90 Thus, neither cross-sectional studies nor controlled trials support a role for any formulation of OCs (tested to date) in the treatment of PMS. Investigators have also examined the efficacy in PMS of estradiol (without the progestin contained in OCs) or testosterone. Trials of supraphysiologic doses of estradiol with or without testosterone have documented beneficial effects compared with placebo in women with PMS.91-93 Preliminary reports suggest that lower (more physiologic)

doses of testosterone alone may also be effective in the treatment of PMS.94-96 Lower doses of estrogen, however, arc no more effective than Nutlin-3a IC50 placebo97 and, therefore, it is possible that the therapeutic benefits Inhibitors,research,lifescience,medical of the higher dose estrogens are secondary to the suppression of ovulation.93 Nevertheless, one cannot infer the efficacy of these compounds to be secondary to ovarian suppression alone, given the lack of efficacy of OCs, which also inhibit ovulation, and the reported efficacy of compounds such as danazol98 when Inhibitors,research,lifescience,medical administered after ovulation in at least one study.99 Several open trials of ovarian suppression, induced surgically or medically, have reported the beneficial Inhibitors,research,lifescience,medical effects of this strategy in the treatment of PMS.100-107 Most,108-111 but not all,112,113 placebo-controlled trials

of GnRH agonists (eg, leuprolide acetate) in PMS have reported the therapeutic efficacy of GnRH agonist-induced ovarian suppression compared with placebo. We observed significant reductions in PMS symptom severity during leuprolide treatment for all symptoms measured.114 In many of the trials, Inhibitors,research,lifescience,medical the degree of individual response to GnRH agonist varied considerably, despite evidence of a beneficial response to ovarian suppression on a group basis. We observed a response rate of approximately Inhibitors,research,lifescience,medical 60% employing relatively conservative selleckchem criteria (ie, the absence within a 2-month time period of 2-weekly mean scores on anxiety, depression, or irritability

greater than 2.5 on a 6-point scale).114 Similarly, Freeman et al reported that 67% of women with PMS responded Anacetrapib to GnRH agonist-induced ovarian suppression.109 Response rates did not differ depending on the presence or absence of a past history of affective disorder in our sample of women with PM’S. However, Freeman et al observed that the presence of persistent depressive symptoms throughout the menstrual cycle was associated with nonresponse to GnRH agonists.109 The reported response rates to selective serotonin reuptake inhibitors (SSRIs) in women with PMS (40%-60%)115-122 appear similar to the rates observed in trials of GnRH agonists. Thus, although the majority of studies would support the short-term use of GnRH agonists or SSRIs in this condition, symptomatic response is not uniform even to complete ovarian suppression.