The menopausal transition—or “The Change”—can cause any number of uncomfortable symptoms in women.

With an average onset of age 51, menopause can trigger hot flashes, sleep problems, mood changes, depression, irritability and a decrease in libido.

But while all women are susceptible to these sometimes severe symptoms, few effective and safe treatments have been developed. The National Institutes of Health is addressing this dilemma by launching the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) initiative, a new multi-center study to conduct clinical trials of promising new menopausal treatments, of which the Penn School of Medicine is part.

Ellen W. Freeman, research professor and co-director of the Human Behavior and Reproduction Unit in Obstetrics and Gynecology at the University, is heading the Penn segment of the study, which will address hot flashes, the primary complaint of nearly three-quarters of menopausal women.

“What we’re looking at is what are associations between reproductive hormones and symptoms that arise around the time of menopause,” she says.

Freeman says the actual cause of hot flashes is unknown, but a common theory is that they involve thermo-regulatory control in the brain, which may be affected by changes in reproductive hormone levels. Reports from the Study of Women’s Health Across the Nation have shown that African-American women experience more hot flashes than Caucasian women, and Asian women suffer fewer hot flashes than both.

Estradiol, a form of estrogen, is currently the only Food and Drug Administration-approved treatment for hot flashes, Freeman says. More effective treatments have not been researched because the drug, which has been used for decades, is so effective.

But it may not be without its faults. Recent findings by the NIH’s Women’s Health Initiative, launched in 1991 to address the most common causes of death, disability and poor quality of life in postmenopausal women, have warned of some increased health risks of taking hormone therapy, including higher rates of breast cancer and cardiovascular disease, which has caused some women to avoid using the drug.

The drug has some unpleasant side effects, too. Estradiol can cause prolonged periods, breast pain, breast enlargement, changes in libido (decrease or increase), abdominal pain, migraine headaches and eye irritation.

Penn’s MsFLASH study, set to begin in June 2009, will look at medicated and non-medicated approaches to treating hot flashes. It will utilize escitalopram, a selective serotonin reuptake inhibitor (SSRI) marketed as Lexapro and prescribed to treat anxiety or depression.

“The reason for looking at that is serotonin is known to affect various mood issues,” Freeman says. “There may be some connection with these menopausal hot flashes as well. We predict that people treated with Lexapro will have fewer hot flashes.”

Yoga, relaxation breathing, exercise programs and other forms of drug-free treatments will also be studied. Freeman says yoga is being examined because it is a good relaxation technique.

“There’s some evidence that tension and anxiety make these things worse so yoga is probably very good for relaxing and maybe will help reduce hot flashes,” she says.