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. 2023 Nov 3;29(3):97–111. doi: 10.6118/jmm.22042

Table 1. Description of articles included in the systematic review.

Reference Type of study Participants/population Intervention(s), exposure(s) Comparator(s)/control Outcome(s)
Skin elasticity
Piérard et al. (1995) [16] Prospective cohort study 114 women MHT group (n = 46): oral MHT • Second group (n = 43), non-menopausal women
• Untreated group (n = 25), who were menopausal and receiving no MHT
BE
• MHT group: 74.6 ± 14.3
• Untreated group: 79.9 ± 12.2
MD
• MHT group: 215.7 ± 88.3
• Untreated group: 287.6 ± 150.5
Piérard-Franchimont et al. (1999) [17] A prospective longitudinal comparative trial 140 postmenopausal women MHT group (n = 90): oral MHT • Control group (n = 50) The regular impairment in BE with aging was significantly abated (P < 0.05) receiving MHT.
The MD increase over the 5 years in MHT-recipient women was less than half of that observed in nonrecipient subjects. This difference did not reach significance (P = 0.14).
Sumino et al. (2004) [11] Observational study of convenience sample 25 postmenopausal subjects MHT group (n = 12): oral MHT • Untreated group (n = 13), menopausal and out of MHT Skin elasticity
• MHT group: from 55.9 ± 7.5 to 61.1 ± 8.7
• Untreated group: from 57.3 ± 7.7 to 56.2 ± 9.8
Sator et al. (2007) [12] A prospective, randomized, double-blind, placebo-controlled study 40 non-hysterectomized, postmenopausal women MHT group (n = 20): oral MHT • Placebo group (n = 20), received continuous treatment with blinded placebo tablets (without active ingredients). Skin elasticity
• MHT group: gross elasticity, net elasticity and portion of elasticity, as compared to the complete curve at the skin covering the right mandibular ramus, increased significantly from baseline (P = 0.006, P = 0.002, and P = 0.005, respectively). The median values increased from 58% to 64%, 48% to 63%, and 35% to 39%, respectively.
• Placebo group: patients showed no significant results for these measurements.
Skin dryness
• MHT group: 0.11 ± 0.46
• Placebo group: 0.17 ± 0.38
Skin thickness
• MHT After 7 months, a significant increase in skin thickness (quartiles of percent of difference: 71.3%, 2.8%, and 8.5% after 6 weeks, and 0.0%, 6.4%, and 14.7% after 7 months of therapy) (P = 0.010).
• Placebo group: did not cause any significant changes.
Piérard et al. (2014) [13] A prospective trial 200 healthy Caucasian women MHT group (n = 75): oral MHT • Untreated group (n = 75), menopausal and out of MHT
• Third group (n = 50), non-menopausal
MD
• MHT group: 0.29 ± 0.08
• Untreated group: 0.34 ± 0.13
BE
• MHT group: 62.1 ± 0.09
• Untreated group: 42.1 ± 0.06
Phillips et al. (2008) [18] A randomized, double-blind, double-dummy, placebo-controlled multicenter study 485 subjects MHT group (n = 162): oral MHT • Placebo group (n = 165) Skin elasticity
Measures did not reveal any significant change between baseline and 48 weeks, except for time shadows in the periorbital area, where there was statistically significant (P = 0.008), but clinically insignificant, change.
Face wrinkles
• MHT group: –0.56 ± 1.29
• Placebo group: –0.27 ± 1.14
Skin dryness
• MHT group: 0.5 ± 1.11
• Placebo group: 0.31 ± 1.16
Piérard et al. (2001) [14] Comparative study 120 healthy postmenopausal Caucasian women The MHT group (n = 60): receiving oral or transdermal MHT • Untreated group (n = 60) MD
• MHT group: before 272.4 ± 153.2, after 277.6 ± 147.9
• Untreated group: before 357.5 ± 131.6, after 272.4 ± 153.2
BE
• MHT group: before 77.8 ± 14.5, after 52.9 ± 18.4
• Untreated group: before 67.4 ± 15.8, after 40.5 ± 17.9
Holzer et al. (2005) [15] A double-blind, vehicle-controlled, randomized study 40 women MHT group (n = 20): transdermal MHT • Placebo group (n = 20) were given the equivalent placebo cream containing just the vehicle. Skin firmness
• MHT group 23.61%
• Placebo group 13.24%
Skin elasticity
• MHT group: from 0.290 ± 0.057 to 0.343 ± 0.096
• Placebo group: from 0.323 ± 0.12 to 0.336 ± 0.093
Skin dryness
• MHT group 0.50 ± 0.69
• Placebo group 0.32 ± 0.47
Haapasaari et al. (1997) [19] Open, non-randomized parallel-groups study 43 postmenopausal women First group (n = 15): oral dose of 2 mg of 17 beta-estradiol and 1 mg of norethisterone acetate • Third control group (n = 14) Skin thickness
• Controls: 1.22 (1.03–1.99)
• E+P: 1.42 (1.01–1.89)
• E: 1.37 (1.17–1.63)
Second group (n = 14): oral dose of 2 mg estradiol valerate daily Skin elasticity
No histological or immunohistological changes were detected in the skin specimens during the 12-month treatment period compared to the baseline or to the skin specimens of the control group.
