Age at natural menopause in women on long-term methotrexate therapy for rheumatoid arthritis

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The aim of the study was to compare the natural menopause ages of healthy women with those of women with methotrexate (MTX)-treated rheumatoid arthritis (RA), and to specifically assess the effect of disease onset and activity and the use of MTX on the age of the last menstruation.


We performed a retrospective review of medical records to identify the ages at which menopause occurred in women with premenopausal RA treated with MTX and in women with postmenopausal onset, irrespective of therapy. Natural menopause ages were also compared between participants with and without RA.


Women with premenopausal onset of RA underwent menopause at a significantly younger age than did healthy women (P < 0.001) or those with postmenopausal disease onset (P = 0.001). Menopause also occurred at younger ages in participants with postmenopausal disease onset than in healthy controls (P = 0.012). The study suggested that menopause age was positively correlated with the age at which RA was diagnosed (R = 0.51; P < 0.001) in women with premenopausal RA onset, but was independent of the participant's age at menarche, number of pregnancies, or MTX therapy. Participants with RA onset at ≤ 35 years of age had a ninefold higher risk of premature menopause (P = 0.008).


The age at which menopause occurs in a patient with RA depends on the patient's age at the time of disease onset and its duration, but is not influenced by MTX treatment.

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