Can progesterone prevent preterm birth?

This review looked at the effect of progesterone on pregnancies at risk of preterm labor. It found that progesterone reduces preterm birth for women with a short cervix or previous preterm birth, but not for women carrying twins.

Between 5% and 18% of births are preterm. Births earlier than 37 weeks into the pregnancy, 3 weeks before the due date, are considered preterm. Babies born preterm are more likely to have a low birth weight, or to have other complications including the lungs not being fully developed at birth. Therefore, preventing preterm birth is an important health goal.

There are a number of health conditions that increase the risk of preterm birth. Twins and triplets are often preterm, as these multiple pregnancies place more stress on the woman’s body. Women who have already had a preterm birth are more likely to go into preterm labor in future pregnancies. Smoking, diabetes, or high blood pressure can increase preterm birth. Also, preterm birth is more common for women with a short cervix (entrance to the uterus).

Progesterone is a hormone involved in reproduction. Progesterone levels are higher during pregnancy and decrease before the start of labor. It is not clear whether synthetic progesterone can reduce preterm labor for pregnant women at risk of preterm birth.

This review used data from 31 studies of 11,644 pregnant women and their 16,185 babies. All the women were at risk of preterm birth. This included carrying twins, having a short cervix, or having had a previous preterm birth.  All of the studies assigned patients to one of two groups. Medications studied included oral or vaginal progesterone or injections of a related medication, 17-hydroxyprogesterone caproate (17-OHPC; Proluton). Placebos or standard care were used as a comparison in most studies, although two studies compared different types of progesterone.

Births that are less than 34 weeks gestation, or more than six weeks before the due date, are considered early preterm. For single pregnancies, vaginal progesterone significantly reduced the risk of early preterm birth by 22%. Vaginal progesterone also significantly reduced the chance the baby would have difficulty breathing, which can be a complication of premature birth. 17-OHPC reduced preterm birth by 17% for single births. Oral progesterone reduced preterm births by 40% in single pregnancies.

10 trials looked at either vaginal progesterone or 17-OHPC for women carrying twins or triplets. Progesterone did not reduce early preterm birth for women carrying twins.

There was a trend toward more pregnancy complications for the mother when taking vaginal progesterone or 17-OHPC, including high blood pressure and infection. There was more of an increase in complications with progesterone for women with high body weight.

This review found that vaginal progesterone or 17-OHPC can reduce preterm birth for women with single pregnancies and risk factors such as a short cervix.

The risk of preterm birth was higher for women with short cervices (less than 25 mm). The authors suggest the benefits of progesterone may be greatest for these women.