In the 1990s, a treatment known as fen-phen — short for fenfluramine/phentermine — captured public attention as a weight-loss miracle. But the wonder drug quickly turned into a nightmare as people taking it started experiencing issues with their hearts, including heart valve disease and pulmonary hypertension (high blood pressure affecting veins in the heart and lungs).

With all the evidence of harm, the U.S. Food and Drug Administration (FDA) withdrew approval of both fenfluramine and a related drug, dexfenfluramine (Redux), in 1997. Phentermine is still available today as a weight-loss drug and has been found to cause cardiovascular side effects.

Fen-phen has since become a prime example of how a medication can induce pulmonary hypertension.

How Does Fen-Phen Work?

Fen-phen is a combination of two drugs: fenfluramine and phentermine. Fenfluramine increases the levels of serotonin — a brain chemical that can act as an appetite suppressant. The more serotonin in the brain, the greater the feeling of fullness a person has.

Phentermine also helps you lose weight by decreasing your appetite, so you consume fewer calories. While each drug individually helped a person lose weight, the effects were much more noticeable when the medications were combined.

Fen-Phen Causes Pulmonary Hypertension and Heart Problems

Although fen-phen delivered on its weight-loss promise, it also led to harmful side effects on the heart and lungs. For example, a French study in 1996 found that using fenfluramine increased a person’s risk for pulmonary hypertension. This risk was higher for people taking the appetite suppressant for more than three months.

The most incriminating piece of evidence came in 1997 when a Mayo Clinic doctor published a study in The New England Journal of Medicine. The research documented the health problems of 24 women taking fen-phen. None of these women had a history of heart disease — but after a year of taking the diet pill, eight developed pulmonary hypertension for the very first time and all of them showed significant heart valve damage. At least five required heart surgery.

How Does Fen-Phen Cause Pulmonary Hypertension?

The problem with fen-phen comes from the very action that helps people lose weight. To raise serotonin levels in the brain, these serotonin inhibitor drugs inadvertently removed the body’s ability to safely get rid of the chemical. Phentermine blocked receptors that would help with the reuptake of serotonin in the brain. Fenfluramine, on the other hand, stopped platelet absorption of serotonin circulating in the blood. Most likely, the excess serotonin forced blood vessels to contract and damaged the ones in the lungs.

Treating Drug-Induced Pulmonary Arterial Hypertension

When a drug leads to the development of PH, it’s known as drug-induced pulmonary arterial hypertension (PAH). Researchers have identified 16 types of compounds associated with drug-induced PAH, including some found in drugs approved by the FDA.

If you suspect you’re developing symptoms of pulmonary hypertension — shortness of breath, swelling of the feet, or chest pain — after taking medication or supplements, it’s important to report your concerns to your doctor immediately. If found early, some of the effects from PAH could be potentially reversible if you stop using the drug. Depending on the damage and how soon you report the problem, you may make a full recovery or find partial improvement in your symptoms.

Phentermine Today

Phentermine, one half of the infamous fen-phen combination, is still in use. Sold under several brand names, phentermine alone is used as a weight-loss drug. Phentermine is only recommended for short-term use — up to three months at a time.

Phentermine is associated with cardiovascular side effects, including palpitations, increased heart rate, and increased blood pressure. There is not a clear link between PH and phentermine the way there is between fenfluramine and PH. However, the drug’s label notes that a possibility of a connection “cannot be ruled out.”

Talk With Others Who Understand

On MyPHTeam, the social network for people with pulmonary hypertension and their loved ones, more than 51,000 members come together to ask questions, give advice, and share their stories with others who understand life with pulmonary hypertension.

Have you ever used fen-phen or another weight loss medication? Have you spoken with your health care provider about how this may have affected your health? Share your experience in the comments below, or start a conversation by posting on your Activities page.