What are the risks associated with Menopause Hormone Therapy?

Become Informed

Most people are unnecessarily scared of hormone therapy. The Women's Health Initiative (2002) came out and sensationalized their findings with quite a bit of panic. On the positive side, we learned a lot about how to NOT use menopause hormone therapy.

This blog post could go on and on about the WHI but what I really want to focus on is educating you around the real risks (and putting them into context) of hormone therapy (MHT). Hopefully this also helps you understand why some of the eligibility criteria exists that I listed in my last blog post here.

Current risk/benefit discernment is most deserved the most scrutiny with respect to:

cardiovascular disease
venous thromboembolism
stroke
hypertension
breast cancer
endometrial cancer

Cardiovascular Risks with Menopause Hormone Therapy

Right off the bat I want you to be confused because you know that MHT can benefit heart health! And this is true. All estrogen therapies can decrease LDL cholesterol, raise HDL cholesterol, improve lipoprotein, lower fibrinogen. Great stuff, why the hazard symbol up above?

Just like when you are considering taking a hormonal contraceptive, using MHT can have an increased clotting risk. This happens by increasing certain clotting protein production and reducing anti-clotting factors. It also increases inflammatory markers like C-reactive protein. And oral estrogen may also lead to an increase in triglycerides and slight increase in blood pressure. Topical estrogen may have a slight blood pressure lowering effect and more profound benefits to cholesterol levels.

There is also the HERS trial (Grady, 2002) where they found that giving MHT to women who have already had a cardiac event (heart attack, bypass, angioplasty, etc.) had an increased risk of a having another major event in the first year after starting MHT. After the first year the risk ended up reducing for the duration of the trial which was a total of 6.8 years.

How about strokes? This is an area that remains possibly of an increased risk in those first six months after starting MHT.

This can all sound scary! Luckily all this is not as doom-and-gloom as you may think. There are some really great studies out there that show MHT can have a significant reduction in risk of heart failure, mortality, or myocardial infarction. It has a big list that includes allowing your blood vessels to dilate more and reducing inflammatory activation. The tricky part is that is a woman already has atherosclerosis then the combination of that with adding in MHT causes some issues. We see less vasodilation, more inflammatory activation, more plaque instability. If you're already on a statin then the MHT may augment some benefits.

Where is the discrepency then? Back to eligibility guidelines, the TIMING of when MHT is started is paramount when it comes to affecting the heart. The benefits to the heart are only seen when MHT is started in recent menopause and under 60 years - not when started outside of this. Another factor is the type/route of the hormones. Oral and transdermal estrogens have different global effects in the body and this can therefore change which may be the best fit for you. Transdermal (gel, patch, cream) has less thrombosis risk. This is how it can be a bit of a mixed bag. Your lifestyle factors (smoking, activity, current health conditions) are also going to have a large impact not only on how you handle MHT, but how you are set up for cardiovascular success.

Bottom line: There is little or no associated increased cardiovascular risk with MHT use when used appropriately.

Cancer Risk with Menopause Hormone Therapy

This is probably the reason why women fear hormone therapy: cancer. Cancer is scary - I get it. Let me help give you more information about the risks here so you can feel more informed.

Breast Cancer

Remember that there are different types of hormone protocols. Broadly for this section there is estrogen-only, and estrogen + progesterone. Progesterone is necessary in the protocol when you have a uterus as it prevents the lining from getting too thick and causing issues. When looking at estrogen alone there is a very minor increase in breast cancer relative risk - negligible in the first 5 years and a relative risk increase of about 18% thereafter. Estrogen + progesterone has a different story to tell depending on the type of progesterone used in the protocol (sorry, medicine is complicated). But to give you the best case numbers, micronized progesterone is able to reduce breast cancer relative risk by about 8% for those first 5 years. After that the relative risk will increase. Synthetic progesterones has a more sustained breast cancer risk that is related to the duration of use.

I keep saying RELATIVE risk which is NOT the same as ABSOLUTE risk. I love a good infographic and this one from the Women's Health Concern titled Understanding the risks of breast cancer is simply lovely. They use a group of 1000 women aged 50-59 and state that statistically, they will:

Women's Health Concern - out of 1000 women aged 50-59 how many will get breast cancer if...?

Do the numbers that I first mentioned about risk look different now that you saw some of those comparisons? When you took the birth control pill were you worried about breast cancer from it?

Another thing to keep in mind is that once MHT is stopped, the breast cancer risk returns back to your baseline.

However. If you have a PERSONAL history of breast cancer, or are already at an increased risk (BRCA1/2 gene mutations) then we really don't have great data to base treatment off of. Some women do have their breasts become more dense after starting MHT and this may warrant more frequent mammography so everyone can feel better about the therapy. It is also important to understand your baseline risk for breast cancer - https://bcrisktool.cancer.gov/calculator.html <-- I love using this with patients so we know what's up.

Bottom Line: Estrogen doesn't cause breast cancer. When we use breast-safe hormones, especially micronized, it doesn't look like there's any substantial increase in risk for the first 5 years. After that it would be a relative risk increase.

Endometrial Cancer

Endometrial Cancer is probably even more nuanced than any other risk factor - and that is saying a lot. I'm going to try and keep it in the most broad top-level as possible else this will be huge.

Remember how progesterone is added to MHT to protect the endometrium? It's kind of a big deal. Estrogen will cause a thickening of the lining of the endometrium without end unless progesterone is in there to stop that from happening. Depending on your symptoms and where you are in your menopause journey, you may be using progesterone cyclically (for example 2 weeks on, 2 weeks off) or continuously (daily).

The biggest increase in endometrial cancer risk from menopause hormone therapy happens when there isn't enough progesterone added to the protocol to counteract the estrogen dosage. This can also happen if someone is using transdermal progesterone (which has been shown to NOT yield enough protection). So if your provider is keeping on top your protocol there is less to be concerned about in this area. In fact, there's evidence showing that being on a continuous progesterone+estrogen MHT protocol can end up having a small LOWERED risk of developing endometrial cancer over those women that never do.