Flash Back

No woman looks forward to the symptoms that come with menopause, and no one disputes that hormone therapy (HT) can relieve the discomfort of hot flashes and night sweats (vasomotor symptoms) and reduce the risk of bone thinning and loss of bone density (osteoporosis). However, just about everything else about HT is in dispute.

HT is a treatment by which estrogen and progestin (synthetic progesterone) are prescribed to replace hormones that are depleted during menopause. HT medications typically cost about $50 each month; initial and follow-up doctor visits typically total about $300. Insurance typically covers the visits and the drugs.

That HT can increase the risk of breast cancer and other major health problems is well-known, but even when it comes to the positive aspects of HT, there’s a catch. For example, to derive HT’s bone-protection benefits, women must remain on HT medications indefinitely. Food and Drug Administration recommends, however, that women should undergo HT for as briefly as is possible. (FDA advises women to check with their doctor every 3 to 6 months to see if HT still is needed.)

Unfortunately, that’s just the beginning of the confusion that surrounds HT.

TIES THAT BIND. That women can develop breast cancer from HT emerged in the Women’s Health Initiative (WHI). This federally funded 15-year study of women’s health stopped its hormone trials on 16,608 women in 2002, which was 3 years before the scheduled completion date, because the trials revealed an increased risk of breast cancer, strokes, heart attacks and blood clots. Other studies link HT to many cancers. In 2009, for instance, two reports in Journal of American Medical Association linked HT to lung and ovarian cancer.

But now there is a renewed push to broaden the use of HT despite its proven dangers. You can’t turn around these days without bumping into an article that suggests that HT not only is not harmful but also might even prevent heart disease and cognitive problems in menopausal and postmenopausal women. These articles have appeared on health websites as well as in newspapers. What’s troubling is that many of the doctors who are quoted in the articles have ties to major drugmakers as paid consultants, speakers, recipients of research funding and grants, and members of advisory boards. Further, the authorship of articles has been called into question by critics who charge that pharmaceutical companies contracted outside companies to write articles to which doctors lent their names.

Big Pharma takes its pro-HT message to doctors in the form of continuing medical education (CME) courses, which are required for doctors to keep their license. In 2009, Pfizer, which makes about 60 percent of the HT drugs that are sold in the United States, spent $2 million to fund CME courses on the importance of estrogen. The courses were held at Duke University, Penn State University and University of Oklahoma medical schools; Cleveland Clinic; and on Medscape, which is the CME site that is connected with WebMD.

Pfizer, which bought HT-maker Wyeth last year, isn’t alone among HT-makers who are patrons of CMEs that favor hormones. Bayer sponsors a hormone CME course at University of Virginia School of Medicine; Solvay sponsors a CME program through the online journal OBM Management; and Warner Chilcott funded a CME course that was offered through North American Menopause Society (NAMS). That’s a lot of education for a therapy that was thought too risky to allow a federal study to continue!

And HT medications now are pushed for uses that go well beyond the relief of symptoms of menopause, thanks to off-label marketing, which is the increasingly common practice of prescribing a drug to treat a condition despite the lack of FDA approval for that treatment. FDA approved HT for use only by otherwise healthy women who suffer from osteoporosis, hot flashes, and vulvar and vaginal atrophy. But since 2006, HT has been peddled as a way to treat just about any condition that women might encounter, including hearing loss and urinary incontinence.

PLAYING FOR KEEPS. Proponents of HT eagerly await the results of a study that is under way to retest HT. The Kronos Early Estrogen Prevention Study (KEEPS), which is being conducted over a 4-year period at nine medical centers across the country, is testing HT at lower doses and in different delivery systems on 720 women ages 42 to 58. (WHI studied women who were 50 to 79.) Some KEEPS centers have completed their trials; others won’t conclude until February 2012. Results will be released later in 2012.

The study is testing what is known as the timing theory, which holds that HT might benefit women who use it before age-related coronary disease or cognitive decline set in. Some doctors don’t buy the timing theory. Although WHI researchers reported after KEEPS started in 2007 that women who begin HT closer to menopause—when they are younger—tend to have less risk of coronary heart disease than do other women, those same researchers cautioned that those findings do “not necessarily imply an absence of harm over prolonged periods of hormone use.” They also said in 2010 that the increased risk of stroke begins as soon as women start HT.

