Lack of influence of menstrual cycle and premenstrual syndrome diagnosis on pregnanolone pharmacokinetics

Objective: Pregnanolone is a 3 alpha-hydroxylated-5 beta-reduced metabolite of the female sex steroid hormone progesterone. The compound is currently being evaluated for anaesthetic purposes. Previous studies have indicated a differential physiological response across the menstrual cycle and a diffe rent response in patients with premenstrual syndrome (PMS). This study was undertaken to determine whether hormonal changes during the menstrual cycle influence pregnanolone pharmacokinetics and to compare PMS diagnosis-relat ed differences in pregnanolone pharmacokinetics. Methods: Seven patients with premenstrual syndrome and seven female control s were given three increasing doses of pregnanolone in the follicular and l uteal phase of the menstrual cycle. Results: Mean pregnanolone elimination half-life varied between 28.4 min an d 31.8 min and clearance between 59.6 ml . min(-1) . kg(-1) and 64.0 ml . m in(-1) . kg(-1), depending on diagnostic group and cycle phase. No signific ant differences in pregnanolone pharmacokinetic properties were found betwe en PMS patients and controls in either phase of the menstrual cycle. Furthe rmore, no differences in pharmacokinetic variables were detected between cy cle phases. Conclusion: Pregnanolone pharmacokinetics do not differ between follicular and luteal phase of the menstrual cycle, nor between PMS patients and contr ol subjects.