Progesterone for preventing pre-eclampsia and its complications

In the past, progesterone has been advocated for prevention of pre-eclampsia and its complications. Although progestogens are not used for this purpose in current clinical practice, it remains relevant to assess the evidence on their possible benefits and harms.

To assess the effects of progesterone during pregnancy on the risk of developing pre-eclampsia and its complications.

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 2), and EMBASE (1974 to August 2005).

Randomised trials evaluating progesterone or any other progestogen during pregnancy for prevention of pre-eclampsia and its complications were included.

Two review authors independently assessed studies for inclusion and extracted data.

Two trials of uncertain quality were included (296 women). These trials compared progesterone injections with no progesterone. There was insufficient evidence to demonstrate any clear differences between the two groups on the risk of pre-eclampsia (one trial, 128 women; relative risk (RR) 0.21, 95% confidence interval (CI) 0.03 to 1.77), death of the baby (two trials, 296 women; RR 0.72, 95% CI 0.21 to 2.51), preterm birth (one trial, 168 women; RR 1.10, 95% CI 0.33 to 3.66), small-for-gestational-age babies (one trial, 168 women; RR 0.83, 95% CI 0.19 to 3.57) or major congenital defects (one trial, 168 women; RR 1.65, 95% CI 0.28 to 9.62). There were no reported cases of masculinisation of female babies (one trial, 128 women). Long-term follow up for the children has been reported in one trial, but the data are excluded from the review as 54% were lost to follow up at one year and 80% at 16 years.

There is insufficient evidence for reliable conclusions about the effects of progesterone for preventing pre-eclampsia and its complications. Therefore, progesterone should not be used for this purpose in clinical practice at present. Unless new and plausible hypotheses emerge for the role of progesterone in development of pre-eclampsia, further trials of progesterone are unlikely to be a priority.