TRT After Ischemic Stroke in Men With Type 2 Diabetes Safety and Mobility

TRT After Ischemic Stroke in Men With Type 2 Diabetes: Safety Signals and Mobility Clues From a Small but Notable Study

Estimated reading time: 9 minutes

Key takeaways

• In a small post-stroke cohort (Morgunov 2018), hypogonadism was prevalent, and TRT with testosterone undecanoate (TU) correlated with mobility and quality-of-life gains over 2–5 years; the nonrandomized design limits causal inference.
• Contemporary randomized data show no clear increase in nonfatal stroke with TRT over ~2 years, but higher rates of certain non–major adverse events (atrial fibrillation, acute kidney injury, pulmonary embolism) were noted.
• In 2025, the FDA removed the boxed warning for major cardiovascular events from TRT labeling and added a class-wide warning that TRT can increase blood pressure.
• In hypogonadal men with T2DM, some trials report improved insulin resistance and metabolic markers with TRT, warranting careful monitoring of blood pressure, hematocrit, and prostate parameters.
• After ischemic stroke, shared decision-making and structured follow-up across endocrinology, neurology, and cardiology are essential when considering TRT.

Men navigating recovery after an ischemic stroke often discover another challenge hiding in plain sight: low testosterone. For men with type 2 diabetes (T2DM), hypogonadism is even more common—and it may influence how well recovery proceeds. One small observational study suggests testosterone replacement therapy (TRT) with testosterone undecanoate (TU) might support mobility and quality of life after stroke in hypogonadal men. At the same time, larger modern trials and updated FDA labeling remind us to weigh TRT stroke risk and cardiovascular safety signals with care.

This article reviews the Morgunov 2018 cohort, places it in context with broader testosterone–cardiometabolic evidence, and outlines practical considerations for men and clinicians considering TRT after stroke in the setting of T2DM.

Why testosterone matters after stroke—especially with T2DM

Low testosterone is common in men with T2DM and has been linked to reduced lean mass, lower exercise capacity, higher visceral fat, and mood changes. After an ischemic stroke, these factors can compound challenges with rehabilitation, balance, endurance, and motivation. Observational work also suggests that lower testosterone measured during or shortly after an ischemic stroke correlates with worse functional outcomes in the months that follow.

The Morgunov 2018 cohort found hypogonadism in roughly two-thirds of men evaluated after ischemic stroke, with a substantial proportion of hypogonadal cases occurring in men with T2DM. Those findings support what many clinicians see in practice: metabolic disease and neurovascular events often travel together, and androgen deficiency is frequently part of the picture.

What Morgunov 2018 found in hypogonadal men after ischemic stroke

Design at a glance

• Population: Men recovering from ischemic stroke; 94 were followed.
• Prevalence: Hypogonadism was identified in ~66% of the cohort overall, with many cases among those with T2DM.
• Intervention: Injectable testosterone undecanoate (TU) for hypogonadal men; follow-up at 2 and 5 years.
• Outcomes: Improvements in biochemical (testosterone levels), physical (mobility measures), and mental/quality-of-life parameters were reported in the TRT group.

What this suggests

• Mobility and independence: TU-based TRT was associated with better mobility and functional markers over time, an outcome that resonates with rehabilitation goals after stroke.
• Quality of life: Improvements in mood and self-reported well-being were described—potentially important drivers of engagement in rehab and physical activity.
• Ischemic events: The authors proposed that testosterone deficiency may contribute to ischemic risk and that long-term TRT could support recovery; however, this inference is hypothesis-generating.

Critical limitations

• Not randomized; no placebo control.
• Potential selection and survivorship bias.
• Modest sample size; single-country experience.
• Not powered to robustly evaluate recurrent stroke or rare adverse events.

Bottom line on Morgunov: It is an intriguing signal—particularly for mobility and quality-of-life outcomes in hypogonadal men with T2DM after stroke—but not definitive evidence. It sets the stage for the key clinical question: can TRT be offered safely to the right post-stroke patient, and under what monitoring framework?

