Progesterone around conception is tied to less gestational hypertension, big cohort finds

Women who took progesterone in the weeks around conception had a lower risk of developing gestational hypertension than women who did not, according to a large population-based cohort study published on 5 November in BJOG [s1]. The link held even after the researchers accounted for the reasons women take the hormone in the first place — but the authors are blunt that the size of the effect is probably too small to change care.

Progesterone is widely prescribed in early pregnancy, particularly to support pregnancies conceived through assisted reproductive technology (ART) and in women with a history of miscarriage or bleeding. Because hypertensive disorders of pregnancy — gestational hypertension and preeclampsia — are among the leading causes of maternal and fetal harm, researchers have long wondered whether hormones given early might nudge that risk up or down. This study set out to measure it directly.

What the study did

The team used statewide pregnancy and birth records from Victoria, Australia, covering 2009 to 2020, linked to hospital and medication-dispensing data [s1]. They restricted the analysis to nulliparous women — those giving birth for the first time — because first pregnancies carry a different baseline risk of hypertensive disorders than later ones.

Women were classed as exposed if they received progesterone in the periconceptual window, defined as six weeks before conception through the end of the first trimester [s1]. Anyone dispensed progesterone later in pregnancy, or with missing dates, was excluded, so the comparison is specifically about early use. To blunt the obvious problem that progesterone users differ systematically from non-users, the researchers used inverse probability-weighted regression adjustment, a statistical technique that reweights the groups to resemble a fairer head-to-head comparison.

The outcomes were straightforward: new-onset gestational hypertension, and preeclampsia (including superimposed preeclampsia).

What it found

Among 386,475 pregnancies, 5,657 women (1.5%) used progesterone in the periconceptual period [s1]. Those women had a statistically significant reduction in the risk of any new-onset hypertensive disorder of pregnancy: an adjusted risk ratio of 0.81 (95% CI 0.67 to 0.98), equivalent to an absolute risk difference of −1.72% (95% CI −3.21% to −0.24%) [s1].

When the researchers split the outcome by type, the signal came almost entirely from gestational hypertension. Progesterone use was associated with an adjusted risk ratio of 0.60 (95% CI 0.43 to 0.83) and an absolute reduction of 1.69% (95% CI −2.52% to −0.86%) [s1]. For preeclampsia, there was no meaningful change: an adjusted risk ratio of 0.97 (95% CI 0.75 to 1.25), with a confidence interval sitting squarely across no effect [s1].

The pattern survived a stricter test. Restricting the analysis to pregnancies conceived through ART alone — a group far more likely to be prescribed progesterone for a genuine clinical reason — the researchers again found a reduction in gestational hypertension (adjusted risk ratio 0.80, 95% CI 0.67 to 0.95) but not preeclampsia (adjusted risk ratio 0.96, 95% CI 0.83 to 1.11) [s1].

How to read it

This is an observational study, not a trial, and that governs how much weight the finding can bear. Women prescribed progesterone differ from those who are not in ways records can never fully capture — prior losses, fertility treatment, underlying conditions — and the statistical adjustment can only correct for what was measured. The authors are careful not to claim progesterone prevents gestational hypertension; they report an association.

The distinction between the two outcomes also matters clinically. Gestational hypertension is raised blood pressure without the organ involvement that defines preeclampsia, and it is generally the less dangerous of the two. A treatment that moves the milder condition but leaves preeclampsia untouched is of limited practical value.

The authors themselves draw the sharpest line. Their stated conclusion is that periconceptual progesterone use was associated with a reduction in gestational hypertension but not preeclampsia, and that these findings "are unlikely to be clinically meaningful" [s1]. An absolute reduction of under two percentage points, concentrated in the less severe disorder, is not a reason to start or stop progesterone.

What to watch

The useful reading of this study is reassurance, not prescription: for the many women already taking progesterone in early pregnancy — most of them after fertility treatment — the data give no sign that it raises the risk of hypertensive disorders, and a hint that it may slightly lower the milder form. Whether that hint reflects a real biological effect or residual confounding can only be settled by a randomised trial designed to test it directly. For wider context, see our coverage of hypertensive disorders of pregnancy and of progesterone in early pregnancy.

This article describes an observational study. It is not medical advice, and decisions about medication in pregnancy belong with a clinician who knows the individual case.