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BMJ Clin Evid. 2008; 2008: 1711.
Published online 2008 December 16.
PMCID: PMC2907965

Wrinkles

Abstract

Introduction

Skin disorders associated with photodamage from ultraviolet light include wrinkles, hyperpigmentation, tactile roughness, and telangiectasia, and are more common in people with white compared with other skin types. Wrinkles are also associated with ageing, hormonal status, smoking, and intercurrent disease.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to prevent and treat skin wrinkles? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: alpha and beta hydroxyl acids, carbon dioxide laser, chemical peel, dermabrasion, facelifts, isotretinoin, natural cartilage polysaccharides (oral or topical), retinyl esters, sunscreens, tazarotene, tretinoin, variable pulse erbium:YAG laser, and vitamin C or E (topical).

Key Points

Skin disorders associated with damage by ultraviolet light include wrinkles, hyperpigmentation, tactile roughness, and telangiectasia, and are more common in white people compared with other skin types.

  • Wrinkles are also associated with ageing, hormonal status, smoking, and intercurrent disease.

We don't know whether sunscreens or topical vitamins C or E prevent wrinkles, as no studies were found.

Exposure to ultraviolet light may be associated with photodamage to the skin. Guidelines suggest that avoiding direct sunlight, either by staying indoors or in the shade, or by wearing protective clothing, is the most effective measure for reducing exposure to ultraviolet light.

We don't know whether topical vitamins C or E improve the appearance of wrinkles, as studies have been small. These vitamins may cause stinging and erythema.

Topical tretinoin improves fine wrinkles compared with placebo cream in people with mild to moderate photodamage, but its effect on coarse wrinkles is unclear.

  • Topical tretinoin may cause itching, burning, erythema, and skin peeling.
  • Isotretinoin cream improves fine and coarse wrinkles compared with vehicle cream in people with mild to severe photodamage, but causes severe irritation of the face in 5%–10% of people.
  • We don't know whether tazarotene is more effective than tretinoin at improving fine and coarse wrinkles in people with moderate photodamage, as studies have given inconclusive results. It can cause burning of the skin.

We don't know whether retinyl esters, topical or oral natural cartilage polysaccharides, alpha or beta hydroxyl acids, or chemical peels are beneficial.

We don't know whether dermabrasion is more effective at improving wrinkles compared with carbon dioxide laser treatment, as studies have given inconclusive results, but adverse effects are common with both treatments, especially erythema.

About this condition

Definition

Wrinkles are visible creases or folds in the skin. Wrinkles less than 1 mm in width and depth are defined as fine wrinkles and those greater than 1 mm as coarse wrinkles. Most RCTs have studied wrinkles on the face, forearms, and hands.

Incidence/ Prevalence

We found no information on the incidence of wrinkles alone; only on the incidence of skin photodamage — which includes a spectrum of features such as wrinkles, hyperpigmentation, tactile roughness, and telangiectasia. The incidence of skin disorders associated with ultraviolet light increases with age and develops over several decades. One Australian study (1539 people, aged 20–55 years, living in Queensland) found moderate to severe photodamage in 72% of men and 47% of women under 30 years of age. Severity of photodamage was significantly greater with increasing age, and was independently associated with solar keratoses and skin cancer. Wrinkling was more common in people with white skin (especially skin phototypes I and II). We found few reports of photodamage in black skin (phototypes V and VI). One study reported that the incidence of photodamage in European and North American populations with Fitzpatrick skin types I, II, and III is about 80%–90%. As Asian skin is more pigmented (Fitzpatrick skin types III–V), wrinkling is not readily apparent until approximately the age of 50 years, with wrinkles being less severe than in white skin of similar age. A prospective study (85 white women living in North America and 70 Japanese women living in Tokyo, aged 20–69 years) comparing age-related changes in wrinkles in eight areas of the facial skin (forehead, glabella, upper eyelid, corner of the eye, lower eyelid, nasolabial groove, cheek, and corner of the mouth) and sagging in the subzygomatic area found more wrinkle formation in all areas of the face in younger age groups of white women than in Japanese women (aged 20–29 years). Another prospective study (160 Chinese women and 160 French women, aged 20–60 years) found that wrinkle onset was delayed by about 10 years in Chinese women compared with French women.

