Female reproductive organ development in girls could be affected by their mothers’ use during pregnancy of paracetamol, suggest researchers, but whether the differences observed in the Danish study of infants have implications for fertility later in life and age at menopause will require long-term follow-up.
Study leader Margit Bistrup Fischer, a postdoctoral researcher in the Department of Growth and Reproduction at the Rigshospitalet in Copenhagen, said the findings should drive future research but shouldn’t yet change how certain symptoms are treated during pregnancy, CNN reports.
Their study doesn’t show that acetaminophen, also known as paracetamol or Tylenol, caused the reproductive changes, and women shouldn’t be “alarmed” by the findings because the research does not establish cause and effect, she added.
Paracetamol has long been known as the safest over-the-counter option to treat fever or pain during pregnancy, although doctors advise using it in moderation and only when necessary.
What the study found
The new study focused on girls’ reproductive organs, with Fischer saying she wanted to conduct the research because several experimental animal studies showed that offspring of mothers given paracetamol during pregnancy had smaller ovaries and fewer eggs.
The medication appeared to interfere with egg formation and division in those experiments, she said.
Published in the journal Human Reproduction Open, this is one of the first studies to assess human use. The scientists enrolled 685 women in Denmark during the first trimester of pregnancy, a crucial time for foetal development, and evaluated 302 of their baby girls when they were three-months-old.
The pregnant women logged their paracetamol use and submitted urine samples so researchers could measure how much of the drug was in their system.
The study found that girls exposed to the medication in the womb had, on average, 40% smaller ovarian volume, 13% smaller uterine volume and 23% fewer ovarian follicles – the structures that contain immature eggs – compared with girls whose mothers did not use paracetamol during pregnancy. They also showed lower levels of a hormone linked to ovarian reserve.
Smaller ovaries can signal that a person has fewer eggs, which may make it harder to get pregnant. Girls are born with all the eggs they will ever have; the body cannot make more.
Having fewer eggs can also hasten earlier menopause. Early menopause, defined as beginning before 45, is a health concern because it means a prolonged absence of oestrogen, the hormone that protects the brain, bones and heart.
However, this study captured only a snapshot in time: the researchers did not follow the girls long-term to determine future fertility.
The American College of Obstetricians and Gynaecologists agreed that more study was needed, saying in a statement that the findings “do not indicate that current clinical recommendations should change”.
It noted that the “clinical significance of these findings is uncertain or unknown”.
“The oldest participants evaluated were adolescents, and the study cannot determine whether the observed differences are associated with future reproductive outcomes such as fertility, ovulatory function, reproductive lifespan, or other measures of reproductive health.”
The researchers also analysed data from 1 210 girls in the Copenhagen Mother Child Cohort who were followed from infancy to adolescence: their mothers reported paracetamol use during the third trimester.
That data showed that foetal paracetamol exposure was associated with smaller ovaries during adolescence and smaller uteruses at
puberty.
‘The safest drug we have’
Fischer said the new findings shouldn’t stop pregnant women from taking paracetamol if they need it. More research is needed to determine whether the drug directly caused the reproductive organ changes, she reiterated.
“But on average, we do see a difference between groups, and we do feel concerned about it,” she said.
Many women in the study took paracetamol for headaches and musculoskeletal pain, Fischer said, and women should weigh alternatives before reaching for an over-the-counter pill.
“I think we really need to have a discussion about why paracetamol is the first thing you grab in your gym bag,” she said. Alternative treatments may help with certain conditions, such as heat for some back pain.
Dr Christian De Geyter, a retired senior scientist at the University of Basel who studies fertility and reproductive toxicology, wrote in a commentary accompanying the research that the “eminent importance” of the findings “cannot be stressed enough!”
He said the “duration and dose must be taken into consideration” and argued that recommendations about the use of paracetamol should be reversed.
“The drug is still safe, to some extent; take it if you need it, but consider alternatives when possible,” he told CNN. “There are many, many things that can be avoided, rather than just always taking medicine.”
But other experts were more cautious about the new study’s findings and worried it could easily be misinterpreted.
Dr Gavin Stewart, a senior lecturer in evidence synthesis at Newcastle University, said the study size was small, and because researchers measured many different potential effects, false positive findings could be difficult to distinguish from true effect.
“When you hunt really hard for a pattern, you inevitably find one. I’m worried that the authors are over-interpreting the one they found,” Stewart, who did not work on the new study, told the Science Media Centre.