Dr. Mitchell Harman, who is the director of the group that coordinates KEEPS, defends the study by pointing out that it uses either a lower dose of estrogen or estrogen that is applied to the skin via a patch. Although studies suggest that the transdermal method puts women at less risk of stroke than do pills, FDA does not consider transdermal methods to be safer.

Harman says KEEPS researchers also use progesterone that is made from plants, instead of the synthetic medroxyprogesterone acetate that was used in WHI’s study. The researchers suspect that the synthetic agent is the “bad actor when it comes to the breast”—in other words, the factor that caused the breast cancers that developed during WHI.  

But some doctors, including Dr. Rowan Chlebowski, who is an oncologist and was a lead researcher in the WHI study, say giving menopausal women any form of estrogen is a bad idea. Combined estrogen plus progestin not only increases breast cancers but also hinders diagnosis of the same, Chlebowski says. That means that cancers might not be detected until they are at a more advanced stage. 

Evidence also shows that HT might harm women’s cognitive abilities. The Women’s Health Initiative Memory Study (WHIMS), the results of which were released at the same time that WHI’s were released, revealed that HT doubles the risk of all forms of dementia, including Alzheimer’s disease, in older women. Of 61 women who developed symptoms that typically signal dementia, 40 had received HT.  

All estrogen medications carry FDA’s sternest warning—the so-called black box warning—which warns of possible links to breast cancer, endometrial (lining of the uterus) cancer, cardiovascular disorders and dementia.

Nevertheless, a substudy of KEEPS, which is called the KEEPS Cognitive and Affective Study, is exploring the cognitive and mood effects of HT on women who are in the same age group as those who are in KEEPS. In other words, the timing theory is in play again. The 4-year substudy is expected to come to an end in April 2012 and is funded by National Institute on Aging (NIA).

Nine of 14 KEEPS researchers are either Pfizer consultants who receive financial support from Pfizer or have worked with its marketing company. This makes us wonder whether NIA’s pursuit of the timing theory is based on the spin of industry-funded researchers who are more interested in having HT make a comeback.   

WRITE THINKING. There’s no question that there’s a link between pharmaceutical companies and pro-HT articles. Instead, the question is to what degree does that conflict of interest influence an article’s content?

A case in point: Journal of General Internal Medicine reported in September that a study of 114 HT articles that appeared in medical journals from 2002-2008 revealed that 110 of the articles favored HT. The articles, which claim that HT could prevent Alzheimer’s disease and heart disease, among other benefits, appeared in Archives of Internal Medicine, Journal of the American Geriatrics Society, Cardiology in Review and other journals. However, only six of those 110 articles disclosed that there were connections between the drugmakers and the doctors who bylined the article. The articles that didn’t disclose those connections were cited in Congress’ 2008 investigation into ghostwriting of medical articles.

The fact is that some articles are “drafted” (read: written) by companies that specialize in medical writing. The doctors who get the bylines have varying levels of involvement with those articles, but exactly how much is questionable. What’s notable is that none of the 110 pro-HT articles has been withdrawn by any of the journals. In fact, the pro-HT articles still are cited widely by HT proponents, particularly as HT’s popularity undergoes a revival.

Court documents in breast cancer lawsuits that were brought against Wyeth in 2008 show that the pro-HT articles were written largely by a company that the drugmaker hired—before the doctors who were listed as the authors even saw the stories. Pfizer spokesperson MacKay Jimeson tells Consumers Digest that it is “inaccurate to describe this process in a manner that suggests the authors merely lent their names and did not have full editorial control over content.” The integrity of these articles has been recognized by multiple courts, he says.

The outside company in question stopped providing writing services to Pfizer and its subsidiaries in 2007, Jimeson says, but when we asked Pfizer if it now uses a different writing company, we were referred only to Pfizer’s posted Public Disclosure and Authorship policy. That policy states, “Where Pfizer hires technical support to help analyze and interpret data or prepare manuscripts and presentations, those contracted service providers must work under the direction of the authors.” In other words, there’s no assurance that pro-HT articles still aren’t written by those who are paid by drugmakers.