Aetiology/ Risk factors

Wrinkles may be caused by intrinsic factors (e.g., ageing, hormonal status, and intercurrent diseases) and by extrinsic factors (e.g., exposure to ultraviolet radiation, and cigarette smoke). These factors contribute to epidermal thinning, loss of elasticity, skin fragility, and creases and lines in the skin. The severity of photodamage varies with skin type, which includes skin colour, and the capacity to tan. It is becoming increasingly clear that brief incidental sun exposures that occur during the activities of daily living add significantly to the average individual's daily exposure to ultraviolet light. One review of five observational studies found that facial wrinkles in men and women were more common in smokers than in non-smokers. It also found that the risk of moderate to severe wrinkles in lifelong smokers was more than twice that in current smokers who had been smoking for a shorter period (RR 2.57, 95% CI 1.83 to 3.06). The effects of pregnancy and menopause on facial wrinkling have also been investigated by some researchers. In postmenopausal women, oestrogen deficiency is thought to be an important contributory factor for development of wrinkles. One observational study (186 Korean women, aged 20–89 years) found that facial wrinkling increased significantly with an increase in the number of full-term pregnancies (OR 1.84, 95% CI 1.02 to 3.31) and the number of years since menopause (OR 3.91, 95% CI 1.07 to 14.28). However, postmenopausal women who had HRT had significantly less facial wrinkling compared with postmenopausal women who had no history of HRT (OR 0.22, 95% CI 0.05 to 0.95).

Prognosis

Wrinkles cannot be considered a medical illness requiring intervention but concerns about changes in physical appearance brought on by aging can have a detrimental effect on quality of life. In some cases, concerns about physical appearance can affect personal interactions, occupational functioning, and self-esteem. Geographical differences, culture, and personal values potentially influence a person's anxieties about ageing. In societies in which the maintenance of a youthful appearance is valued, the demand for interventions that ameliorate visible signs of ageing grows as ageing populations expand.

Aims of intervention

To prevent skin wrinkling; to improve fine and coarse wrinkling in adults; and to improve quality of life, with minimal adverse effects of treatment.

Outcomes

Wrinkle improvement includes physician and patient evaluation of improvement in skin texture that reduces the visibility of wrinkles; quality of life; and adverse effects of treatment. We excluded RCTs based solely on non-clinical outcomes, such as histological assessment, photography, or optical profilometry.

Methods

Clinical Evidence search and appraisal April 2008. The following databases were used to identify studies for this systematic review: Medline 1966 to April 2008, Embase 1980 to April 2008, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2008, Issue 1. Additional searches were carried out using NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, at least single-blinded, and containing more than 20 people of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. Most RCTs in the review recruited people with moderate to severe photodamage and wrinkles, rather than people with wrinkles alone. To aid readability of the numerical data in our reviews, we round percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as RRs and ORs. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table
GRADE Evaluation of interventions for Wrinkles.

Glossary

Erbium:YAG laser
An yttrium aluminium garnet laser.
Fitzpatrick skin phototype classification
I = always burns easily, never tans; II = always burns easily, tans minimally; III = burns moderately, tans gradually (light brown); IV = burns minimally, always tans well (brown); V = rarely burns, tans profusely (dark brown); VI = never burns, deeply pigmented (black).
Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Mild/moderate/severe photodamage
A spectrum of features including wrinkles, hyperpigmentation, tactile roughness, and telangiectasia. Usually measured on a scale from 0–9 (0 = none, 1–3 = mild, 4–6 = moderate, and 7–9 = severe).
Very low-quality evidence
Any estimate of effect is very uncertain.

Notes

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

Contributor Information

Juan Jorge Manríquez, Unidad Docente Asociada de Dermatologia, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.

Daniela Majerson Gringberg, Pontificia Universidad Católica de Chile, Santiago, Chile.

Claudia Nicklas Diaz, Universidad de La Frontera, Temuco, Chile.

