Female pattern hair loss (FPHL) is widely common and negatively impacts the quality of life. FPHL is more challenging to treat than male pattern hair loss with minoxidil being the gold standard treatment. Several studies used 17α-estradiol solution for treating FPHL with variable results either alone or combined with minoxidil. to study the safety and efficacy of topical 17α-estradiol 0.01% combined with minoxidil 2% in comparison to minoxidil 2% in the treatment of FPHL. Forty-three women with FPHL were asked to blindly apply 6 puffs twice daily of a spray on solution containing either 17α-estradiol 0.01% combined with minoxidil 2% (EMX group) or minoxidil 2% alone (MX group). Treatment continued for 6 months. Clinical and trichoscopic assessments were performed at baseline and at the end of the treatment. At the end of the treatment period, both groups showed signs of improvement. Improvement parameters were better for the EMX group Vs the MX group, but this was not statistically significant. More patients in the EMX group experienced menstrual irregularities. Limited number of patients and follow-up periods. Estradiol effect was not studied on cellular or molecular levels and systemic absorption of both medications was not determined. the use of a 0.01% 17α-estradiol with 2% minoxidil solution in the treatment of FPHL does not seem to offer a statistically significant advantage than minoxidil alone and may carry a higher risk of associated menstrual irregularities.