Beijing, Jan 10 : Early menopause -- before the age of 45, taking hormone replacement therapy (HRT), and having 4 or more children are among several hormonal and reproductive factors linked to a heightened risk of rheumatoid arthritis in women, finds a long term study. Women are more susceptible to this autoimmune disease than men, said the researchers from Anhui Medical University in China. They are 4-5 times as likely as men to develop rheumatoid arthritis under the age of 50, and twice as likely to do so between the ages of 60 and 70. And the disease seems to take a greater physical toll on women than it does on men, revealed the study published in the open access journal RMD Open. While the study "is observational", the findings nevertheless prompt the researchers to suggest that hormonal and reproductive factors should be carefully evaluated in women diagnosed with rheumatoid arthritis. "The findings of this study are significant and form a basis on which novel and target-specific intervention measures to curb the risk of in women may be developed," the team said. For the study, the researchers drew on 2,23,526 UK Biobank participants whose health was tracked for an average of 12 years. During this time, 3,313 (1.5 per cent) women developed rheumatoid arthritis, and several hormonal and reproductive factors were associated with heightened disease risk, after accounting for potentially influential factors, such as lifestyle, level of social and economic deprivation, ethnicity and weight (BMI). Starting periods after the age of 14 was associated with a 17 per cent higher risk when compared with starting them at the age of 13, while going through the menopause below the age of 45 was associated with 46 per cent heightened risk compared with going through it at the age of 50-51. Fewer than 33 reproductive years -- defined as the interval between starting periods and going through the menopause -- was associated with a 39 per cent heightened risk. And compared with having 2 children, 4 or more was associated with an 18 per cent higher risk. Hysterectomy or removal of one or both ovaries (oophorectomy) was associated with 40 per cent and 21 per cent higher risks, respectively, although only a few women had these procedures. While no clear association emerged between the use of the pill and rheumatoid arthritis risk, HRT use and to a lesser extent, its duration, were associated with, respectively, 46 per cent and 2 per cent higher risks, the team said. /IANS