Hormone Replacement Therapy for Men:
Hormone Replacement Therapy for Men:
A Complete Clinical Guide to TRT, Benefits, Risks, and Treatment Options
Medically Reviewed by Courtney LaSumner Bass, NP | Board-Certified Nurse Practitioner | Military Veteran
Last Updated: December 2025 | Reading Time: 15 minutes
Key Takeaways
Testosterone replacement therapy (TRT) is an evidence-based treatment for men with clinically diagnosed hypogonadism (low testosterone)
Clinical diagnosis requires testosterone levels below 300 ng/dL on two separate morning blood tests plus the presence of symptoms
Research demonstrates improvements in sexual function, body composition, bone density, energy, and quality of life
The landmark TRAVERSE trial (2023) established cardiovascular safety in men with or at risk for heart disease
Treatment requires ongoing medical supervision with regular monitoring of testosterone levels, hematocrit, and prostate health
What Is Hormone Replacement Therapy for Men?
Hormone replacement therapy (HRT) for men—more commonly known as testosterone replacement therapy (TRT)—is a clinician-prescribed medical treatment designed to restore testosterone levels when the body can no longer produce adequate amounts on its own. Testosterone serves as the primary androgen hormone in men, playing essential roles in sexual function, muscle development, bone health, cognitive function, mood regulation, and metabolic processes.
When testosterone production declines significantly—whether due to aging, medical conditions, or other factors—men may experience a constellation of symptoms that substantially impact quality of life. This clinical condition, known as hypogonadism or testosterone deficiency syndrome, affects an estimated 2 to 4 million American men, though experts believe only a fraction currently receive treatment.
According to population-based research, testosterone levels decline approximately 1-2% annually after age 30, with the decrease accelerating in later decades. The Massachusetts Male Aging Study found that up to 39% of men between ages 40-70 have testosterone levels below 400 ng/dL, though the prevalence of symptomatic hypogonadism requiring treatment is lower, ranging from 6-12%.
Understanding Testosterone: The Master Male Hormone
Testosterone production begins in the brain, where the hypothalamus releases gonadotropin-releasing hormone (GnRH), which signals the pituitary gland to produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH then stimulates the Leydig cells in the testes to synthesize testosterone. This complex feedback system, known as the hypothalamic-pituitary-gonadal (HPG) axis, maintains hormonal balance throughout a man's life.
Physiological Functions of Testosterone
Testosterone influences virtually every organ system in the male body:
Sexual Health: Regulates libido, erectile function, sperm production, and overall sexual performance
Musculoskeletal System: Promotes protein synthesis for muscle development and maintains bone mineral density
Metabolic Function: Influences fat distribution, insulin sensitivity, and energy metabolism
Hematological Effects: Stimulates erythropoiesis (red blood cell production) and hemoglobin levels
Neuropsychological Impact: Affects mood, cognitive function, spatial reasoning, and memory
Cardiovascular Influence: Impacts vascular reactivity, lipid profiles, and inflammatory markers
Recognizing Low Testosterone: Signs and Symptoms
The clinical presentation of testosterone deficiency varies among individuals, but research has identified specific symptoms most strongly associated with low testosterone levels. The European Male Aging Study established that sexual symptoms demonstrate the strongest correlation with androgen deficiency.
Primary Sexual Symptoms
Decreased sexual desire (low libido)
Erectile dysfunction or reduced erectile quality
Reduced frequency of morning erections
Physical Symptoms
Loss of muscle mass and strength (sarcopenia)
Increased body fat, particularly abdominal adiposity
Decreased bone mineral density (osteopenia/osteoporosis)
Chronic fatigue and reduced energy levels
Reduced physical endurance and exercise tolerance
Gynecomastia (breast tissue development)
Psychological Symptoms
Depressed mood and irritability
Difficulty concentrating and cognitive fog
Decreased motivation and sense of well-being
Sleep disturbances
How Is Low Testosterone Diagnosed?
Accurate diagnosis of testosterone deficiency requires both clinical evaluation and laboratory confirmation. The Endocrine Society and American Urological Association have established clear diagnostic criteria to ensure appropriate patient selection for therapy.
Diagnostic Criteria
According to current clinical guidelines, a diagnosis of hypogonadism requires:
Total testosterone below 300 ng/dL (10.4 nmol/L) as established by the American Urological Association
Two separate early morning blood tests (drawn between 7-10 AM when testosterone peaks)
Presence of clinical signs and symptoms consistent with testosterone deficiency
Testing performed in fasting state (glucose can temporarily suppress testosterone levels)
Additional Laboratory Testing
A comprehensive hormone evaluation typically includes:
Free Testosterone: Measures the biologically active fraction not bound to proteins
Sex Hormone-Binding Globulin (SHBG): Affects bioavailable testosterone levels
Luteinizing Hormone (LH): Helps distinguish primary from secondary hypogonadism
Prolactin: Screens for pituitary tumors that can suppress testosterone
Complete Blood Count: Establishes baseline hematocrit for safety monitoring
Prostate-Specific Antigen (PSA): Baseline prostate health assessment
Metabolic Panel: Evaluates glucose, lipids, and organ function
Evidence-Based Benefits of Testosterone Therapy
Multiple randomized controlled trials and meta-analyses have established the therapeutic benefits of testosterone replacement in men with documented hypogonadism. The Testosterone Trials (TTrials), a coordinated set of seven placebo-controlled studies, provided landmark evidence for TRT efficacy.
