Circulating levels of anticonvulsant metabolites of progesterone in women with partial epilepsy in the intercritical phase

Abstract

The 3alpha-hydroxy metabolites of progesterone (P), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone, A-PREG) and 3alpha-hydroxy-5beta-pregnan-20-one (pregnanolone, PREG), have been found to be among the most potent ligands of gamma-aminobutyric (GABA)-A receptors; in experimental animals, they have been found to have anxiolytic, hypnotic and anticonvulsant effects. Similar to those of the benzodiazepines and barbiturates that interact with GABA-A receptors. The present study was undertaken to determine plasma A-PREG and PREG concentrations in the luteal phase in women with partial epilepsy, in order to determine if an impaired metabolism of P occurs in this convulsive disorder. We measured plasma P, A-PREG and PREG levels in 15 women with partial epilepsy in the intercritical phase, and in 15 age-matched healthy women, during the luteal phase of the ovarian cycle (22nd-24th day). The mean plasma +/- S.E. A-PREG levels (three blood samples) were 0.7 +/- 0.6 ng/ml in the epileptic women and 0.5 +/- 0.2 ng/ml in controls, with no significant difference between the two groups (p = NS); the PREG levels were also similar (1.4 +/- 1 ng/ml and 1 +/- 1.1 ng/ml, respectively: p = NS). A significant correlation was found between P levels and both A-PREG and PREG levels (r = 0.72, p < 0.001 and r = 0.79, p < 0.001, respectively). There were no significant differences between the two groups in terms of serum adrenocorticotropic hormone, cortisol, dihydroepiandrosterone-sulfate, follicle stimulating hormone, prolactin, luteinizing hormone or estradiol levels.

Progesterone and Testosterone Modulate the Convulsant Actions of Pentylenetetrazol and Strychnine in Mice

“…Several investigations have shown a relationship between reproductive steroids and central nervous system excitability. The active metabolite of progesterone, allopregnanolone, is a neurosteroid which exhibits hypnotic, anxiolytic and anticonvulsant actions (Bitran et al 1991(Bitran et al & 1995Galli et al 1996;Korneyev & Costa 1996;Wilson & Biscardi 1997). Allopregnanolone exhibits potent inhibitory actions in the central nervous system, acting on the GABA-benzodiazepine-chloride channel macromolecular complex by an allosteric interaction with the GABA A receptor, with potentiation of the chloride channel current (Schumacher & Baulieu 1995;Rupprecht et al 1996;Brot et al 1997;Kellog et al 1998).…”

Circulating Levels of Allopregnanolone, an Anticonvulsant Metabolite of Progesterone, in Women with Partial Epilepsy in the Postcritical Phase

“…It has been shown that allopregnanolone acts as a ligand to the GRC and increases Cl − current induced by GABA, decreasing brain excitability. In a previous experience, serum allopregnanolone levels were measured in 15 women with partial epilepsy in the intercritical phase, and no significant differences were found between patients and control subjects (18). The naturally occurring allopregnanolone is more potent than progesterone itself (16), and recent data suggest that hypnotic effects of progesterone are mediated through this metabolite (17).…”

Circulating Levels of Allopregnanolone, an Anticonvulsant Metabolite of Progesterone, in Women with Partial Epilepsy in the Postcritical Phase

“…The naturally occurring allopregnanolone is more potent than progesterone itself (16), and recent data suggest that hypnotic effects of progesterone are mediated through this metabolite (17). In a previous experience, serum allopregnanolone levels were measured in 15 women with partial epilepsy in the intercritical phase, and no significant differences were found between patients and control subjects (18).…”