Expert Discusses Estrogen Use in Women With BRCA Mutations

Many women who find out that they are positive for the BRCA gene mutation, therefore at higher risk for cancers such as breast and ovarian, will often opt for an oophorectomy, which is the removal of one or both of the ovaries to decrease cancer risk. However, this procedure will often cause early-onset menopause, bringing about a whole new class of risks and possible effects.

Can you give an overview of estrogen use for BRCA-positive women?

CURE spoke with Mache Seibel, M.D., a national expert in helping women in and around menopause improve their symptoms, about these risks, and how taking estrogen may be able to decrease the severity and mitigate some of the side effects that follow preventative surgery.Women who have the BRCA mutation have an increased risk of breast and ovarian cancer. If you remove the ovaries and the fallopian tubes, it lowers the risk of the ovarian cancer by about 90 percent and it lowers the risk of breast cancer by about 50 percent.

What are some of the risks, and what should people be aware of when thinking about early-onset menopause?

However, there is some confusion about hormones. Only about half of the women eligible, which would be nearly all of them, are taking estrogen. The issue is that they are being thrown into menopause at this very early age — typically before age 40 – because most of these women are going to have surgery between 35 and 40 years old, and the mean age of menopause is 51. Well, the reason that they have the surgery is to lower the risk. But what they often don't realize is that the women who go into menopause before age 45, and absolutely those who go into it before age 40, are a different set of people than the women who go into menopause at the natural age. They face a different set of conditions by going early. What ends up happening is that they end up facing a much greater increased risk of fatal heart attack, not to mention non-fatal heart attacks, too, by not taking estrogen. Studies have shown that there is somewhere between a 23 to 67 percent increased risk of fatal heart attack if they don't take estrogen and they go into early menopause. This is a big issue for these women.

One study from this year, published in the Journal of Clinical Endocrinology, showed that these women have a 47 percent lower risk of death by fatal cardiac disease if they take estrogen. The sooner they start it the better. Most recently, a study from JAMA Cardiology, published in September, showed a 23 percent increased risk of fatal heart attack for women who don't take estrogen. Heart disease alone is something that many women, and even their providers, often don't realize is such a major issue.

If that is the case, why are some women not taking estrogen?

When you move organ systems and then you look at conditions of the brain, you start looking at early menopause, again, as a whole different subset of problems. They have an increased risk of depression, increased risk of anxiety and some women may become suicidal. There's a tremendous — 50 percent or so – increase in cognitive impairment and the risk of Alzheimer's, can go up as much as 70 percent if they don't get treated with estrogen. So we're talking about major life consequences. The reason they don't want to do it is because of a study called the Women's Health Initiative, which took place in 2002. It was the first of the reported ones. The study was thought, prematurely, because of a perceived increase risk of breast cancer. That is the reason that women quit taking this. They said that estrogen caused an increased risk of breast cancer, heart disease and dementia.

The reason why women are so confused, and it's what my book, The Estrogen Window, is about, is when you look at the study design of the Women's Health Initiative, part of it wasn't about estrogen. It was about estrogen plus a synthetic progesterone called Provera. This particular medication was the only type of progesterone medication that was available. There wasn't oral bioidentical progesterone at the time of that study. So they used a combination. The Provera is known to cause negative effects like depression. It's known to be able to stimulate breast cancer cells, and so it was a medicine that was poorly chosen, but nevertheless what was in the medicine. The second thing is that the women who got the medication, 75 percent of them were between 60 and 79 years old. That is compared to the women who got the placebo, who were largely between 50 and 59 years old. So they were basically comparing 50 to 59-year-old women on a placebo to women who were 60 to 79 years old who had the medication. And, to make it worse, many of the women who received the medication were smokers, had diabetes and had high blood pressure. The women who got the placebo were by and large healthy women.

In 2013 when they re-evaluated the same exact data but took into account age and took the other 25 or so percent of women and matched them up by age, what they found was in fact, the estrogen-only group breast cancer risk was actually reduced. All cancer risk was reduced. All fractures were reduced. Heart disease was reduced, death from any cause was reduced significantly and diabetes was reduced. All of these things were improved by taking estrogen.

Are there any risks of taking estrogen?

In subsequent studies, when they have given estrogen or estrogen and progesterone of any kind to women who started taking it in other studies who took it in the 40 to 50-year-old range, in other words the time of the surgery up until the time of natural menopause, they had no increase risk of breast cancer. Any time you take a medication, you have potential risks, of course. In this young group, which is the 30 to 45 year olds who have the surgery, taking estrogen up until the time of menopause does not increase risks. It lowers risks.

Unless they already have some kind of cancer or some bleeding problems or tendency to blood clot, and even then, there may be some way to work around it. Let's just say they have one of the sections where they shouldn't, in the first line, think of estrogen in the same way as the general population. That minority, that small subset of women aside, if you just take the average woman, the benefits are not only neutrality plus loss of symptoms, it's not only preventing their symptoms and their risk for future diseases, but it's lowering their risk for future diseases. It's amazing.

Understandably, this is a very worried group of women. They just had surgery to reduce their risk of cancer, and now they find out about something that can increase their risk. And if you look at women like Angelina Jolie, she ended up having her ovaries removed and tubes removed. And yet she went on estrogen and she had an IUD that secreted progesterone. She had very good advice.