TRT Side Effects: What's Common, What's Serious, What to Monitor

Most of what goes wrong on testosterone therapy shows up in a blood test or a blood-pressure cuff before you feel it. This guide sorts the side effects the labels and guidelines describe into common, serious and formulation-specific, and lists what gets monitored for each.

Short answer: the side effects most clearly tied to testosterone therapy are a rising hematocrit, acne and oily skin, lower sperm production (which can mean infertility and smaller testes), and the detection of an existing prostate cancer.¹ Blood pressure tends to rise a few mm Hg, and current labels ask for it to be checked periodically.^4,5 Fluid retention, breast enlargement and worsening sleep apnea also occur, but less often or with weaker evidence.^1,5 In the largest safety trial, TRAVERSE, testosterone did not increase heart attacks, strokes or cardiovascular deaths compared with placebo. It did come with more atrial fibrillation, acute kidney injury and pulmonary embolism.³

This page draws on the prescribing information for three injectable products (Depo-Testosterone, Xyosted and Aveed), the Endocrine Society and American Urological Association (AUA) guidelines, and the TRAVERSE trial. Several topics have their own full guides and are only summarized here: high hematocrit on TRT, estradiol on TRT, and TRT bloodwork for the testing schedule itself.

TRT side effects at a glance

What the guidelines count as common

The 2018 Endocrine Society guideline splits the adverse effects of testosterone into two groups. The first group has clear evidence of a link: erythrocytosis, acne and oily skin, detection of subclinical prostate cancer, growth of metastatic prostate cancer, and reduced sperm production and fertility. The second group is uncommon and only weakly linked: gynecomastia, male-pattern balding in men with a family history, growth of breast cancer, and new or worsening obstructive sleep apnea.¹ The guideline adds a third list of problems that depend on the formulation. For intramuscular injections these are mood or libido swings across the dosing interval, pain at the injection site, and coughing episodes right after an injection.¹

Trial data give a sense of scale. In Xyosted's one-year study of 150 men on weekly subcutaneous testosterone enanthate, the most frequent adverse reactions were increased hematocrit (14.0%), hypertension (12.7%) and increased PSA (12.0%). Acne and peripheral edema were each reported in 2.7% of men, and sleep apnea syndrome in 2.0%.⁵ Those figures come from one product in one trial population, so they are a rough guide rather than a prediction for other protocols. The top three are all lab or cuff findings, which is why monitoring matters more than waiting for symptoms.

Acne and oily skin

The Depo-Testosterone label lists acne and seborrhea together with hirsutism and male-pattern baldness under skin effects.⁴ Acne sits on the Endocrine Society's list of effects with clear evidence of a link to testosterone.¹ Whether a given breakout reflects your testosterone level is something only a blood test drawn at the right point in the cycle can show.

Fluid retention and edema

Testosterone causes the body to retain sodium and water. The Depo-Testosterone label lists retention of sodium, chloride, water and several minerals under its adverse reactions. It warns that edema, with or without congestive heart failure, "may be a serious complication" in men with existing heart, kidney or liver disease.⁴ The Endocrine Society guideline makes the same point about edema and heart failure.¹ Mild ankle swelling in an otherwise healthy man is a different situation from new swelling in someone with heart failure, and the second is a reason to call the prescriber promptly.

Breast tenderness and gynecomastia

Some testosterone is converted to estradiol, and breast tissue can respond to it. The Depo-Testosterone label says gynecomastia may develop and "occasionally persists" in men treated for hypogonadism, and the Xyosted label carries a similar warning.^4,5 The Endocrine Society rates the evidence linking testosterone to gynecomastia as weak.¹ Whether to measure estradiol, and what the guidelines say about aromatase inhibitors, is covered in our estradiol on TRT guide.

Hematocrit: the side effect bloodwork catches

Testosterone stimulates red blood cell production. In the trials pooled for the Endocrine Society guideline, erythrocytosis (hematocrit above 54%) was about eight times more frequent on testosterone than on placebo (relative risk 8.14).¹ In Xyosted's two studies, 12 of 283 men (4.2%) reached a hematocrit of 55% or more within a year, and mean hematocrit rose 5.4 percentage points by one year.⁵ The AUA notes that trials point to injectable testosterone as causing the largest increases in hemoglobin and hematocrit.²

The Endocrine Society recommends checking hematocrit at baseline, at 3–6 months, and then yearly. If it goes above 54%, the recommendation is to stop therapy until it falls to a safe level, check for hypoxia and sleep apnea, and restart at a lower dose.¹ The AUA treats 54% as the point that calls for a dose reduction or a pause.² Thresholds, causes and what prescribers do next are covered in detail in high hematocrit on TRT.

