Steroids push the body’s clotting system into overdrive through several overlapping mechanisms: they ramp up production of proteins that help blood clot, slow down the processes that dissolve clots, and damage the lining of blood vessels. This applies to both glucocorticoids (the anti-inflammatory steroids prescribed for conditions like asthma, lupus, and arthritis) and anabolic-androgenic steroids (the muscle-building kind), though each type does it differently. The result is a measurable increase in the risk of dangerous blood clots, and the biology behind it is more layered than most people realize.
How Glucocorticoids Shift the Clotting Balance
Your blood maintains a constant tug-of-war between clotting and clot dissolution. Glucocorticoids tilt that balance toward clotting by acting on several fronts at once. A systematic review found that in healthy volunteers, glucocorticoid treatment caused a clear rise in the activity of clotting factors VII, VIII, and XI, all of which play roles in building the protein scaffolding of a blood clot.1PubMed. Systematic review on the effect of glucocorticoid use on procoagulant, anti-coagulant and fibrinolytic factors Glucocorticoids also boost production of von Willebrand factor, a sticky protein that helps platelets latch onto damaged vessel walls and onto each other, which is an early and critical step in clot formation.2PubMed Central. Role of von Willebrand factor in venous thromboembolic disease
At the same time, glucocorticoids hobble the body’s ability to break clots down. They stimulate production of a molecule called PAI-1, which blocks the enzymes responsible for dissolving clots. In laboratory studies, this increase in PAI-1 was substantial enough to suppress the generation of plasmin, the key clot-dissolving enzyme.3PubMed. Mechanism of action of angiostatic steroids: suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis So the body makes clots more readily and clears them less efficiently, a dangerous combination.
There is also a vascular component. The cells lining your blood vessels produce nitric oxide, which keeps vessels relaxed, smooth, and resistant to clot formation. Research on endothelial cells has shown that prednisolone, a common glucocorticoid, significantly reduces the expression of the enzyme that makes nitric oxide while simultaneously boosting the production of damaging superoxide molecules.4PubMed Central. Prednisolone augments superoxide formation in porcine pulmonary artery endothelial cells through differential effects on the expression of nitric oxide synthase and NADPH oxidase Less nitric oxide and more oxidative stress means the vessel wall becomes a more hospitable surface for clots to start forming.
Proving the Drug Itself Is the Problem
For decades, a stubborn question dogged researchers: are steroids themselves to blame for blood clots, or is it the underlying inflammatory disease that requires steroid treatment? Conditions like inflammatory bowel disease, rheumatoid arthritis, and severe asthma are all independently associated with higher clotting risk. Teasing apart the drug effect from the disease effect is genuinely difficult.
A narrative review of the evidence acknowledged this challenge directly, noting that it seems virtually impossible to fully separate the role of glucocorticoids from the role of the underlying condition. However, the review also pointed out that a procoagulant state has been reported even in healthy people receiving oral glucocorticoids versus a placebo, which strongly suggests the drug contributes independently.5PubMed. Use of Glucocorticoids and Risk of Venous Thromboembolism: A Narrative Review
A placebo-controlled trial in healthy subjects confirmed this directly. After just ten days of prednisolone treatment, participants showed increases in peak thrombin generation, PAI-1, and von Willebrand factor compared with those receiving placebo. The study’s conclusion was unequivocal: oral prednisolone induces a procoagulant state in healthy subjects, suggesting that corticosteroid treatment itself may increase thromboembolic risk.6PubMed. The influence of corticosteroids on hemostasis in healthy subjects This matters because these subjects had no inflammatory disease at all. The drug alone was enough to shift their blood toward clotting.
How Large Is the Risk?
A large self-controlled case-series and cohort study found that the risk of a first venous blood clot was roughly three and a half times higher during periods of oral glucocorticoid treatment compared with periods when patients were not taking the drug. That risk was not evenly distributed over time. In the first seven days after starting treatment, the risk spiked to about five times higher. It remained elevated at roughly three and a half times higher out to six months, then gradually settled closer to baseline with prolonged treatment beyond six months.7PubMed Central. Glucocorticoid use and risk of first and recurrent venous thromboembolism: self‐controlled case‐series and cohort study
That same study found something interesting: a dose-dependent relationship was not observed. Whether the initial dose was high or low, and whether the cumulative dose over 30 days was large or small, the elevated risk was broadly similar. This is counterintuitive. You might expect higher doses to be more dangerous, but the data did not bear that out, at least for venous events.
