BACKGROUND: Aging is a complex process due to the interplay of intrinsic factors (such as genetics and hormones) and extrinsic factors (including ultraviolet radiation and pollution). A significant cause of intrinsic aging in women is the loss of estrogen as a result of the onset of menopause. OBJECTIVE: A single site experience trial to assess the efficacy of Emepelle (Biopelle, Ferndale Pharma Group, Ferndale, MI), a skin care regimen containing Methyl Estradiolpropanoate (MEP)®, for the treatment of Estrogen Deficient Skin (EDS). The secondary objective was to assess patient tolerability and satisfaction. METHODS: Fourteen female subjects aged 53-68 years who were amenorrheic for 1-10 years (mean, 5 years), with at least a Grade II in Wrinkling (fine to moderate-depth wrinkles, moderate number of lines) and score of at least 5 (of 9; moderate-to-severe) in elastosis on the clinician-assessed Fitzpatrick-Goldman Classification of Wrinkling and Elastosis Scale, and a 3 or greater on the Investigator Facial Skin Hydration Scale, were included in the study. The subjects were instructed to apply the product Emepelle Serum in the morning, and the product Emepelle Night Cream in the evening to the entire freshly washed and dried face. Follow up visits were performed at 8 weeks, 14 weeks, and 20 weeks to evaluate efficacy and safety. Canfield Visia Complexion Analysis and standard photography was performed at baseline and at each follow up visit. RESULTS: On a 0-4 Facial Hydration Scale, 100% of study participants by week 20 showed at least one-grade improvement and 93% saw two grades or more improvement in hydration. 100% of study participants showed aesthetic improvements per investigator-assessed Global Aesthetic Improvement Scale (GAIS) at week 14. By week 20, 93% of study participants responded that the combination of Emepelle Serum and Night Cream regimen helped improve wrinkles, texture, and color, and 86% of study participants responded that Emepelle helped improve sun-damage, thickness, and integrity. In the Quality of Life questionnaire, 86% responded that Emepelle helped alleviate some or all of the skin issues they developed since entering menopause. Investigator clinical assessment scored patients with a 53% improvement in texture, 21% improvement in keratoses, and 15% improvement in laxity on the Alexiades-Armenakas Comprehensive Grading Scale for Assessment of Skin Aging and Photodamage by the end of the study at week 20. CONCLUSIONS: Patients in the study indicated satisfaction with the formulations of Emepelle Serum and Night Cream. Younger patients showed significant improvement by about 8 weeks. For patients who have been in menopause longer, significant improvement was seen by week 20, suggesting MEP’s potential ability to reactivate dormant estrogen receptors. J Drugs Dermatol. 2019;18(12):1226-1230.