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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: When and why should a woman opt for hormone therapy? What is the profile of women who should not take hormone therapy?
DR. SCHIFF: Menopausal women who experience hot flashes, vaginal dryness, sexual problems or other symptoms, and who have no contraindications should consider hormone therapy to feel better. Contraindications would include any history of heart attack, stroke or an estrogen-sensitive cancer, like breast cancer or endometrial cancer. Also, women with a history of phlebitis or liver problems should not take hormones orally.
Women who smoke should definitely not take low dose birth control pills as the combination increases the risks of blood clots and strokes and heart attacks. The reason given is with the birth control pill you are trying to prevent the ovaries from functioning and thus you are using a significantly high dose to take over that role. With hormone therapy, the dose is much lower and thus the effects of smoking are not apparent.
CBS CARES: When you advise a patient, do you provide information about the benefits and risks of hormone therapy, and then let her decide?
DR. SCHIFF: Yes, exactly. It's always ultimately the patient's decision, with input from me, based on my knowledge of her medical condition and her personal risk factors. It is essential for a woman to be as informed as possible.
I feel very strongly that every woman should have a partnership with her health care provider. If your health care provider is not your partner and doesn't have time to answer your questions, you should change your health care provider.
CBS CARES: So you're basically a proponent of hormone therapy for women with difficult menopausal symptoms?
DR. SCHIFF: Yes, and I am basically a proponent of discussing it. Unless there's a history or very high risk of breast cancer, heart attack or stroke, there's no reason for a woman to suffer needlessly through a difficult menopause. The key to hormone therapy is balance: using the lowest effective dose for the shortest necessary time.
CBS CARES: What is the most widely used hormone therapy for menopausal women in the U.S.?
DR. SCHIFF: The most commonly prescribed hormone in the U.S. is Premarin, which is comprised of conjugated estrogens derived from pregnant mare urine.
CBS CARES: Are the hormones that women produce really similar to those found in the urine of pregnant mares?
DR. SCHIFF: No, this is a substance that differs from what women produce and is actually a combination of a number of different conjugated estrogens. However, although this is a substance that is not natural for women, but rather, natural for horses, it is an effective therapy for menopausal symptoms. And because it has been around for 60 years, it is also the most studied therapy and we have the most information about it, versus other treatments. Premarin is also found in Prempro, which is a combination of Premarin and Provera, which is a synthetic progesterone known as progestin.
CBS CARES: With its heritage and decades of use, it sounds like Premarin is figuratively and literally the work "horse" of hormone therapy! What gave scientists the idea to experiment with urine from pregnant mares?
DR. SCHIFF: It was in the early 20s that Edgar Allan and Edward Doisy first isolated estrogen from pig ovaries. Doisy was able to isolate estrone from the urine of pregnant women in 1929 and estradiol from sow ovaries. However, they were unable to get large amounts. In the 30s the Ayerst Company in Canada (now Wyeth) was extracting estrogens from urine of pregnant women but not very successfully. They had problems because it was tough to get, the activity was very low and it had an odor and a bad taste.
Thus they decided to do so from horses, the result being Premarin. Premarin was first prescribed in Canada and in the United States in the early 40s for the treatment of menopausal symptoms, and was found to be effective.
CBS CARES: Wouldn't estrogen activity in the urine of pregnant women more closely resemble estrogen that menopausal women used to make? If so, why not use modern technology to try and solve the problems they encountered in the 1930's and develop a drug from this, rather than from horses?
DR. SCHIFF: Yes, estrogen in pregnant women's urine is closer. But one of the other issues with the estrogen in pregnant women's urine is that it is predominantly estriol, which is not especially effective.
CBS CARES: In which ways is estriol not very effective? Does it provide any benefits?
DR. SCHIFF: I got involved in estriol about 25 years ago because there was an investigator in Nebraska by the name of Lemon who made the point that women who had babies had less of a risk for breast cancer compared to women who went through life who never had children. The predominant estrogen a pregnant woman is making is estriol. Estriol may be safe but the problem is that because it is so weak biologically it does not prevent osteoporosis and it does not relieve hot flashes. It's probably safe because it's like using a placebo.
CBS CARES: Well, which scientifically proven effective hormone is the closest to what a woman naturally produces before menopause?
DR. SCHIFF: The most natural, effective hormone for menopausal symptoms is a hormone that the ovary used to produce, which is estradiol. Estradiol is the most potent estrogen produced by the ovary, while estrone and estriol are weaker estrogens also made by the ovaries.
CBS CARES: If estradiol is so potent, what's the best way for a woman to take it to maximize safety, while maintaining efficacy? Specifically, is it best taken by mouth or by a patch or cream applied and absorbed through the skin?
DR. SCHIFF: If you take estradiol by mouth it gets converted by the liver after passing through the stomach and small intestine, into another estrogen called estrone. Estrone is natural also, but not the predominant estrogen of younger women. If you want to get the exact hormone that your ovaries used to produce, you want to use estradiol as a cream that you rub on the body or a skin patch or a pill placed in the vagina or a vaginal ring. It goes right through the skin, directly into the blood. This avoids the stomach and liver, which means less risk of blood clots or phlebitis. You would have to take higher doses of oral estradiol to equal the effect of estradiol that is absorbed through the skin.
CBS CARES: Why then don't all women on hormone or estrogen therapy just use an estrogen cream or patch instead of taking the hormones by mouth?
DR. SCHIFF: Women in the United States apparently prefer to take oral medications. Women in France preferred to use the patch or cream. About 70% of the women in France used the latter while in the United States only about 10-20%.
CBS CARES: You said earlier that the estrogen in Premarin differs from what a woman would naturally produce. Despite these differences, do Premarin and Prempro still mimic a woman's natural hormone functions, or do they essentially act as a drug to just relieve peripheral symptoms?
DR. SCHIFF: Premarin is an estrogen-like agent, and it will mimic what a woman's cycle did pre-menopause, which was to make estrogen the first two weeks of the month. It functions very similarly to the natural hormone estradiol. Provera, which is synthetic progesterone (progestin), and functions very similarly to progesterone made by the body.
Prempro, on the other hand, is a combination of estrogen and progesterone taken throughout the month, which is different from the way the ovary used to work. In the reproductive woman, the first two weeks prior to ovulation, only estrogen was produced. After two weeks, then the body produced estrogen and progesterone. And if the woman didn't get pregnant, she had a period. Remember, the ovulating woman makes estrogen initially, then estrogen and progesterone. But with Prempro, a woman is getting estrogen with progesterone every day of the month instead of just the last two weeks.
CBS CARES: Why would a woman take estrogen and progesterone every day of the month, which, from what you've just described, is different from the way her ovaries used to naturally work?
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