By Pamela Ferdinand
Endocrine-disrupting chemicals (EDCs) — substances that interfere with the body’s hormone systems — may contribute to a wide range of female reproductive health problems, including reduced fertility, early or delayed puberty, premature menopause and polycystic ovary syndrome (PCOS), according to a new review of more than 250 human and animal studies.
Researchers increasingly suspect that environmental toxins, detected in everything from urine and blood serum to breast milk and amniotic fluid, play a significant role in increasingly common female reproductive health disorders.
EDCs include a wide array of everyday chemicals in our environment that are produced and marketed by industry. They include plastic additives such as phthalates and bisphenols in food packaging, household items and personal care products, as well as pesticides that contaminate soil, water, air and food.
Published in May in Nature Reviews Endocrinology, the article underscores the urgent need for stronger female reproductive health protection laws and regulations to limit EDC exposure throughout life, starting in early development.
Reproductive health problems linked to EDCs not only increase infertility risk but may also raise the chance of other conditions like heart disease and osteoporosis.
The review found that EDCs impact female reproductive health in multiple ways, including:
- Reducing egg (ovum) supply and quality.
- Interfering with ovarian follicle growth and speed up egg loss.
- Increasing the risk of early menopause.
- Disrupting the timing of puberty.
- Contributing to rising rates of PCOS.
- Lowering the success of fertility treatments like in vitro fertilization (IVF).
“This Review highlights some critical processes that are essential to female reproductive health and presents compelling evidence that EDCs disrupt ovarian development and function,” the researchers say.
They noted that multiple factors can influence female fertility and reproductive health, such as genetics, lifestyle, socioeconomic status, BMI and age.
Still, they say, a “growing body of evidence points to an important contribution from endocrine-disrupting chemicals (EDCs).”
EDCs may cause early harms that persist
The findings come at a time when female reproductive disorders have steadily increased, the researchers say, and global female infertility rates have surged, with women in their late 30s facing the highest risk.
The average age at which girls in the U.S. have their first periods has also decreased, indicating a higher risk of adverse health outcomes later in life, including breast cancer and Type 2 diabetes.
Female fertility and reproductive health depend on a series of developmental steps, from the formation of germ cells and an embryo through puberty and the healthy functioning of the reproductive system in adulthood.
Two of the most important factors are:
- Adequate ovarian reserve, the lifetime supply of follicles formed before birth that produce eggs and female sex hormones. The ovarian reserve declines with age, leading to menopause (end of natural fertility) when it is depleted.
- Hormone-regulating system known as the hypothalamic-pituitary-gonadal axis, which helps regulate healthy reproduction and sexual development.
EDCs can disrupt these early stages — and continue to affect reproductive health and fertility — by interfering with the body’s hormonal control signals, reproductive organs and production of key hormones such as estrogen, the researchers say.
For instance, exposure can cause egg cells to grow too quickly, stop important follicles from growing properly and increase the death of egg cells. This can lead to irregular periods and may lower fertility over time.
Chemicals may damage early reproductive system development
The effects of EDCs depend on when exposure occurs — but animal and human studies show clear patterns of harm.
For example:
- EDCs like bisphenol A (BPA), atrazine and di-2-ethylhexyl phthalate (DEHP) can disrupt meiosis, the process that forms egg cells, causing poor egg quality or abnormal chromosomes.
- Exposure in the womb to diethylstilbestrol (or DES, a synthetic estrogen), whose use was banned by the U.S. Food and Drug Administration in 2000, has been linked to shorter reproductive lifespans and increased infertility, likely due to fewer or faster loss of egg follicles.
- High lifetime exposure to EDCs has been associated with earlier menopause. One study found that women with the highest levels of combined exposure to 111 EDCs began menopause nearly four years earlier than those with the lowest exposure.
- EDCs may also speed up follicular atresia, the natural loss of immature eggs, possibly by causing oxidative stress and other cellular damage.
- In rats and mice, EDCs lower levels of key reproductive hormones — including estradiol (a form of estrogen), luteinizing hormone or LH and follicle-stimulating hormone or FSH — and disrupt normal reproductive cycles, even months after exposure ends.
