Scientific research has suggested a link between hormone pregnancy tests and birth defects since the 1960s. On this page, the ACDHPT highlights some of the key studies, letters and papers.
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2025
Review: hormone pregnancy tests were teratogenic by the same failed abortion and hypoxia-related mechanism as misoprostol
Studies in the 1960s–1980s associated HPTs with teratogenicity and some countries banned their use in the early 1970s. Following renewed scientific and political interest, studies were published from 2014–2023 and reviewed by this paper, co-authored by Bengt Danielsson.
“The evaluation shows that HPT teratogenicity is identical to the established human teratogen misoprostol, with limb reductions, neural tube defects and urinary‐renal system defects as the most significant,” said this review.
“The evaluation also presents evidence for abnormal uterine contractions and failed abortion (but the embryo survives) and hypoxia/ROS‐related damage (including vascular disruption) in the embryo secondary to compression of uterine/embryonic vessels, as underlying the teratogenicity.
“Animal studies show human malformations associated with HPTs could be induced by a single period of embryonic hypoxia, and that HPTs have both abortive and teratogenic potential.”
It concluded: “Altogether, HPTs fulfil criteria to be characterised as a human teratogen.”
- Danielsson BR and Ritchie HE (2025). Review: Hormone Pregnancy Tests Were Teratogenic by the Same Failed Abortion and Hypoxia‐Related Mechanism as Misoprostol, Birth Defects Research 117(3): e2462. https://doi.org/10.1002/bdr2.2462
2023
Teratogenicity and reactive oxygen species after transient embryonic hypoxia: experimental and clinical evidence with focus on drugs causing failed abortion in humans
One aim of this article was to review and compare the pattern of malformations produced by transient embryonic hypoxia of various origins in animal studies, with malformations associated with transient embryonic hypoxia in human pregnancy due to a failed abortion process.
“The results showed that transient hypoxia and compounds with potential to cause failed abortion in humans – such as misoprostol and hormone pregnancy tests like Primodos – have been associated with a similar spectrum of teratogenicity,” read the abstract.
“The spectrum includes limb reduction, cardiovascular and central nervous system defects.”
- Danielsson B, Vargesson N and Danielsson C (2023). Teratogenicity and reactive oxygen species after transient embryonic hypoxia: experimental and clinical evidence with focus on drugs causing failed abortion in humans, Reproductive Toxicology 122: 108488. https://doi.org/10.1016/j.reprotox.2023.108488
2018
Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis
The groundbreaking University of Oxford study that suggested a clear link between Primodos and congenital malformations.
Researchers performed a systematic review and meta-analysis of case-control and cohort studies that included data from pregnant women and were exposed to HPTs within the estimated first three months of pregnancy, if compared with a relevant control group.
“We found 16 case control studies and 10 prospective cohort studies, together including 71,330 women, of whom 4,209 were exposed to HPTs,” said the study. “Exposure to oral HPTs was associated with a 40 per cent increased risk of all congenital malformations.
“This systematic review and meta-analysis shows that use of oral HPTs in pregnancy is associated with increased risks of congenital malformations.”
- Heneghan C, Aronson JK, Spencer E, Holman B, Mahtani KR, Perera R and Onakpoya I (2018). Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research B:1725. https://doi.org/10.12688/f1000research.16758.2
- Carl Heneghan explained the findings of the research to Sky News following its publication.
2014
Congenital bladder exstrophy associated with Duogynon hormonal pregnancy tests – signal for teratogenicity or consumer report bias?
Amid continuing public concern about the safety of these drugs – and legal proceedings being instituted against the medicinal authorisation holder – this study evaluated 296 consumer reports of the German Duogynon database and compared the reported birth defects with data from a population-based birth registry.
“The most striking result is an increase of bladder exstrophy,” it reported. “Neural tube defects and renal agenesis were also significantly increased.
“Bladder exstrophy may be a yet undetected teratogenic effect of Duogynon, but may also represent a reporting bias. The present study highlights the difficulties of evaluating consumer reports which may be influenced by public media.”
Tümmler G, Rißmann A, Meister R and Schaefer C (2014). Congenital bladder exstrophy associated with Duogynon hormonal pregnancy tests – signal for teratogenicity or consumer report bias?, Reproductive Toxicology 45: 14-19. https://doi.org/10.1016/j.reprotox.2013.12.007
1967
Hormonal pregnancy tests and congenital malformation
The letter that started it all off – Dr Isabel Gal’s letter to the scientific journal Nature that first suggested a link between HPTs and birth defects.
“During a survey of babies born with meningomyelocele or hydrocephalus, 100 mothers of such children provided histories of the relevant pregnancy,” it reads. “Among other things they were questioned as to the drugs which they had taken. The same information was obtained from a matched control group of 100 mothers recently delivered of healthy babies.
“As part of the survey the mothers were asked how their pregnancy was diagnosed. Nineteen mothers in the survey group and four of the control mothers reported having received oral tablets for the diagnosis of pregnancy. There was no significant difference between the two groups with respect to any other drugs taken in the first trimester.”
- Gal I, Kirman B and Stern J (1967). Hormonal pregnancy tests and congenital malformation, Nature 216: 83. https://doi.org/10.1038/216083a0