NAMS also endorses HT in the March 2010 issue of the journal Menopause, but it at least notes restrictions. (The article reveals that 11 of NAMS’ 16 trustees and 10 of 16 advisory-panel members are either paid consultants for, receive funding from or speak for HT-makers.) NAMS cautions that HT is not for women who have a history of endometrial cancer or for older women (no age given) who have a history of smoking. NAMS states that HT also should not be used for primary prevention of stroke, dementia or coronary problems.

HT detractors, however, draw the line more firmly: American Heart Association denies that HT has any heart benefits. United Nations’ International Agency for Research on Cancer has ruled it a carcinogen.

FLAWED FIXES. HT isn’t the only option that women have when it comes to treating the symptoms of menopause. Bioidentical hormones have risen in popularity since 2008, after they were promoted by taste-maker Oprah Winfrey. Unfortunately, there are problems with these HT alternatives.

Bioidentical hormones are plant-based substances that are made by a pharmacist to a patient’s specifications, sometimes by analyzing a woman’s hormone levels. These come in the form of creams, gels, lozenges, suppositories, pills and injections, some of which are available without a prescription.

However, bioidenticals are not approved by FDA. FDA in 2008 issued warning letters to seven pharmacies that make bioidenticals. FDA says the pharmacies claimed that their bioidentical formulations “can be used to prevent or treat Alzheimer’s disease, various forms of cancer, stroke and other serious illnesses” with “no reliable scientific support for any of these claims.”

We found no unbiased studies that certify the safety or effectiveness of bioidenticals. One study, for example, which was in an Australian medical journal in 2007, found a link between bioidentical hormones and endometrial cancer in three women. Of course, that’s too small of a number to be conclusive, and the article was written by an author who was named in the Wyeth ghostwriting investigation. In other words, it was written by a proponent of HT. Other studies that found bioidenticals to be safe are linked to groups that sell bioidenticals.

National Women’s Health Network, which is an advocacy group that takes no money from pharmaceutical companies, says health professionals who promote bioidenticals might have as many conflicts of interest as do doctors who act as HT representatives. The network urges women to scrutinize bioidenticals in the same way that they would HT.

And you should know that bioidenticals might cost more than typical HT. Initial consultations with bioidentical practitioners typically cost at least $400 and involve follow-up visits, lab costs and the price of at least $30 a month for the formulations. This can push the annual cost above $1,000, although prices can vary widely depending on the formulations and the number of required follow-up visits (compared with $900 for HT). Insurers increasingly cover the cost of prescribed bioidenticals and some of the lab costs, although typically at only about half of the lab fees’ cost.  

APPROACH WITH CAUTION. We believe that doctors can help menopausal women best by using HT only for specific symptoms and not for chronic conditions or prevention of diseases.

“My whole treatment program comes from the ‘If it ain’t broke, don’t fix it’ school of thought,” says Dr. Catherine Shanahan of Catholic Medical Center’s Family Health & Wellness Center in Bedford, N.H. Shanahan says that if a woman has menopausal symptoms, such as sleep disruption, irritability, heart palpitations or tingling in her fingers, she sees potential benefits in prescribing HT. (Those symptoms aren’t always linked to menopause.) In these cases, she starts with natural progesterone. It can be used without estrogen—the problem drug, she says—because the body can convert it into estrogen.

Dr. Jerilynn C. Prior, who is a professor of endocrinology at University of British Columbia in Vancouver and the author of “The Estrogen Errors: Why Progesterone is Better for Women’s Health,” echoes Shanahan’s concerns. She believes that the safest course is to use bioidentical oral progesterone for hot flashes only. But, she tells us that low estrogen and progesterone levels of menopause are perfectly normal and not evidence of some disease that needs treatment. Exercise, eating well and maintaining a normal weight is the best care that a menopausal woman can give herself, Prior says.  

In other words, when it comes to dealing with the symptoms of menopause, Mother Nature, not Big Pharma, knows best.

Martha Rosenberg writes about public health. Her work has appeared in the Boston Globe, Chicago Tribune and Los Angeles Times.