Clinical overview
Progesterone is the hormone of pregnancy maintenance, and the question of exogenous progesterone supplementation runs through almost every chapter of complicated obstetrics — threatened and recurrent miscarriage, the prevention of spontaneous preterm birth, luteal-phase support after assisted reproduction, and the long-discarded fashion of using it to "rescue" any bleeding early pregnancy. The registrar must be able to separate the evidence-based, guideline-endorsed indications from the historical and the speculative, because progesterone is cheap, widely available, perceived as harmless, and therefore heavily over-prescribed. It is one of the commonest "just-in-case" prescriptions handed out in early-pregnancy units and antenatal clinics, often with no clear indication and no defined stopping point.
The contemporary picture, anchored by the PRISM and PROMISE trials and the large preterm-birth literature, is more disciplined than the prescribing habit. There are now two reasonably well-defined situations in which vaginal progesterone earns its place — selected women with early-pregnancy bleeding and a history of miscarriage, and women with a short cervix or a prior spontaneous preterm birth — and a much larger penumbra of uses that are either unsupported or actively negative (for example, in unselected threatened miscarriage, or in multiple pregnancy for preterm-birth prevention). This chapter describes those uses in turn, weighting the discussion toward the mechanisms and the indications because the objective verb is "describe the use of." In the South African setting, where the National Integrated Maternal and Perinatal Care Guideline (NDoH, 2024) governs antenatal practice across the district–regional–tertiary network, the practical message is to reserve progesterone for evidence-based indications and to avoid it as a reflexive response to a positive pregnancy test and a little bleeding.
Core knowledge
Physiology — what progesterone actually does in pregnancy
Progesterone (literally "pro-gestational steroid") is secreted first by the corpus luteum and, from roughly the 7th–9th week, increasingly by the placental syncytiotrophoblast, which then becomes the dominant source for the remainder of pregnancy. This handover is the luteoplacental shift: before it, the pregnancy is dependent on luteal progesterone (hence luteal-phase support after IVF, and the rationale for progesterone where corpus-luteum function might be impaired); after it, the placenta autonomously produces large quantities and exogenous supplementation has a weaker physiological rationale.
Its actions relevant to pregnancy maintenance:
- Myometrial quiescence — progesterone promotes uterine relaxation and opposes the contractile, pro-inflammatory effects of oestrogen and prostaglandins. The "progesterone withdrawal" concept (functional withdrawal in humans, via altered progesterone-receptor isoform expression, rather than a fall in serum level) is part of the cascade toward labour. This underpins the preterm-birth-prevention hypothesis.
- Decidualisation and endometrial receptivity — progesterone transforms the endometrium into secretory decidua that supports implantation and early placentation.
- Immunomodulation — it favours a maternal-tolerance (broadly Th2-skewed) immune environment at the materno-fetal interface; this is the proposed mechanism behind any benefit in recurrent miscarriage.
- Cervical competence — progesterone is thought to maintain cervical integrity and reduce the inflammatory remodelling that precedes cervical shortening.
Preparations and routes
The agent used in obstetrics is micronised natural progesterone (bio-identical), not the synthetic progestogens of contraception.
- Vaginal micronised progesterone is the route with the best obstetric evidence (pessary/gel/capsule), achieving high local uterine concentrations via a "first uterine pass" with relatively low systemic levels. This is the form used in the PRISM/PROMISE early-pregnancy work and in short-cervix preterm-birth prevention.
- Oral preparations (including dydrogesterone, an orally active retroprogesterone) are also used, particularly for threatened/recurrent miscarriage in some guidelines; dydrogesterone featured in the LOTUS luteal-support and some miscarriage literature.
- Intramuscular 17-hydroxyprogesterone caproate (17-OHPC) was historically used for preterm-birth prevention after a prior preterm birth but its efficacy has been seriously undermined (see below).
A typical regimen described in the PRISM/PROMISE programme is vaginal micronised progesterone 400 mg twice daily, started in early pregnancy and continued to around 16 weeks; for short-cervix preterm prophylaxis a commonly described dose is vaginal progesterone ~200 mg daily continued into the early-mid third trimester (around 34–36 weeks). These doses are widely-cited standard regimens; confirm against the current product label and local protocol before prescribing — flagged in notes.