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ROCHESTER, Minn. - A popular combination of weight-loss medications may have caused heart problems in relatively healthy young women, Mayo Clinic researchers and the U.S. Food and Drug Administration said Tuesday.

The diet drugs fenfluramine and phentermine were prescribed to 18 million people last year in a combination commonly called "fen-phen," and may have been responsible for a thickening of the heart valves in at least 24 previously disease-free women.

"We began to notice that otherwise healthy young women, presenting with this unusual form of valve disease, were also on fen-phen," cardiologist Heidi Connolly said in a statement.

The Mayo Clinic physicians found some 24 women with an average age of 43 who had taken the medications for an average of one year had developed cardiovascular symptoms or heart murmurs.

"We don't know how fen-phen may cause injury to the heart valves," Connolly said. "We do know that fenfluramine and phentermine alter the way the brain chemical serotonin is metabolized, and serotonin that circulates in the blood can cause (heart) valve injury."

The valve damage caused blood to leak back into the heart, making it work harder, Connolly said.

Prozac and other popular anti-depressants also work on the amount of serotonin in the brain.

Also Tuesday, the FDA sent a letter to doctors alerting them to possible heart problems associated with the drug combination, and told the drugs' makers to meet with FDA officials to discuss possible labeling changes.

"These are drugs that should be taken only by obese patients in conjunction with a weight loss regimen that includes a reduced-calorie diet and an exercise program," lead deputy FDA Commissioner Michael Friedman said in a statement.

The FDA has received reports of 33 cases of unusual abnormalities in heart valves in women between the ages of 30 and 72 who had been taking fen-phen for as little as one month and as long as 28 months, the FDA statement said.

The FDA referred to the Mayo Clinic study, but noted there was "no conclusive evidence of a cause-effect relationship" between the drugs and heart valve disease. But because the valve problems are so serious and the women who suffer them are obese but otherwise healthy, the FDA said it decided to inform patients and health care professionals.

The Mayo Clinic said its findings will be published next month in the New England Journal of Medicine, which agreed to allow the information to be disseminated early.

Previous research has indicated the fen-phen combination raised blood pressure in arteries between the heart and the lungs in some patients.

The FDA said it will keep monitoring the situation, with special interest in information from patients on how much of the drugs they took and for how long, whether they had a history of heart problems and whether they were taking any other medications on a chronic basis.

Drug maker Wyeth Ayerst Laboratories issued a statement saying it was working with the Mayo Clinic to develop a rigorous study to examine whether the drugs were harmful.

It noted many people taking the drugs were unhealthily obese, the second-leading preventable cause of death in the United States after tobacco, and that some overdo the dosage. In addition, fenfluramine was meant to be taken only for a short time and was not approved for use in combination with phentermine.