A. Zeta potential analysis on Progesterone (10%) formulation administered topically in 66 postmenopausal women submitted to THRT during 60 months. Zetasizer Nano ZS90 (Malvern Instruments Ltd., UK, England). B. Zeta potential analysis on Progesterone (10%) formulation administered topically in 66 postmenopausal women submitted to THRT during 60 months. Zetasizer Nano ZS90 (Malvern Instruments Ltd., UK, England). C. Scanning Electron Microscopic Analyses of progesterone particles morphology administered topically in 66 postmenopausal women submitted to THRT during 60 months (TESCAN SEM-Model VEGA/XMU, Brno, Czech Republic). D. Raman Confocal spectroscopy analysis on skin layers. The skin depth concentration of progesterone was measured at 1, 3, 6, 21 and 24 hours in Stratum Cornum (SC); Viable Epidermis (EPI); Dermis (D) after transdermal application. Mean values are shown, SEM is indicated by error bars. *p<0.05 was considered significantly different compared to the first hour values (Model 3510 SCA, River Diagnostics, Rotterdam, The Netherlands).