Influence of menstrual cycle and hormonal contraceptive use on MS symptom fluctuations: A pilot study

Abstract

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.

Keywords: Contraception; Estrogen; Hormone; Menstrual cycle; Multiple sclerosis; Symptom.

Fig. 1.. Hypothesized symptom severity changes according to contraceptive group across the menstrual cycle phases.

In females on oral contraceptives (OCs), the follicular (day 4–10), midcycle (day 10–17) and luteal (day 17–24) points are collapsed into “ON hormone”, and the perimenstrual (day 25–3) phase as “OFF hormone” (when taking placebo).

Fig. 2.. STROBE Diagram detailing study participation.

Fig. 3.. Comparison of symptom score variability between Continuous, Cyclic and No OC groups. Continuous OC users appear to have less variability in fatigue and hassles scores over their menstrual cycles

Comparison of survey score variability in Modified Fatigue Impact Scale (MFIS) (A) and Daily Hassles (B) between Continuous, Cyclic, and No OC groups. Comparisons performed using ANOVA. * p < 0.05, ** p < 0.01, *** p < 0.001.