 Subjects will be randomly allocated to either treatment group 2.5 mg E4, 5 mg E4, 10 mg E4, 15 mg E4, or placebo in a 1:1:1:1:1 ratio. All treatments E4 or Placebo will be administered once daily QD per os for at least 12 consecutive weeks until the last biological assessments Day 90 maximum have been performed. 