Chrono

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Her Health
by Leslie Laurence

Chronobiologists Develop Treatments Using Body's Rhythms

Women's menstrual cycles are more likely to start in the morning. Heart attacks are more likely to occur within a few hours of awakening. Women are most apt to go into labor in the late evening or early hours after midnight. And asthma attacks are more likely to occur in the middle of the night.

Coincidence? Hardly. All of these conditions or bodily processes are governed by circadian rhythms, or our biological clocks.

"When we look at the physiology of our system we find it is not constant over time but is programmed in time," says Michael Smolensky, Ph.D., director of the Hermann Center for Chronobiology and Chronotherapeutics in Houston. "The day-night patterns in diseases are due to the underlying biological rhythms within our body." Likewise, our menstrual and hormonal cycles can demonstrate rhythmic abnormalities.

Tracking biological rhythms, which are controlled by a master clock in the brain, has enabled chronobiologists to develop specially formulated medications that deliver more of a drug to the body when symptoms are most severe. The goal is to both enhance effectiveness and reduce drug side effects.

"Chronotherapeutics has tremendous potential," says Smolensky. "Although it has been in practice for a while, it's unrecognized by the medical community in many cases."

A recent Gallup Poll of 320 primary care doctors, conducted for the American Medical Association and presented in late February at a meeting in New York City, found that 75 percent to 80 percent of doctors are aware that circadian rhythms influence hypertension (high blood pressure), chest pain, asthma and migraine headache.

But 42 percent do not think the onset of menstruation occurs at a certain time of day, and roughly one-third do not know that there is a time of day in which hay fever and rheumatoid arthritis symptoms worsen, or when labor occurs.

All this circadian flux can have a major impact on treatment. For instance, because people have their most dramatic increases in heart rate and blood pressure in the hours after waking up, they're more likely to suffer heart attacks and some strokes in the morning.

People with high blood pressure who use conventional medication, however, have less of the drug in their bodies when they need it most. In contrast, Covera-HS, a recently approved chronotherapy for hypertension and chest pain developed by Searle, gears medication to circadian changes in heart rate and blood pressure.

"The medication is taken at bedtime instead of first thing in the morning," says Dr. William White, M.D., professor of medicine at the University of Connecticut School of Medicine.

The drug, which is released into the bloodstream hours later, packs its most powerful punch between the early morning hours and noon, when blood pressure and heart rate rise most precipitously. As pressure drops in the evening, the concentration of the drug wanes, says White, who participated in clinical trials of the new formulation.

The next step: a study of 15,000 patients to learn whether Covera-HS is better than existing blood pressure drugs at lowering the incidence of morning strokes and heart attacks.

Chronotherapy is also being applied to a number of women's health concerns. Studies suggest, for instance, a higher cure rate for women who undergo breast cancer surgery the week after ovulation rather than around the time of menstruation.

To prevent preterm delivery, which is more apt to occur in the late evening, doctors are having women administer medication at home in the late afternoon and early evening.

At the University of California, San Diego, Medical Center, Dr. Barbara Parry is studying the timing of bright light and sleep therapy for premenstrual depression and infertility. She says chronobiology may also provide clues to treating postpartum depression and the mood swings that affect some women at menopause.

Asthma also responds to timed treatment. "Most physicians are taught to give equally divided doses of (the drug) theophylline twice daily so there's a relatively constant blood level," says Dr. Richard Martin, head of the pulmonary division at the National Jewish Center for Immunology and Respiratory Medicine in Denver. But a specially formulated once-daily tablet taken at 7 p.m. delivers more medication at 3 a.m. to 5 a.m., when the lung function of asthmatics is worst, says Martin.

Likewise, because hay fever symptoms peak in the early morning, taking an antihistamine in the evening instead of during the day helps prevent symptoms before a person wakes up, Martin says.

Administering medication to people with rheumatoid arthritis at night provides a higher concentration of the drug in the morning when their pain is most severe, says Gaston Labrecque, Ph.D., professor of pharmacology at Laval University in Quebec. Taking medication for osteoarthritis at noon helps relieve the pain that peaks at night, he says.

As promising as chronotherapeutics are, Smolensky cautions people not to change doses on their own. That's because most drugs have not been tailored to match our biological rhythms. "Taking a conventional dosage all at once to mimic a chronotherapy may lead to adverse effects," he warns. For more information on chronotherapy: Contact the Hermann Center for Chronobiology, 6410 Fannin, Suite 833, Houston, Texas 77030. (Leslie Laurence is the co-author of "Outrageous Practices: The Alarming Truth About How Medicine Mistreats Women" (Ballantine).)

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