IntroductionDysmenorrhea is a physical and mental burden for women, negatively affecting health-related quality of life (HRQL) and work productivity. However, data on HRQL and work productivity of Japanese women are scarce.MethodsIn this prospective observational study, 397 Japanese women received low-dose estrogen/progestin (LEP) or non-LEP treatment (non-steroidal anti-inflammatory drugs or Chinese herbal medicines) for primary/secondary dysmenorrhea and completed survey questionnaires online regarding menstrual symptoms, HRQL, and work productivity. Regression analysis was performed to compare the groups and evaluate outcomes over time using the paired t test. Subgroup analysis was performed using stratification by patient background, and correlations between improvement in menstrual symptoms/HRQL and work productivity were investigated using Spearman’s rank correlation coefficient.ResultsSignificant reductions in the modified Menstrual Distress Questionnaire (mMDQ) total score were shown in the LEP group (n = 251) (P < 0.01), but not the non-LEP group (n = 146). Significant improvements in HRQL, measured by the 36-Item Short-Form Health Survey v2.0 (SF-36v2.0), were shown in the LEP group, but not the non-LEP group. Improvements were seen in mental component summary and 7/8 domains (role physical, bodily pain, general health, role emotional, mental health, vitality, and social functioning) in the LEP group, but not the non-LEP group. There were no differences in the physical component summary and role functioning in either group. Improvements in work productivity, measured by the modified Work Productivity and Activity Impairment Questionnaire (mWPAI), were greater in the LEP group vs. non-LEP group. Regression analysis showed differences in improvements between the groups in the mMDQ total score, SF-36v2.0, and mWPAI. A correlation between mMDQ or HRQL and work productivity was seen.ConclusionIn Japanese women, dysmenorrhea is associated with reduced HRQL and work productivity. In real-world clinical practice, improvements in physical and mental menstrual symptoms, HRQL, and work productivity were observed with LEP treatment.Trial RegistrationNCT04607382 (ClinicalTrials.gov).Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02118-0.