BACKGROUND: In clinical practice, females with MS often report menstrually-related symptom fluctuations. Hypothetically, use of oral contraceptives (OCs) could reduce these fluctuations, particularly continuous OCs (11+ weeks of consistent exogenous hormones followed by 1 week placebo). OBJECTIVES: To prospectively capture (1) whether neurologic and generalized symptoms vary with menstrual cycle phase and (2) whether type of contraception impacts symptom fluctuations. METHODS: In this two-center pilot study, females with MS and a regular menstrual cycle prospectively tracked their menstrual cycles and completed symptom surveys for up to 6 months. Participants were categorized as 1) users of oral contraceptives, either a) cyclic or b) continuous, or 2) endogenously cycling, either c) hormonal intrauterine device (IUD) users or d) none users (e.g. no hormonal contraception; included condoms, copper IUD, tubal ligation, fertility awareness methods). There was no correction for multiple analyses. RESULTS: Altogether, 47/70 participants (67%) provided >4 weeks of data and were included in the analyses. Mean (SD) age was 35.0 (0.9) years, median (IQR) EDSS was 1.5 (1-2) and mean (SD) SymptoMScreen score was 10.4 (9.6). For endogenously cycling patients (IUD and none users), fatigue (MFIS) was lower in the perimenstrual period than in the luteal period (p < 0.05). For continuous OC users, variability in symptoms was lower than for endogenously cycling females (MFIS: p < 0.01; Daily Hassles, from Uplift & Hassles Survey: p < 0.05) or cyclic OC users (MFIS: p < 0.001). CONCLUSIONS: In this pilot study, symptom severity did not definitively fluctuate in relationship to the menstrual cycle in endogenously cycling participants. However, fatigue and daily hassles were less variable for participants using continuous OC than for cyclic OC users or no-OC users. Future confirmatory studies are warranted to further examine whether contraceptive choice can be leveraged to manage symptom fluctuation in cycling females with MS. Such studies could enroll larger cohorts over fewer cycles or employ incentivization and hormonal measurements to enhance participant retention and statistical power.