Evidence explainerMen's Hormones & TRT
TRT Side Effects: Hematocrit, Acne, Sleep Apnea, Fertility and What Guidelines Do About Each
Thicker blood (a rising hematocrit) is the most common side effect of testosterone therapy, and injections raise it most. Acne, worse sleep apnea in some men, lower sperm counts and a small rise in blood pressure are the others that labels and guidelines flag.
Key takeaways
- A rise in hemoglobin and hematocrit is the most frequent adverse event of testosterone therapy; it usually climbs for the first six months and then levels off [1].
- Form matters: in one series, 19% of men on testosterone injections developed polycythemia, compared with 12.5% on pellets and 5.4% on gels [1].
- The AUA says a hematocrit of 54% or higher on treatment warrants action [1]; the Endocrine Society says to stop until it falls, look for sleep apnea, and restart at a lower dose [2].
- Testosterone labels list acne, warn that therapy may worsen sleep apnea in men with risk factors, and warn that it may lead to azoospermia (no sperm in the semen) [3].
- On 24-hour monitoring, AndroGel 1.62% raised average blood pressure by 1.9/1.3 mm Hg after 16 weeks [3].
Hematocrit: the side effect blood tests catch first
Testosterone stimulates red blood cell production. The American Urological Association (AUA) calls a rise in hemoglobin and hematocrit the most frequent adverse event of testosterone therapy and notes that levels generally rise for the first six months and then plateau [1]. In five placebo-controlled trials the guideline pooled, 19 of 1,094 men on testosterone developed polycythemia, against 1 of 1,093 on placebo [1].
The form of testosterone matters. In the AUA's analysis, hemoglobin rose more with short- and long-acting injections than with gels or patches, likely because of the high, sometimes above-normal levels in the days after an injection. A retrospective series of 175 men found polycythemia in 19% of men on injections, 12.5% on pellets and 5.4% on gels [1].
Why it gets watched: in a large database study of men on testosterone, those whose hematocrit reached 52% or more had more major heart events or blood clots in the first year than matched men whose hematocrit stayed normal (5.15% vs 3.87%) [4]. That study was observational, so it shows an association rather than proof of cause.
The hematocrit thresholds guidelines use
The two main US guidelines and the labels use slightly different numbers and schedules. These are decisions for the prescriber; the point of knowing them is to ask good questions.
- Before starting (AUA): measure hemoglobin and hematocrit, and consider holding testosterone if hematocrit is above 50% until the cause is explained [1].
- On treatment (AUA): a hematocrit of 54% or higher warrants intervention. If testosterone levels are high, the dose is adjusted first; if they are normal, SHBG and free testosterone are checked; if those are normal too, referral to a hematologist for possible phlebotomy is suggested [1].
- Endocrine Society: if hematocrit is above 54%, stop therapy until it falls to a safe level, evaluate for low oxygen and sleep apnea, and restart at a reduced dose [2].
- Labels: check hematocrit before starting, again 3 to 6 months after starting, and then once a year; if it becomes elevated, stop until it comes down [3].
Acne, oily skin and hair
Acne is listed among adverse reactions on testosterone labels; the testosterone cypionate label also lists oily skin (seborrhea) and male-pattern baldness [5][3].
Gels add a different skin issue: transfer. Children have shown signs of virilization after contact with unwashed or unclothed application sites, and women who are exposed can develop acne or changes in body hair, so the label asks users to cover and wash the area [3].
Sleep apnea
Labels warn that testosterone may make sleep apnea worse in some men, especially those with obesity or chronic lung disease [3]. In a randomized trial of 67 obese men with severe obstructive sleep apnea on a weight-loss diet, testosterone injections worsened overnight oxygen dips by about 10 events an hour at 7 weeks compared with placebo; by 18 weeks the difference was no longer significant [6].
The Endocrine Society recommends against starting testosterone in men with untreated severe obstructive sleep apnea [2].
Sperm production
Testosterone taken from outside switches off the brain's LH and FSH signals that drive sperm production. Labels warn it may lead to azoospermia [3], and the AUA says it should not be prescribed to men who are trying to conceive [1].
