Unexpected effects of testosterone therapy you should know

Testosterone therapy can boost energy, muscle, and sex drive, but the most important risks are often the ones no one mentions. Here are the unexpected effects of testosterone therapy you should understand, monitor, and manage with your clinician.

The relationship

Testosterone is a steroid hormone, which means it is a fat-based chemical messenger your body makes from cholesterol. In men, most testosterone comes from the testicles, with smaller amounts from the adrenal glands. Levels peak in the late teens and early 20s, then fall about 1% each year after age 30.^[1]

When levels drop below about 350 ng/dL in a man with clear symptoms such as low libido, fatigue, or loss of strength, guidelines suggest he is likely to benefit from testosterone replacement therapy, often called TRT.^[2] If total testosterone is borderline, free testosterone below about 100 pg/mL strengthens the case for treatment. Those numbers are not magic lines, but they are useful decision thresholds when symptoms are real and persistent.

Most people who start TRT hear about higher sex drive, bigger lifts in the gym, and better mood. Yet the unexpected effects of testosterone therapy you are less likely to see in ads include water retention, changes in blood counts, mood swings, acne, and shifts in fertility. Large trials and meta-analyses show these effects are common enough that they should be part of every informed consent discussion.^[3]

How it works

The unexpected effects of testosterone therapy you may experience all trace back to how this hormone interacts with blood, skin, brain, and other hormone systems. Understanding these pathways makes side effects more predictable and easier to manage.

Blood thickening and red blood cell changes

Testosterone stimulates the bone marrow, the soft tissue inside bones that makes blood cells. This often raises hemoglobin and hematocrit, the lab values that show how concentrated your red blood cells are.^[4] When hematocrit climbs above about 54%, blood can become “thicker,” which doctors call erythrocytosis. Erythrocytosis means an abnormal rise in red blood cell mass that can increase the risk of blood clots.

Meta-analyses suggest up to 15%–20% of men on TRT develop elevated hematocrit, and the risk is higher with injections than with gels or patches.^[3],[4] This is one of the most important unexpected effects of testosterone therapy you must monitor, because it is silent until a lab test picks it up.

Fluid retention and blood pressure

Testosterone increases sodium reabsorption in the kidneys. Sodium reabsorption means the kidneys pull more salt back into the bloodstream instead of letting it go out in urine. More sodium pulls in more water, which can cause fluid retention, ankle swelling, and small bumps in blood pressure, especially early in therapy.^[5]

For most healthy men, this fluid retention is mild and settles as the body adapts. It becomes more concerning if you already have heart failure, uncontrolled high blood pressure, or kidney disease, because extra volume can strain those systems.

Skin, oil glands, and hair follicles

Inside the skin, testosterone converts into dihydrotestosterone, or DHT, through an enzyme called 5-alpha reductase. DHT is a more potent androgen, a type of hormone that drives male traits. DHT increases oil production in sebaceous glands, which are the tiny oil factories in your skin, and it can speed up growth cycles in hair follicles.^[6]

This is why acne, oily skin, and changes in body or facial hair are among the unexpected effects of testosterone therapy you might see within weeks. In men with a genetic tendency to male pattern baldness, higher DHT can accelerate hair thinning on the scalp even as it thickens hair elsewhere.

Brain chemistry and mood pathways

Testosterone interacts with receptors in many brain regions involved in motivation, reward, and emotional control, including the amygdala and prefrontal cortex. It also influences levels of neurotransmitters, the brain’s chemical messengers, such as serotonin, dopamine, and GABA.^[7]

These effects help explain why some men report improved mood, confidence, and drive on TRT, while others notice irritability, anxiety, or swings in energy. Rapid dose changes, very high levels, or underlying bipolar disorder may all make mood-related unexpected effects of testosterone therapy you more likely.

Reproductive axis and fertility

The hypothalamic–pituitary–gonadal axis is the hormone loop that runs from brain to testicles. The hypothalamus is a brain region that releases GnRH, a signal that tells the pituitary gland to send out LH and FSH. Those pituitary hormones then tell the testicles to make both testosterone and sperm.

When you take testosterone from outside the body, circulating levels rise. The brain senses that rise and turns down its own GnRH production. Pituitary LH and FSH fall, and testicular sperm and testosterone production drop. Over time, this can shrink testicles and sharply lower sperm counts, sometimes to zero.

This “feedback shutdown” is one of the most serious unexpected effects of testosterone therapy you must consider if you hope to father biological children in the next few years.

