The information on this website is not intended for diagnosis or treatment. Please consult your physician for health concerns.

+90 850 321 50 00

Testosterone Replacement Therapy — Safety & TRAVERSE Trial Era

Comprehensive safety assessment of testosterone replacement therapy in adult men with confirmed hypogonadism, integrating TRAVERSE trial cardiovascular outcomes, prostate, hematologic, and fertility considerations into individualized treatment plans.

Written by: Saygı Hospital Health Guide Editorial Board
Last updated:

This content has been compiled by the Saygı Hospital Health Guide Editorial Board and is periodically reviewed by a specialist physician.

References (5)

This content is for informational purposes only and does not constitute medical advice. You can book an appointment at our Endokrinoloji department. Book Appointment →

What is Testosterone Replacement Therapy — Safety & TRAVERSE Trial Era?

Adult male hypogonadism is diagnosed by combination of compatible symptoms and unequivocally low morning total testosterone (under 264–300 ng/dL on two separate measurements) accompanied by appropriate gonadotropin pattern (primary testicular versus secondary hypothalamic-pituitary).

TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE in Hypogonadal Men) randomized 5246 men aged 45–80 with cardiovascular risk to testosterone gel or placebo for 22 months; major adverse cardiac events were not increased (HR 0.96, 95% CI 0.78–1.17).

However, TRAVERSE detected higher rates of pulmonary embolism, atrial fibrillation, and acute kidney injury in the testosterone arm, prompting careful monitoring; previous Endocrine Society guidance and 2023 American Urological Association guidelines incorporate these findings.

Symptoms

Decreased libido, erectile dysfunction, decreased morning erections, decreased spontaneous erections
Loss of body hair, decreased shaving frequency, gynecomastia, testicular atrophy
Fatigue, low mood, depression, decreased motivation, cognitive complaints
Decreased muscle mass and strength, increased body fat (particularly visceral)
Decreased bone density, osteopenia, osteoporosis, low-trauma fractures
Hot flashes (in profound hypogonadism), infertility from impaired spermatogenesis

Risk Factors

Aging (age-related testosterone decline) is not by itself indication; functional hypogonadism due to obesity, opioids, glucocorticoids, type 2 diabetes
Klinefelter syndrome, cryptorchidism, prior chemotherapy or radiation, testicular trauma — primary hypogonadism
Pituitary tumor, hemochromatosis, hyperprolactinemia, opioid use — secondary hypogonadism
Prior breast cancer, prostate cancer, severe untreated obstructive sleep apnea, untreated severe lower urinary tract symptoms — contraindications
Erythrocytosis (hematocrit over 54%), uncontrolled heart failure, venous thromboembolism, recent stroke or MI — caution or contraindication
Active fertility plans — testosterone suppresses spermatogenesis; alternative such as clomiphene or hCG preferred

When to See a Doctor?

If you experience any of the following symptoms, seek medical attention promptly:

  • Symptomatic adult male with morning total testosterone under 264 ng/dL on two occasions — endocrinology or urology evaluation
  • Hematocrit over 54% during therapy — phlebotomy and dose adjustment or treatment hold
  • New chest pain, dyspnea, leg swelling, severe headache — emergency evaluation for thromboembolism, MI, or stroke
  • PSA rise of 1.4 ng/mL or more in any year, abnormal DRE, or urinary symptom worsening — urology referral
  • Considering pregnancy or fertility — switch to fertility-preserving therapy before testosterone

Treatment Methods

01
Treatment indicated only after confirmed symptomatic hypogonadism with two morning total testosterone measurements; address reversible causes (weight loss, OSA treatment, opioid reduction) first
02
Formulations: transdermal gel 1.62–2% (start 2.5–5 g/day), patches, intramuscular testosterone enanthate or cypionate 50–100 mg weekly or 100–200 mg every two weeks, subcutaneous testosterone undecanoate, oral testosterone undecanoate (with food), nasal gel
03
Baseline labs: total testosterone (morning, fasting), CBC, PSA (in age over 40), hematocrit, lipid panel, liver function; repeat at 3, 6, 12 months then annually
04
Target mid-normal total testosterone (400–700 ng/dL); monitor hematocrit, PSA, symptoms; offer phlebotomy or dose reduction if hematocrit exceeds 54%; counseling about VTE/AF/cardiovascular events from TRAVERSE
05
Fertility-preserving alternatives: human chorionic gonadotropin (hCG) 1500–3000 IU 2–3 times/week, clomiphene citrate 25–50 mg every other day, or aromatase inhibitor; testosterone is contraindicated in men actively trying to conceive

Which Department to Visit?

You can visit our Endokrinoloji department for these complaints. Our specialist physicians will create the most suitable treatment plan for you.

Learn About Endokrinoloji Department

Let us help you

You can make an appointment with our specialists or contact us for your concerns.

Book AppointmentContact Us

Related Health Topics

Other articles from the same department you may want to explore.

Anaemia

Dahiliye (İç Hastalıkları)

Anaemia is a low haemoglobin level that reduces oxygen delivery, causing fatigue, pallor, and shortness of breath. It is not a disease itself but a sign of many underlying conditions. Most cases are correctable with appropriate diagnosis and treatment.

Iron Deficiency Anaemia

Dahiliye (İç Hastalıkları)

Iron deficiency anaemia develops when dietary intake, absorption, or losses create an iron shortfall, most often affecting women and children. Identifying the underlying cause is the core of management, alongside iron replacement.

Vitamin B12 Deficiency

Dahiliye (İç Hastalıkları)

Vitamin B12 deficiency can cause megaloblastic anaemia, neurological symptoms, and cognitive impairment. Early treatment with intramuscular or oral B12 largely prevents irreversible complications.

Hypertension (High Blood Pressure) Management

Dahiliye (İç Hastalıkları)

Hypertension is often called the silent killer because it progresses symptom-free for years and can damage the heart, brain, kidneys, and eyes. Regular monitoring, lifestyle change, and evidence-based drug therapy dramatically reduce cardiovascular risk.

Chronic Kidney Disease

Dahiliye (İç Hastalıkları)

Chronic kidney disease is one of the most common complications of chronic conditions such as diabetes and hypertension, and can be silent in its early stages.

Hepatitis B (HBV)

Dahiliye (İç Hastalıkları)

Hepatitis B is a DNA virus infection causing acute and chronic hepatitis with risk of cirrhosis and hepatocellular carcinoma; diagnosis integrates HBsAg, HBeAg, anti-HBc, and HBV DNA with management based on disease phase using nucleos(t)ide analogues (entecavir, tenofovir) and universal infant vaccination.

Hepatitis C (HCV)

Dahiliye (İç Hastalıkları)

Hepatitis C is an RNA virus causing chronic hepatitis that may progress to cirrhosis and hepatocellular carcinoma; modern direct-acting antiviral (DAA) pangenotypic regimens (sofosbuvir/velpatasvir, glecaprevir/pibrentasvir) achieve sustained virologic response over 95% in 8–12 weeks with universal adult screening and cure for nearly all patients.

Fatty Liver Disease

Dahiliye (İç Hastalıkları)

Non-alcoholic fatty liver disease (NAFLD) is closely related to obesity and metabolic syndrome and is largely reversible with early treatment.

Health Disclaimer: The information on this page is prepared for general informational purposes only. It does not replace medical diagnosis and treatment. Please consult your physician for your complaints. Saygı Hospital does not accept responsibility for actions taken based on the information on this page.