Estrogen and Blood Clots: What's the Real Risk?

If you’ve ever been told you can’t take estrogen because of the risk of blood clots, you’re not alone. This warning traces back to the Women’s Health Initiative (WHI) study — a huge trial that made headlines in the early 2000s. But here’s the thing: the details really matter, and what we know now has evolved quite a bit since then.

When the WHI study began, the only available form of estrogen replacement was oral estrogen — pills you swallow. The study did find that women taking these oral forms had a higher risk of developing blood clots (things like deep vein thrombosis, or DVT, and pulmonary embolism, or PE).

Here’s why that happens: when you take estrogen by mouth, it travels to your liver first before entering your bloodstream. That “first pass” through the liver increases production of certain clotting factors — which can raise the risk of forming a clot.

But here’s the good news.

When estrogen is absorbed through the skin — as with patches, gels, or sprays — it skips that liver step entirely. It goes straight into the bloodstream, meaning it does not increase the risk of blood clots the same way oral estrogen does.

In fact, the ESTHER study (published in 2007) confirmed this: transdermal estrogen does not increase the risk of blood clots.

Headline from the ESTHER study published in February 2007.

The ESTHER study concluded that transdermal [systemic] estrogen does not increase the risk of blood clots.

By the late 1990s, several topical systemic estradiol options were approved — and they’ve become go-tos for many menopause specialists (myself included). These include patches, gels, and sprays.

For many women, these options provide all the benefits of estrogen without the added clotting risk.

That said, oral estrogen isn’t off-limits for everyone. It can still be a safe and effective choice for some women who don’t have risk factors for blood clots.

So if you’ve been told, “You can’t have estrogen because of clot risk,” it might be worth a second look. Talk with a menopause-informed clinician who can help you sort through the options and see if topical systemic estrogen could be right for you. Because the truth is — not all estrogen therapies are created equal.