In a separate analysis of neurosurgical patients, those receiving corticosteroids were about 55% more likely to develop a deep vein thrombosis and roughly 47% more likely to have a pulmonary embolism compared with patients not receiving steroids, after adjusting for other risk factors.8PubMed. Association of Steroid Use with Deep Venous Thrombosis and Pulmonary Embolism in Neurosurgical Patients: A National Database Analysis The effect sizes are smaller in this surgical population than in the general-population study, which likely reflects the fact that surgical patients already have a high baseline clotting risk, making the additional steroid contribution proportionally smaller.
Does the Route of Administration Matter?
How you take steroids makes a meaningful difference. Oral glucocorticoids consistently carry higher risks compared with injectable forms, according to a nationwide case-control study.9JAMA Internal Medicine. Use of Glucocorticoids and Risk of Venous Thromboembolism: A Nationwide Population-Based Case-Control Study This makes biological sense: oral steroids enter the bloodstream and reach the liver, blood vessels, and bone marrow at systemically high levels, while injected steroids given locally (for example, a cortisone shot into a joint) produce much lower systemic concentrations.
Inhaled corticosteroids fall somewhere in between. A study of recurrent pulmonary embolism found that current use of oral corticosteroids carried nearly a fourfold increased risk, while inhaled corticosteroids showed a similar but weaker pattern that did not reach statistical significance.10PubMed. Oral and inhaled corticosteroid use and risk of recurrent pulmonary embolism For anyone using a steroid inhaler for asthma or COPD, this is somewhat reassuring. The systemic absorption from an inhaler is much lower than from a pill, and the clotting risk appears correspondingly smaller.
One practical takeaway: if you are on oral steroids and your doctor tapers you off, the risk does not linger indefinitely. In the recurrent-PE study, past use of oral corticosteroids was actually associated with a lower risk of recurrent embolism compared with non-users, suggesting that any procoagulant effect fades once the drug clears the system.
Why the First Week Is the Riskiest
The spike in clot risk during the first week of glucocorticoid therapy deserves attention. As the self-controlled study noted, the risk of a first clot was already elevated (about two and a half times higher) in the week before treatment even started, reflecting the fact that the underlying condition was flaring and itself raising clot risk.7PubMed Central. Glucocorticoid use and risk of first and recurrent venous thromboembolism: self‐controlled case‐series and cohort study Then, once the glucocorticoid was added on top, the risk jumped further to about fivefold during the first seven days of treatment.
The practical implication is clear: the period when you are sickest and starting a new steroid course is exactly when you are most vulnerable to a blood clot. Doctors managing conditions that require pulse steroid therapy, like severe flares of autoimmune disease, need to factor this compounding of risks into their decision-making. For patients, it means being especially attentive to symptoms like leg swelling, warmth, or unexplained shortness of breath during those early days of a new steroid course.
Cushing’s Syndrome as a Natural Experiment
Cushing’s syndrome provides perhaps the most compelling evidence that cortisol itself, not just the diseases treated with steroids, drives clotting. People with Cushing’s syndrome produce too much cortisol from their own adrenal glands, without any external steroid medication. This endogenous hypercortisolism is associated with a state of hypercoagulability that significantly increases the risk of thromboembolic disease, especially venous events.11PubMed Central. Preventive strategies for hypercoagulation in Cushing’s syndrome: when and how
A review spanning 50 years of evidence concluded that the increased risk of venous blood clots in Cushing’s syndrome has been confirmed in virtually all available studies, including meta-analyses, and the risk applies to both the endogenous form (the body overproducing cortisol) and the exogenous form (steroid medications causing Cushing’s features).12PubMed Central. Cushing’s Syndrome, a Risk Factor for Venous Thromboembolism Is a Candidate for Guidelines This is important because Cushing’s patients who overproduce cortisol endogenously do not have the confounding factor of an inflammatory disease being treated. Their elevated clot risk comes purely from excess cortisol, making the causal link much cleaner.
Anabolic Steroids Work Through Different Pathways
Anabolic-androgenic steroids, the synthetic testosterone derivatives used by some athletes and bodybuilders, also increase clot risk, but through a largely distinct set of mechanisms. The overlap is important to acknowledge: a review covering both types of steroids noted that anabolic steroid use predisposes users to both venous and arterial blood clots, driven by androgen-induced increases in red blood cell production, platelet hyper-aggregability, procoagulant shifts in blood proteins, and vascular injury.13PubMed Central. Thrombotic complications of glucocorticoids and anabolic steroids
Polycythemia, the overproduction of red blood cells, is one of the most well-known effects. Testosterone and its derivatives stimulate the bone marrow to produce more red blood cells, thickening the blood and making it flow more sluggishly. This alone raises the probability that a clot will form, particularly in veins where flow is already slower.
