NEW ORLEANS—Levels of anti-Mullerian hormone, a marker of the perimenopausal period, are associated with total gray matter volume and disability in patients with multiple sclerosis (MS), independent of chronological age and disease duration, according to data presented at the ACTRIMS 2016 Forum. The study also indicates that women with MS have no reduction in follicular reserve, compared with healthy women, and therefore have normal fertility.
Women with MS tend to have a more benign initial course than men with MS do, but the former often transition to secondary progressive disease near the time of menopause. To date, research has not clarified whether ovarian decline contributes to the accumulation of disability in women with MS.
Jennifer S. Graves, MD, PhD, a neurologist at the University of California, San Francisco Medical Center, and colleagues initiated a study to determine whether ovarian decline, as measured by levels of anti-Mullerian hormone, is associated with clinical disability or brain atrophy in women with MS. They examined 412 women with MS (mean age, 42.6) and 180 healthy controls (mean age, 44) from a longitudinal research cohort that had as many as 10 years of clinical and MRI follow-up. The investigators measured anti-Mullerian hormone levels in batch using a highly sensitive enzyme-linked immunosorbent assay on plasma samples from baseline, year 3, year 5, and years 8 to 10. They analyzed the data with logistic, linear, and mixed-model regression techniques, with adjustments for age, disease duration, smoking, race, ethnicity, vitamin D level, disease modifying therapy, birth control, and hormone replacement therapy as appropriate.
Jennifer S. Graves, MD, PhD
Dr. Graves and colleagues found that in models controlling for age, anti-Mullerian hormone levels were similar in women with MS and healthy controls. In a multivariable model of women with MS, including rigorous adjustments for age and disease duration, ovarian reserve (per twofold decrease in anti-Mullerian hormone pg/mL) was associated with total normalized gray matter volume (β = -3.29 mm3) and MS Functional Composite z-scores (β = -0.060) at baseline. After adjustment for age, white matter volumes were also associated with anti-Mullerian hormone levels (β = -2.64 mm3) at baseline, but the association did not remain statistically significant after additional adjustments (β = -1.49 mm3).
Having undetectable levels of anti-Mullerian hormone (28% of subjects) was associated with 0.60-point higher Expanded Disability Status Scale score. In a multivariable random-intercept-random-slope model using all observations over time, a twofold decrease in anti-Mullerian hormone (pg/mL) was associated with a 1.85-mm3 decrease in gray matter volume over the follow-up period. The researchers' longitudinal analyses of participants' clinical outcomes is ongoing.