Blood pressure: what the labels say now

Blood pressure is where the labels have changed most. Xyosted, a weekly subcutaneous autoinjector, used to carry a boxed warning about blood pressure increases. That boxed warning was removed in March 2025, and the information now sits in the label's Warnings and Precautions section.⁵ The numbers themselves did not change. In the label's 24-hour ambulatory monitoring study, 62 men had usable recordings at baseline and week 12. Their mean systolic pressure rose 3.9 mm Hg and diastolic 1.5 mm Hg. Over the one-year study, 10% of Xyosted-treated patients either started blood-pressure medication or needed a change to it.⁵

The Depo-Testosterone label now carries the general version of this warning. It says testosterone "can increase blood pressure", which can raise cardiovascular risk over time. It asks for periodic BP checks, especially in men with hypertension, and says testosterone products are not recommended for anyone with uncontrolled hypertension.⁴ A 4 mm Hg average hides individual variation. That is why the labels ask for BP measurements rather than assuming the average applies to you.

Heart attack and stroke: what TRAVERSE showed

For about a decade, whether testosterone causes heart attacks was the main open question about TRT. TRAVERSE was designed to answer it. The trial enrolled 5,246 men aged 45 to 80 who had symptoms of hypogonadism, two fasting testosterone levels below 300 ng/dL, and either existing cardiovascular disease or a high risk of it. They were randomized to daily 1.62% testosterone gel or placebo gel.³ Over a mean follow-up of 33 months, the primary endpoint (cardiovascular death, nonfatal heart attack or nonfatal stroke) occurred in 7.0% of the testosterone group and 7.3% of the placebo group. The hazard ratio was 0.96, which met the trial's test for noninferiority.³

The same trial found three problems that were more common on testosterone: atrial fibrillation, acute kidney injury and pulmonary embolism.³ As summarized in the Xyosted label, venous thromboembolism occurred in 1.7% of the testosterone group versus 1.2% on placebo, and pulmonary embolism in 0.9% versus 0.5%.⁵ The labels tell prescribers to evaluate leg pain, swelling, warmth or redness for deep vein thrombosis, and sudden shortness of breath for pulmonary embolism, and to stop testosterone if a clot is suspected.^4,5

Fertility, sperm count and testicular size

Injected testosterone signals the pituitary to cut back luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Without them, the testes make less of their own testosterone and less sperm. The Endocrine Society states plainly that testosterone therapy suppresses spermatogenesis. It recommends against TRT for men planning fertility in the near term, and says men unsure about future children may want to bank sperm.¹ The AUA calls the recommendation not to prescribe testosterone to men currently trying to conceive a strong one, based on Grade A evidence.²

How strong the effect is shows up in male-contraception research. In a World Health Organization study, 271 healthy men received 200 mg of testosterone enanthate weekly, and 65% became azoospermic (no sperm in the ejaculate) within six months.⁷ Suppression usually reverses. In a pooled analysis of 1,549 men from 30 hormonal contraception studies, sperm concentration recovered to 20 million/mL in 67% of men within 6 months of stopping, 90% within 12 months, and 100% within 24 months. Recovery was slower after longer treatment and longer-acting preparations.⁸ Those were healthy men with normal baseline fertility, so the figures may not hold for men with hypogonadism.

Smaller testes are the visible side of the same suppression. The Depo-Testosterone label lists testicular atrophy, subfertility and infertility among reactions reported in men, in its section on abuse and misuse.⁴ What guidelines say about keeping fertility on or off TRT, including gonadotropin therapy, is covered in TRT vs enclomiphene.

