From the Guidelines
Low free testosterone, or hypogonadism, can have significant implications on a man's quality of life, including decreased libido, erectile dysfunction, fatigue, and decreased muscle mass, and should be addressed through lifestyle changes, hormone replacement therapy, or treating underlying causes, as recommended by the most recent guidelines 1.
Implications of Low Free Testosterone
The implications of low free testosterone are far-reaching and can affect various aspects of a man's life. Some of the common symptoms include:
- Decreased libido
- Erectile dysfunction
- Fatigue
- Decreased muscle mass
- Increased body fat
- Mood changes
Diagnosis and Treatment
Diagnosis of low free testosterone typically involves a morning total testosterone level test using an accurate and reliable assay 1. If the total testosterone levels are close to the lower limit, it is reasonable to determine free testosterone concentrations either directly from equilibrium dialysis assays or by calculations that use total testosterone, sex hormone binding globulin, and albumin concentrations 1.
Lifestyle Modifications
Lifestyle modifications are essential in managing low free testosterone and include:
- Regular exercise, especially strength training
- Maintaining a healthy weight
- Getting adequate sleep (7-9 hours)
- Managing stress
- Eating a balanced diet rich in zinc, vitamin D, and healthy fats
Testosterone Replacement Therapy
If clinically indicated, testosterone replacement therapy may be prescribed as injections (typically 50-200mg every 1-2 weeks), daily transdermal gels (AndroGel, Testim), patches, or pellets implanted every 3-6 months 1. Treatment should be monitored with regular blood tests to check testosterone levels, complete blood count, and PSA (prostate-specific antigen).
Underlying Causes
Low testosterone can result from conditions like hypogonadism, pituitary disorders, obesity, diabetes, or medication side effects, so identifying and treating these underlying causes is essential 1.
Risks and Benefits
Testosterone therapy carries potential risks including acne, sleep apnea, enlarged breasts, reduced sperm production, and increased red blood cell count 1. However, the benefits of testosterone replacement therapy, including improved sexual function, well-being, muscle mass and strength, and bone density, should be weighed against the potential risks 1.
Cardiovascular Risk
While some studies have associated low testosterone levels with increased cardiovascular risk, the evidence is not conclusive, and testosterone replacement therapy in older men with hypogonadism has been associated with increased coronary artery plaque volume, but no conclusive evidence of increased cardiovascular risk in hypogonadal men 1.
Routine Measurement
Testosterone level should be routinely measured in men with erectile dysfunction, and replacement considered when appropriate, as recommended by the Princeton III consensus recommendations 1.
Lifestyle Advice
Lifestyle advice, including smoking cessation, regular dynamic exercise, weight loss, a healthy diet, and moderate alcohol consumption, can help reduce cardiovascular risk and improve erectile function 1.
From the FDA Drug Label
Testosterone cypionate injection is indicated for replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).
The implications of low free testosterone (hypogonadism) include:
- Primary hypogonadism: testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy.
- Secondary hypogonadism: idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.
- Symptoms of deficiency or absence of endogenous testosterone: which may require replacement therapy. 2 3
From the Research
Implications of Low Free Testosterone (Hypogonadism)
The implications of low free testosterone, also known as hypogonadism, can be significant and far-reaching. Some of the key implications include:
- Sexual dysfunction, including low libido and erectile dysfunction 4, 5
- Tiredness and reduced muscle strength 6, 5
- Reduced quality of life 6, 5
- Increased risk of sarcopenia and muscle deterioration 6
- Increased risk of diseases such as angina pectoris, arteriosclerosis, obesity, metabolic syndrome, and dementia 6
- Cognitive impairment and decreased mental function 6
Diagnosis and Evaluation of Hypogonadism
Diagnosing hypogonadism typically involves measuring fasting serum total testosterone in the morning on at least 2 separate days, or free testosterone by equilibrium dialysis or calculated free testosterone in men with conditions that alter sex hormone-binding globulin or serum total testosterone near lower limit of normal 7. Further evaluation is performed to identify the specific cause of hypogonadism and whether it is potentially reversible or an irreversible pathologic disorder 7.
Treatment and Management of Hypogonadism
Testosterone replacement therapy is commonly used to treat hypogonadism, and has been shown to improve health-related quality of life in patients with late-onset hypogonadism (LOH) 6. The safety and efficacy of testosterone replacement therapy have been evaluated in several studies, with findings suggesting that it improves sexual function and quality of life without adverse effects on blood pressure, serum lipids, or glycaemic markers 5. However, rigorous long-term evidence assessing the safety of testosterone replacement therapy and subgroups most benefiting from treatment is needed 5.
Monitoring and Follow-up
Monitoring of testosterone replacement therapy is crucial to ensure that benefits are optimized, risks are minimized, and any adverse effects are identified early and managed appropriately 8. A standardized plan should be used for monitoring, including evaluation of symptoms, side effects, adherence, and measurement of testosterone and hematocrit 8. Shared decision making should be used to determine whether to screen for prostate cancer, informed by age, baseline cancer risk, and patient preference 8.