From DES to Makena and More: The Dangers of Endocrine Disruptors

endocrine disruptors
Mid-section portrait of unrecognizable woman during last months of pregnancy holding her big belly gently standing against wall in blue room
Emma Yasinski
Emma Yasinski Staff Writer

On this day, half a century ago, a study showed that a drug called diethylstilbestrol (DES) given to pregnant mothers to reduce preterm births, instead raised the risk of a rare vaginal cancer in their daughters to 40 times that of the general population. Since then, scientists have discovered that these so-called DES daughters, sons, grandchildren and the DES mothers are also more likely to experience malformed reproductive organs, breast cancer and a slew of reproductive problems. MedShadow’s founder, Suzanne Robotti, is one of those daughters.   “Between five and 10 million pregnant women were prescribed DES over 30 years,” says Robotti, who is also executive director of DES Action, a member organization for those exposed to DES. “Mothers trusted their doctors when they were told they needed to take this drug to have a healthy baby. Those mothers were devastated when they discovered how misled they’d been, and how they’d taken a drug that harmed their child and become endocrine disruptors.,,

The study was the first to demonstrate that exposure to particular types of chemicals could disrupt a person’s endocrine system, the glands and organs in our bodies that release hormones responsible for guiding our growth, development, metabolism, reproduction and more.  

Since 1971, researchers have continued to follow the women and their children and grandchildren. In April of 2021, 50 years after that initial study, researchers presented results from a study at the Endocrine Society’s annual meeting about the drug Makena, a synthetic progesterone. DES is a synthetic estrogen. The study, finally published on Nov 8, 2021 showed that the children of women who were prescribed Makena during pregnancy had higher rates of cancer than those who were not exposed to the drug in utero. The research also revealed that children, now ages 18 to 58, born to the 181 mothers in the study who had been prescribed the drug, were twice as likely to have any cancer diagnosis, four times as likely to have had prostate cancer and five times as likely to have had colon or rectal cancers.   

But it’s not just DES and the various newer-generation versions of the drug that can disrupt a person’s endocrine system. These exposures are just the easiest to study. “The model endocrine disruptor has always been [DES], which is a synthetic estrogen,” says Barbara Cohn, PhD, an epidemiologist and the senior author of the new study. The drug has helped researchers understand how chemicals can mess with our endocrine systems, but it is far from the only chemical capable of doing so.

Since that first study in 1971, scientists have identified more than 1,000 similar chemicals in our plastics, cosmetics and even foods. It’s more difficult to isolate the effects of these everyday exposures on our bodies, but the research on DES and similar drugs made it clear that these chemicals can cause myriad birth defects and cancers, not only in those exposed, but also in their children and even their children’s children.

The DES Story

After DES was invented in 1938, doctors began prescribing it to pregnant women almost immediately, in hopes of prolonging their pregnancies and increasing the likelihood of a healthy birth. “It was marketed as a way to make normal pregnancy more normal,” says Martha Cody, a DES daughter who has suffered endometriosis and an ectopic pregnancy, likely as a result of her exposure to the chemical.

The first hints that the drug didn’t actually help prolong pregnancy or prevent miscarriages came in 1953. However, with few other options, many doctors continued to prescribe the drug, thinking that it caused no harm, and could possibly help.

“Doctors believed that they were helping people. It was true that this clinical trial in the fifties suggested it didn’t do much. But clinical trials were new in the 1950s,” says Cohn. “And we also have on the other side, patients who are desperate to have babies, who want help. It’s a formula for potential disaster.”

In the late 1960s, eight girls between the ages of 15 and 22 were diagnosed with a rare vaginal cancer, adenocarcinoma (CCA). The cancer was rare for all ages, but especially in a group this young. Researchers made the connection that these girls had been exposed to DES in utero, when their mothers were pregnant and published that  observation in the New England Journal of Medicine on April 22, 1971. The Food and Drug Administration (FDA) then notified doctors that they shouldn’t prescribe the drug. That caused many doctors to reach out to patients to let them know they should be screened for vaginal cancer. Since then, researchers have uncovered increased risks of breast cancer, endometriosis, infertility, malformed uteruses and more.

The Problem Continues

That wasn’t the end of endocrine disruptors. It wasn’t even the end of using synthetic estrogen during pregnancy. After DES was taken off the market in1971, manufacturers introduced a new version, Delalutin. In 2008, the FDA removed that drug, too. Later, the agency approved a  new version called Makena. 

Makena, like its predecessors, has been shown to be ineffective. The Center for Drug Evaluation and Research (CDER) proposed that it, and its generic forms, be removed from the market in March 2021. DES Action advocated for this decision.

“Preterm birth is a really terrible thing that has awful consequences. There aren’t any easy treatments for recurrent preterm birth,” says Cohn. For that reason, Makena had been approved through a special accelerated approval pathway for medicines that treat conditions for which there are no other choices. It was approved long before releasing the Phase III clinical trial results. As it turns out, the trials demonstrated the drug’s lack of efficacy. 

