Sulphates of 3beta-hydroxy-5-ene steroids in women with epilepsy.

Epilepsy is associated with various reproductive disorders and some antiepileptic drugs also influence the steroid metabolism. There is only limited data concerning the role of steroid sulphates in human epilepsy. Moreover, the substitution treatment with therapeutic substances also improves cognitive functions in humans. Therefore, we evaluated the balance between free and Delta5 sulphated steroids in women with epilepsy on various antiepileptic drugs. The study included 28 patients (17.0-51.0 years), with generalized (n=16) or catamenial epilepsy (n=12) followed in the follicular (FP) and luteal (LP) phases of menstrual cycle. Fifteen patients were on monotherapy and 13 were on polytherapy with 2 or 3 drugs. RIA was used for the steroid analyses. Statistical evaluation was done by Mann-Whitney tests and multivariate regression with reduction of dimensionality (Orthogonal Projections to Latent Structures, O2PLS). The final O2PLS model found a single significant predictive component extracting the variability shared between carbamazepine therapy, age of the subjects, and steroid levels and correlating with the variables as follows pregnenolone sulphate (PregS)-FP: R= -0.844, p<0.01; DHEAS-FP: R= -0.923, p<0.01; PregS-LP: R= -0.876, p<0.01; DHEAS-LP: R= -0.902, p<0.01; carbamazepine therapy: R=0.441, p<0.01; age of the participants (R=0.584, p<0.01). Carbamazepine significantly decreased DHEAS in both FP (p=0.02) and LP (p=0.003) and PregS in LP (p=0.03) and tended to decrease the PregS levels in FP (p=0.10), while primidone decreased DHEAS in both FP and LP (both p=0.05) and did not significantly change the levels of PregS. In conclusion, carbamazepine and primidone therapies significantly suppressed the sulphated steroids in serum.

The identification and simultaneous quantification of neuroactive androstane steroids and their polar conjugates in the serum of adult men, using gas chromatography-mass spectrometry.

Certain androstane steroids (AS) modulate ionotropic receptors, as do the pregnane steroids. Whereas women produce significant amounts of neuroactive progesterone metabolites, the steroid neuromodulators in men originate mainly from the 3-oxo-4-ene C(19)-steroids, which are converted to their 3alpha- and 3beta-hydroxy-5alpha/5beta-reduced metabolites. The neuromodulating effects of AS prompted us to monitor circulating levels of the steroids to estimate metabolic pathways in the periphery that may influence brain concentrations of AS. Hence, the serum levels of 20 steroids and 16 steroid polar conjugates including 17-oxo- and 17beta-hydroxy-derivatives of 5alpha/beta-androstane-3alpha/beta-hydroxy-androstane steroids were quantified in 15 men (16-62 years of age) using GC-MS. The conjugated AS for the most part reached micromolar concentrations, these being two or three orders of magnitude higher than those of the free steroids. The ratios of conjugates to free steroids were one to two orders of magnitude higher than the values for the corresponding pregnane steroids. This data suggested that conjugation may considerably restrain the transport of free AS from the periphery into the central nervous system.