But nearly 60 years after “The Pill” first came on the market, scientists still don’t understand exactly why oral contraceptives cause a heightened risk for blood clots.
Two Colorado School of Mines professors hope to unravel that medical mystery with help from a five-year $3.4 million grant from the National Institutes of Health.
Keith Neeves, associate professor of chemical and biological engineering, and Nanette Boyle, assistant professor of chemical and biological engineering, are the co-lead investigators on a National Heart, Lung and Blood Institute project to identify the mechanisms by which sex hormones – the effective ingredients in oral contraceptives – modulate platelets, a key agent in the formation of a type of clotting disorder called venous thromboembolism, or VTE.
Together with a team of hematologists and gynecologists at CU Denver, Children’s Hospital of Colorado and the National Cancer Center in Aviano, Italy, the two Mines professors will take a systems biology approach to the question, looking at how coagulation and platelets work together to form clots.
“There’s been a long-known relationship between oral contraception and venous thromboembolism, a type of thrombosis, but how that relationship actually works is a little up in the air,” Neeves said. “We’re bringing a different skill set to the table. This approach is called systems biology, and the idea is that it’s not so reductionist, where you’re always trying to break things down. You’re essentially trying to put things back together to understand how things work across an entire system.”
To do that, researchers will follow a cohort of premenopausal women prior to and for two years after the start of oral contraceptives, doing extensive blood workups every four to six months. At Mines, Neeves and Boyle will use a combination of computer modeling and laboratory experiments to create predictive tools to better understand their risk of clots.
“What Nanette and I do is build computer models of systems to make predictions. We can take out some of the empiricism and correlative nature of this field – if we know X, Y and Z about somebody, we can make some predictions on how they will respond to estrogen or progesterone or some other drug,” Neeves said.
Neeves is an expert in platelet physiology, while Boyle specializes in metabolism. Boyle’s part of research will focus on measuring how metabolism changes in response to estrogen, as well as modeling those changes.
“There are some known hormones that affect the clotting process that come from metabolism, namely lipids and fatty acids,” Boyle said. “We want to see how metabolism plays a role in clotting and if certain responses make the platelets more sticky and likely to clot.”
The ultimate goal is to identify specific genetic traits or other factors that may increase the risk of women developing clots while on oral contraceptives. In one relevant case study, a common genetic mutation among people with Northern European ancestry was shown to increase the risk of developing a VTE some eightyfold.
“The risk of venous thromboembolism with oral contraceptive use is significant but it’s also small – you’re at three to four times the risk level of somebody not on oral contraceptives, but the risk for a healthy woman to have a VTE is really low,” Neeves said. “What we want to do is be able to identify who are those people who are at higher risk. Right now, we blanket it – everyone who is on oral contraceptives gets this warning that you may be at a higher risk for clotting, but ideally you’d be able to identify those people a priori and either not put them on oral contraceptives in the first place or have them be monitored a little more closely.”
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