The purpose of this study was to reveal the effect of connective tissue manipulation (CTM) on long-term pain severity, fatigue, sleep quality, premenstrual symptom severity, general health status, anxiety, and depression in women with primary dysmenorrhea (PD). Thirty-five women with PD were divided into two groups. CTM was applied to the participants in each group on the days when they were not on menstruation between two menstrual cycles for the group 1 (n=18) and between three menstrual cycles for the group 2 (n=17). Intensity of menstrual pain, the sleep quality, and fatigue status of the participants during dysmenorrhea were evaluated by the Visual Analog Scale (VAS). Depressive symptoms and anxiety were evaluated using the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI), respectively. Also, the Premenstrual Syndrome Scale (PMSS) and the General Health Questionnaire (GHQ) were used to investigate the severity of premenstrual symptoms and mental health status during menstrual period. A significant decrease in the pain severity and fatigue of the participants was observed in both group 1 and group 2 after treatment, after 3rd, and 6th month follow-up (p=0.001). Also, this decrease lasted for 12th month follow-up after treatment in group 2 (p=0.0001). There was no statistically significant improvement in sleep quality within each group (p>0.05). Moreover, none of the parameters were significantly different between two groups (p>0.05). We can suggest that 2-cycle CTM treatment should be preferred in clinical settings to obtain long-lasting effects for decreasing pain, fatigue, and premenstrual symptoms in women with PD. CLINICAL TRIAL NUMBER: NCT04509934. Registration date: 8 November 2020.

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