Conditions linked to it

The unexpected effects of testosterone therapy you hear about in headlines usually involve long-term health conditions. The data here are more complex than simple “good” or “bad,” and they depend on dose, baseline health, and how closely you are monitored.

• Cardiovascular risk: Some early trials suggested higher rates of cardiovascular events such as heart attacks in older men with pre-existing heart disease who started high-dose TRT.^[3],[8] More recent meta-analyses and guideline reviews show that, in men with clear hypogonadism who are well monitored, TRT does not significantly increase major cardiovascular events and may even improve some risk factors like fat mass and insulin resistance.^[3],[8]
• Prostate health: Testosterone can slightly enlarge the prostate, the gland below the bladder that helps make semen. Modern data do not show a strong link between TRT and new prostate cancer, but therapy can speed up detection of an existing, undiagnosed cancer by raising PSA, the blood marker used to screen the prostate.
• Sleep apnea: Obstructive sleep apnea is a condition where the airway repeatedly collapses at night, blocking breathing. TRT can worsen existing sleep apnea in some men by altering airway muscle tone and central breathing control, especially at higher doses.^[9]
• Metabolic effects: In properly selected men, testosterone therapy often reduces fat mass, increases lean mass, and can improve insulin sensitivity and waist circumference over months.^[1],[3] These changes are usually benefits, but rapid shifts in body composition are another set of unexpected effects of testosterone therapy you might not fully anticipate when you start.

Limitations note: Many trials are relatively short, often 6–36 months, and include men with well-defined hypogonadism. Data in older, frailer men or in those using high, non-medical doses for bodybuilding are more limited and suggest higher risk.

Symptoms and signals

The unexpected effects of testosterone therapy you should watch for tend to fall into a few clear buckets. Use this list as a personal checklist between lab visits.

• Signs of blood thickening or clot risk
  • New or worsening headaches
  • Feeling flushed or unusually warm
  • Blurred vision or lightheadedness
  • Pain, redness, or swelling in a calf or thigh
  • Sudden chest pain or shortness of breath, which is an emergency
• Fluid retention and blood pressure changes
  • Puffy ankles or feet by the end of the day
  • Tight rings or shoes that used to fit loosely
  • New headaches or pounding in your temples
  • Higher readings on a home blood pressure monitor
• Skin, hair, and body composition shifts
  • New acne on face, shoulders, or back
  • Oily skin or more frequent need to wash your face
  • Faster growth of facial or body hair
  • Noticing more hair in the shower drain or on your pillow
  • Rapid gains in scale weight that feel like “bloat” rather than muscle
• Mood, sleep, and energy changes
  • Feeling more irritable, impatient, or “on edge”
  • Unusual bursts of energy followed by crashes
  • New snoring or gasping at night reported by a partner
  • Waking unrefreshed despite more sleep
  • Anxiety or restlessness that feels different from your usual baseline
• Sexual and reproductive changes
  • Higher or lower sex drive than expected
  • Changes in erections, either better or sometimes worse initially
  • Smaller testicle size over months on therapy
  • Difficulty conceiving with a partner despite regular intercourse

If one or more of these symptoms show up, it does not automatically mean you must stop TRT. It does mean you should tell your prescriber and check labs. Many unexpected effects of testosterone therapy you notice can be managed by adjusting the dose, the form, or your other medications.

What to do about it

Managing the unexpected effects of testosterone therapy you may face comes down to three steps: get the right testing, choose smart treatment options, and monitor regularly.