“These studies provide causal proof for the numerous reported associations between EDC exposure in adulthood, lower follicle density and premature menopause,” the researchers say.
EDCs and puberty timing: Sooner or later
Puberty begins when the brain reactivates hormonal control pathways, leading to breast development and the first period. Studies over the past 30 years show a global trend of earlier puberty onset, with girls starting puberty earlier worldwide, by nearly three months per decade in some countries.
It can take years between chemical exposure and the start of puberty to study its impacts, and human evidence is limited.
Yet some patterns indicating reproductive health harms have emerged, the review shows:
- EDCs may act like estrogen or block hormone production, affecting when puberty starts. Higher levels of EDCs have been linked to changes in the brain’s release of gonadotropin-releasing hormone or GnRH, which helps control puberty. For example, BPA exposure in young rats delayed puberty and hindered the maturation of GnRH neurons.
- In girls, early exposure to BPA and DES has been linked to both early and delayed breast development, but consistently delayed menstruation. Phthalates, which block male hormones, have also been linked to delayed puberty.
- Some EDCs may also affect puberty timing by changing how genes turn on and off across generations. In one study, a first generation of rats exposed to a mix of 13 EDCs had a third generation with delayed puberty and altered gene regulation.
PCOS and fertility treatment outcomes
A major cause of female infertility, PCOS is the most common endocrine disorder in women, affecting up to 15% of women globally. While genes play a role in its development, the review suggests that EDCs may upset the hormone balance during fetal development, affecting puberty signals, egg growth and hormone production — and raising the risk of developing PCOS.
While data linking EDCs to PCOS are limited, the review cites studies that found:
- Women with PCOS have higher levels of EDCs in their blood, especially PFAS.
- A Swedish study of women found that those living in areas with high PFAS contamination had more than twice the risk of developing PCOS.
- A U.S. study of women seeking fertility evaluation and treatment linked higher per- and polyfluoroalkyl substance (PFAS) levels, especially perfluorooctane sulfonate, to increased PCOS risk. PFAS is used to make non-stick coatings on cookware, and protective coatings for products like carpets and food packaging coatings.
- Exposure to chemicals like BPA, tributyltin and DEHP can cause PCOS-like symptoms in animals, including hormone imbalances, fewer mature follicles and ovarian cysts — hallmarks of PCOS.
Some research also links EDC exposure to lower success rates in IVF and other fertility treatments, but findings are not consistent, the researchers say. In the U.S., about 13% of reproductive-age women seek treatment for infertility each year.
Two articles in the review found that chemicals like BPA, phthalates and parabens in the fluid surrounding developing eggs were linked with fewer mature eggs, lower fertilization rates and disrupted hormone levels.
Higher chemical levels were linked to lower ovarian sensitivity, meaning a weaker response to fertility drugs. Inflammation and hormone disruption in the ovaries, caused by chemicals like DEHP, may further reduce fertility, studies showed.
Gaps in knowledge and future research needs
Despite the strong evidence proving that a direct cause-and-effect relationship in humans is challenging, the researchers caution. Many factors influence reproductive health, and the effects of EDCs may take years to appear.
They highlight the need for advanced tools — like single-cell and spatial transcriptomics — to study how EDCs affect specific cells in the brain, ovaries and pituitary gland. They also suggest EDCs affect the gut microbiome and the placenta, which plays a key role in brain and reproductive tract development.
Other female health issues — such as preterm birth, endometriosis and breast cancer — have also been linked to EDC exposure, increasing the urgency to understand how these chemicals affect our health, they say.
“Remaining knowledge gaps and ongoing discussions should not negate the urgency to act through coordinated strategies and demonstrably effective measures, prevent exposure to EDCs, and protect the reproductive health of women and future generations,” the researchers say.
Originally published by U.S. Right to Know.
Pamela Ferdinand is an award-winning journalist and former Massachusetts Institute of Technology Knight Science Journalism fellow who covers the commercial determinants of public health.
