The side effect of starting testosterone therapy may include increased red blood cell levels, acne, fluid retention, lower fertility, breast tenderness, and possible worsening of sleep apnea.
However, these effects do not occur in every patient. Many risks of testosterone use depend on dose, delivery method, pre-existing health conditions, and follow-up care.
What Is TRT
According to the U.S. Food and Drug Administration (FDA), testosterone replacement therapy (TRT) is a prescription treatment approved for men who have low testosterone caused by certain medical conditions associated with hypogonadism, such as disorders affecting the testicles, pituitary gland, or brain. It is not FDA-approved simply for age-related testosterone decline alone.
FDA-approved testosterone products may be given in several forms, depending on the product and clinical need, including testosterone injections, topical gel, transdermal patch, buccal system, nasal gel, and implantable pellet.
TRT should only begin after a clinical diagnosis supported by symptoms and repeated laboratory testing of testosterone levels through a blood test.
Why Doctors Recommend TRT Despite Possible Side Effects
Doctors may recommend TRT because untreated testosterone deficiency can also reduce health and quality of life. Symptoms may include fatigue, low libido, poor mood, reduced muscle mass, increased body fat, low bone density, and impaired sexual function.
When symptoms are significant, TRT may offer measurable potential benefits that outweigh manageable risks in the right patient. Treatment should only be considered after clinical diagnosis, multiple risk factors assessment, and repeat laboratory confirmation through a blood test.
Potential Benefits of TRT Supported by Published Research: Positive Effects of Testosterone
- A major study in The New England Journal of Medicine found improvements in sexual activity, sexual desire, and erectile function. Some men also reported better mood and energy.
- Research in theJournal of Clinical Endocrinology & Metabolism found that TRT can improve bone density. It may also increase bone strength in older men with low t.
- The same journal also reports changes in body composition. Some men may gain lean muscle mass. Body fat may also decrease when treatment is properly
- A review of published studies found similar results. TRT may help improve muscle-to-fat balance in men with low testosterone.
- A study in JAMA Psychiatry suggests TRT may improve mood in some men. However, not everyone responds the same way.
TRT Side Effects: What’s Real, What’s Reported, and How It’s Managed
TRT is often associated with many possible side effects online and in discussions. However, clinical studies show that some of these are well-established, while others are not consistently proven or vary per individual. Below are the most commonly mentioned effects and what current evidence shows.
High Red Blood Cell Count
Why It Happens
TRT can increase red blood cell production. This is due to higher stimulation of bone marrow activity.
Why It Matters
If hematocrit becomes too high, blood viscosity may increase.
How It Is Managed
Doctors often monitor CBC bloodwork, lower the dose, change the delivery method, pause therapy, or use therapeutic phlebotomy when appropriate.
Acne or Oily Skin
Why It Happens
TRT increases androgen activity. This can increase oil production in the skin.
What Clinical Evidence Shows
Clinical reviews show acne is an infrequent side effect of TRT. When it happens, it is usually mild.
Fluid Retention
Why It Happens
Androgens may influence sodium and water balance, causing mild swelling in some individuals.
What Clinical Evidence Shows
Clinical guidelines report fluid retention (edema) as a known but generally uncommon adverse effect of testosterone therapy.
Reduced Fertility
Why It Happens
External testosterone can suppress the hypothalamic–pituitary–gonadal (HPG) axis, reducing LH and FSH signaling. These lower signals that support sperm production.
How It Is Managed
In men who are actively trying to conceive, testosterone replacement therapy may be avoided or discontinued because it can suppress spermatogenesis. In selected clinical settings, specialists may use therapies such as human chorionic gonadotropin (hCG) to stimulate intratesticular testosterone production, or selective estrogen receptor modulators (SERMs) like clomiphene citrate to maintain LH and FSH signaling.
Breast Tenderness
Why It Happens
Some testosterone converts to estradiol through aromatase. In some people, this may contribute to swollen or tender breasts.
What Clinical Evidence Shows
Similarly in a clinical guidelines report this effect is uncommon and usually reversible.
Worsening Sleep Apnea
Why It Happens
Research suggests testosterone may influence airway control or breathing regulation in predisposed patients. Some studies suggest no clear association, while others report an increased risk of worsening sleep apnea.
How It Is Managed
In a study it was recommended that patients be screened before treatment. Symptoms are monitored during therapy.
Prostate Cancer
Why It Happens
Current clinical evidence does not show that TRT directly causes prostate cancer. It was mentioned that there is no consistent increase in prostate cancer incidence among men receiving testosterone therapy. However, testosterone may promote growth of pre-existing, undiagnosed prostate cancer.
How It Is Managed
Baseline prostate screening is recommended before starting TRT. This includes assessment for benign prostatic hyperplasia. PSA levels and prostate health are monitored during therapy. Hormone therapy may be paused or reassessed if abnormal findings occur.
Heart Attack and Stroke Risk
Why It Happens
A common concern is that TRT increases cardiovascular risk. However, this stems largely from older observational studies that have since been superseded by more rigorous evidence.
What Clinical Evidence Shows
A large randomized controlled trial of over 5,200 men at high cardiovascular disease risk found TRT was non-inferior to placebo for major adverse cardiac events, including heart attack, heart failure, and stroke. A meta-analysis of 14 randomized trials confirmed TRT did not significantly increase the potential risk of heart disease, myocardial infarction, stroke, pulmonary embolism, or venous thromboembolism in many men with low testosterone.
