In many cases, it is unclear whether the diagnosis should be PMDD or whether the clinical presentation consists of an aggravation of other psychiatric

entities during the luteal or late luteal phase. The prevalence of PMDD is estimated to be in the order of 3% to 5% of women of childbearing age, but it might be higher. Minor forms of premenstrual syndrome are present in 20% to 50% of women. PMDD can start at selleck inhibitor adolescence, but it is more manifest in women of 20 to 35 years; it is very rare after the Inhibitors,research,lifescience,medical menopause has ostensibly occurred. PMDD is a risk factor for the development of other mood disorders, particularly during the post-partum period. The mechanism Inhibitors,research,lifescience,medical of PMDD quite certainly involves the endocrinology of reproduction, despite several negative findings. No difference has been clearly proven to exist between PMDD and control women in LH, gonadotrophs, melatonin, estrogen, and also anxiolytic neurosteroids such as allopregnalone.140 These hormones have been studied as to their mean concentration and as to the temporal circadian

Inhibitors,research,lifescience,medical organization of secretion at different days of the menstrual cycle, with no significant changes, although Parry and her colleagues did find a lower melatonin secretion in a third of patients, throughout the cycle141; some abnormalities in circulating neurosteroids have also been described.142 No changes in the genetics of monoamine oxidase A, tryptophan hydroxylase or the serotonin transporter was found.143 That

the endocrinology of reproduction is involved is attested by the fact that blockade of estrogen and progesterone secretion by an agonist Inhibitors,research,lifescience,medical of GnRH leads to cessation of the PMDD symptoms,144 and giving either estrogen or progesterone to women having received a GnRH agonist leads to the reappearance of symptoms. The change in sex hormone concentration does not explain the changes Inhibitors,research,lifescience,medical in mood, because mood alterations were not observed in women who were included in the same protocol but who had no history of PMDD.145 These findings led Rubinow and Schmidt146 SB-3CT to suggest that PMDD results from an abnormal response to normal hormonal menstrual changes and probably involves interactions between hormones and neurotransmitters. PMDD illustrates that a regularly periodic syndrome might have an origin other than biological clocks. It has been suggested that PMDD might be close to the entity of panic disorder,147 since there is an increased sensitivity, in terms of panic induction, to several substances such as CO2, or cholecystokinine,148 or flumazenil149; these responses fit with the false-alarm theory of panic attacks.150 Another suggestion is that PMDD results from the evolutionary selection of immunological changes, resulting in a low probability of early fetal rejection.