Putting Morgunov into context: What do we know about TRT stroke risk?

Evidence on TRT and cardiovascular events has evolved. Earlier retrospective studies raised concerns about composite risks of mortality, myocardial infarction, and stroke in some populations, while others suggested lower event rates when testosterone was normalized. A 2024 narrative review summarized the conflicting landscape and highlighted that study design, patient selection, and whether testosterone levels were actually restored are crucial variables.

The most consequential update comes from more recent, larger randomized data in men at high cardiovascular risk:

• Noninferiority for MACE, neutral for stroke: A major cardiovascular-outcomes trial reported that TRT did not increase major adverse cardiovascular events compared to placebo over a median follow-up of about two years, and no signal emerged for increased nonfatal stroke.
• Non-MACE safety signals: The same program found higher rates of certain non-MACE outcomes—atrial fibrillation (AF), acute kidney injury (AKI), and pulmonary embolism (PE)—in the TRT arm. These findings matter in a post-stroke population, where AF can complicate secondary prevention and PE/VTE risk is already a consideration.

What this means for TRT ischemic safety

• Stroke specifically: Current high-quality evidence suggests no clear excess in nonfatal stroke with TRT over roughly two years in high-CV-risk men.
• Broader vascular risk: Caution remains appropriate due to AF, AKI, and PE signals, and because some observational analyses have noted a transient early increase in venous thromboembolism shortly after starting TRT.
• Individual risk varies: Baseline cardiovascular status, mobility limitations, hydration status, and use of anticoagulation or antiplatelet therapy may modify individual risk.

2025 FDA label changes: A clearer, still-cautious safety picture

In February 2025, the FDA made two notable updates for all testosterone products:

• Removed: The boxed warning for major adverse cardiovascular events (reflecting noninferiority for MACE in a large outcomes study).
• Added: A class-wide warning that TRT can raise blood pressure. This stems from ambulatory blood pressure monitoring data, especially with oral testosterone undecanoate formulations approved in recent years.

Practical implications

• Blood pressure: Even modest, sustained increases in BP can matter after stroke. Clinicians often assess baseline BP carefully and track it during titration and maintenance.
• Formulation choice: While the BP warning is class-wide, the BP signal was most clearly characterized in the context of oral TU; injectable and transdermal preparations may have different pharmacokinetics and monitoring considerations.

What about metabolic benefits in T2DM?

Several trials in hypogonadal men with T2DM or metabolic syndrome report improved insulin resistance and some favorable shifts in glycemic and lipid parameters with TRT. For example, a 12‑month transdermal study documented reductions in HOMA-IR and improvements in components of metabolic control compared with placebo, without a significant difference in serious adverse events.

How this matters post-stroke:

• Improved metabolic health may indirectly support rehabilitation by enhancing energy levels, lean mass, and readiness for physical therapy.
• Not all studies agree, and glycemic responses can differ by baseline status and adherence. Continuous diabetes care and lifestyle measures remain foundational whether or not TRT is used.

