Introduction
Progesterone is essential for the female reproductive cycle, having
roles in the menstrual cycle, blastocyst implantation and maintenance of
pregnancy.1,2 During the luteal phase of the menstrual
cycle after ovulation, progesterone is secreted by the corpus luteum and
instigates secretory transformation of the endometrium into an
implantation-receptive state.2 Progesterone continues
to be produced during pregnancy, where it is involved in modulating the
maternal immune response, reducing uterine contractility and regulating
the utero-placental circulation, thus contributing to the maintenance of
pregnancy.1
Insufficient exposure to progesterone to enable normal secretory
transformation of the endometrium and implantation (luteal phase
deficiency) is associated with infertility and early pregnancy
loss.2,3 Luteal phase deficiency also occurs following
controlled ovarian stimulation used in assisted reproduction, with
potentially adverse effects on implantation in this
setting.2 Later, in established pregnancy, a
functional withdrawal of progesterone activity within the uterus is
associated with onset of labour, whether at term or
preterm.4
Exogenous progesterone is used to treat various obstetric conditions
associated with reduced progesterone activity. Progestogens widely
approved for use in pregnancy include natural progesterone, and the
synthetic progestogens 17α-hydroxyprogesterone caproate (17OHP-C) and
dydrogesterone. Synthetic progestins mimic some of the effects of
progesterone, but have variable affinities for other steroid receptors
(androgen, glucocorticoid, and mineralocorticoid receptors) which
results in differential progestogen activity and safety
profiles.5
The most common routes for delivery of progesterone in the obstetric
field are intramuscular (IM), vaginal and oral.117OHP-C is administered by IM injection6 and
dydrogesterone is administered orally.7 Since the
early 1990s, natural progesterone for exogenous administration has been
formulated in micronised particles to enhance its bioavailability after
oral administration.8 Despite this improvement, oral
natural micronised progesterone (oral NMP) requires multiple daily doses
due to first-pass metabolism and is associated with adverse events (e.g.
drowsiness and/or dizziness) due to active
metabolites.8 A sustained-release formulation of NMP
(NMP-SR) has been developed to overcome the limitations of oral NMP.
NMP-SR has a better tolerability profile than conventional oral NMP and
is more bioavailable, allowing for once-daily dosing.9
This narrative review examines available evidence from clinical studies
investigating oral NMP and oral NMP-SR in the obstetric indications of
luteal phase support during assisted reproduction; prevention of
threatened miscarriage; prevention of preterm delivery; and high-risk
pregnancy.