Your Resource for all Things Relating to Factor V Leiden

Factor V Leiden and Hormone Replacement Therapy

Hormone replacement therapy (HRT) or just hormone therapy (HT) is a treatment that is used to supplement the body with either estrogen alone or estrogen and progesterone in combination. When the ovaries no longer produce adequate amounts of these hormones (as in menopause), HT can be given to supplement the body with adequate levels of estrogen and progesterone. HT helps to replenish the estrogen, relieving some of the symptoms of menopause such as:

  • Hot flashes
  • Vaginal dryness that can result in painful intercourse
  • Other problematic symptoms of menopause, such as night sweats and dry, itchy skin

There are two main types of hormone therapy:

Estrogen Therapy (ET)

Estrogen is taken alone. Doctors most often prescribe a low dose of estrogen to be taken as a pill or patch every day. Estrogen may also be prescribed as a cream, vaginal ring, gel or spray. You should take the lowest dose of estrogen needed to relieve menopause symptoms and/or to prevent osteoporosis. This type of HT is used if a woman has had a hysterectomy.

Estrogen Progesterone / Progestin Hormone Therapy (EPT or PHT)

Also called combination therapy, this form of HT combines doses of estrogen and progesterone (progestin is a synthetic form of progesterone). This type of HT is used if a woman still has her uterus.


While hormone therapy helps many women get through menopause, the treatment (like any prescription or even non-prescription medicines) is not risk-free. Known health risks include:

  • An increased risk of endometrial cancer (only if a woman still has her uterus and is not taking a progestin along with estrogen) .
  • Increased risk of blood clots and stroke. However, in women within 5 years of menopause there was no statistically significant increase in stroke risk. Also, studies suggest that using estrogen delivered from the skin via a patch/cream might further lessen the risk of blood clots.
  • Increased chance of gallbladder/gallstone problems.
  • Increased risk of dementia if hormone therapy is started after a woman has been in menopause for 10 years. It is not yet known if it might be beneficial for women who start HT in their 50s.

What are the risks of getting a blood clot by being on hormone therapy?

As with birth control methods that contain estrogen, or estrogen with progestin, hormone therapy does not cause blood clots.  Rather, hormone therapy and estrogen increases a woman’s risk for developing a blood clot. These are typically blood clots that form in the deep veins of the body and are called a venous thrombosis or VTE.


For the average woman taking postmenopausal hormone therapy, the absolute risk of a blood clot is small.


Hormone therapy increases a woman’s risk of blood clots up to three times compared to a woman not on hormone therapy.


The absolute risk of blood clots with hormone therapy is 1 in 300 per year.


This risk increases with age and the presence of additional risk factors including the presence of cardiovascular disease, obesity, fracture, or renal disease.


This risk is much higher for a woman who has had a previous blood clot or a woman with thrombophilia like Factor V Leiden.


According to the American College of Obstetricians and Gynecologists (ACOG), these risk factors are not rare. Therefore, it is prudent for the healthcare professional to carefully assess the personal and family history of patients before prescribing HT or ET.


As part of the shared decision-making process, he or she should weigh the risks against the benefits when prescribing HT or ET, and counsel the patient accordingly.

What are the risks of getting a blood clot by being on hormone therapy if I have Factor V Leiden?

As you might expect, Factor V Leiden combined with any hormone therapy involving estrogen increases the risk of VTE in a multiplicative fashion.


According to the National Institutes of Health, women with Factor V Leiden who are also on hormone therapy were 14-16 times more likely to have a venous blood clot or VTE compared to women who don’t have Factor V Leiden and are not on hormone therapy.


A study in Canada found that postmenopausal women who used the estrogen-progestin HRT and also carried the Factor V Leiden mutation appeared to have a 17-fold increased risk of a VTE compared to women without these blood abnormalities and did not use HRT.


The Cleveland Clinic published very similar results as well showing that women who are taking Progestin Hormone Therapy (PHT) and carry the Factor V Leiden mutation have a 15-fold increase in the risk of VTE compared with women who do not have the mutation and do not use PHT.


The relative risk of a VTE in women who take estrogen therapy or ET seems to be even greater if the treated population has preexisting risk factors such as obesity, immobilization, or a fracture according to the American College of Obstetricians and Gynecologists (ACOG).


Also, some studies have shown that transdermal PHT (giving the dosage through the skin) seems to reduce the risks for VTE compared to oral PHT.

The risk for blood clots due to hormone therapy and Factor V Leiden is, of course, much lower for women who are on anticoagulation therapy or blood thinning medication.


Careful and individual risk-to-benefit analysis between you and your healthcare professional is always advised when considering hormone therapy.

How can you reduce your risk?

For women looking to avoid the risk of blood clots connected to hormone therapy, the troublesome physical effects of menopause, such as mood changes, hot flashes, sleeplessness and vaginal dryness, can be managed without estrogen for symptomatic relief. It is also important to keep in mind that most women, but not all women, will experience the severity of menopause symptoms for about six months before they begin to subside.


Work with your healthcare professional to choose the safest and most effective treatment methods for your menopause symptoms.

Where can I find more information?

Soon you will be able to visit our Research and Resource Library to obtain very in-depth information about Factor V Leiden and how it relates to hormone replacement therapy. We will share with you the latest research and recommendations from the best professionals in their field.

In the meantime, the National Blood Clot Alliance (NBCA), working with the Alexandra L. Rowan Memorial Foundation, has put together some excellent information on hormone replacement therapy and the prevention of blood clots. To visit their website, click here.

To Learn More About Women & Blood Clots...

Each year, up to 900,000 people are affected by blood clots, and about 100,000 people will die because of blood clots. However, many of these deaths can be prevented simply by sharing life-saving information. To learn more about women and blood clot risks, signs and symptoms, and prevention, please visit and share

Scroll to Top