A Double-Blind Randomized Pilot Study Evaluating the Safety and Efficacy of Topical MEP in the Facial Appearance Improvement of Estrogen Deficient Females
November 2018 | Volume 17 | Issue 11 | Original Article | 1186 | Copyright © November 2018
Zoe Diana Draelos MD
Dermatology Consulting Services, PLLC, High Point, NC
Facial skin aging is accelerated in postmenopausal females due to decreased collagen, reduced hydration, and loss of skin elasticity constituting the characteristics of estrogen deficient skin (EDS). The presence of estrogen receptors on dermal fibroblasts and epidermal keratinocytes confirms the role of estrogen in skin health. This research examined the efficacy and tolerability of topical methyl estradiolpropanoate (MEP) as an anti-aging cosmeceutical with estrogen like cutaneous effects in postmenopausal women who had never taken hormone replacement therapy (HRT). MEP was applied to the face twice daily for 14 weeks but was metabolized in the skin to an inactive compound avoiding estrogen side effects, as demonstrated by the safety study. The efficacy study investigator noted MEP induced statistically significant improvement from baseline at week 14 in dryness (P less than 0.001), laxity (P=0.001), atrophy (P=0.003), and dullness (P less than 0.001) as compared to vehicle. Four of nine subjects in the biopsy sub study demonstrated an increase in fibroblasts estrogen receptor staining. The novel concept of a safe and efficacious soft estrogen facial cosmeceutical may provide appearance benefits for postmenopausal women.J Drugs Dermatol. 2018;17(11):1186-1189.
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While the benefits of a moisturizer’s ability to place a smooth light reflective film over the skin to improve facial appearance are well received by consumers and recommended by dermatologists, there is a need for cosmeceuticals that address underlying physiologic skin changes associated with aging.1 Accelerated skin aging begins with menopause where women are expected to spend more than one-third of their life.2 Estrogen loss at menopause results in skin atrophy, decreased collagen content, reduced water content, and loss of skin elasticity characterizing estrogen deficient skin (EDS)3 The role of estrogen in the skin has been substantiated by the discovery of estrogen receptors in dermal fibroblasts, epidermal keratinocytes, blood vessels, and hair follicles. Additionally, two enzymes involved in estrogen formation, aromatase, and 17 beta-hydroxysteroid dehydrogenase type I are found in the skin.4The loss of skin collagen, resulting in facial wrinkling, may reach 30% in the first 5 years of menopause, with a further decline of 2.1% per postmenopausal year over a period of 15 years. This decline can be prevented with hormone replacement therapy (HRT).5 Chen et al found HRT treated women had a 10% greater skin thickness than nonsupplemented women.6 However, HRT is controversial as the Women's Health Initiative trial clearly identified associated risks, such as increased risk of breast cancer, stroke, and thromboembolic disease, with no coronary artery disease benefits.7 This has led to interest in topical estrogen delivery as a possible safe and efficacious alternative. Topical administration of estradiol for 3 months demonstrated a 38%increase in skin collagen, but other trials have produced less dramatic results.8 Since estrogen is a drug with side effects, it is not appropriate for use in cosmeceuticals, creating the need for another approach to the antiaging in the estrogen deficient female.9An evolving concept in antiaging medicine is the development of soft drugs. Soft drugs exhibit local action on the tissue to which they are applied due to rapid metabolic inactivation, but do not achieve systemic effects. This concept can also be applied to cosmeceuticals. For example, a soft cosmeceutical can be applied topically to exert an effect, but undergo rapid inactivation with hydrolytic enzymes, such as esterases, that are widely distributed in the blood and other tissues. Thus, the ester form of the cosmeceutical is active in the skin, but it is rapidly converted in the blood to the hydrolyzed carboxylic acid byproducts, which are inactive. This concept has been utilized in the development of methyl estradiolpropanoate (MEP), a synthetic sterol, as a possible anti-aging active ingredient in topical formulation that has estrogen-like cutaneous effects, but is metabolized in the blood to an inactive compound avoiding estrogen side effects.10 The singular mode of action and inactivation process of this cosmeceutical synthetic sterol indicates that it may have unique value in topical formulations for EDS.The objectives of this single-site vehicle-controlled double-blinded study were to evaluate the clinical efficacy and tolerability of MEP as compared to vehicle for the management of facial aging in postmenopausal females who had never received HRT.