its effects at receptor sites, or addressing underlying metabolic issues that contribute to excess androgen production. It is essential to note that the management of testosterone deficiency, as discussed in the American College of Physicians guideline 1, focuses on accurate assessment of total testosterone levels, symptoms, and signs, as well as proper on-treatment monitoring to ensure therapeutic testosterone levels are reached and symptoms are ameliorated. However, the primary concern in the context of this question is the management of elevated testosterone levels, which requires a different approach. The American Urological Association guideline 1 provides recommendations for the evaluation and management of testosterone deficiency, but it also highlights the importance of addressing the underlying cause of elevated testosterone levels. In the case of PCOS, the guideline recommends a comprehensive approach that includes lifestyle modifications, hormonal treatments, and anti-androgen therapy. Ultimately, the goal of treatment is to reduce morbidity, mortality, and improve the quality of life for patients with elevated testosterone levels.
From the Research
Causes of Elevated Testosterone
- Congenital Adrenal Hyperplasia (CAH) is a genetic disorder that can cause elevated testosterone levels, particularly in individuals with 21-hydroxylase deficiency 2
- Testicular adrenal rest tumors (TARTs) are a common complication in males with CAH, which can produce adrenal-specific steroids and express adrenal-specific enzymes, leading to elevated testosterone levels 3
- Poor hormonal control and advanced bone age can contribute to the development of TARTs in young males with classic CAH 4
- Elevated androgens levels in CAH can also be caused by the accumulation of precursors such as 17-hydroxypregnenolone and 17-hydroxyprogesterone, which are directed to the synthesis of androgens through the enzyme 17-hydroxylase/17,20 lyase 2
Management of Elevated Testosterone
- Optimal steroid replacement is the treatment of choice for TARTs, which can lead to regression of the lesion in the majority of cases 5
- Histopathological evaluation is helpful in cases where there is a strong need for excluding a malignancy, and can confirm the diagnosis of TARTs 5
- Longitudinal studies are needed to understand the individual predisposition to TARTs and the age at which to begin screening patients with CAH 4
- Management of CAH should also focus on controlling androgen excess, which can affect the hypothalamic-pituitary-gonadal axis and lead to chronic anovulation and infertility 2