By noon on the day the story hit the news, I’d received a dozen emails from (sensibly) concerned patients asking what the study meant for them. First appearing in JAMA (the Journal of the American Medical Association) and then picked up by the wire services and spread around the world, the article addressed phase two of the Women’s Health Initiative (WHI) Study that was originally published in 2002.
To refresh you on the details of that study: Researchers gave 16,608 women either Prempro—which is Premarin (estrogen derived from horse urine) plus medroxyprogestin (a synthetic hormone)–or a look-a-like placebo. After 5.6 years, they stopped the study early because there was a small but measurable increased risk of breast cancer in the hormone-taking group over the placebo group.
Although the study did come under some criticism (namely, that many women might have entered the study with early-stage undiagnosed breast cancer, so that strictly speaking the Prempro did not cause the cancer), its effect was dramatic. Over the next few years there was a 32% drop in the sales of hormone replacement therapies (HRT) and, more importantly, a steady decline in breast cancer–in part, researchers believe, because of this decline in HRT use.
The current study tracks as many of these same women as they could locate (12,788) from 2005 to 2009, now completely off hormones. And the findings? Among the HRT group there were more breast cancers than in the non-HRT group (385 cancers vs. 293), a small but statistically significant difference. More worrisome, however, among the HRT group who had developed cancer was that the disease was a more advanced form (called “node positive”) than the breast cancer diagnosed in non-HRT users.
Does this mean that hormone replacement therapy is bad? That HRT will give you breast cancer, and metastatic breast cancer to boot? That no matter how physically and emotionally healthy you feel on your HRT, you should race out, bottle grasped in kitchen tongs, and bury your HRT deeply in a remote area?
Not at all.
My own issues with the original WHI study as well as this follow-up have to do with the “not real life” question that haunts virtually all clinical studies like this. In real life, there’s a significant difference between a study designed like this one and what actually happens in a doctor’s office. Let me elaborate.
No doctor would prescribe hormones just for the sake of putting someone on hormones, but that’s exactly what these investigators did. For example, no physician would ever start a symptom-free 58-year-old woman on hormones, but these investigators, mainly interested in “what would happen,” did so.
A practicing physician would review each woman’s case individually, adjust the dose according to her needs, and then discontinue the hormones when she no longer needed them. The only criteria these investigators used for starting hormones was essentially “menopausal female, regardless of age” with everyone receiving the same dose and staying on hormones continually.
Researchers would counter with “But the variations in doctors’ offices throw in too many outside factors (called “confounding variables”) that will prevent any substantive data from emerging. There will be no study, no worthwhile data.”
“Well, okay,” I’d answer, “but maybe you’re barking up the wrong tree and as a result, frightening women unnecessarily.” For example: The initial WHI study randomly selected 16,608 women between the ages of 50 and 79 to receive HRT or a placebo. Now, considering only about one third of women ever get menopausal symptoms so severe they merit HRT in the first place, we can assume that a lot of women were receiving a medication they didn’t need.
Recruiting patients is a big-dollar business these days and likely a lot of women dutifully swallowed their HRT without question. Feminists might view this as a form of low-level prostitution, and, you know, they’re right. The women in the study were recruited (with payment to both them and their recruiting physician) with the goal of “let’s see what happens if you stay on hormones.” Currently, recruited patients receive a little badge that reads “Medical Hero” (along with their check), which ironically might be pinned exactly over their breast cancer.
Doctors are paid big bucks to cull guinea pigs for research from their private practices. But in real life, women don’t seek–and doctors won’t prescribe–medications that are simply not needed.
Since menopause symptoms are pretty much limited to the perimenopause years (48-55), we can conclude that in the WHI study hormones were given to many symptom-free women (ages 56-79). I don’t fault the researchers for this decision, but it does change one’s perspective on what was actually accomplished.
Of those women who did suffer hot flashes and night sweats, none received suggestions for lifestyle and dietary changes, herbs, or other forms of alternative medicine to reduce their symptoms. But with this statement, the researcher would sputter, “That would destroy my study” and again I’d answer, “Your study isn’t what happens in my office.”
And finally, my longstanding gripe: Why do we persistently equate molecules found in the dehydrated residue of concentrated horse piss with the molecule produced by the ovary of a human female? Premarin (a name derived from Pregnant Mare Urine), produced by Ayerst Labs, is still cynically labeled “a natural product for women,” although this statement is removed from Prempro because of the synthetic medroxyprogesterone, a progesterone-like molecule also not produced by any woman I know.
Bioidentical hormones are molecularly identical to the hormones produced by the human female ovary. The estrogen in these hormones is extracted from soybeans, the progesterone from the Mexican wild yam. To date, there has been no significant research on the risks of using low doses of bioidentical hormones in women with menopause symptoms for only as long as they need them.
The only data we have come from doctors themselves, communicating with each other. And here the data are very good. I first heard of the safety of bioidenticals from Christiane Northrup, MD, who has been prescribing them for years. She believes they actually have a protective effect on the female breast. And to this day, her large Women to Women website states that the risk of bioidentical hormone is extremely low.
What should you take away from this new data emerging from the WHI study?
• Don’t take any medicine you don’t need.
• Don’t take Prempro, especially for long periods of time.
• If you have menopause symptoms, ask your doctor about bioidentical hormones.
• Take bioidentical hormones for only as long as you need them. Go off for a month once a year and if your symptoms seem to have disappeared, don’t renew your prescription.
• Don’t take any hormones at all if you have a strong family history of breast cancer. Use alternatives therapies, like Chinese medicine, instead. If you have no access to an alternative practitioner, ask your doctor about antidepressants. Both Lexapro and Pristiq (again for a limited time, until your symptoms subside) can reduce your symptoms. This is called “off-label use” of a prescription drug, meaning the FDA hasn’t approved these meds for menopause, but they seem to work anyway.
P.S. All those years ago at the start of the first WHI study, certain voices in the wilderness protested that it was basically immoral to initiate it using Premarin and Prempro. Studies from Europe had already shown a slightly increased breast cancer risk, so what would be gained by doing it twice? The researchers argued that Prempro might have additional benefits–specifically heart disease prevention. To this statement, Dr. Christiane Northrup sensibly responded, “What woman in the world would want to reduce her heart disease risk but place herself at risk for breast cancer?” And as it turned out, by the time they called a halt to the study, Premarin was shown to increase a woman’s risk of both breast cancer and heart disease.