Sleep apnea

Untreated severe obstructive sleep apnea is on the Endocrine Society's list of conditions in which it recommends against starting testosterone.¹ The guideline rates the evidence that testosterone induces or worsens sleep apnea as weak. The Xyosted label still warns that testosterone "may potentiate sleep apnea in some patients", especially in men with obesity or chronic lung disease.^1,5 There is a practical link to hematocrit: when hematocrit goes above 54%, the guideline asks clinicians to check for sleep apnea and hypoxia, since both can push red cell counts up on their own.¹

Prostate effects

The Endocrine Society's list of established effects includes two prostate items: bringing an existing, undiagnosed cancer to light, and speeding the growth of metastatic prostate cancer.¹ The labels also warn that men with benign prostatic hyperplasia (BPH) may see urinary symptoms worsen.⁵ The AUA recommends a PSA test before starting in men over 40.² The Endocrine Society recommends urology referral if, during the first year, PSA rises more than 1.4 ng/mL above baseline, exceeds 4.0 ng/mL, or the exam finds an abnormality.¹

Formulation-specific risks

Some risks come from the product rather than from testosterone itself. Intramuscular injections of cypionate, enanthate or undecanoate can cause pain at the site and brief coughing episodes right after the shot.¹ The Depo-Testosterone label lists inflammation and pain at the injection site.⁴

Long-acting testosterone undecanoate (Aveed) carries the only boxed warning among the injectables discussed here. It covers pulmonary oil microembolism (POME): urge to cough, shortness of breath, throat tightening, chest pain, dizziness and fainting during or right after the injection. It also covers anaphylaxis, including life-threatening reactions. Either can happen after any injection in the course of therapy, including the first. Patients have to be observed in the clinic for 30 minutes after every injection, and Aveed is only available through a restricted REMS program.⁶

Less common items on the Depo-Testosterone label include changes in liver function tests, nausea, headache, anxiety, depression, increased or decreased libido, and rare central serous chorioretinopathy, a fluid buildup under the retina.⁴ Hepatic adenomas and peliosis hepatis are linked on the label principally to prolonged high doses of 17-alpha-alkylated androgens, a different class from injected testosterone esters.⁴

Warning signs worth a call to your prescriber

1. Sudden shortness of breath, chest pain, or one swollen, painful, warm leg: possible clot, which the labels say should stop treatment while it is evaluated^4,5
2. Coughing, throat tightness, dizziness or fainting during or right after an undecanoate injection⁶
3. New swelling of the ankles or legs, especially with heart, kidney or liver disease^1,4
4. Home blood-pressure readings that are higher than before you started^4,5
5. Loud snoring, gasping at night, or new daytime sleepiness^1,5
6. Weaker urinary stream or more urgency and frequency⁵
7. Breast tenderness or a lump behind the nipple⁴
8. Hematocrit results trending up on successive draws, even below 54%¹

How monitoring is organized

Most of the side effects above are found through a short list of checks, not through symptoms. The Endocrine Society plan covers symptoms and adverse effects at 3–12 months and then yearly. It checks testosterone at 3–6 months and hematocrit at baseline, 3–6 months and yearly. In men who choose prostate monitoring, PSA and a rectal exam are done at 3–12 months.¹ The labels add periodic blood pressure and lipid checks.^4,5 Exact timing, including why cypionate and enanthate are drawn midway between injections, is laid out in TRT bloodwork.

Several of these side effects depend on dose and peak levels, which is why the guidelines target mid-normal testosterone and not the top of the range.^1,2 Keeping each lab result, BP reading and symptom tied to the dose and injection day it came from makes it easier for you and your prescriber to see whether a change helped. Dose decisions stay with your prescriber.

FAQ

References

Primary sources — PubMed / NEJM / The Lancet.

1. 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. https://academic.oup.com/jcem/article/103/5/1715/4939465
2. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and Management of Testosterone Deficiency: AUA Guideline. J Urol. 2018;200(2):423-432. https://www.auanet.org/documents/Guidelines/PDF/Testosterone-Deficiency-JU.pdf
3. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy (TRAVERSE). N Engl J Med. 2023;389(2):107-117. https://www.nejm.org/doi/full/10.1056/NEJMoa2215025
4. DailyMed. DEPO-TESTOSTERONE (testosterone cypionate) injection, solution — Prescribing Information. U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cfbb53d4-b868-4a28-8436-f9112eb01c39
5. DailyMed. XYOSTED (testosterone enanthate) injection — Prescribing Information. U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8a3d204c-be26-49e0-8599-0ac12a272e81
6. DailyMed. AVEED (testosterone undecanoate) injection — Prescribing Information. U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f80f025b-17d8-40af-8739-20ce07902045
7. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet. 1990;336(8721):955-959. https://pubmed.ncbi.nlm.nih.gov/1977002/
8. Liu PY, Swerdloff RS, Christenson PD, Handelsman DJ, Wang C; Hormonal Male Contraception Summit Group. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet. 2006;367(9520):1412-1420. https://pubmed.ncbi.nlm.nih.gov/16650651/