Does Hormone Therapy Increase the Risk of Blood Clots or Stroke?

Content Courtesy of Our Partner

This article was generously contributed by Dr. Gretchen Reis as part of ForeverBetty's commitment to providing trusted, evidence-informed education from experienced menopause and hormone health professionals. The views expressed are those of the author and are intended for educational purposes only. They should not replace personalized medical advice from your healthcare p

For the way hormone therapy is most often prescribed today, the answer is largely no. Current research indicates that transdermal (through-the-skin) estradiol started near menopause does not appear to increase the risk of blood clots or stroke at standard doses. The reputation that “hormone therapy causes blood clots and strokes” comes largely from one specific scenario — oral synthetic estrogen started in women who were well into their 60s and many years past menopause — and even there, the elevated risk is tied to the oral route, which is typically not prescribed for perimenopausal and menopausal women in a risk-aware practice. The complete, honest answer is that risk depends on which hormone you take, how you take it, your age, and your personal health history. With the right route and the right timing, it is low and highly modifiable — and the delivery route you choose matters more than almost anything else.

Key Points

• Route matters most. The clot-and-stroke risk is tied to oral estrogen, which passes through the liver and increases the production of clotting proteins. Transdermal estradiol largely bypasses the liver and, at standard doses, does not appear to increase the risk of blood clots or stroke. For this reason, oral estrogen is typically not prescribed for perimenopausal and menopausal women in a risk-aware practice.
• The scary headlines have a specific source. Most clot-and-stroke fear traces back to the Women’s Health Initiative, which studied oral conjugated estrogen in women averaging about 63 years old — not transdermal estradiol started near menopause.
• Stroke risk is small in absolute terms. Oral hormone therapy carries a small, statistically real increase in stroke risk that is concentrated in older women and higher doses. Low-dose transdermal therapy appears lower-risk.
• Timing is a major lever. Starting before age 60 or within 10 years of menopause carries the most favorable overall risk-to-benefit ratio.
• For men, the concern is different. Testosterone can raise red blood cell count (hematocrit), which can thicken the blood — the reason hematocrit is monitored on therapy.
• Your history changes the math. A personal or family history of clots, stroke, or an inherited clotting disorder shifts the calculation and must be reviewed before starting.

Understanding Blood Clots, Stroke, and Hormone Therapy

Two different risks often get lumped together. Venous thromboembolism (VTE) refers to clots that form in the veins — a deep vein thrombosis (DVT), usually in the leg, or a pulmonary embolism (PE), when a clot travels to the lungs. Stroke is a problem in the arteries supplying the brain, most commonly when blood flow is blocked (ischemic stroke). Estrogen influences both systems, but not equally and not in every form.

The mechanism behind the clotting risk is well understood. When estrogen is swallowed as a pill, it is absorbed through the gut and routed through the liver before reaching the rest of the body — the “first-pass” effect. The liver responds by producing more clotting factors and shifting the blood toward a more clot-prone state. Pooled data show that oral hormone therapy roughly doubles the risk of VTE compared with no therapy. Estrogen absorbed through the skin skips that first liver pass and has minimal effect on those clotting markers, which is why transdermal estradiol behaves so differently from an estrogen pill.

Much of the public fear dates to 2002, when one arm of the Women’s Health Initiative was stopped early after showing increased clots, stroke, and other risks. That trial is important, but it tested a single regimen — oral conjugated equine estrogen with a synthetic progestin — in women whose average age was about 63, many of them more than a decade past menopause. Later reanalysis by age showed that women who started near menopause had a far more favorable profile, and the findings do not automatically transfer to transdermal estradiol or to younger women starting at the right time. The risk was real for the population studied; the problem was treating one result as if it applied to every hormone, every route, and every age.

Why the Delivery Method Changes the Risk

If there is one practical takeaway in this entire discussion, it is that how estrogen enters your body changes its risk profile more than almost any other single factor. This is the reason a careful provider does not just decide whether to use hormone therapy — they decide which route.

• Transdermal estradiol (patch, gel, cream): Absorbed through the skin, bypassing first-pass liver metabolism. Current evidence indicates that at standard doses it does not increase the risk of blood clots, and — unlike oral estrogen — it does not appear to raise stroke risk either. It is the preferred route for women with any clotting or cardiovascular risk factors, and the default choice in a risk-aware practice.
• Oral estrogen (pill): Convenient and well-studied, but the first-pass liver effect raises clotting factors and carries the clearest increase in blood clot risk along with a small increase in stroke risk. This is the route responsible for most of hormone therapy’s clot-and-stroke reputation — and it is typically not prescribed for perimenopausal and menopausal women in a risk-aware practice, where transdermal delivery is preferred.
• Vaginal estrogen (local): Used for genitourinary symptoms such as dryness or discomfort, it is absorbed in such small amounts that it is generally considered safe even for many women who cannot use systemic hormone therapy.