Testosterone also directly affects platelets. Research has shown that testosterone treatment increases the density of a specific receptor on platelets that makes them more prone to clumping together. In a study of men receiving testosterone, the maximum platelet aggregation response increased significantly at four weeks, then returned to baseline by eight weeks after stopping.14PubMed. Testosterone increases human platelet thromboxane A2 receptor density and aggregation responses This means platelets become stickier while testosterone levels are elevated, an effect that is reversible but real.
On top of this, anabolic steroids wreak havoc on cholesterol levels. A case study of a bodybuilder using anabolic steroids documented a 100% increase in LDL cholesterol and a 90% reduction in HDL cholesterol.15International Journal of Sports and Exercise Medicine. Extremely Low HDL Cholesterol and Increased LDL Cholesterol Induced by the use of Anabolic Steroids in a Body Builder: A Case Study These changes accelerate atherosclerosis, the buildup of fatty plaques inside artery walls, which creates the conditions for arterial clots. When a plaque ruptures, it triggers a cascade that can block an artery entirely, leading to a heart attack or stroke.
When Clots Hit Arteries, Not Just Veins
Most of the discussion around steroids and clots focuses on venous thromboembolism: deep vein thrombosis in the legs and pulmonary embolism in the lungs. But the risk extends to arteries as well. A review of thrombotic complications noted that glucocorticoids are associated with arterial events in addition to venous ones.13PubMed Central. Thrombotic complications of glucocorticoids and anabolic steroids Arterial clots cause strokes and heart attacks, which are obviously more immediately life-threatening than most venous clots.
For anabolic steroids, the arterial risk may be even more prominent. A case report described an ischemic stroke in a 34-year-old recreational bodybuilder following three months of anabolic steroid use followed by a month of post-cycle therapy drugs. The report highlighted this as a rare but important cause of stroke in younger patients, particularly relevant given the increasing casual use of these drugs among fitness enthusiasts.16PubMed Central. Anabolic steroid use and ischaemic stroke in a young fitness enthusiast A healthy person in their thirties having a stroke is unusual enough that clinicians should consider anabolic steroid use as a potential cause.
The mechanisms behind arterial clots from anabolic steroids layer on top of each other. Thickened blood from polycythemia, stickier platelets, damaged vessel linings, and rapidly worsening cholesterol profiles all converge. Where glucocorticoids mainly push the coagulation system toward venous clotting through changes in clotting factors and clot-dissolving enzymes, anabolic steroids hit the cardiovascular system more broadly, affecting blood viscosity, platelet behavior, and artery health simultaneously.
Post-Cycle Therapy and Hidden Risk Windows
People who use anabolic steroids recreationally often follow a cycle with a period of “post-cycle therapy,” taking drugs like tamoxifen or clomiphene to restart their natural testosterone production. The stroke case in the 34-year-old bodybuilder occurred during this post-cycle therapy phase, not during the steroid use itself.16PubMed Central. Anabolic steroid use and ischaemic stroke in a young fitness enthusiast This is a detail that many users overlook. Tamoxifen, one of the drugs commonly used in post-cycle therapy, is itself associated with increased clotting risk. So the period after a steroid cycle, when users assume they are “recovering,” may actually carry its own distinct set of dangers.
This creates a situation where the clotting risk from anabolic steroid use does not end when the last injection is given. The cardiovascular changes, particularly polycythemia and cholesterol disruption, take time to normalize. Layering a procoagulant post-cycle drug on top of an already stressed cardiovascular system extends the window of vulnerability. Anyone using anabolic steroids recreationally should understand that the risk of a serious clotting event persists well after they consider the cycle “finished.”
Why Some People on Steroids Never Get Clots
Given that millions of people take glucocorticoid prescriptions every year, it is worth noting that most of them do not develop blood clots. A three-to-fivefold increase in relative risk sounds alarming, but the absolute risk of venous thromboembolism in the general population is low to begin with. If the baseline annual risk is roughly one or two per thousand people, a fivefold increase still leaves the absolute risk relatively modest for any individual patient.
Individual vulnerability varies widely. People who already carry other risk factors for clotting, such as obesity, immobility, recent surgery, cancer, pregnancy, hormonal contraceptive use, smoking, or an inherited clotting disorder, face a much higher absolute risk when steroids are added to the mix. Steroids do not create clotting risk in a vacuum; they amplify whatever baseline risk already exists. This is why a short course of prednisone for a mild asthma flare in an otherwise healthy, active 25-year-old is a very different proposition from the same prescription in a 65-year-old cancer patient who recently had surgery and is largely bedbound.
For clinicians, this means the decision to prescribe steroids should factor in a patient’s overall clotting risk profile, not just the condition being treated. For patients, it means being honest with your doctor about all of your risk factors, and being vigilant about symptoms of a potential clot, especially during the first week of a new steroid course when the data suggest risk peaks.