“I am very concerned that this exploratory study will be misinterpreted. Pregnant women already have a limited choice of pain medication, and paracetamol has an extremely high safety profile. They should not conclude from this study that paracetamol will harm their child.”
While “impressive,” the new study does not show that paracetamol exposure causes reproductive organ changes, noted Dr Hugh Taylor, a specialist in obstetrics and gynaecology and reproductive endocrinology at Yale School of Medicine.
“What are the other things they took the paracetamol for? Did they have a fever during pregnancy? Was an infection at play, which we know causes congenital defects, as do infectious diseases and high temperatures? This study cannot answer that,” said Taylor, who was not involved with the new research.
There are good reasons pregnant people need relief from pain and fever, he said, and “paracetamol is the safest drug we have when it’s needed”.
Study details
Foetal exposure to paracetamol is associated with altered markers of ovarian development and reduced uterine volume in girls: the COPANA study
Margit B Fischer, Gylli Mola, Karin Sundberg et al.
Published in Human Reproduction Open on 8 September 2026
Abstract
Study question
Is foetal exposure to paracetamol associated with markers of ovarian function in infancy?
Summary answer
Mild to moderate doses of prenatal paracetamol exposure, assessed by detailed maternal reports and urinary measurements, are associated with ovarian morphology and activity as well as reduced size of oestrogen-responsive tissues in infant girls.
What is known already
Maternal use of paracetamol is widespread. Across multiple independent animal studies, foetal exposure consistently impairs the formation of primordial ovarian follicles, causing subfertility and premature estropause in female offspring.
Study design, size, duration
The Copenhagen Analgesic study (COPANA) is a single-centre, prospective, observational cohort study conducted at a university hospital (March 2020 to November 2022). From 3425 eligible participants, 685 healthy singleton pregnant women of Caucasian origin, were enrolled in the first trimester of pregnancy, and 302 infant daughters were examined at follow-up. Exclusion criteria included maternal diabetes or thyroid disease, pre- or post-term delivery, or severe infant illness.
Participants/materials, setting, methods
Pregnant women reported paracetamol use biweekly and provided first-trimester urinary samples which were analysed for paracetamol levels (LC-MS/MS) and adjusted for urinary osmolarity (n = 299). Girls were classified by timing of initial exposure: early foetal life (<17 weeks, n = 92), mid–late foetal life (≥17 weeks, n = 67), or unexposed controls (n = 143). Of the 92 girls initially exposed in early foetal life, a subgroup was exposed exclusively in early foetal life (n = 22).
In an independent confirmatory cohort, 1 210 girls were followed from infancy to adolescence. Their exposure was maternal self-reported (any) use of paracetamol during pregnancy and reported early in the third trimester (yes/no).
Main results and role of chance
Early foetal exposure was associated with reduced ovarian volume (−0.11 cm3, 95% CI −0.19 to −0.03) and reduced uterine volume (−0.18 cm3, −0.35 to −0.01), whereas mid–late foetal exposure was associated with fewer ovarian follicles (−1.05 follicles, −1.71 to −0.39) compared to unexposed girls. AMH levels were lower in girls exposed exclusively in early foetal life (−0.45 SDS, −0.87 to −0.03) compared to unexposed girls. Maternal urinary paracetamol concentrations were inversely associated with ovarian and uterine volume as well as breast tissue diameter. In the independent confirmatory cohort, foetal paracetamol exposure was associated with reduced uterine volume at puberty (−4.11 cm3, −7.29 to −0.92) and smaller ovarian volume during adolescence (−2.76 cm3, −4.82 to −0.70).
Limitations, reason for caution
The observational design of the study allows evaluation of exposure outcome associations, while the causality interpretation is supported by consistency with experimental models demonstrating comparable effects. Residual confounding by indication for paracetamol use cannot be completely excluded, although the results were robust after accounting for fever and other maternal factors. The analytic design of the current study limited our ability to evaluate whether frequency or patterns of paracetamol use influenced the observed associations.
Wider implications of the findings
In this prospective cohort study of infant girls, prenatal exposure to paracetamol was associated with differences in several markers of ovarian development, including ovarian volume, follicle number, and circulating AMH, as well as uterine volume and breast tissue diameter. The associations with reduced ovarian and uterine size were also observed in a confirmatory cohort followed to adolescence. Whether these early-life differences have long-term clinical relevance, including effects on reproductive lifespan, remains uncertain and requires analyses in studies with extended follow-up.
See more from MedicalBrief archives:
Paracetamol: Precautions necessary during pregnancy — Consensus Statement
Painkillers during pregnancy could affect fertility of the unborn child
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