Thicker blood (high hematocrit)
Testosterone stimulates red blood cell production. Over time that can push hematocrit (the share of your blood made of red cells) high enough to thicken the blood, which raises concern about clotting. It is the side effect your bloodwork is most likely to flag.
How often depends heavily on the format. In one retrospective review of 178 hypogonadal men followed for up to three years, hematocrit rose above 50% in 66.7% of men on injections, 35.1% on pellets, and 12.8% on gels. That was a retrospective review, and rates vary with dose and study, but the pattern is consistent: all formulations raise hematocrit, and injections tend to raise it the most.
As summarized from the Endocrine Society's 2018 guideline, hematocrit is checked before starting and again 3 to 6 months into treatment. If it climbs above 54%, therapy is paused until it comes down and is then restarted at a lower dose, with a check for low oxygen levels and sleep apnea first. A hematocrit above 50% before you start is a reason for caution. See who shouldn't start TRT.
Blood pressure
FDA says ambulatory blood pressure studies required of testosterone makers confirmed that blood pressure rises with all testosterone products. In February 2025 it required every label to carry blood pressure information or a new warning. The average rise is small but real. For example, the label for the oral product Kyzatrex reports an average increase of about 1.8/0.6 mm Hg in a 6-month ambulatory study, and about 3.1/1.0 mm Hg in men with hypertension already on treatment, and says it is not recommended for men with uncontrolled hypertension.
FDA also removed the cardiovascular-risk language from the boxed warnings in 2025 after TRAVERSE, and the Kyzatrex label records removal of its boxed blood pressure warning in July 2025 while keeping a standard warning. Small average increases still matter when they land on top of existing high blood pressure, so check yours at home before you start and periodically after. Blood pressure guide →
Heart rhythm, clots, and kidneys
TRAVERSE enrolled 5,246 men aged 45 to 80 with hypogonadism and existing or high risk of heart disease. Major cardiovascular events (cardiovascular death, heart attack, stroke) occurred in 7.0% of men on testosterone gel and 7.3% on placebo, which met the trial's noninferiority bar. That is reassuring.
The same trial found more atrial fibrillation, more pulmonary embolism, and more acute kidney injury in the testosterone group. These were secondary findings, but they are the reason prescribers watch for palpitations, sudden breathlessness, and leg swelling. Details and the limits of the trial are in our cardiovascular safety section.
Sleep apnea
Testosterone can make sleep apnea worse, at least at first. In a randomized trial of 67 obese men with severe obstructive sleep apnea, a testosterone injection worsened oxygen desaturation (by about 10 events per hour) after 7 weeks compared with placebo. By 18 weeks the difference was no longer significant, so the effect looked mild and temporary in that trial, but it was a small, short study.
If you snore, wake unrefreshed, or are very sleepy in the day, get screened before starting. Untreated severe sleep apnea is one of the guideline's "proceed with caution" conditions. Sleep apnea in men → · Sleep and testosterone
Prostate
The worry that testosterone feeds prostate cancer has not held up well in controlled trials, but the evidence is thinner than for the heart. TRAVERSE's prostate analysis followed 5,204 men for about 14,300 person-years. High-grade prostate cancer was found in 5 of 2,596 men on testosterone and 3 of 2,602 on placebo, a difference that was not statistically significant (hazard ratio 1.62, with a very wide confidence interval of 0.39 to 6.77). Any prostate cancer, urinary retention, prostate procedures, and urinary-symptom drug starts did not differ between groups. PSA did rise more on testosterone.
Two caveats: the numbers of cancers were tiny, and the trial excluded men with a PSA above 3.0 ng/mL, severe urinary symptoms, or other high-risk features, so it can't speak for those men. As summarized from the Endocrine Society guideline, a confirmed PSA above 4.0 ng/mL, or a rise of more than 1.4 ng/mL within a year, prompts a urology referral. PSA and TRT →
Bones and fractures
Low testosterone weakens bone, so you might expect treatment to protect it. TRAVERSE tested that directly in a fracture substudy of 5,204 men followed a median of 3.2 years. Clinical fractures occurred in 3.50% of men on testosterone and 2.46% on placebo (hazard ratio 1.43, 95% confidence interval 1.04 to 1.97). Testosterone did not reduce fractures, and the numbers were slightly higher with it. The authors did not design the trial to explain why.
The practical takeaway: testosterone is not a bone-protection strategy, and men at high fracture risk should discuss other treatments with their doctor.