1. Step 1: Get a full baseline before you start
   • Ask for at least two early-morning total testosterone levels, drawn before 10 a.m., on different days. If your total is borderline, request a free testosterone level as well.
   • Have baseline labs for hematocrit, PSA if you are 40 or older or at risk, liver function, fasting glucose, and lipids.^[2]
   • Tell your clinician if you want children in the future. If yes, discuss alternatives like clomiphene or hCG, which can raise testosterone without shutting down sperm production in some men.
   • If you snore loudly, are very sleepy during the day, or have resistant high blood pressure, consider a sleep apnea evaluation before or soon after starting TRT.^[9]
2. Step 2: Use a “minimum effective dose” plan
   • Work with your clinician to start at a conservative dose and titrate slowly. Aim for testosterone levels in the mid-normal range, not bodybuilder levels.
   • Consider route: gels and patches tend to give smoother levels and a lower risk of high hematocrit than injections, though they can be less convenient.^[4]
   • Support basics that make TRT safer and more effective:
     • Sleep 7–9 hours per night to stabilize hormone signals
     • Train with resistance 2–4 days per week to direct the anabolic, or tissue-building, effects toward muscle rather than fat
     • Limit alcohol and stop smoking to reduce clot and blood pressure risk
     • Keep salt intake moderate to blunt fluid retention
   • Remember that some unexpected effects of testosterone therapy you feel early, like mild acne or water retention, often fade as your body adapts over 2–3 months.
3. Step 3: Monitor and adjust like a long-term training plan
   • Recheck testosterone, hematocrit, and PSA after 3–6 months on therapy, then at least once a year. More often if there are symptoms or dose changes.^[2]
   • If hematocrit rises above about 54%, your clinician may lower your dose, change your formulation, pause therapy, or recommend therapeutic phlebotomy, which is a supervised blood draw to bring levels down.^[4]
   • If your partner notices louder snoring or pauses in breathing, ask for a sleep study. Treating sleep apnea with CPAP often allows continued TRT more safely.^[9]
   • Track your own health data: blood pressure, body weight, waist size, mood notes, and workout logs. These day-to-day signals often pick up unexpected effects of testosterone therapy you might miss if you rely only on labs.

Myth vs Fact: testosterone therapy

• Myth: “Testosterone therapy always causes heart attacks.”
  Fact: In men with documented low testosterone who are monitored, large reviews do not show a major increase in heart attacks or strokes. Risk seems higher mainly in men with severe existing heart disease, high doses, or poor follow-up.^[3],[8]
• Myth: “If your levels are low-normal, a little extra testosterone is harmless ‘optimization’.”
  Fact: Pushing levels much above normal brings more erythrocytosis, acne, mood swings, and fertility loss with no clear long-term benefit. The unexpected effects of testosterone therapy you want to avoid show up faster at supraphysiologic, or above-normal, doses.^[4]
• Myth: “Once you start testosterone, you can never come off.”
  Fact: Many men can taper off TRT with medical guidance. Natural production often recovers over months, especially in younger men, though sperm and hormone recovery are not guaranteed and may be incomplete.
• Myth: “Over-the-counter boosters are safer than prescription testosterone.”
  Fact: Many “boosters” are unregulated, under-studied, and sometimes spiked with hidden steroids. Prescription TRT at monitored doses is usually safer than mystery capsules that can hit the same pathways without lab follow-up.^[6]
• Myth: “If you feel great, labs don’t matter.”
  Fact: You can feel fantastic while your hematocrit, PSA, or blood pressure are quietly rising. The number one way to catch unexpected effects of testosterone therapy you cannot feel is regular lab and blood pressure checks.

Bottom line

Testosterone therapy can restore energy, muscle, mood, and sexual function in men with real, documented deficiency. At the same time, the unexpected effects of testosterone therapy you rarely see in marketing materials are very real: thicker blood, fluid retention, acne, mood shifts, sleep apnea flares, and fertility loss. The difference between a life-changing tool and a long-term problem is not luck. It is careful selection, the lowest effective dose, and regular monitoring of both symptoms and labs. If you treat TRT like a serious medication, not a shortcut, you can capture most of the upside while keeping the surprises under control.

References

1. Saad F, Aversa A, Isidori AM, et al. Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review. Current diabetes reviews. 2012;8:131-43. PMID: 22268394
2. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and Management of Testosterone Deficiency: AUA Guideline. The Journal of urology. 2018;200:423-432. PMID: 29601923
3. Hudson J, Cruickshank M, Quinton R, et al. Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis. The lancet. Healthy longevity. 2022;3:e381-e393. PMID: 35711614
4. Haddad RM, Kennedy CC, Caples SM, et al. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clinic proceedings. 2007;82:29-39. PMID: 17285783
5. Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of Testosterone Treatment in Older Men. The New England journal of medicine. 2016;374:611-24. PMID: 26886521
6. Clark RV, Hermann DJ, Cunningham GR, et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. The Journal of clinical endocrinology and metabolism. 2004;89:2179-84. PMID: 15126539
7. Pope HG, Cohane GH, Kanayama G, et al. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. The American journal of psychiatry. 2003;160:105-11. PMID: 12505808
8. Corona G, Maseroli E, Rastrelli G, et al. Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert opinion on drug safety. 2014;13:1327-51. PMID: 25139126
9. Hoyos CM, Yee BJ, Phillips CL, et al. Body compositional and cardiometabolic effects of testosterone therapy in obese men with severe obstructive sleep apnoea: a randomised placebo-controlled trial. European journal of endocrinology. 2012;167:531-41. PMID: 22848006