MD1-increased deformation of the skin under traction, BE-biological elasticity
Piérard et al. (1995) [16] Prospective cohort study 114 women MHT group (n = 46): oral MHT • Second group (n = 43), non-menopausal women
• Untreated group (n = 25), who were menopausal and receiving no MHT
BE
• MHT group: 74.6 ± 14.3
• Untreated group: 79.9 ± 12.2
MD
• MHT group: 215.7 ± 88.3
• Untreated group: 287.6 ± 150.5
Piérard-Franchimont et al. (1999) [17] A prospective longitudinal comparative trial 140 postmenopausal women MHT group (n = 90): oral MHT • Control group (n = 50) The regular impairment in BE with aging was significantly abated (P < 0.05) receiving MHT.
The MD increase over the 5 years in MHT-recipient women was less than half of that observed in nonrecipient subjects. This difference did not reach significance (P = 0.14).
Piérard et al. (2014) [13] A prospective trial 200 healthy Caucasian women MHT group (n = 75): oral MHT • Untreated group (n = 75), menopausal and out of MHT
• Third group (n = 50), non-menopausal
MD
• MHT group: 0.29 ± 0.08
• Untreated group: 0.34 ± 0.13
BE
• MHT group: 62.1 ± 0.09
• Untreated group: 42.1 ± 0.06
Piérard et al. (2001) [14] Comparative study 120 healthy postmenopausal Caucasian women The MHT group (n = 60): receiving oral or transdermal MHT • Untreated group (n = 60) MD
• MHT group: before 272.4 ± 153.2; after 277.6 ± 147.9
• Untreated group: before 357.5 ± 131.6; after 272.4 ± 153.2
BE
• MHT group: before 77.8 ± 14.5; after 52.9 ± 18.4
• Untreated group: before 67.4 ± 15.8; after 40.5 ± 17.9
Skin thickness
Fuchs et al. (2003) [22] A prospective, randomized, double-blind study 65 postmenopausal women The estradiol group (n = 22): estradiol • Combination group (n = 22), a combination of the estradiol and glycolic acid
• Control group (n = 21), to glycolic acid
Skin thickness
• The estradiol treatment: produced a 23% increase in (P = 0.0458)
• Control group: 27% increase (P = 0.0467)
• The combination: 38% increase (P = 0.00181)
Creidi et al. (1994) [20] Randomised, double-blind, parallel group study 54 women MHT group (n = 27): transdermal MHT • Placebo group (n = 27), placebo cream Skin thickness
• MHT group: from 1.56 ± 0.20 mm to 1.68 ± 0.19 mm
• Placebo group: from 1.52 ± 0.20 mm to 1.59 ± 0.19 mm
Face wrinkles
• MHT group: –0.5 ± 0.6
• Placebo group: 0 ± 0.7
Haapasaari et al. (1997) [19] Open, non-randomized parallel-groups study 43 postmenopausal women First group (n = 15): oral dose of 2 mg of 17 beta-estradiol and 1 mg of norethisterone acetate • Third control group (n = 14) Skin thickness
• Controls : 1.22 (1.03–1.99)
• E+P : 1.42 (1.01–1.89)
• E : 1.37 (1.17–1.63)
Second group (n = 14): oral dose of 2 mg estradiol valerate daily Skin elasticity
No histological or immunohistological changes were detected in the skin specimens during the 12-month treatment period compared to the baseline or to the skin specimens of the control group.