The progestogen component matters too. When a woman with a uterus uses systemic estrogen, a progestogen is needed to protect the uterine lining. Micronized progesterone (the bioidentical form) has been associated with a more favorable risk profile than some older synthetic progestins, which is part of why bioidentical formulations are often preferred when estrogen must be paired with a progestogen.

For men, hormone therapy raises a separate, route-independent concern. Testosterone stimulates red blood cell production, and if hematocrit (the proportion of red cells in the blood) climbs too high, the blood becomes more viscous and clot risk rises. This is manageable and predictable: it is caught with routine bloodwork, and addressed by adjusting the dose, changing the delivery method, or, occasionally, donating blood. It is a reason testosterone therapy requires monitoring — not a reason to avoid it in appropriately screened men.

Who It’s For And Who Should Be Cautious

Hormone therapy’s clot-and-stroke risk is low for many people and substantial for a smaller group. The point of a thorough evaluation is to tell which group you are in before anything is prescribed.

Generally lower-risk candidates:

• Healthy women starting near menopause (before age 60 or within 10 years of their last period), particularly using transdermal estradiol.
• Women who need local vaginal estrogen for genitourinary symptoms, even some who cannot use systemic therapy.
• Men with clinically low testosterone and a normal baseline hematocrit, who are willing to monitor their bloodwork.

Caution — or a more individualized approach:

• A personal history of blood clots (DVT or PE), stroke, or transient ischemic attack (TIA).
• A known inherited clotting disorder, such as Factor V Leiden or a prothrombin gene mutation, or a strong family history of clots.
• Migraine with aura, uncontrolled high blood pressure, active cardiovascular disease, smoking, significant obesity, or prolonged immobility.
• For men: a significantly elevated hematocrit, untreated sleep apnea, or other factors that compound clotting risk.

For many people in the caution group, hormone therapy is not automatically off the table — it often means choosing transdermal over oral, using the lowest effective dose, or relying on local therapy. For some, the safest answer is to avoid systemic estrogen entirely. That decision is individual, and it is made with your full history in front of the provider.

Risks, Side Effects, and Monitoring

Responsible hormone care is built around lowering the very risks this article describes, then watching for them over time:

• Route selection as risk reduction: Choosing transdermal estradiol for anyone with clotting or cardiovascular risk factors is one of the simplest and most effective ways to keep the risk low.
• Baseline assessment: Personal and family history of clots and stroke, blood pressure, and relevant labs are reviewed before starting, with clotting-disorder screening considered when history warrants it.
• Ongoing monitoring: Symptom check-ins and periodic labs. For men on testosterone, hematocrit is tracked specifically because of the clot-related concern; blood pressure is followed for everyone on systemic therapy.
• Situational caution: Clot risk rises temporarily around major surgery, serious injury, or long periods of immobility (including long-haul travel). Tell your provider about planned procedures so therapy can be adjusted if needed.
• Dose and reassessment: The lowest effective dose is used, and the plan is revisited over time rather than left on autopilot.

Safety

Blood clots and stroke are medical emergencies. Call your local emergency number right away if you notice the warning signs below — do not wait to see if they pass. Face drooping on one side, Arm or leg weakness or numbness (especially on one side), Speech that is slurred or hard to understand — and Time to call for emergency help immediately. Also seek urgent care for sudden confusion, sudden trouble seeing, loss of balance, or a sudden, severe headache unlike any you’ve had before.

Swelling, pain, warmth, or redness in one leg or calf (possible DVT); or sudden shortness of breath, chest pain that worsens with breathing, a racing heartbeat, or coughing up blood (possible pulmonary embolism). If you are currently taking medications for blood pressure, clotting, hormones, or any other condition, any changes should be coordinated with your prescribing physician. We work collaboratively with your healthcare team to ensure safe, integrated care. Never adjust or discontinue medications without medical guidance.

Sources and Citations

• The Journal of Clinical Endocrinology & Metabolism — Oral vs Transdermal Estrogen Therapy and Vascular Events: A Systematic Review and Meta-Analysis
• Archives of Gynecology and Obstetrics — Effects of Transdermal Versus Oral Hormone Replacement Therapy in Postmenopause: A Systematic Review
• Cleveland Clinic — Hormone Therapy for Menopause Symptoms
• The New England Journal of Medicine — Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol (ELITE Trial)