Systemic lupus erythematosus (SLE) primarily affects women, who may need hormone therapy (HT) in menopause. There is, however, some concern as to its efficacy and safety. This systematic review aimed to determine the effect of HT on the activity of SLE and its safety. The study was a qualitative systematic review. Research was conducted with data retrieved from Embase, MEDLINE and Cochrane databases using MESH terms up to April 2021, with no bar on date or language. Sixteen studies were selected for analysis. Most of them showed HT to be effective in the treatment of menopausal symptoms with no impact in SLE activity, but one randomized clinical trial showed an increase in the number of thrombotic events. The present systematic review demonstrated the efficacy of HT for treating the menopausal symptoms of SLE patients. The risk of flare and thrombosis seems to be very low.