Considering TRT after stroke in T2DM: Practical, safety-first themes

• Confirmation of hypogonadism
  • Diagnosis typically requires both symptoms and consistently low morning testosterone on two separate days.
  • Secondary causes (acute illness effects, certain medications, sleep disorders, pituitary disease) are considered before initiating therapy.
• Timing relative to stroke
  • Many interventional studies exclude men with a very recent stroke, and timing is individualized. Stabilization of cardiovascular status and blood pressure usually precedes any decision about hormone therapy.
• Formulation and goals
  • Injectable testosterone undecanoate (as used in Morgunov) offers infrequent dosing and stable levels for many patients. Transdermal formulations provide dose-adjustability and easier reversal if needed.
  • Goals often include symptom relief, functional gains (mobility, endurance), and metabolic support—balanced against cardiovascular, hematologic, and prostate safety.
• Monitoring and risk mitigation
  • Blood pressure: The class-wide FDA warning makes routine BP tracking central, particularly early after initiation and with dose changes.
  • Hematocrit: TRT can raise red blood cell mass (erythrocytosis), which can thicken blood and potentially elevate thrombotic risk; clinicians generally monitor hematocrit and adjust therapy if it rises too high.
  • Prostate: Baseline PSA and ongoing assessment are common in age-appropriate men, with attention to urinary symptoms and shared decision-making around prostate cancer screening.
  • Cardiometabolic profile: Lipids, glycemic measures, weight, and symptom diaries can help tie treatment decisions to real-world function and quality of life.
  • Rhythm and thromboembolic risk: Given AF and PE signals in large trials, attention to arrhythmia symptoms, mobility plans, hydration, and VTE history is prudent. Coordination with neurology and cardiology can align TRT decisions with secondary stroke prevention.
• Who may not be a good candidate
  • Men with uncontrolled hypertension, very high hematocrit, active or high-risk prostate cancer, or recent thromboembolic events are often deferred or managed with extreme caution.
  • Fertility plans matter: exogenous testosterone suppresses sperm production and is not a fertility therapy.
• Setting expectations
  • Benefits, when they occur, are typically gradual. Mobility and quality-of-life gains—like those suggested by Morgunov—are best pursued alongside structured rehabilitation, nutrition, sleep optimization, and diabetes control.

Open questions

• Can randomized trials in post-stroke hypogonadal men with T2DM confirm the mobility and quality-of-life gains suggested by Morgunov?
• What is the optimal timing to initiate TRT after ischemic stroke, and what monitoring cadence best balances symptom relief with cardiovascular safety?
• How do different TRT formulations compare on BP effects, erythrocytosis risk, and adherence in a post-stroke population?
• How do modern diabetes therapies (e.g., GLP-1 RAs, SGLT2 inhibitors) interact with TRT on mobility, body composition, and vascular outcomes?

How Taurus Meds can help

• Evidence-grounded counseling on TRT stroke risk and cardiometabolic trade-offs.
• Coordination across endocrinology, neurology, cardiology, and primary care to align TRT with secondary stroke prevention plans.
• Practical monitoring pathways for blood pressure, hematocrit, and prostate parameters, tailored to the chosen formulation.
• Ongoing symptom and function tracking—so therapy remains tied to goals that matter: mobility, energy, and quality of life.

Conclusion

For hypogonadal men with T2DM recovering from ischemic stroke, the Morgunov 2018 cohort offers a cautiously optimistic signal: TRT with TU was associated with improved mobility and quality-of-life measures over years of follow-up. Larger, contemporary trials suggest no clear increase in nonfatal stroke with TRT, although non-MACE signals (AF, AKI, PE) and a class-wide FDA warning about blood pressure underscore the need for careful selection and monitoring.

The path forward is individualized. When hypogonadism is confirmed and symptoms are meaningful, a structured, team-based approach can responsibly test whether TRT helps—anchored in blood pressure vigilance, hematologic and prostate safety checks, and clear functional goals. Until dedicated randomized trials in post-stroke T2DM populations are completed, shared decision-making remains the best compass.

Disclaimer

This article is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Decisions about testosterone therapy should be made with a qualified clinician who can assess individual risks and benefits.

Sources

• Morgunov N et al. Testosterone Replacement Therapy and Recovery of Men After Ischemic Stroke
• Testosterone therapy, cardiovascular disease, and stroke—current evidence and controversies (Narrative review, 2024)
• Jones TH et al. Testosterone therapy in men with type 2 diabetes/metabolic syndrome: metabolic effects
• FDA summary basis for approval: Oral TU (Tlando)—ambulatory blood pressure findings and labeling context
• Safety signals beyond MACE (AF, AKI, PE) in contemporary TRT outcomes research