He Said, She Said
Date: May 14, 2012
Every day, Marlene Williams sees heart attack patients in the cardiac care unit who arrive in a dark mood. “I worry that they won’t take their meds and follow up,” says the Johns Hopkins Bayview cardiologist and CCU director.
We know that men and women with heart disease and depression are at higher risk for heart attacks and mortality, she says. And we know that women are twice as likely to suffer from depression. But does that mean depressed women are also more likely than depressed men to develop heart disease? When a grant to study gender-specific medicine from the Legato Foundation came through, Williams seized the chance.
For clues, she turned to her research on the role of platelets in heart disease. Working alongside cardiologist Roy Ziegelstein, who studies heart disease and depression, Williams is focusing on brain-derived neurotrophic factor (BDNF). Depletion of this protein, she explains, can lead to decreased survival of brain cells found in depression. But BDNF is of special interest to Williams because it’s stored in platelets. The new grant could help her flush out any connection between abnormal platelets, depression, and heart disease and—if she’s lucky—turn up a gender connection.
“We’ve already learned our lesson that men and women are different when it comes to heart disease,” Williams says. “Wouldn’t it be great if simply adjusting medications to increase BDNF levels for certain patients could prevent both heart disease and depression?”
Like Williams, fellow Legato awardee Jennifer “Jenna” Mammen is probing the role of gender biology, but in the prevalent condition autoimmune thyroid disease, in which the body builds an immune response against its own thyroid tissues. Found more in women, it can be either rapidly progressive or transient.
Mammen, an endocrinologist, and her rheumatology colleagues hope to understand who’s more likely to develop thyroid progressive dysfunction and why. In their studies with the immune overseer interferon, they found that almost 20 percent of patients taking interferon for hepatitis C will develop some thyroid abnormalities. What surprised Mammen was that, 9-to-1, those who developed a particularly symptomatic form of the problem were women.
Now she plans to compare characteristics between the thyroids of men and women about to have interferon therapy and match these with outcomes. Learning more about the mechanism from this group, she says, could help her develop ways to preserve thyroid function and blunt the autoimmune response in all thyroid patients. Already, Mammen’s research is changing the way she’s practicing medicine. A single flare-up in an abnormal thyroid—with interferon therapy or in postpartum women, for example—may not require long-term treatment, she says. “We need to step back and assess what’s happening to the patient over time. Less may be more.”
Using a similar approach, endocrinologist Kendall Moseley is comparing metabolic bone disease in men and women with type II diabetes, thanks to her Legato grant. Looking at living bone tissue and cells, she’s measuring bone quantity and quality by gender, to help determine why men and women with type II diabetes experience bone fractures.
Patients with diabetes, she says, may have decent bone quantity based on DXA scans but tend to fracture hips and other bones more frequently than they should. Though the quantity of the bone may be fine—particularly in men—the bone construction, or quality, could be shoddy. “Treating bone disease is not a one size fits all,” she notes. So when Moseley sees a female patient with fragile bones, she digs deeper, asking when she got her period or entered menopause and about any history of thyroid trouble or other endocrine problems. Studying the cells within the bone, she says, should tease out the mechanisms of bone loss on a molecular level.
And, she adds, though most osteoporosis research is focused on women, millions of men experience rapid bone deterioration, often because of prolonged use of steroids or anti-hormone therapy, such as that used in prostate therapy. “Just because men don’t go through menopause doesn’t mean their bone quality is uniformly better,” she says. Exhaustive gender medicine studies like these, she adds, could prevent devastating bone fractures for both sexes. Judy F. Minkove