Fertility
Testosterone from outside the body signals the brain to cut the hormones that drive sperm production, so sperm counts often fall, sometimes to zero. The Endocrine Society guideline advises against starting testosterone therapy in men who plan to have children in the near term. This is usually reversible after stopping, but not always on a predictable timeline. Options that keep fertility intact exist, and we cover them in TRT and fertility and the HCG section of the main guide. If children are in your plans, raise it before your first prescription.
Estrogen, breasts, skin, and fluid
These are common and usually manageable, though they are worth knowing about:
- Higher estrogen and breast tissue growth (gynecomastia). Some testosterone converts to estradiol. Address breast tenderness early, since it is harder to treat after a year or more. Managing estrogen →
- Fluid retention. Fairly common in the first few months and usually settles on its own.
- Acne and oily skin. Commonly reported when testosterone rises.
- Cholesterol changes. Variable between studies; in the formulation comparison above, lipid changes were inconsistent and HDL did not change significantly.
Side effects by format
The format you use changes which problems are likelier. Use this table as a starting point for the conversation with your prescriber.
| Format | What stands out |
|---|---|
| Injections (cypionate, enanthate) | Highest rate of raised hematocrit in the comparisons above; peaks and dips between doses, so more frequent small doses give steadier levels. |
| Long-acting injection (Aveed) | Boxed warning for serious lung oil microembolism and allergic reactions; given only in certified healthcare settings with 30 minutes of observation after each dose. |
| Gels and creams | Lower hematocrit effect, but boxed warning for secondary exposure: virilization has been reported in children who touch treated skin. Wash hands, cover the site, and keep children away from it. |
| Pellets | Intermediate hematocrit effect in the review above; minor procedure each time they are placed. |
| Oral capsules | Blood pressure monitoring is a specific focus; label warnings apply. |
| Enclomiphene (not testosterone) | Different drug with a different side-effect profile. See the delivery methods. |
What monitoring should look like
Side effects are manageable mainly because they are checked for. As summarized from the Endocrine Society guideline, a sound monitoring plan includes:
- 1Baseline labs before the first dose: repeated morning testosterone, hematocrit, and a PSA discussion where appropriate. See the starter panel.
- 2A check-in 3 to 6 months after starting: symptoms, side effects, testosterone level, and hematocrit.
- 3Blood pressure checks at visits and at home.
- 4PSA and prostate follow-up according to your age and risk, with referral if PSA rises past the thresholds above.
- 5Ongoing labs after that. The AUA guideline calls for testosterone and hematocrit every 6 to 12 months once you are stable. See the full bloodwork schedule, and ask your provider for theirs in writing.
This is also why our Atlas Score weights medical safeguards most heavily (30%): baseline labs, ongoing monitoring, and a live clinician visit are what separate providers. See how we score providers, and compare them in the ranked list. Skipping follow-up labs is the first item on our common mistakes list.
When to call your doctor
Call your prescriber promptly for: a racing or irregular heartbeat, new swelling in a leg, a persistent headache, much higher home blood pressure readings, breast pain or a lump, trouble urinating, or breathing that is worse at night. Tell them before your next dose; don't wait for the scheduled lab visit.
Call 911 for chest pain, sudden shortness of breath, coughing up blood, sudden weakness or numbness on one side, trouble speaking, or sudden vision loss. If you are using a gel and a child develops unexplained signs like early body hair or an enlarged genital area, stop exposure and tell your doctor right away.
Sources
- Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy (TRAVERSE). N Engl J Med. 2023;389(2):107-117. PubMed
- Bhasin S, Travison TG, Pencina KM, et al. Prostate safety events during testosterone replacement therapy in men with hypogonadism. JAMA Netw Open. 2023;6(12):e2348692. PubMed
- Snyder PJ, Bauer DC, Ellenberg SS, et al. Testosterone treatment and fractures in men with hypogonadism. N Engl J Med. 2024;390(3):203-211. PubMed
- Pastuszak AW, Gomez LP, Scovell JM, et al. Comparison of the effects of testosterone gels, injections, and pellets on serum hormones, erythrocytosis, lipids, and PSA. Sex Med. 2015;3(3):165-173. PubMed
- Hoyos CM, Killick R, Yee BJ, et al. Effects of testosterone therapy on sleep and breathing in obese men with severe obstructive sleep apnoea. Clin Endocrinol. 2012;77(4):599-607. PubMed
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. PubMed. Monitoring thresholds as summarized in this primary care summary.
- U.S. Food and Drug Administration. FDA issues class-wide labeling changes for testosterone products (February 2025), and Testosterone information (updated June 2026).
- Kyzatrex (testosterone undecanoate) prescribing information, DailyMed. AndroGel and Aveed boxed warnings are in their FDA prescribing information.