Physician Referral Online

A free and confidential service
of Yale-New Haven Hospital.

Physician Referral Online
Using your own criteria, you can request information from a database of 900 area physicians who have registered to participate.

Request an appointment
We would be happy to assist you in scheduling an appointment with a member of the hospital's medical staff. Use the link above or call:

203-688-2000
or toll free
1-888-700-6543
to talk with a referral coordinator.

For the 12th year in a row, Yale-New Haven has been highly ranked by U.S. News & World Report for its programs in gynecology.

PPA and the risk of hemorrhagic stroke

The Hemorrhagic Stroke Project was motivated largely by a handful of reports that first emerged in the early 1980s that suggested young women who had hemorrhagic strokes had reported taking diet medications containing the chemical PPA. Then, in 1990, Senator Widen of Oregon held hearings about the ingredient, and those hearings, combined with the earlier reports, prompted the study.

Phenylpropanolamine has been around since the 1930s, and as the FDA implemented new safety measures throughout the years, PPA was grandfathered in for these more stringent tests of safety and efficacy. PPA is, or was, extremely common in over-the-counter (OTC) preparations. Billions of doses were taken each year in cough and cold medications as well as appetite suppressants. It was the eighth most common ingredient found in OTC medications.

Study part of larger look at stroke
The study was a challenge to design for several reasons, including the relative rarity of hemorrhagic stroke in the population. It took us more than five years to design the study and to compile enough data to draw meaningful conclusions. This study turned out to be the largest study of the causes of hemorrhagic stroke in young people ever done.

Our interest in PPA and stroke is really part of our broader interest in hemorrhagic stroke among young people and the role of various risk factors such as smoking, oral contraceptives and heredity. Our report in the New England Journal of Medicine is the first of several papers we will publish based on this unique dataset.

PPA associated with hemorrhagic strokes
The results, somewhat to my surprise, did show an association between PPA and hemorrhagic stroke—in fact, women who took PPA experienced a three to 16-fold increase in the risk of hemorrhagic stroke compared to those who did not use PPA products.

The absolute risk, however, is exceedingly small. We would estimate the probability of taking a pill with PPA and having a stroke to be between one in 500,000 and one in three million doses of PPA.

Study limitations
Many of the critics of the study failed to understand why and how the study was designed. As with any research project, questions remain that were beyond the scope of our work such as whether men are at risk as much as women and whether cough and cold medications present the same risk as appetite suppressants. To answer these questions would have required additional patients and several more years of study.

Once we identified the existence of a potential health risk, our obligation was to share our findings with the FDA. We worked to define the presence of an increased risk for stroke. It is the FDA's responsibility to develop policy.

Risk vs. benefit of PPA
When formulating its policy, the FDA considered the risk versus the benefit of these medications. In the case of cough and cold drugs, there is considered to be a well-established beneficial effect; however, there were several alternatives to PPA. There is not as much evidence that PPA is effective for weight reduction in diet medications.

What to do
Since manufacturers have removed these products from market shelves, the question about PPA is relatively moot. PPA is no longer available in OTC medications in the U.S. However, because of the popularity of these products, there are many people who probably still have them in their homes.

Should you dispose of them? As I have said, the absolute risk is very small, but my experience has been that people are more comfortable, particularly if they have small children, without PPA products in their medicine cabinets. And, I might add, my wife removed all of these products from our home before I had time to consider the decision for our family.

Duration of increased risk
Some people who have taken these products over the years may be concerned about the residual effect on their health. Our study found an increased risk only among those who had taken the substance within a three-day period, and this risk was concentrated in the first 24 hours.

Over the next few years, my colleagues and I will be releasing several additional findings from our investigation into the role of risk factors and hemorrhagic stroke that will have a larger impact in terms of the number of affected young men and women.

Dr. Brass is a professor of neurology and epidemiology and public health at the Yale University School of Medicine and an attending neurologist at Yale-New Haven Hospital. He is also chief of neurology at the VA Connecticut Healthcare System.