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).