Giving progesterone in early pregnancy could reduce preeclampsia risk, say Tommy's researchers

Women prescribed a vaginal progesterone treatment in the first trimester of pregnancy are 39% less likely to develop the potentially fatal condition preeclampsia, a new review of international research suggests.

Researchers from the Tommy’s National Centre for Miscarriage Research have analysed the findings of 11 recent studies involving 11,640 women.

These studies were originally designed to explore progesterone’s impact on reducing miscarriage or preterm birth rates. In every study, data was also collected on whether the same treatment affected rates of preeclampsia or other high blood pressure (hypertensive) disorders in women during pregnancy.

A review published in the British Journal of Obstetrics and Gynaecology on 08 November 2023 is the first to analyse the data on these disorders.  

It concludes that vaginal progesterone appears to reduce the risk of hypertensive disorders in pregnancy, but only when treatment is started in the first trimester.

The review shows that 400mg of progesterone used twice a day is linked to a 39% reduction in preeclampsia and a 29% reduction in the rate of other hypertensive disorders such as gestational hypertension.

The review found no clear evidence to suggest that starting progesterone in the second or third trimester has a similar effect.  

Frequency, quantity, and method of use are also important: 400mg used twice daily as a vaginal pessary showed a benefit in reducing risk of preeclampsia and other hypertensive disorders but using 400mg once a day did not.  

The 11 studies analysed by the Tommy’s team, led by Dr Pedro Melo at the Tommy’s National Centre for Miscarriage Research at the University of Birmingham and the Nuffield Department of Women’s and Reproductive Health at the University of Oxford, focused on groups of pregnant women who either had a history of recurrent pregnancy loss or had a threatened miscarriage (that is, they were experiencing early pregnancy bleeding).

The review recommends that future studies are needed to explore the link further, to find out whether the reductions of 29-39% are relevant to all women and birthing people and whether the effect could be larger for those who are at higher risk of preeclampsia.

Preeclampsia is a condition that affects some pregnant women, usually during the second half of pregnancy or soon after their baby is delivered.  It can range from mild to severe, and at present there is no guaranteed way to prevent it.

It can lead to fetal growth restriction which can cause premature birth. If severe, mothers may experience liver or kidney failure, blood clotting disorders, stroke or fluid in the lungs.

Dr Pedro Melo, who is also an NIHR-funded clinical lecturer at the University of Oxford says:  

“The recent PROMISE and larger PRISM trials led to an exciting breakthrough in finding evidence that progesterone can reduce miscarriage risk in some women when used in the first trimester. This evidence led to updated NICE guidelines in 2023 recommending its use. But the signal we found in the data for progesterone’s effectiveness in reducing hypertensive disorders had not previously been demonstrated.  

"These are exciting findings, but they were secondary results of trials focusing on the use of progesterone for the prevention of miscarriage and preterm birth, not preeclampsia. We need more research focusing specifically on women and birthing people at risk of preeclampsia to confirm our hypothesis that progesterone supplementation may tackle abnormal implantation in this subgroup of people.”

Kate Davies, Research Director at Tommy’s says: 

“This research further supports Tommy’s calls for women with a history of miscarriage and pregnancy bleeding to be given progesterone in the early stages of pregnancy. We must continue to keep exploring progesterone’s potential and improve understanding of what it can be used for, who it works best for, when, and how.”