How ‘everywhere chemicals’ help uterine fibroids grow

Common chemicals called phthalates found in hundreds of household products have been linked to uterine fibroids—non-cancerous tumors ranging from the size of a seed to a soccer ball that grow in or around the uterus. These fibroids affect millions of women and can cause pelvic and back pain, heavy menstrual bleeding, pain during sex, or reproductive problems.

Phthalates are known to interfere with hormones and have been the subject of health research for over a decade. Several studies have identified greater risks of fibroids among women exposed to these chemicals. In a 2017 analysis of five studies, researchers from China found increased risks of fibroids in women with escalating levels of byproducts of one phthalate called DEHP—a chemical that’s commonly added to plastics to make them flexible—in their urine. In a 2019 preliminary study, Ami Zota, an environmental health scientist now at the Columbia University Mailman School of Public Health, and her colleagues found that higher levels of phthalates in urine, particularly byproducts of DEHP, were associated with larger fibroids and an enlarged uterus in Black women in the United States undergoing surgery for fibroids.

In the U.S., an estimated 26 million women between the ages of 15 and 50 have uterine fibroids, and more than half of them will experience its debilitating symptoms. Currently there are no medications that can permanently reduce the size of the tumor. These tumors can shrink on their own, particularly after menopause, and many women may not need treatment unless the symptoms become hard to manage.

Some medications can alleviate the symptoms, but surgery is the only option when the drugs prove ineffective or the fibroids make it hard for a woman to get pregnant. Patients can opt for treatments like a myomectomy to surgically remove the fibroids, which can be minimally invasive and preserve the uterus, but in certain situations a hysterectomy to remove the uterus becomes necessary.

Even though uterine fibroids are incredibly common, Zota says, they’re poorly understood.

Scientists don’t know what causes these growths, although genetic mutations, sex hormone imbalance, and risk factors like age, race, obesity, and synthetic chemicals have been linked to them. But a recent study found that exposing fibroid cells to a metabolic byproduct DEHP stimulated the growth of these cells in the laboratory and delayed their death.“We’re not saying that phthalates start the tumors,” says gynecologist Serdar Bulun at the Northwestern University Feinberg School of Medicine, who led the research. “However, phthalates help these tumors grow to large sizes.” His team identified a molecular pathway that fosters the survival and growth of these tumor cells, providing strong mechanistic evidence connecting phthalate exposure with fibroids.

This research reinforces the link between these ubiquitous chemicals and a disease that’s greatly underappreciated, says Tracey Woodruff, a University of California, San Francisco, scientist studying the impact of environmental contaminants on reproductive health who wasn’t involved in Bulun’s research.

But phthalates are poorly regulated, Zota says, and almost impossible to avoid.

How phthalates enter our body

Called “everywhere chemicals,” phthalates are a family of chemical compounds that are manmade and often used as plasticizers to lend softness, flexibility, and durability to materials like polyvinyl chloride or PVC—one of the most widely used plastics—and synthetic rubber. They are present in many household items ranging from food packaging and processing equipment to shower curtains, building materials, and car interiors. Phthalates are also used as solvents in cosmetics and other personal care products and to coat or encapsulate certain pharmaceutical pills and dietary supplements.

The chemicals can leach out of these products and enter food, air, and water, meaning people can swallow, inhale, or absorb these phthalate particles through direct skin contact. The body then metabolizes these chemicals, yielding byproducts that several studies have detected in human urine, breastmilk, and blood.

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While the U.S. Environmental Protection Agency often uses animal studies to determine safe exposure levels for humans, research suggests that certain phthalates can cause adverse effects on human health even at levels below the defined thresholds. For example, exposure to low levels of phthalates like DEHP, DBP, BBP, and DIBP during pregnancy were associated with neurological issues, including delayed cognitive development and memory impairment in children. These chemicals have also been linked with genital abnormalities in baby boys.

How phthalates impact uterine fibroids

In laboratory experiments, scientists have found that DEHP exposure allowed uterine fibroid cells in petri dishes to live longer and multiply more.

It’s also known that many fibroid cells harbor mutations in a gene called MED12, which may trigger tumor formation. The mutation may happen in a single stem cell, Bulun says, and then the cells just keep dividing and form the entire tumor. DEHP can enhance this process.

In a November 2022 study, Bulun and his colleagues demonstrated the molecular mechanism behind how a major DEHP byproduct called mono-(2-ethyl-5-hydroxyhexyl) phthalate affects tumor cells. Scientists often study such phthalate byproducts because the body rapidly breaks down the parent compound an individual may have been exposed to, yielding a family of metabolites that are excreted in the urine. The team found that the chemical helps tumor cells absorb an amino acid called tryptophan that gets converted to a compound called kynurenine which activates a protein receptor called AHR (aryl hydrocarbon receptor) that is known to initiate cancer. This active receptor promotes the growth of fibroid cells leading to larger growths.

“We’re thinking that if we can target and stop the conversion of tryptophan to kynurenine, then we can stop or block AHR activation,” Bulun says, “which could stabilize the tumors or shrink them.”

Living with uterine fibroids

While living with symptomatic uterine fibroids can be physically painful, the emotional toll of undergoing a hysterectomy for women who still aspire to get pregnant is heart-wrenching, says 46-year-old Saudia Davis, based in Chicago.

In August 2021, her fibroids had grown rapidly. Her tummy bulged. “I went from appearing to be four months pregnant to seven months,” Davis says. But the tumors were causing tremendous pain in her left butt cheek and with every sneeze or cough, she would feel a bit of incontinence. Davis underwent a hysterectomy that year. “I had to reconcile with the fact that I can’t bear my own child,” she says. “My fibroids were so large and encased in the uterus, they had to go.”

Neither Davis nor her doctors know why she developed these tumors in the first place or what triggered their sudden growth. Research shows that compared to white women, Black women like Davis are two to three times more likely to have uterine fibroids and their tumors tend to be larger and more numerous, leading to severe symptoms and higher rates of hysterectomy. Why they face heightened risks remains unclear.

She wonders if it was the hair relaxers she used from a young age until she was 42 years old to straighten her curly hair. These products can contain phthalates and their use could potentially be linked to uterine fibroids.

But it’s not easy to establish causation, says environmental health scientist Kyungho Choi at South Korea’s Seoul National University. The time it takes for phthalates to break down in our body is hours, he says, and the levels can fluctuate over a couple of orders of magnitude every day. Knowing the exposure levels when the disease initiates is also important, Choi adds, but almost impossible to determine in the real world.

While we cannot change our age, our sex, or genetics, “we can still reduce the amount of chemicals we use,” he says. “Their contribution may be small, but we still have a handle on it.”