You have heard it over and over on TV – drug advertising that touts the benefits of a remedy only to conclude with a laundry list of its potentially harmful side effects.  It is a 30-second emotional roller coaster – a "hey, great" and an "uh-oh" all rolled into one. 

Millions of post-menopausal women felt they had hit the bottom of the ride on July 9, 2002.  That was the day the National Heart, Lung, and Blood Institute (NHLBI) announced they were suspending one arm of their large clinical trial, the Women's Health Initiative (WHI), because the risks of combined estrogen and progestin hormone replacement therapy (HRT) outweighed its benefits.¹  WHI results showed that, instead of protecting women against heart disease as had been initially thought, the therapy could actually increase their risk for that disease as well as for breast cancer, stroke and blood clots.  Women who had been taking the drugs – some for many years – were frightened and confused, and they abandoned their use of HRT in droves.   

In May 2003 the Women's Health Initiative Memory Study (a sub-study of the WHI) reported that HRT may double the risk of Alzheimer's disease and other dementias in women over 65.²  In March 2004 WHI suspended the estrogen-only arm of the study because they found it can put women at increased risk of stroke.³   Then, in October 2004 WHI investigators reported that HRT increases breast density, making breast cancer more difficult to detect.⁴

How could this happen in an era where drugs go through such a long period of development, testing, and review?  The short answer is that no drug will ever be 100 percent safe for every individual.  Raymond Woosley, MD, Ph.D., the founding President and Chairman of the Board of The Critical Path Institute (a non-profit corporation formed by the Food and Drug Administration) said in an interview for the PBS program Frontline: Dangerous Prescription, "I think Americans need to recognize that every time they put a pill in their mouth, especially a new pill that they've never taken before, it's an experiment. How big an experiment depends on the pill and how well it's been studied...Even the old [drugs] that we think we know a lot about, we're learning every day that we missed something along the way.  At the same time, I have to say we know more about a new medicine today when it goes on the market than we've ever known before."

What, you ask, about the clinical trials required by the Food and Drug Administration before a new drug can be brought to market?  Trials have limitations.  Phase III clinical trials, the final stage before a drug is approved for sale, are generally conducted on patient populations of 300 to 3,000; they can not show that a drug is risk-free for all individuals.  They also must, of necessity, be of limited duration and can not show whether a drug might have unexpected long-term side effects.  The FDA has a tough job.  Do you get promising new drugs to people who need them as soon as possible or do you slow the process down to study risks more fully?  There are compelling arguments on both sides.           

Today, the HRT debate continues.  Based on further analysis of WHI data as well as new information from follow-up studies, scientists now believe:

• Age is a crucial factor.  After looking at data for different age ranges in the WHI age 50 to 79 population (average age 63), investigators think healthy women between 50 and 59 and those who begin HRT less than 10 years after starting menopause may not be at increased risk for heart disease or impaired cognition.
  
  
• Pre-existing conditions and lifestyle must be considered.  Many of the WHI study group were former smokers, obese and had a history of hypertensive disorders.⁵   However, this doesn't mean they are not representative of the population of women who will need to make a decision about HRT.  Second Opinion panelist and Immediate Past President of the Board of Directors of WomenHeart, Kathy Kastan reveals, "Eighty percent of women age 40 to 60 have one or more risk factors for heart disease."
  
  
• Treatment for menopausal symptoms should start with the lowest effective dose. The dose of 0.625 mg/day used in the WHI study was higher than many lower-dose versions available today.
  
  
• Women who use HRT for two to five years are less likely to be at an increased risk for breast cancer in the short term (long-term risk is still unknown).  An increased risk of breast cancer was seen only in women who had taken HRT prior to study entry.

¹ NHLBI Stops Trial of Estrogen Plus Progestin Due to Increased Breast Cancer Risk, Lack of Overall Benefit; Press Release; July 9, 2002.
² Rates of Dementia Increase Among Older Women on Combination Hormone Therapy; Press Release; May 27, 2003.
³ NIH Asks Participants in Women's Health Initiative Estrogen-Alone Study to Stop Study Pills, Begin Follow-up Phase; Press Release; March 2, 2004.
⁴ HRT Doubles Breast Density, Abnormal Mammogram Possible; Healthcare in the News, October 20, 2004.  Article on presentation at meeting of the American Association for Cancer Research; Lead researcher Dr. Anne McTiernan.
⁵ Issues to debate on the Women's Health Initiative (WHI) study. Epidemiology or randomized clinical trials-time out for hormone replacement therapy studies?; Human Reproduction, Vol. 18, No. 11, 2241-2244, November 2003.

Learn more about Hormone Replacement Therapy:

Key Point 1: Research brings out new and sometimes confusing information all the time.  It can be frustrating for patients and doctors alike.  You need to stay in touch with your doctor to make sure that your care is as up to date as possible. 

Key Point 2:  Hormone replacement therapy is a viable option for some women.  As with any other therapy, there are pluses and minuses.  There is controversy around HRT.  All those TV reports are not about you.  You really need to talk with your doctor about your specific risks and benefits.