How to increase free testosterone in males?

How to Increase Free Testosterone in Males

The most effective approach to increase free testosterone in males is weight loss through lifestyle modifications—specifically increased physical activity combined with caloric restriction—which should be the first-line intervention before considering testosterone replacement therapy. 1, 2

Lifestyle Modifications as Primary Treatment

Weight Loss Strategy

• Weight loss is the cornerstone intervention for increasing free testosterone, particularly in overweight and obese men where adipose tissue increases aromatization of testosterone to estradiol, creating a negative feedback loop that suppresses pituitary luteinizing hormone secretion 1, 2
• Both moderate and significant reductions in BMI are associated with notable increases in serum testosterone levels, with improvements in insulin sensitivity, reduced inflammation, and lower aromatase activity 2
• Weight loss produces improvements in fasting plasma glucose, insulin resistance, triglyceride levels, HDL cholesterol, lean body mass, and waist circumference 1

Physical Activity Priority

• Increased physical activity has a greater effect than caloric restriction alone on raising testosterone levels during lifestyle modification programs 3
• Aerobic exercise training combined with resistance training is most effective, with a significant positive correlation between increased step count and serum testosterone levels 3
• The high physical activity group showed significantly higher testosterone levels compared to low activity groups, an effect not observed with calorie restriction alone 3

Dietary Considerations

• Low-carbohydrate and Mediterranean diets have been linked to increased testosterone production in men with obesity 2
• Both high-protein (35% protein, 40% carbohydrate, 25% fat) and high-carbohydrate (17% protein, 58% carbohydrate, 25% fat) energy-restricted diets increase total testosterone, sex hormone binding globulin, and free testosterone with no significant difference between diet types 4
• Ensure adequate intake of zinc, magnesium, vitamin D, and polyphenols, as nutritional deficiencies adversely impact the hypothalamic-pituitary-gonadal axis 5

Diagnostic Workup Before Treatment

Initial Testing Protocol

• Measure morning total testosterone between 8-10 AM on at least two separate occasions, as testosterone shows diurnal variation with highest levels in the morning 1, 6
• Measure free testosterone by equilibrium dialysis (gold standard) or calculate using validated formulas incorporating total testosterone, sex hormone-binding globulin, and albumin 1, 6
• In obese patients, low total testosterone due solely to low sex hormone-binding globulin may show normal free testosterone levels—making free testosterone measurement essential 1

Distinguishing Primary vs. Secondary Hypogonadism

• Measure serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 1, 6
• If testosterone is low with concomitantly low LH/FSH (secondary hypogonadism), measure serum prolactin and iron saturation 1, 6
• Men with testosterone <150 ng/dL combined with low or low-normal LH should undergo pituitary MRI regardless of prolactin levels 6

Symptom Assessment

• Document specific symptoms: decreased energy, libido, muscle mass, body hair, hot flashes, gynecomastia, infertility, erectile dysfunction 1, 6
• Perform targeted physical examination: body mass index/waist circumference, gynecomastia, testicular size and consistency, prostate examination 6

Testosterone Replacement Therapy

Indications for Treatment

• Testosterone replacement should be considered when morning free testosterone by equilibrium dialysis is frankly low on at least 2 separate assessments and the hypogonadism workup has ruled out etiologies unrelated to obesity 1
• Normal total testosterone range for adult men is 300-800 ng/dL in most laboratories 1
• Target testosterone levels should be in the middle tertile of the normal reference range (450-600 ng/dL) 1

Treatment Options

• Transdermal preparations (gel, patch) are preferred for most hypogonadal men due to relative stability of day-to-day testosterone levels and avoidance of injection discomfort 1, 6, 7
• Intramuscular testosterone injections (e.g., testosterone cypionate) offer the benefit of avoiding daily administration with approximately 8-day half-life, advantageous for patients with reduced disease-management skills 1, 7
• Implantable testosterone pellets provide longer-term alternative but require a procedure for implantation 1

Monitoring Protocol

• Test testosterone levels 2-3 months after treatment initiation and after any dose change to ensure normal serum concentrations are achieved 1, 6
• For intramuscular injections, measure levels midway between injections targeting mid-normal value (500-600 ng/dL) 1
• For transdermal preparations, levels can be measured at any time, with peak values occurring 6-8 hours after patch application 1
• Once stable levels confirmed, monitoring every 6-12 months is typically sufficient 1
• Measure hemoglobin/hematocrit and assess cardiovascular disease risk factors prior to and during therapy 6

Critical Contraindications and Warnings

Absolute Contraindications

• Exogenous testosterone should NOT be prescribed to men currently trying to conceive, as it interrupts normal spermatogenesis and can cause severe oligospermia or azoospermia 1, 6
• Men interested in fertility should have reproductive health evaluation performed prior to testosterone replacement 6

Cardiovascular Considerations

• Testosterone therapy should not be commenced for 3-6 months in patients with recent cardiovascular events 1
• Counsel patients that current evidence does not definitively demonstrate whether testosterone therapy increases or decreases cardiovascular risk (myocardial infarction, stroke, cardiovascular-related death) 1
• Men on testosterone therapy should report cardiovascular symptoms (chest pain, shortness of breath, dizziness, transient loss of consciousness) during follow-up 1

Other Warnings

• The FDA requires labeling regarding post-marketing reports of venous thromboembolic events, though observational studies since 2014 have not shown increased VTE risk 1
• Testosterone therapy in men with in-situ prostate cancer on active surveillance or previously treated prostate cancer should be made with caution 1

Common Pitfalls to Avoid

• Do not rely on screening questionnaires alone to identify candidates for testosterone therapy due to variable specificity and sensitivity 6
• Do not treat asymptomatic men with low testosterone, as treatment in this population is controversial 1
• In obese men, recognize that low total testosterone may be due solely to low sex hormone-binding globulin with normal free testosterone—always measure free testosterone 1
• Avoid starting testosterone replacement before completing full hypogonadism workup to rule out secondary causes requiring different management 1
• Be aware that transdermal gels can be inadvertently transferred to others via prolonged skin contact and absorption can be variable 1