Background: Multiple sclerosis (MS) is an autoimmune disease that is associated with demyelination of the neurons axon in the central nervous system. The predominant age range of this disease is related to adolescence and its prevalence rate in women is two to three times more than in men. Indentifyingthe factors and conditions cause diseases recurrence and in other words providing disease conditions can be effective in the prevention of diseases occurrence or recurrence. One of these conditions and requirements is menstrual cycle of women and hormonal changes that can be effective on the occurrence or recurrence of the disease and therefore indentifying the relationship between hormonal changes during menstruation seem necessary for the disease recurrence.Methods: In this study, 196 women with MS, who had regular menstrual cycle had referred due todisease attack, were studied in terms of the time of occurring the attack in menstrual cycle. Menstrual cycle of the patients was divided into three phases based on the estrogen and progesterone levels. The first phase is three days after onset of menstrual cycle until the time of ovulation and is simultaneous with increased estrogen. The second phase is since probable ovulation time (Approximately 14th day in a 28-day cycle or 14 days before the period in the other cycles) until three days before onset of the next menstruation; in this phase, the levels of both estrogen and progesterone increase. The third phase is equal to three days before bleeding until three days after the onset (decreased estrogen and progesterone levels). According to the LMP date of patients and time of attack, the phase of attack occurrence in menstrual cycle was determined for each of them.Findings: The highest recurrence rate of attack (99 attacks which was equal to 50.6% of the total attacks) occurred at the third phase of menstrual cycle in which the levels of both estrogen and progesterone was low. Twenty-seven percent of the attacks recurrence occurred at the first phase (which the estrogen level is high) and 22.4 percent of the attacks recurrence occurred at the second phase (which both estrogen and progesterone levels are high) that the results showed no significantdifference.Conclusion: The disease might be influenced by the female sex hormones and sex steroids can alter the disease activity. Estrogen may play a protective role in the disease and reduce estrogen is associated with increased recurrence of attacks.