Sexual Function
Research consistently demonstrates that testosterone therapy improves multiple domains of sexual function. A systematic review for the American College of Physicians found statistically significant improvements in libido, erectile function, sexual activity frequency, and overall sexual satisfaction compared to placebo. The TestES evidence synthesis, analyzing 35 trials with 5,601 participants, confirmed that TRT improved sexual function across virtually all patient subgroups.
Body Composition
Testosterone replacement produces favorable changes in body composition through multiple mechanisms. Clinical trials demonstrate increases in lean body mass ranging from 3-6 kg over 6-12 months of treatment, accompanied by reductions in fat mass. These changes occur through enhanced protein synthesis, increased myofibrillar protein content, and metabolic effects on adipose tissue.
Bone Health
Testosterone plays a critical role in maintaining bone mineral density. Meta-analyses indicate beneficial effects on lumbar spine bone density in hypogonadal men, with most treated patients maintaining bone density above fracture thresholds. Research demonstrates improvements in both trabecular and cortical bone mineral density, independent of age and hypogonadism type.
Metabolic Parameters
Long-term registry data demonstrate that sustained testosterone therapy leads to progressive improvements in metabolic health markers. An 8-year study found that TRT completely prevented progression from pre-diabetes to type 2 diabetes in hypogonadal men, while also reducing body weight, waist circumference, and improving lipid profiles.
Quality of Life and Vitality
The TTrials demonstrated significant improvements in vitality, energy levels, and overall well-being in men with low testosterone. Patients commonly report enhanced motivation, improved mood stability, and greater physical and mental energy within the first several months of treatment.
Cardiovascular Safety: The TRAVERSE Trial
For years, conflicting data created uncertainty regarding testosterone therapy's cardiovascular effects. The FDA mandated manufacturers conduct a definitive cardiovascular outcomes trial, resulting in the landmark TRAVERSE study published in the New England Journal of Medicine in 2023.
This multicenter, randomized, double-blind, placebo-controlled trial enrolled 5,246 men aged 45-80 with hypogonadism and either established cardiovascular disease or high cardiovascular risk. After a mean follow-up of 33 months, the trial found that testosterone replacement was noninferior to placebo regarding major adverse cardiac events (MACE)—defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
TRAVERSE Trial Key Finding
"In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events."
— Lincoff AM, et al. New England Journal of Medicine, 2023
Based on this evidence, the FDA removed the cardiovascular risk warning from testosterone product labels, though labels still note that TRT may raise blood pressure in some patients.
Potential Risks and Side Effects
Like all medical treatments, testosterone therapy carries potential risks that require careful consideration and monitoring. Understanding these risks enables informed decision-making and appropriate safety protocols.
Erythrocytosis (Elevated Red Blood Cells)
The most common dose-related side effect of testosterone therapy is polycythemia—an increase in red blood cell production. While testosterone's erythropoietic effect can benefit men with anemia, excessive elevation (hematocrit above 54%) increases blood viscosity and theoretical thrombotic risk. Regular monitoring and dose adjustment effectively manage this concern.
Fertility Considerations
Exogenous testosterone suppresses the HPG axis, reducing natural testosterone production and spermatogenesis. Men planning to father children should discuss alternative approaches such as selective estrogen receptor modulators (SERMs) or human chorionic gonadotropin (hCG), which can maintain or stimulate testosterone production while preserving fertility.
Prostate Health
Contrary to historical concerns, contemporary evidence does not support a causal relationship between testosterone therapy and prostate cancer development. Multiple longitudinal studies have failed to find an association between endogenous testosterone levels and subsequent prostate cancer risk. Current guidelines recommend baseline PSA screening and regular monitoring during therapy, with urological referral if PSA rises significantly.
Other Potential Side Effects
Sleep Apnea: May worsen obstructive sleep apnea in predisposed individuals
Skin Reactions: Acne, oily skin, or application site reactions with topical formulations
Gynecomastia: Breast tissue enlargement from testosterone aromatization to estrogen
Testicular Atrophy: Decrease in testicular volume due to HPG axis suppression
Mood Changes: While most men experience improved mood, some may notice irritability if levels become too high
Testosterone Delivery Methods
Multiple testosterone formulations are available, each with distinct pharmacokinetic profiles, advantages, and considerations. Selection depends on patient preference, lifestyle factors, and clinical goals.
