Table 1.
Studies evaluating the effect of topical estrogen on the skin in postmenopausal women
| Study group | Treatment group (n) | N | Treatment length | Treatment Location | Outcome of interest |
|---|---|---|---|---|---|
| Brincat et al., 1987, Brincat et al., 1987 | 1.5 mg estradiol gel | 16 | 12 months | Lower abdomen | - Skin collagen content in the abdomen (gel application site) statistically higher compared with baseline - Skin collagen content in the thigh (distant site) increased but did not reach significant levels |
| Punnonen et al., 1987 | 1 mg oestriol ointment | 14 | 3 weeks | Lower abdomen | - Elastic fibers in the papillary dermis were thickened, better orientated, and slightly increased in number in 50% of patients compared with 0% of the controls - Epidermal thickness slightly increased in 29% of patients and 17% of controls - No significant change observed in epidermal cell size, epidermal mitotic activity, dermal vascularization, or inflammatory infiltrate in specimens taken before or after the treatment |
| Bolognia et al., 1989 | Transdermal 17beta-estradiol patch (Estraderm) | 18 | 6 months | n/a | - Frequency of cutaneous flushing was the only cutaneous finding significantly decreased in the treatment group when compared with the placebo group - No significant differences between the treatment and placebo groups for the following cutaneous signs: dryness, scaling, excoriations, bruises, scalp scaling number of lentigines, and number of seborrheic keratosis |
| Jemec and Serup, 1989 | 17beta-estradiol gel (0.1 mg/g and 1.0 mg/g concentrations) | 8 | 180 days | Ventral aspect of forearm | No statistically significant differences observed with regard to skin conductance, capacitance, elasticity, distensibility, and hysteresis when estrogen-treated areas were compared with placebo-treated areas |
| Castelo-Branco et al., 1992 | 50 ug/day transdermal 17beta-oestradiol | 28 | 12 months | Application site: N/A Biopsy site: Lower abdomen |
Skin collagen concentration was significantly increased compared with baseline (+ 5.1%; p < .01) |
| Schmidt et al., 1994 | 0.3% estriol cream or 0.01% estradiol cream | 18 | 6 months | Face | - Skin aging symptoms (vascularization, firmness, elasticity, moisture, wrinkle depth, and pore size) improved in both groups, but the effects of the topical estriol group were slightly superior to those of the estradiol group with regard to extent and onset |
| Creidi et al., 1994 | 1 g Premarin cream (0.625 mg conjugated estrogen/g of cream) | 27 | 24 weeks | Face | - Skin thickness significantly increased in the treatment group compared with placebo (p = .013) - Fine wrinkles significantly improved in the treatment group compared with placebo (p = .012) - Improvement in roughness, laxity, and mottled pigmentation but did not reach statistical significance between the groups |
| Varila et al., 1995 | 2.5 mg of estradiol gel (Estrogel, same as 1.5 mg of 17B-oestradiol) | 12 | 3 months | Lower abdomen | - Amount of skin collagen, as measured by skin hydroxyproline content, significantly increased during oestradiol treatment (p = .012) - Levels of carboxyterminal propeptide of human type 1 procollagen significantly increased after treatment - Levels of aminoterminal propeptide of human type III procollagen increased, but not statistically significant |
| Piérard-Franchimont et al., 1995 | Cyclic transdermal hormone replacement therapy using estradiol 3.2 mg (Systen TTS, Cilag) | 15 | 1 year | Lateral arm | - Water-holding capacitance of the stratum corneum was significantly increased in the treatment group, as measured with the plastic occlusion stress test |
| Callens, 1996 | 17B-etsradiol gel (Estrogel) or oestradiol transdermal system (Estraderm TTS) | 49 | 58 months (range: 2-170 months) | Thigh, buttocks, abdomen, arm, inner forearm, outer forearm, or neck | - Skin thickness (measured with skin echography) and sebum (measured with Sebumeter) significantly increased in the treated group compared with the untreated one - Hydration (measured by capacitance) and microtopography (measured by image analysis) not significantly different between the treated and untreated groups |
| Schmidt et al., 1996 | 0.01% estradiol, 0.3% estriol cream | 59 | 6 months | Face and neck | - Elasticity and firmness of the skin markedly improved and wrinkle depth and pore sizes decreased in both treatment groups - Type III collagen significantly increased in both treatment groups |
| Ashcroft et al., 1999 | Evorel hormone replacement therapy patch, 25 ug estradiol/24 hr | 9 | 80 days | Upper inner arm | Increased wound healing observed with decreased wound size, increased collagen levels, and increased fibronectin levels in the treatment group at the site of the wound |
| Sator et al., 2001 | Transdermal estrogen (Estraderm TTS) | 13 | 6 months | Temporal bone, inner upper arm, suprasternal region | - Skin surface lipids significantly increased when oral progesterone added to the regimen; but when only estrogen given, significant decrease in skin lipids - Epidermal hydration, skin elasticity, and skin thickness significantly increased in the treatment group compared with controls |
| Fuchs et al., 2003 | 0.01% estradiol cream | 44 | 6 months | Face (temple hairline) | - Epidermal thickness significantly increased by 23% compared with controls - Markers of skin aging (rete peg pattern, epidermal thickness) significantly improved/reversed |
| Son et al., 2005 | 0.01% 17B-estradiol | 13 | 2 weeks | Buttock | - Expression of type 1 procollagen, tropoelastin, fibrillin-1 mRNAs increased - MMP-1 protein levels reduced - Keratinocyte proliferation and epidermal thickness increased |
| Patriarca et al., 2007 | 0.01% micronized 17B-estradiol gel | 15 | 16 weeks | Face | - Epithelial and dermal thickness significantly increased compared with baseline - Amount of collagen significantly increased compared with baseline |
| Rittié et al., 2008 | 0.01%, 0.1%, 1%, or 2.5% estradiol | 40 | 2 weeks | Sun-protected hip, photo-damaged forearm, face | - Collagen production (quantified by procollagen I and III mRNA and collagen 1 protein levels) stimulated in sun-protected hip skin but not in photo-aged forearm or face skin in postmenopausal women |
| Sumino et al., 2009 | 17-beta estradiol patch (Estraderm M) | 19 | 12 months | Forearm | - Skin elasticity significantly increased from baseline to after treatment (64.1 to 67.4%; p < .05) |
| Moraes et al., 2009 | 0.01% 17-beta estradiol | 18 | 24 weeks | Face | Statistically significant increase in epidermal thickness, number of dermal papillae, fibroblasts, and dermal vessels |
| Neder and Medeiros, 2012 | 0.05% estradiol cream | 40 | 30 days | Pre-auricular region | Metalloproteinase-1 enzyme expression not significantly different in keratinocytes, fibroblasts, and endothelial cells before and after treatment |
| Patriarca et al., 2013 | 0.01% 17-beta estradiol gel | 15 | 24 weeks | Face | Hyaluronic acid concentration significantly increased |
| Masuda et al., 2013 | 0.06% estradiol gel (l’estrogel) | 79 | 8 + 16 weeks | Arms | Fineness of texture (measured by digital microscope) increased in application site (forearm) and cheek (unapplied site) |
| Silva et al., 2017 | 0.01% 17-beta estradiol | 15 | 24 weeks | Face | Types I and III facial collagen significantly increased at the end of treatment |