Serum Allopregnanolone Levels in Pregnant Women: Changes during Pregnancy, at Delivery, and in Hypertensive Patients

Abstract

Allopregnanolone is a neuroactive steroid measurable in peripheral circulation. The aim of the present study was to investigate the presence and the possible changes in serum allopregnanolone and progesterone levels in pregnant women during gestation, at delivery, and in patients with chronic hypertension, with or without superimposed preeclampsia. We also evaluated allopregnanolone in cord blood. Three groups of pregnant women were studied: 1) healthy controls followed longitudinally throughout gestation (n = 14); 2) at vaginal or cesarean delivery (n = 66); and 3) with chronic hypertension (n = 12), with (n = 7) or without (n = 5) superimposed preeclampsia. Allopregnanolone and progesterone levels were measured in maternal and cord serum by RIA. In healthy pregnant women, serum allopregnanolone and progesterone levels progressively increased throughout gestation. Whereas no changes were found at vaginal delivery, serum allopregnanolone and progesterone levels were significantly lower at delivery by emergency cesarean section (P < 0.01). Umbilical cord serum allopregnanolone and progesterone levels in emergency cesarean were significantly lower than those found at vaginal delivery (P < 0.01). Patients with chronic hypertension, with or without superimposed severe preeclampsia, showed serum allopregnanolone levels significantly higher than those of healthy women at the same gestational age (P < 0.01). In conclusion, maternal serum allopregnanolone levels increased during normal gestation were lower in women who underwent emergency cesarean and higher in patients with chronic hypertension, with or without preeclampsia. Because allopregnanolone is active on the central nervous system and in the control of systemic blood pressure, an involvement of this neurosteroid in the adaptive processes induced by pregnancy is suggested.

Pharmacokinetic and behavioral effects of allopregnanolone in healthy women

“…This concentration is similar to that found during third-trimester pregnancy (Hill et al , 2001Luisi et al 2000;Parizek et al 2005); it produced significant effects in objective and subjective measures of sedation. Given the pronounced effect of acutely administered allopregnanolone found in this study, it is conceivable that a gradual tolerance to the sedative effects of allopregnanolone occurs during pregnancy.…”

“…Plasma concentrations of allopregnanolone temporally follow those of progesterone, and levels of approximately 6-10 nmol L −1 have been found in the mid-luteal phase of the menstrual cycle (Genazzani et al 1998;Wang et al 1996), and during third-trimester pregnancy, allopregnanolone levels up to 150 nmol L −1 have been found in maternal blood and umbilical cord blood (Hill et al , 2001Luisi et al 2000;Parizek et al 2005).…”

The neuroactive steroids alphaxalone and pregnanolone increase the conductance of single GABAA channels in newborn rat hippocampal neurons

“…Their increasing clinical significance derives from their involvement in many physiological and pathophysiological conditions such as depression, pregnancy and recovery after brain damage [12][13][14] and their possible function as endogenous anxiolytic agents. However, the effects of different neurosteroids on GABA A receptors are not homogenous.…”

Brexanolone as adjunctive therapy in super‐refractory status epilepticus

“…This is equivalent to the highest endogenous concentrations measured during pregnancy (approximately 50ng/ml during the third trimester),29 which is well tolerated by women without apparent adverse events (AEs). The brexanolone dose selected to achieve this target concentration was 86μg/kg/h, which is considered the standard maintenance dose.…”