# Review: Hormone Pregnancy Tests Were Teratogenic by the Same Failed Abortion and Hypoxia‐Related Mechanism as Misoprostol

## TL;DR

This review shows that hormone pregnancy tests from the 1950s–1980s caused birth defects through the same mechanism as misoprostol, including limb and neural tube issues.

## Contribution

Demonstrates that HPTs are teratogenic via failed abortion and hypoxia-related mechanisms, similar to misoprostol.

## Key findings

- HPTs cause limb reductions, neural tube defects, and urinary-renal system defects like misoprostol.
- Abnormal uterine contractions and hypoxia/ROS-related damage are key mechanisms of HPT teratogenicity.
- Animal studies confirm HPTs can induce human-like malformations through embryonic hypoxia.

## Abstract

Hormone pregnancy tests (HPTs), containing synthetic progesterone and oestrogen, were used to diagnose pregnancy in the 1950s to early 1980s. An existing pregnancy was purported to be unaffected while expulsion of the uterine lining (withdrawal bleed) was supposed to occur if the woman was not pregnant. However, 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.

This review evaluates whether HPTs fulfil scientific criteria to be teratogenic based on results in old and newer human, animal and mechanistic studies.

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. 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.

Altogether, HPTs fulfil criteria to be characterised as a human teratogen.