Effects of Methotrexate Therapy on the Levels of Gonadotropic Hormones in Rheumatoid Arthritis Patients of Reproductive Age

Abstract

Purpose: To determine the effects of methotrexate (MTX) therapy on gonadotrophic hormones i.e follicular stimulating hormone (FSH) and luteinising hormone (LH) levels and menopausal symptoms in female rheumatoid arthritis (RA) patients of reproductive age. Methods: This was a cross sectional study conducted in University Kebangsaan Malaysia Medical Centre (UKMMC), from January 2018 to July 2018. Women with RA aged between 15 to 49 years who were on MTX therapy for at least 6 months, were consecutively recruited. All subjects were interviewed to gather information on their menstrual history and menopausal symptoms. The medical records were reviewed to obtain further data on the disease characteristics and RA treatment. The RA disease activity was determined using the DAS 28 scoring system. All subjects were tested for their serum FSH and LH levels. Results: A total of 40 patients were included in this study. The median dose of MTX used by the subjects was 12.5 mg weekly. The mean cumulative MTX dose was 1664.92 ± 738.61 mg. More than half (53.1%) of the subjects reported menopausal symptoms especially hot flushes. We found that FSH levels had a significant positive correlation with cumulative MTX dose ([r = 0.86], p < 0.001) and the duration of MTX therapy ([r = 0.84], p < 0.001). Besides, there was a significant relationship between disease activity based on DAS 28 and FSH levels (p < 0.01). Age, body mass index, disease duration and weekly MTX dose showed no associations with the FSH levels. On multivariate analysis, DAS 28 was the only parameter which remained significant (β = 1.74 (95% CI 1.17-2.31), p < 0.001). The LH levels, on the other hand, were not associated with the MTX therapy or disease activity. Conclusion: Higher levels of FSH; which is an indicator of diminished ovarian reserve, have a significant positive relationship with disease activity, cumulative dose and duration of MTX therapy in RA.