“People are wanting to prevent this and to do a better job at helping women avoid this outcome of their pregnancies,” adds Cohn. She explained that the naturally occurring hormone progesterone is known to “contribute to the quieting of the uterus and to the ability to contain the pregnancy and keep it there. That’s how these treatments were devised.” 

Unfortunately, we’ve seen time and time again that, in practice, these synthetic hormones don’t act upon the body in the identical manner as do naturally produced hormones.

The new study may just be the start of our understanding of the harms that Makena may have caused. As the women age, more effects may become clear, just as they did with DES.

Cohn explains that she and her researchers were inspired to look at Makena’s impacts because the rate of colon cancer in people under 50 has doubled over the past 30  years. However, even the fivefold increase in risk of colon cancer they found among those exposed to Makena in utero can’t explain all 18,000 cases that experts estimate will be diagnosed this year. There must be other factors at play, one of which may be endocrine disruptors seeping into our everyday lives.

Endocrine Disruptors All Around Us

While DES and Makena were designed to have biological effects on our bodies, many endocrine-disrupting chemicals (EDCs) came about by accident. Most were never intended to be consumed, but now they find their way into our bodies as pesticides on food, BPA in our water bottles and  even absorbed through our skin in lotions and cosmetics. We continue to learn about more EDCs , like polyfluoroalkyl substances (PFASs) in our food packaging or the microplastics leaching into the ocean. In the early 2010s, several national and international organizations, including the World Health Organization (WHO) and the United Nations Environment Programme recognized EDCs as a serious threat to the health of both humans and wildlife. 

In 2018, a trio of researchers set out to advance our understanding of endocrine disruptors beyond the synthetic estrogens given to pregnant women. The team researched a variety of chemicals thought to interfere with our endocrine system and published a study outlining four different categories of endocrine disruptors, using bisphenol A (BPA), phthalates, polychlorinated biphenyls (PCBs) and vinclozolin, thereby laying the groundwork for major progress in the field. 

One well-known endocrine disruptor is dichlorodiphenyltrichloroethane (DDT)—the now-banned pesticide. Cohn and her team published a study in April 2021 that showed that the grandchildren of women who’d been exposed to DDT went through puberty at a younger age and were more likely to develop obesity than those who weren’t exposed. The team has been following women who had DDT in their blood during and shortly after pregnancy for decades. A previous study showed that the women and their daughters were both at higher risk for breast cancer than women who were not exposed to the chemical. Since the granddaughters in the current study were a median age of 26, it’ll probably be another couple decades before we know if, like their mothers and grandmothers, they’re at higher risk for breast cancer. 

Other endocrine disruptors in the environment have been linked with lower sperm levels in men and attention deficit hyperactivity disorder (ADHD) in adolescents.

“We know that endocrine disruptors can affect at least three generations. We need a lot more research on what level of endocrine exposure, if any, is safe: can endocrine disruptors accumulate in the body over time to toxic levels? Do different endocrine disruptors have differing effects on the body and the children of those exposed?” says Robotti. “And, most importantly, we need to know how each individual can limit their exposures.” 

Researchers have identified thousands of different chemicals that may act as endocrine disruptors. They’re in canned foods, detergents, toys and brake fluid. One of the most well-known today is bisphenol-A (BPA), found in water bottles, canned foods and other plastics. Since laboratory tests showed that the chemical was capable of disrupting hormones, several countries have restricted its use. The FDA as well as some states have banned BPA in some products, such as baby bottles, but it is still legally used in many others. 

Simultaneously, many companies now make products labeled “BPA-free,” even if they aren’t designed for babies. Researchers have pointed out, however, that exposure to the chemicals used to replace BPA, such as bisphenol S (BPS) and bisphenol F (BPF), may be just as bad for our health as BPA.

What You Can Do

The Endocrine Society offers a  list of ways to minimize your and your children’s exposure to endocrine disruptors at home. The Environmental Working Group provides one as well. Some of the suggestions include: 

  • Read labels
    • On plastic bottles, a #1, #2 or #4 in the recycling sign means that the product is free of BPA, a still commonly used EDC. Shower curtains, raincoats, flooring and outdoor furniture will be similarly labeled for polyvinyl chlorides (PVCs) or “PVC-free,” as will canned food with BPA-free liners. Labels on cleaning supplies, facial washes and detergents also indicate the presence or absence of some EDCs, such as phthalates, known to be a potential risk.
  • Reduce plastic use
    • Use plastic rarely and limit your exposure to it.
    • Keep plastic containers out of the heat and sun, which can cause chemicals to leak from the plastic into food or water.
    • Use only phthalates-free face wipes and cleaning supplies, whose toxic products will be indicated on labels. .
  • Avoid bottled water. Drink filtered instead, whenever possible.
  • Reduce pesticide use at home; bugs have a role in the environment, so try to put up with them. 
  • Wash fruits and vegetables from the store with tap water.
  • Avoid canned food. Cans can be lined with BPA or similar toxic products.

The Endocrine Society regularly advocates for legislation  that helps the public understand endocrine disruptors in their environment and minimize their risks. You can keep up to date on its website

if you were exposed to DES through your mother or grandmother, or think you might have been, go to the DES website to learn more. 

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