Maheux et al. (1994) [21] Randomized, double-blind, placebo-controlled study 60 postmenopausal women MHT group (n = 30): oral MHT • Placebo group (n = 30) Skin thickness
• MHT group: 2.44 ± 0.06 mm
• Placebo group: 2.41 ± 0.07 mm
After 6 months
• MHT group: 2.55 ± 0.06 mm
• Placebo group: 2.44± 0.07 mm
After 12 months
• MHT group: 2.50 ± 0.06 mm
• Placebo group: 2.73 ± 0.07 mm
Sauerbronn et al. (2000) [23] Randomized, double-blind, placebo-controlled study 38 postmenopausal women MHT group (n = 19): oral MHT • Placebo group (n = 19) control received 21 tablets of placebo Collagen content
• MHT group: from 21,897.4 (S.D. 1,635.33) to 23,318.2 (S.D. 2,027.6)
• Placebo group: from 22,014.6 (S.D. 1,858.1) to 22,057.2 (S.D. 2,405.7)
Skin thickness
There were no significant differences between baseline and 6-month treatment in both groups.
Sator et al. (2007) [12] A prospective, randomized, double-blind, placebo-controlled study 40 non-hysterectomized, postmenopausal women MHT group (n = 20): oral MHT • Placebo group (n = 20) received continuous treatment with blinded placebo tablets (without active ingredients) Skin elasticity
• MHT group: gross elasticity, net elasticity and portion of elasticity, as compared to the complete curve at the skin covering the right mandibular ramus, increased significantly from baseline (P = 0.006, P = 0.002, and P = 0.005, respectively). The median values increased from 58% to 64%, 48% to 63%, and 35% to 39%, respectively.
• Placebo group: patients showed no significant results for these measurements.
Skin dryness
• MHT group: 0.11 ± 0.46
• Placebo group: 0.17 ± 0.38
Skin thickness
• MHT after 7 months, a significant increase in skin thickness (quartiles of percent of difference: 71.3%, 2.8%, and 8.5% after 6 weeks, and 0.0%, 6.4%, and 14.7% after 7 months of therapy) (P = 0.010).
• Placebo group: did not cause any significant changes.
Collagen content
Sauerbronn et al. (2000) [23] Randomized, double-blind, placebo-controlled study 38 postmenopausal women MHT group (n = 19): oral MHT • Placebo group (n = 19) control received 21 tablets of placebo Collagen content
• MHT group: from 21,897.4 (S.D. 1,635.33) to 23,318.2 (S.D. 2,027.6)
• Placebo group: from 22,014.6 (S.D. 1,858.1) to 22,057.2 (S.D. 2,405.7)
Skin thickness
• There were no significant differences between baseline and 6-month treatment in both groups.
Castelo-Branco et al. (1992) [24] A randomized, placebo-controlled study 118 women First group (n = 28): 0.625 mg/day conjugated equine oestrogens (CEE) over a 25-day cycle each month. • Untreated group (n = 30), no treatment Collagen content
• 1 group: collagen at 0 month (115.1 ± 0.8) vs. collagen after 12 months (117.1 ± 0.7); + 1.8%
• 2 group: collagen at 0 month (114.0 ± 1.2) vs. collagen after 12 months (119.8 ± 0.6); + 5.1%
• 3 group: collagen at 0 month (114.0 ± 0.9) vs. collagen after 12 months (117.8 ± 1.0); + 3.0%, P < 0.05
• Untreated group: collagen at 0 month (116.5 ± 1.1) vs. collagen after 12 months (112.8 ± 0.9); –3.2%, P < 0.05
Second group (n = 28): 50-day transdermal 17/3-oestradiol over a 24-day cycle each month
Third group (n = 32): 0.625 mg/day CEE every day of the month.
Effects of raloxifene and MHT on forearm skin elasticity
Sumino et al. (2009) [25] Prospective cohort study 47 Japanese postmeno-pausal women MHT group (n = 19): transdermal MHT • A raloxifene group (n = 17) received continuous raloxifene treatment (60 mg/day); a control group (n = 11) women did not receive either therapy Skin elasticity
• Raloxifene group: from 52.4% ± 3.8% to 55.1% ± 4.7%
• MHT group: from 64.1% ± 7.2% to 67.4% ± 7.4%
• Control group: from 55.8% ± 5.8% to 52.7% ± 8.3%
Skin firmness
Holzer et al. (2005) [15] A double-blind, vehicle-controlled, randomized study 40 women MHT group (n = 20): oral MHT • Placebo group (n = 20) were given the equivalent placebo cream containing just the vehicle Skin firmness
• MHT group: 23.61%
• Placebo group: 13.24%
Skin elasticity
• MHT group: from 0.290 ± 0.057 to 0.343 ± 0.096
• Placebo group: from 0.323 ± 0.120 to 0.336 ± 0.093
Skin dryness
• MHT group: 0.50 ± 0.69
• Placebo group: 0.32 ± 0.47

MHT: menopausal hormone therapy, MD: mean difference, BE: biological elasticity, E: estradiol, P: progesterone, S.D.: standart deviation.