A drug given to pregnant women in the mid-20th century may be partly to blame for rising cancer rates in younger adults, a new preliminary study suggests. And the same drug, administered later in pregnancy, is currently the only one available in the U.S. to prevent preterm births in women who previously experienced one.
Researchers discovered that mothers who received the drug 17-OHPC, or 17α-hydroxyprogesterone caproate, early in pregnancy were more likely to have children who would develop various cancers between ages 18 and 58. Epidemiologist Caitlin Murphy, an assistant professor at the University of Texas Southwestern Medical Center, will present an abstract of these preliminary findings March 23 at ENDO 21, the Endocrine Society's annual conference.
Using data on 14,507 women receiving prenatal care or giving birth from 1959 to 1967, along with the California Cancer Registry, Murphy and her colleagues from the Child Health and Development Studies, a nonprofit run by the Public Health Institute, found an especially high risk of colon cancer in children whose mothers received 17-OHPC, known then as Delalutin.
Overall, the researchers found 954 instances of cancer in the cohort of 18,751 live births, with 20% being breast cancer, 7.1% colorectal and 10.9% cervical. But for the 181 mothers who received the drug, the risk of colon cancer in their children was about five times greater than those who were not exposed, and the risk of prostate cancer was three times higher.
"It's just quite striking to me how much of a strong and consistent association we saw across the board," Murphy said. "Even though, relatively speaking, we had a small number of cases, we're still able to detect these really strong and consistent associations, and perhaps may explain why we're seeing those rates of cancers increasing in younger adults."
In the mid-20th century, 17-OHPC was primarily used during early pregnancy, from days one to 140 of gestation, to help prevent miscarriage. Today, the drug is still available under the brand name Makena. It was approved by the U.S. Food and Drug Administration in 2011 to help prevent preterm births in women who had previously experienced one.
But last year, an FDA panel proposed Makena's withdrawal from the market after a manufacturer study failed to find any clinical effectiveness at preventing preterm births, leaving OBGYN doctors with tough decisions and few alternatives.
"Let's say for 10 years you've been using this drug to help women with preterm birth, and then suddenly a new trial comes out that totally challenges what you've thought about this drug for 10 years," Murphy said. "Even though the evidence might be compelling, I think sometimes we have to appreciate that it really challenges what someone's done in their clinical practice for a long time, and [they] want to take their time evaluating the evidence."
Because Makena is used to prevent preterm birth, not miscarriage, it is used later in pregnancy than Delalutin was. And while, after only 10 years of later-term use, it is still too early to tell if 17-OHPC can raise cancer risk in grown children, it is a type of synthetic hormone, which are sometimes known as endocrine disruptors because they disrupt natural endocrine processes in the body. According to Murphy, prior research has linked hormone disruption to cancer, and the use of synthetic hormones during pregnancy could disturb vulnerable, growing cells and affect what happens to them later in life.
"The fact that you see these elevated risks with all sorts of different types of cancers really emphasizes the importance of that critical period of growth and development, where the entire fetus is going to be susceptible to the effects of these drugs," Murphy said. "We don't know the exact mechanism, but we certainly believe that it has something to do with disrupting that pattern of signaling and endocrine function in the body."
In future research, Murphy would like to work with toxicologists and look to animal studies to figure out the biological mechanism between the elevated risk of cancer and 17-OHPC.
"I think the important thing is to show that things that happen in utero, during those really early and critical periods of development, have a lifelong impact on our risk of cancer," said Murphy. "We can clearly see that here and with just a small number of people who are exposed to the drug in utero."
The abstract, "In Utero Exposure to 17α-Hydroxyprogesterone Caproate May Contribute to Increasing Incidence Rates of Early-onset Cancer," to be presented March 23 at ENDO 21, was authored by Caitlin C. Murphy, University of Texas Southwestern Medical Center; and Piera M. Cirillo, Nickilou Y. Krigbaum and Barbara A. Cohn, Child Health and Development Studies, Public Health Institute.