Up to 80% of women experience physical and emotional changes that are related to their menstrual cycle. Among the nearly 150 reported cyclically recurrent emotional and somatic symptoms, the most common include irritability, fatigue, depression or mood swings, breast tenderness, bloating, and food cravings [1][2][3]. Approximately 3%-8% of reproductive-age women experience mood, behavioral and/or physical symptoms during the fi nal week of their menstrual cycle that are severe enough to meet the criteria for premenstrual dysphoric disorder (PMDD) [4][5][6]. PMDD is thought to result from the complex interaction among ovarian steroid production, endogenous opioid peptides, central neurotransmitters, prostaglandins, and peripheral autonomic and endocrine systems [7][8][9]. Of the wide range of medications available for this treatment approach, the most commonly used agents are oral contraceptives and antidepressants. As a clinician faced with patients who complain of premenstrual symptoms, it is difficult to predict which symptoms will benefit from treatment with which drug. In some cases, it is puzzling on the part of both patients and physicians whether premenstrual distress requires medical treatment at all. Often, patients read about alternative remedies advertised in beauty magazines, newspapers, television ads, the internet, and seek advice from friends and family. There is overwhelming amount of information on which underwear to wear, which foods to eat and avoid, special herbs, drinks, even lucky charms. In the midst of all the available remedies, one wonders what role medications can have in the competition. This paper aims to summarize and help readers understand the evidence, and ultimately help physicians make practical decisions about pharmacotherapy for PMDD. The primary objective of this review is to search for signals regarding the following questions: Premenstrual dysphoric disorder (PMDD) is a common condition that temporarily, but repetitively affects patient's global function. Patients and physicians alike are often uncertain whether prescription medication for PMDD is suffi ciently effective. The primary objective of this analysis is signal detection in effi cacy of pharmacological treatments in PMDD. Secondary objective is to review which symptoms are likely to respond to which medications. The review included otherwise healthy women with clinician confi rmed diagnosis of PMDD who participated in phase 3 clinical trials for the treatment of PMDD. Twelve pair-wise comparisons of drug and placebo for 2,420 patients with PMDD were performed. Oral contraceptives and selective serotonin receptor inhibitor were effective in alleviating symptoms of PMDD compared to placebo. Both Intermittent and continuous administration were more effective than placebo. This meta-analysis provides a signal that pharmacological treatment of PMDD is effective.