PO:13:188 | Menstrual alterations among women with rheumatoid arthritis: a comparative study across treatment modalities with focus on JAK inhibitors

Angelica Napoletano¹, Francesca Arezzo², Marco Fornaro¹, Giuseppe Lopalco¹, Gennaro Cormio², Vincenzo Venerito¹, Florenzo Iannone¹. | ¹University of Bari, Rheumatology Unit Department of Precision and Regenerative Medicine, Jonica Area, Bari; ²Gynecologic Oncology, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy.

Background. Rheumatoid arthritis (RA) often affects women during reproductive age. While the reproductive safety of conventional and biologic DMARDs is well described, evidence regarding Janus kinase inhibitors (JAKi) remains limited. Recent studies on human ovarian sections have demonstrated the expression of the JAK-STAT pathway in granulosa cells, suggesting a possible alteration of menstrual characteristics in women taking JAKi. This study aimed to assess menstrual alterations among women with RA receiving different treatment classes, with particular focus on JAKi.

Methods. We conducted a cross-sectional study at rheumatology and gynecology centers using structured questionnaires to evaluate menstrual cycle characteristics before and during therapy. Clinical and treatment data were collected. Menstrual outcomes were compared across treatment groups using chi-square tests. Multivariable logistic regression assessed the association between JAKi use and amenorrhea, adjusting for disease activity (DAS28).

Results. A total of 100 women with RA were included. The median age was 34.8 years (IQR 27.0–42.8), BMI 26.0 (IQR 24.0–27.0), and DAS28 score 2.99 (IQR 2.70–3.24) (Table 1). Thirty patients (30.0%) were treated with JAK inhibitors: Upadacitinib (n=17, 56.7%), Filgotinib (n=11, 36.7%), and Baricitinib (n=2, 6.7%) (Figure 1). Amenorrhea during therapy was reported by 10 patients (10.0%). Metrorrhagia was reported by 20 patients (20.0%), and menorrhagia by 14 patients (14.0%). Changes in menstrual frequency were noted in 41 patients (41.0%), including increased frequency in 12 (12.0%) and decreased frequency in 29 (29.0%). There were no statistically significant differences in these outcomes across treatment groups (p > 0.25 for all) (Figure 2). In multivariable analysis adjusting for DAS28, JAKi use was not associated with increased odds of amenorrhea (adjusted OR = 3.05, 95% CI: 0.31–30.37; p = 0.341).

Conclusions. In this cross-sectional study of women with RA, treatment with JAK inhibitors was not associated with an increased risk of menstrual alterations, including amenorrhea, metrorrhagia, or menorrhagia. These preliminary findings suggest a reassuring gynecologic safety profile for JAK inhibitors, but confirmation in larger, prospective studies is needed.