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 Interview with Dr. Isaac Schiff, Joe Vincent Meigs Professor of Gynecology at Harvard Medical School and Chief of the Vincent Obstetrics and Gynecology Service at the Massachusetts General Hospital.
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CBS CARES: There seems to be a lot of confusion about the risks of hormone therapy. Can you clarify the situation for women visiting this website?
DR. SCHIFF: The risks of hormone therapy are complex. Estrogen increases the risk for endometrial cancer, but adding progesterone is thought to protect against this type of cancer. This is why, as I've already touched on, Prempro is prescribed for women with an intact uterus, while Premarin may be prescribed for women who have had hysterectomies. It is thought that the longer you remain on hormone or estrogen therapy, the higher the risks for breast cancer. They also increase the risk for stroke, as well as venous thromboembolic phenomenon. This refers to an increased tendency to develop clots in the vascular system, which can lead to heart attack, stroke or phlebitis. The major risks appear to be estrogen related. As always, it is important to discuss the benefits and risks with your physician.
CBS CARES: Is there anything that can be done to decrease these risks? How long is it safe for women to remain on these therapies?
DR. SCHIFF: Ideally, the lowest possible dose of estrogen should be used for the shortest possible period of time. It's thought that the longer you remain on hormone or estrogen therapy, the higher the risks. Each year, I ask the patient if she wants to continue on hormone therapy and I describe the benefits and risks. If she is not committed to hormone therapy, I might suggest that we stop and see how she does.
The health risks probably start to go up in as soon as two to three years. But the moment you stop the hormones, the risks go away soon after. For symptomatic relief, a patient may remain on hormone therapy or estrogen therapy for as long as she needs to, as long as she understands the risks. What we need to do is get better at finding out who is at increased risk when they take hormones.
CBS CARES: Is it fair to say that, paradoxically, estrogen taken early upon onset of menopause may be protective against Alzheimer's, whereas taken much later may cause the death of brain cells?
DR. SCHIFF: Yes, that is precisely the concern with Alzheimer's disease: On the one hand, some observational studies suggest that estrogens prevent Alzheimer's disease in women who start estrogens soon into menopause. And, there are other studies that have shown that women who have surgical menopause and are given estrogens immediately might have better results on a test for recall of numbers. But on the other hand, it's thought that when you start hormones later in life, as was the case in the WHI, there is already disease in the blood vessels and this creates a hypercoagulable state where you are prone to little clots or strokes.
CBS CARES: Would that mean that even women without symptoms might benefit by taking low doses of estrogens early on?
DR. SCHIFF: Yes.
CBS CARES: At this time, would you recommend HT or ET for menopausal women without symptoms to protect against Alzheimer's and osteoporosis?
DR. SCHIFF: There is not enough data to recommend it for prevention of Alzheimer's disease but it can be used for osteoporosis if the patient understands that benefit: risk profile and she has been made aware of other agents available for her.
CBS CARES: Does estrogen therapy increase the risk of developing breast cancer or does it essentially accelerate a pre-existing cancer?
DR. SCHIFF: There is ample evidence to support the conclusions that women who take hormone therapy are more likely to develop breast cancer than women who do not. Whether it accelerates an existing cancer or causes development of a new cancer, is not known.
The size of the increase per year of hormone use is the same as that associated with delayed menopause (meaning that women were exposed to their own estrogen longer than those who went through menopause earlier) by year. Based on a meta-analysis of 51 studies as well as the WHI, there would be 20 extra cases per 10,000 women after taking hormone therapy for five years, 60 cases after ten years and 120 after 15 years of use. As I mentioned before, once hormones are stopped, the risk disappears.
Hormone therapy does increase the incidence of breast cancer with the best evidence for estrogen plus progestin. Although observational studies suggest a small increase in breast cancer risk for women with hysterectomies taking unopposed estrogen, the WHI study did not. Keep in mind that the WHI was a randomized trial. They looked at all the aspects. In other words, the WHI women who got placebo versus women who got the hormone intervention, at baseline, had the same risk factors. There were no differences, and that's one of the advantages of the WHI. When you deal with thousands of patients and you randomize them, essentially the risk factors will be the same for the intervention group as for the women who receive the placebo. I was not surprised by the Prempro data because I think this was known for some time. The Nurses Health Study over ten years ago suggested an increased risk with Premarin only.
CBS CARES: Some recent studies suggest that progesterone may be the culprit in accelerating breast cancer, not estrogen. What are your comments about those studies?
DR. SCHIFF: While it's starting to look more and more like the progesterone component could be a culprit, there are still enough studies out there involving the use of estrogen only that show it can increase breast cancer risk, at least when used for an extended time.
Women who take estrogen alone have had hysterectomies, which means that usually (not always) their ovaries were removed. That, in and of itself, may alter a woman's risk for breast cancer, because her exposure to estrogen has been reduced. So I wouldn't remove the progesterone component of hormone therapy in women who have a uterus. It does protect against endometrial cancer.
CBS CARES: So, both estrogen and progesterone may increase breast cancer risks to some extent?
DR. SCHIFF: Progesterone may increase it even further, but I don't think we should say it is all progesterone. However, there are many excellent studies where there is no increased risk of breast cancer with estrogen. So, it is not like cigarette smoking, where the data show that if you smoke, you are at a marked increased risk for lung cancer. It's not as dramatic as that, but the change is big enough that we can say there is a small increased risk of breast cancer with the use of estrogen.
CBS CARES: Can someone who has had a hysterectomy and is taking only estrogen remain on estrogen therapy for life?
DR. SCHIFF: Yes, as long as they're aware of the potential risks. We do not know how long the safety window is. It depends on which study you use to answer the question. Thus, it is important to be familiar with all of the studies and to say that the data about the five years came from the Nurses Health Study. The WHI did not have the same findings. So, we try to do our best for our patients by describing the various studies and pointing out which one may be the most relevant for the individual woman.
CBS CARES: Does it concern you that, as we speak, women are still ingesting or absorbing synthetic or natural hormones without any definitive idea of just how safe and effective they are?
DR. SCHIFF: Well, any time I prescribe anything I worry about it. All drugs have side effects and risks. If I prescribe penicillin for a patient, I hope they don't have a penicillin reaction, which may have serious consequences. With any medication you prescribe as a physician or health care provider, you have to wonder, what is it going to do to the patient? If someone takes a lot of acetaminophen, you have to wonder what it's doing to their liver. If they take aspirin or ibuprofen for joint pain, are they going to bleed from an ulcer in their stomach? You worry about everything when you prescribe a medication including, of course, whether it is going to be effective for the indication you have selected.
Along those lines, in terms of estrogen, it's is a very high profile medication. Any risks get a lot of publicity, but there are infinitely more drugs that have significantly more dangers involved. This is a very emotional agent and I share all of the benefits and risks with the patient, but frankly, I prescribe a lot of estrogen and I make it very clear to my patients what the risks are.
Now, of course, I see a self-selected group of women who want to see me because they want me to prescribe the hormones for them. But I have never been on the estrogen bandwagon in the sense of aggressively prescribing it. Even in the late 80's and early 90's, before the WHI data came out, I always believed that the data to suggest that estrogen prevents heart disease was way over done. I used to say in my lectures that the suggested benefits to the heart are exaggerated and we have better agents to prevent heart disease, like the statins, to lower cholesterol.
So, I've never been a strong proponent of hormone therapy, but I've prescribed a lot of it and I can tell you that, when I prescribe it, I worry about breast cancer and blood clots. But there are other drugs that I've prescribed that I've worried about a lot more.
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