Perimenopause Is Associated With Increased Disease Activity in Psoriatic Arthritis

Objectives Perimenopause is associated with a wide spectrum of symptoms, including mood changes, sleep disturbances, and joint pains. We assessed whether PsA disease activity worsens during perimenopause compared to pre- and post- menopause stage. Methods We analyzed data on female patients with PsA followed in a prospective cohort from 1978 to 2024. Data on PsA disease activity, medications, co-morbidities, and age at menopause were collected using standard protocols. Pre-perimenopause and post-menopause stages were defined as >2 years before and after the final menstrual period (FMP), respectively, while the perimenopause stage was within 2 years (before or after) of the FMP. PsA disease activity was assessed at each visit using Disease Activity in PsA (DAPSA), tender and swollen joint counts, PASI, CRP, and FACIT-fatigue. Disease activity during the perimenopause stage was compared to the pre-perimenopause and post-menopause visits. The association between menopausal stages and PsA disease activity measures was assessed with a Generalized Additive Model with splines (considering time from FMP as continuous) and with linear mixed-effects models (menopausal stages as categorical variables). Each model was adjusted for age, disease duration, and medication use, and accounted for repeated observations via a subject-specific random effect. We assessed the mediating effects of BMI and fatigue on the change in DAPSA across menopause stages. Results A total of 477 female patients provided data for 8381 visits over a mean follow-up of 12.1 years. Mean age at first visit was 44.9±13.9 years and mean age at menopause was 48.7 years. Hormone replacement therapy had only been used during 1.5% of visits. A rise in DAPSA scores was found during perimenopause years, followed by a slight drop post menopause (Figure 1A). Linear mixed models found an association between being in perimenopause and higher DAPSA vs pre-perimenopause (β=1.92, p<0.001) and post-menopause stages (β=1.56, p=0.001, Figure 1B). Significantly higher tender and swollen joint counts were found in perimenopause vs both pre- and post-menopause. Higher PASI was found in perimenopause vs post-menopause stage. Increase in fatigue levels during perimenopause only partially mediated the increase in DAPSA score during perimenopause, explaining 12% to 18% of this change. BMI did not have a mediating effect on DAPSA change during perimenopause. Conclusion Perimenopause is associated with an increase in PsA disease activity which includes both patient-reported outcomes but also objective measures of activity. These findings may warrant consideration of hormone replacement therapy in perimenopausal PsA patients.