Method
Advantages
Considerations
Intramuscular Injections
Cost-effective, well-established, flexible dosing, can self-administer
Peak-trough fluctuations, weekly or biweekly administration
Topical Gels
Steady-state levels, non-invasive, daily application
Transfer risk to others, daily compliance, skin irritation possible
Subcutaneous Pellets
Longest duration (4-6 months), consistent levels, low maintenance
Minor surgical procedure, difficult to adjust dosing, cost
Transdermal Patches
Mimics circadian rhythm, consistent delivery
High rate of skin reactions, daily application, visibility
Nasal Gel
No transfer risk, rapid absorption
Multiple daily applications (2-3x), nasal irritation
Who Is a Candidate for TRT?
Testosterone therapy is appropriate for men who meet specific clinical and laboratory criteria while not having contraindications to treatment.
Appropriate Candidates
Men with confirmed low testosterone (two morning tests below 300 ng/dL)
Presence of clinical symptoms consistent with testosterone deficiency
Men willing to commit to regular monitoring and follow-up
Those who understand the benefits, risks, and treatment expectations
Contraindications to Therapy
The Endocrine Society recommends against testosterone therapy in men with:
Active or history of breast cancer
Known or suspected prostate cancer
Baseline hematocrit above 50%
Severe untreated obstructive sleep apnea
Uncontrolled heart failure
Myocardial infarction or stroke within the past 6 months
Known thrombophilia or high risk of venous thromboembolism
Men actively trying to conceive
Lifestyle Optimization: Complementing TRT
Testosterone therapy achieves optimal results when combined with healthy lifestyle practices. Research demonstrates that exercise, nutrition, sleep, and stress management all influence hormone levels and treatment outcomes.
Exercise and Physical Activity
Resistance training and high-intensity exercise transiently boost testosterone levels and enhance the muscle-building effects of TRT. Regular physical activity also improves insulin sensitivity, cardiovascular health, and body composition—all factors that influence hormonal balance.
Nutrition and Body Composition
Obesity is strongly associated with reduced testosterone levels through increased aromatase activity in adipose tissue, which converts testosterone to estrogen. Weight loss through caloric restriction and exercise can significantly improve endogenous testosterone production. Meta-analyses confirm that weight loss reverts obesity-associated hypogonadotropic hypogonadism.
Sleep Quality
The majority of daily testosterone secretion occurs during sleep, particularly during REM stages. Sleep deprivation and disorders such as obstructive sleep apnea significantly reduce testosterone levels. Optimizing sleep hygiene and treating sleep disorders supports hormonal health and TRT efficacy.
Stress Management
Chronic stress elevates cortisol, which antagonizes testosterone's anabolic effects and can suppress the HPG axis. Stress reduction techniques, adequate recovery time, and work-life balance support optimal hormonal function.
Treatment Monitoring and Follow-Up
Proper monitoring ensures treatment safety and efficacy. Clinical guidelines recommend structured follow-up protocols.
Initial Monitoring (3-6 Months)
Testosterone levels to assess adequacy (goal: mid-normal range, 500-800 ng/dL)
Hematocrit to monitor for erythrocytosis
PSA for prostate health surveillance
Clinical symptom assessment
Ongoing Monitoring (Annually)
Annual testosterone and hematocrit levels
PSA and digital rectal examination as appropriate for age
Lipid panel and metabolic parameters
Assessment of symptom improvement and quality of life
Bone density evaluation in men with osteoporosis risk (every 1-2 years)
Why Choose Arsenal Men's Health for TRT?
Arsenal Men's Health provides Utah men with expert, clinician-led testosterone therapy through a convenient telehealth platform. Our approach combines evidence-based medicine with personalized care.
Expert Clinical Leadership: Board-certified nurse practitioner with specialized training in men's health and hormone optimization
Comprehensive Evaluation: Thorough diagnostic workup including complete hormone panels and health assessment
Individualized Protocols: Treatment plans customized to your symptoms, goals, and lifestyle
Convenient Telehealth Access: Consultations from anywhere in Utah—no waiting rooms or scheduling hassles
Transparent Pricing: Cash-pay model with HSA/FSA acceptance—no insurance complications
Ongoing Support: Regular monitoring, dose optimization, and direct provider access
Discretion Guaranteed: Private, confidential care with medications delivered to your door
Ready to Take Control of Your Hormone Health?
Schedule your free consultation with Arsenal Men's Health today.
Call (385) 666-6292 or visit arsenalmenshealth.com
Trusted by 1,200+ Utah Men
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Medical Disclaimer
This article is for educational purposes only and does not constitute medical advice. Treatment decisions should be made by a licensed healthcare provider based on individual evaluation. If you are experiencing symptoms of low testosterone, please consult with a qualified medical professional.
