Introduction: Women with RA have higher grades of disease activity and more declines in health status than men with RA; this recommends a relationship between estrogen and disease activity and severity. Aim: Our aim was to detect the effect of sex hormone fluctuations and menopause on functional disability and quality of life of postmenopausal RA patients. Methods: This is an observational cross-sectional study that was carried out on 84 postmenopausal rheumatoid arthritis patients who fulfilled the ACR/EULAR2010 classification criteria of RA attending to Rheumatology and Rehabilitation inpatient and outpatient clinics at Zagazig University Hospitals. All cases were exposed to full history taking, clinical examination, and laboratory investigations; acute phase reactants, rheumatoid factor (RF), anticyclic-citrullinated peptide (anti-CCP) antibodies, estrogen (E2) and follicular stimulating hormone (FSH). Functional disability measured by modified health assessment questionnaire (MHAQ). Menopause Rating Scale (MRS) assessed menopausal quality of life. Results: Our results revealed a significant correlation between menopausal duration and the MHAQ score. Estrogen (E2) levels but not FSH levels in postmenopausal RA patients were positively correlated with MHAQ and MRS scores. In addition, a significant correlation was found between disease activity parameters (SJC, ESR and DAS28) and the MRS scores. Moreover patients with higher MHAQ scores had higher MRS scores. Psychological and somatic domains of the MRS scale were the most affected.