65 No diagnosis-related differences in reproductive hormones have been consistently observed during the luteal phase that would distinguish a woman with PMS from a woman without PMS.66 Despite the lack of evidence of ovarian dysfunction in women with PMS, the association of PMS symptoms with the luteal phase of the menstrual cycle perpetuated clinicians’

views that an abnormality of corpus luteum function caused PMS. Thus, multiple trials were conducted involving the administration of Inhibitors,research,lifescience,medical progesterone or progestin in women with PMS.67 However, the widespread use of progesterone in women with PMS was considerably diminished by the results of several recent studies: first, two large double-blind,

placebo-controlled trials of natural progesterone (both suppository and oral forms) definitively demonstrated the lack of efficacy of progesterone Inhibitors,research,lifescience,medical compared with placebo in PMS.68,69 Second, a study employing a progesterone receptor antagonist, Inhibitors,research,lifescience,medical Stem Cells inhibitor RU-486, with or without human chorionic gonadotropin, demonstrated that the normal symptoms of PMS could occur independently of the luteal phase of the menstrual cycle70 and, therefore, a luteal phase abnormality as a cause of PMS was no longer tenable. The belief that PMS reflected a disturbance in ovarian function led to several trials of OCs to suppress or regulate ovarian function in this condition. Inhibitors,research,lifescience,medical Earlier crosssectional studies suggested that women using OCs experienced fewer PM’S symptoms than nonusers.71-73 However, studies also reported the opposite,74 and most results demonstrated that women on OCs reported fewer physical symptoms (ie, breast pain, bloating), but did not report fewer or less

severe mood symptoms than nonusers.75-77 In fact, similar prevalence rates of cyclic mood symptoms regardless of Inhibitors,research,lifescience,medical OC use were prospectively documented by Sveindottir et al,78 with 2% to 6% of women meeting criteria for severe PMS in both OC users and nonusers. Moreover, observations suggest that the severity of mood symptoms do not vary with different preparations of OCs (eg, Mannose-binding protein-associated serine protease monophasic versus triphasic)79-80; however, one study did observe that the progestin desogestrel (reported to have less androgenic activity) was associated with fewer mood symptoms than lcvonorgestrel.81 Despite similar prevalence rates of negative mood symptoms in OC users and nonusers, some clinicbased studies suggested that a subgroup of women with PM.S reported an improvement in mood symptoms while on OCs.82-87 None of the recent controlled trials of OCs in PMS have observed significant improvement (or worsening) in mood symptoms relative to placebo.