By: Dr. Jackie Piasta, DNP, WHNP-BC

First Things First: Why Do “We” Associate Estrogen with Blood Clots?

The connection between estrogen and blood clots goes back decades, largely tied to the oral contraceptive pill and early studies of oral menopausal hormone therapy (MHT), specifically an estrogen, conjugated equine estrogen known by the brand name Premarin.

Estrogen taken by mouth undergoes what’s called the first-pass effect in the liver, which stimulates increased production of clotting factors such as fibrinogen, factor VII, and prothrombin, while also lowering natural anticoagulant proteins. This cascade tips the balance toward a pro-thrombotic state, making clots more likely to form in susceptible women.

Importantly, this risk signal was specific to oral formulations. Over time, large observational studies showed that transdermal estrogen does not carry the same pro-clotting effect, because it bypasses the liver entirely. Yet the historical association between “estrogen” and “blood clots” has persisted, leading to broad, overly cautious recommendations that fail to differentiate by route of administration.

What the Science Really Says About Transdermal Estrogen

🩸 Estrogen Therapy and Blood Clots: Separating Risk by Type and Delivery

For decades, women with a history of blood clots or genetic clotting disorders like Factor V Leiden have been told one thing: no estrogen, ever. That meant years of untreated hot flashes, disrupted sleep, bone loss, and diminished quality of life.

But the truth is more nuanced. Not all estrogens are the same, and not all ways of delivering estrogen carry the same risks. In fact, transdermal estrogen may be a safe and effective option—even for women with a clotting history.

When estrogen is delivered through the skin—via patch, gel, spray, or ring—it bypasses the liver entirely. And that changes the risk profile dramatically.

🧬 The Science: Transdermal Estrogen and Clotting Risk

Multiple studies, including the landmark ESTHER study, confirm the difference between oral and transdermal estrogen:

Oral estrogen users: 4.2-fold increased risk of venous thromboembolism (VTE)
- Reminder that this is with oral Premarin and not estradiol.
- The risk of taking oral estradiol is extremely low.
Transdermal estrogen users: No significant increase in risk (odds ratio 0.9 vs. non-users)

The American College of Obstetricians and Gynecologists (ACOG) backs this up. In Committee Opinion No. 556, ACOG states that transdermal estrogen has “little or no effect” on clotting risk.

🔬 What About Genetic Clotting Disorders?

For women with inherited thrombophilias—like Factor V Leiden, prothrombin G20210A mutation, or protein C/S deficiency—the conversation has been even more restrictive. Historically, estrogen was considered absolutely off-limits.

But recent evidence shows that transdermal estradiol, when appropriately prescribed, does not carry the same clotting risk as oral estrogen—even in these higher-risk groups.

This doesn’t mean every woman with a clotting disorder should automatically start estrogen. It means decisions should be based on individual risk assessment and evidence, not blanket prohibitions.

🌿 The Role of Progesterone

Progesterone is often prescribed alongside estrogen, especially if the uterus is intact. But here’s where nuance matters:

Natural micronized progesterone (Prometrium): ✅ No increased clot risk
Synthetic progestins (like medroxyprogesterone acetate): ❌ Linked to higher VTE risk

So, not only does the route of estrogen matter, but the type of progesterone matters too.

What About Vaginal Estrogen?

Let’s clear up another common misconception: vaginal estrogen is not a clotting risk.

Because the absorption is so low, local vaginal estrogen used for genitourinary syndrome of menopause (GSM) has no meaningful effect on systemic clotting factors. It’s safe even in women with prior DVTs, pulmonary embolism, or known clotting disorders.

And beyond safety, vaginal estrogen is crucial for preventing UTIs, improving tissue health, and restoring comfort.

⚠️ The Consequences of Overgeneralization

When providers say “no estrogen, ever” without clarifying the difference between oral and transdermal, women pay the price:

Persistent hot flashes, night sweats, and sleep loss
Accelerated bone loss and increased fracture risk
Higher risk of frailty and falls in later life
Missed opportunities for cardiovascular and cognitive protection
Overuse of other medications (antidepressants, gabapentin, sleep aids) that don’t address the root cause

This isn’t just about comfort—it’s about long-term health.

🤝 Shared Decision-Making: Giving Women the Full Story

ACOG is clear:

“When prescribing estrogen therapy, the gynecologist should take into consideration the possible thrombosis-sparing properties of transdermal forms of estrogen therapy and counsel the patient accordingly.”

In other words, patients deserve the whole truth—not a one-size-fits-none answer.

Shared decision-making means presenting the evidence, weighing risks and benefits, and empowering women to make informed choices that align with their values and health priorities.

💡 What This Means for You

If you’ve been told estrogen is off-limits because of your clotting history, here are questions worth asking your provider:

Could transdermal estrogen be an option for me?
Are we using micronized progesterone instead of synthetic progestins?
Is my provider aware of the latest ACOG guidance and studies like the ESTHER trial?
Should we consult with a menopause-informed specialist or hematologist for a personalized plan?

At Monarch Health, we believe midlife care should never be reduced to blanket prohibitions and outdated dogma. Your history, your risks, and your quality of life all matter.

Some estrogens do increase clot risk. But not all estrogens are created equal. The science is clear: transdermal estrogen is different.

You deserve a care plan built on precision, science, and respect for your autonomy—not fear.

📚 References: ACOG Committee Opinion No. 556; ESTHER Study

Estrogen and Blood Clotting Disorder…Am I a candidate?