Hormone therapy controversy raises drug safety issues

The history of hormone therapy drugs – once thought of as almost magic pills to keep women healthy, vital and young – shows why it is so important to conduct research studies to identify the risks and benefits of drugs, say researchers from Wake Forest University Baptist Medical Center.

“The hormone therapy debate is one more example of a larger issue: are the medications that doctors prescribe safe, and do the benefits outweigh any risks?” said Michelle Naughton, Ph.D., lead author of an article in the current issue of Journal of Social Issues.

The researchers review the 75-year history of hormone therapy (HT), including the Women’s Health Initiative (WHI) research that found increased risk of breast cancer, dementia, heart attacks and strokes in women taking combination hormone therapy – and increased risk of strokes in women taking estrogen alone. Naughton and co-authors Alison Snow Jones, Ph.D., and Sally Shumaker, Ph.D., all from Wake Forest Baptist, examine why there has been so much controversy surrounding the research findings and why many women and physicians are reluctant to accept the “lost promise” of HT. HT gained popularity in the 1950s and 1960s and is considered the best treatment for hot flashes and night sweats, which affect as many as two-thirds of menopausal women in the United States. But HT was also marketed as a way women could retain a youthful appearance and stave off the aging process and was prescribed for prevention of heart disease and dementia.

What began as a therapy for bothersome menopausal symptoms that dissipate within a couple of years for most women, became a potential long-term therapy for the prevention and treatment of three of the most common health issues for women – heart disease, dementia and osteoporosis, write the authors. “The intent was good,” said Naughton, an associate professor of public health sciences. “There was some evidence showing the drugs might be beneficial for heart disease and dementia,” she said, “but the WHI, a large-scale, scientifically conducted clinical trial, found otherwise.”

Yet even after the WHI research, which the authors say the Food & Drug Administration found to be definitive, controversy continues about the study results and about use of HT. “In the face of such strong evidence that, at a minimum, HT does not help the postmenopausal woman beyond the osteoporosis benefit … and can actually harm the aging woman, why has there been resistance among many physicians and women to changing beliefs and practice patterns?” the researchers ask. They conclude that the conflicting interests of women, physicians and drug companies played a role in the popularity of HT (at one time it was one of the most commonly prescribed drugs in the United States) and fuel the continued controversy. They examine the issue from the perspectives of the various stakeholders. For women in the United States, who can expect to live a third or more of their lives after menopause, the stakes are a higher quality of life through their later years. In spite of evidence to the contrary, some women continue to believe that hormone therapy will provide them with better health, the authors said.

Health care professionals are influenced by the needs of their patients and well as information provided by drug manufacturers. In addition, they make their decisions based on years of clinical experience with HT, and may be reluctant to change prescribing patterns based on research findings that small numbers of study participants suffered adverse affects. “Physicians have learned that hormone therapy does provide relief to their patients,” the authors write. “How can a drug that does such immediate good, and that appeared to do such long-term good, be so wrong?”

For hormone manufacturers, the stakes are millions of dollars in revenue. HT revenues were reported to be about $2.5 billion a year prior to the WHI study and sales fell to $266 million in the first quarter of 2004. Drug companies work to identify and promote drugs that offer the most promise to patients, but also must consider benefits to their stockholders.

Naughton said the HT controversy, as well as recent controversy surrounding Vioxx and other pain medications, raise issues about drug safety. “Implications of these controversies are the need for better mechanisms for establishing drug safety and monitoring, including the reporting of negative as well as positive trials of new or approved drugs,” she said.