Recovery after stopping is usual but slow. In contraception studies of 1,549 healthy men given testosterone-based regimens, sperm counts took a median 3.4 months to recover, with 67% recovered within 6 months, 90% within 12 months and all within 24 months [7]. Our TRT and fertility guide covers the options for men who want children.
Blood pressure, clots, prostate and breasts
Four more effects appear on labels and in guidelines.
- Blood pressure: on 24-hour monitoring, AndroGel 1.62% raised average blood pressure by 1.9/1.3 mm Hg after 16 weeks, and by 3.0/2.2 mm Hg in men already on blood-pressure medicine. Labels say testosterone is not recommended with uncontrolled high blood pressure [3].
- Blood clots: in the TRAVERSE trial, venous clots were numerically more common on testosterone gel than placebo (1.7% vs 1.2%), including pulmonary embolism (0.9% vs 0.5%) [3].
- Prostate: PSA rose more on testosterone than placebo in the first year of TRAVERSE, but in men screened to exclude high prostate-cancer risk, rates of prostate cancer and urinary problems were low and similar in both groups [8].
- Breasts: the AUA recommends an estradiol test in men who develop breast tenderness or enlargement (gynecomastia) while on testosterone [1].
Where to go next
For the heart question, see testosterone and heart risk; for the full lab schedule, see TRT blood tests and monitoring.
This guide explains what guidelines and studies say. It is not medical advice: a licensed clinician decides whether testosterone or any alternative is right for you, and at what dose.
Quick answers
What is the most common side effect of TRT?
A rise in hemoglobin and hematocrit (thicker blood). The AUA calls it the most frequent adverse event of testosterone therapy; it usually rises over the first six months and then levels off [1].
Do testosterone injections cause more side effects than gels?
For hematocrit, yes: injections raised it more than gels or patches in the AUA's analysis, and one series found polycythemia in 19% of men on injections versus 5.4% on gels [1]. Gels carry their own risk of transferring testosterone to children or partners by skin contact [3].
At what hematocrit is TRT paused or changed?
The AUA says a hematocrit of 54% or higher on treatment warrants intervention [1]. The Endocrine Society says to stop at above 54%, check for sleep apnea and low oxygen, and restart at a lower dose once it falls [2].
Can TRT make sleep apnea worse?
It can in some men. Labels warn of this, especially with obesity or lung disease [3], and a trial in obese men with severe sleep apnea found worse overnight oxygen levels at 7 weeks on testosterone, which faded by 18 weeks [6].
Does TRT raise blood pressure?
Slightly, on average. The AndroGel 1.62% label reports a 1.9/1.3 mm Hg rise on 24-hour monitoring after 16 weeks, and the FDA now requires a blood-pressure warning on testosterone labels [3].
More in Men's Hormones & TRT
- Men's Hormones & TRT hub
- TRT and Fertility: hCG, Clomiphene, Enclomiphene and What the AUA Guidelines Allow
- Testosterone and Heart Risk: What the TRAVERSE Trial Found and What the FDA Changed
- TRT Blood Tests: What Gets Checked Before and During Testosterone Therapy, and When
- Clomiphene for Men: How It Raises Testosterone, What Studies Show, and the Off-Label Caveats
- TRT vs Natural Testosterone Boosters: Which Supplements Have Trials, and How Big the Effects Are
References
- [1]Evaluation and Management of Testosterone Deficiency (2024). American Urological Association, 2024.
- [2]Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2018.
- [3]AndroGel (testosterone gel) 1.62% prescribing information. DailyMed, U.S. National Library of Medicine, 2025.
- [4]Secondary Polycythemia in Men Receiving Testosterone Therapy Increases Risk of Major Adverse Cardiovascular Events and Venous Thromboembolism in the First Year of Therapy. J Urol, 2022.
- [5]Depo-Testosterone (testosterone cypionate) injection prescribing information. DailyMed, U.S. National Library of Medicine, 2026.
- [6]Effects of testosterone therapy on sleep and breathing in obese men with severe obstructive sleep apnoea: a randomized placebo-controlled trial. Clin Endocrinol (Oxf), 2012.
- [7]Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet, 2006.
- [8]Prostate Risk and Monitoring During Testosterone Replacement Therapy. J Clin Endocrinol Metab, 2024.