Levels of progesterone and allopregnanolone during pregnancy and
postpartum
Estradiol, progesterone and allopregnanolone are endogenous steroids,
which are abundantly produced in the periphery by adrenal glands and
ovaries and by the brain de novo from cholesterol (14). These
neuroactive steroids play important neurophysiological roles by
modulating inflammatory processes and behavior. Estradiol and
progesterone exerts important peripheral and neuronal functions mediated
by genomic influencing nuclear receptor. Allopregnanolone, instead, acts
as a positive allosteric modulator of the action of GABA at
GABAA receptors (15), which has been recently associated
with rapid and long-lasting improvement of postpartum depression (16).
Circulating levels of estradiol, progesterone and allopregnanolone rise
drastically during the second and third trimester of pregnancy before
decreasing dramatically following childbirth (10-12). Estradiol and
allopregnanolone levels closely parallel progesterone level increase
during pregnancy and in the early postpartum period (10-12). This
hormonal progression during pregnancy is consistent with a physiological
role as hormonal modifiers in pregnancy and postpartum
pathophysiological processes (Figure 1A, B) (12-15).
In healthy pregnant women, serum allopregnanolone, estradiol and
progesterone levels increased significantly during pregnancy, reaching
the highest levels at term (11). In another study, levels of
progesterone were markedly elevated specifically from the second to the
third trimester. They reached a 100-fold higher concentration compared
to baseline at 36.6 weeks of pregnancy. Concentration of
allopregnanolone increased from the first to second trimester, and then
remained relatively elevated until after delivery. Postpartum
concentrations of both progesterone and allopregnanolone decreased
sharply to pre-pregnancy baseline levels (11-13).
Peripartum concentrations of estradiol, progesterone and
allopregnanolone have consistently been associated with behaviorally
alterations in the spectrum of mood swings and postpartum depression,
and increased inflammation in more than 10% of pregnant women (13).