References

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3. Tsukahara K, Fujimura T, Yoshida Y, et al. Comparison of age-related changes in wrinkling and sagging of the skin in Caucasian females and in Japanese females. J Cosmet Sci 2004;55:351–371. [PubMed]
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10. Alsarraaf R. Outcomes research in facial plastic surgery: a review and new directions. Aesthetic Plast Surg 2000;24:192–197. [PubMed]
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13. Preventive Services Task Force. Counselling to prevent skin cancer: recommendations and rationale of the U.S. Preventive Services Task Force. MMWR Recomm Rep 2003;52:13–17. [PubMed]
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15. Phillips TJ, Gottlieb AB, Leyden JJ, et al. Efficacy of 0.1% tazarotene cream for the treatment of photodamage. Arch Dermatol 2002;138:1486–1493. [PubMed]
16. Kang S, Leyden JJ, Lowe NJ, et al. Tazarotene cream for the treatment of facial photodamage. Arch Dermatol 2001;137:1597–1604. [PubMed]
17. Lowe NJ, Gifford M, Tanghetti E, et al. Tazarotene 0.1% cream versus tretinoin 0.05% emollient cream in the treatment of photodamaged facial skin: a multicenter, double-blind, randomized, parallel-group study. J Cosmet Laser Ther 2004;6:79–85. [PubMed]
18. Weiss JS, Shavin JS, Nighland M, et al. Tretinoin microsphere gel 0.1% for photodamaged facial skin: a placebo-controlled trial. Cutis 2006;78:426–432. [PubMed]
19. Lipson AH, Collins F, Webster WS. Multiple congenital defects associated with maternal use of topical tretinoin. Lancet 1993;341:1352–1353. [PubMed]
20. Camera G, Pregliasco P. Ear malformation in baby born to mother using tretinoin cream. Lancet 1992;339:687. [PubMed]
21. Jick SS, Terris BZ, Jick H. First trimester topical tretinoin and congenital disorders. Lancet 1993;341:1181–1182. [PubMed]
22. Sendagorta E, Lesiewicz J, Armstrong RB. Topical isotretinoin for photodamaged skin. J Am Acad Dermatol 1992;27:S15–S18. [PubMed]
23. Stiller MJ, Bartolone J, Stern R, et al. Topical 8% glycolic acid and 8% L-lactic acid creams for the treatment of photodamaged skin. A double-blind vehicle-controlled clinical trial. Arch Dermatol 1996;132:631–636. [PubMed]
24. Gin I, Chew J, Rau KA, et al. Treatment of upper lip wrinkles: a comparison of the 950 µsec dwell time carbon dioxide laser to manual tumescent dermabrasion. Dermatol Surg 1999;25:468–474. [PubMed]
25. Reed JT, Joseph AK, Bridenstine JB. Treatment of periorbital wrinkles. A comparison of the SilkTouch carbon dioxide laser with a medium-depth chemical peel. Dermatol Surg 1997;23:643–648. [PubMed]
26. Chew J, Gin I, Rau KA, et al. Treatment of upper lip wrinkles: a comparison of 950 microsec dwell time carbon dioxide laser with unoccluded baker's phenol chemical peel. Dermatol Surg 1999;25:262–266. [PubMed]
27. Newman JB, Lord JL, Ash K, et al. Variable pulse erbium:YAG laser skin resurfacing of perioral rhytides and side-by-side comparison with carbon dioxide laser. Lasers Surg Med 2000;26:208–214. [PubMed]
28. Ross EV, Miller C, Meehan K, et al. One-pass CO2 versus multiple-pass Er:YAG laser resurfacing in the treatment of rhytides: a comparison side-by-side study of pulsed CO2 and Er:YAG lasers. Dermatol Surg 2001;27:709–715. [PubMed]
29. Khatri KA, Ross V, Grevelink LM, et al. Comparison of erbium:YAG and carbon dioxide lasers in resurfacing of facial rhytides. Arch Dermatol 1999;135:391–397. [PubMed]
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32. Eskelinen A, Santalahti J. Special natural cartilage polysaccharides for the treatment of sun-damaged skin in females. J Int Med Res 1992;20:99–105. [PubMed]
33. Lassus A, Eskelinen A, Santalahti J. The effect of Vivida® cream as compared with placebo cream in the treatment of sun-damaged or age-damaged facial skin. J Int Med Res 1992;20:381–391. [PubMed]
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2008; 2008: 1711.
Published online 2008 December 16.

Sunscreens

Summary

We don't know whether sunscreens prevent wrinkles, as no studies were found.

Exposure to ultraviolet light may be associated with photodamage to the skin. Guidelines suggest that avoiding direct sunlight, either by staying indoors or in the shade, or by wearing protective clothing, is the most effective measure for reducing exposure to ultraviolet light.

Benefits and harms

Sunscreens:

We found no systematic review or RCTs.

Comment

We found two non-systematic reviews that reported the effects of sunscreens on the incidence of photodamage and skin cancer, but they did not assess the effectiveness of sunscreens in preventing wrinkles.

Clinical guide:

A history of mainly outdoor activities has been loosely linked with photodamage to the skin in men, but not in women. Wrinkles caused by exposure to ultraviolet light — extrinsic ageing — may be prevented or partially reversed by avoiding direct sunlight; but this is not the case for wrinkles caused by intrinsic ageing. Guidelines developed by US Preventive Services Task Force suggest that staying indoors or in the shade, or wearing protective clothing, are the most effective measures for reducing exposure to ultraviolet light. However, no studies of sun avoidance to prevent photoageing, wrinkles, and skin cancer have been identified.

Substantive changes

No new evidence

2008; 2008: 1711.
Published online 2008 December 16.

Vitamin C or E (topical)

Summary

We don't know whether topical vitamins C or E prevent wrinkles, as no studies were found.

Benefits and harms

Vitamin C or E (topical):

We found no systematic review or RCTs.

Comment

None.

Substantive changes

No new evidence

2008; 2008: 1711.
Published online 2008 December 16.

Tazarotene

Summary

We don't know how tazarotene and tretinoin compare at improving fine and coarse wrinkles in people with moderate photodamage, as studies have given inconclusive results. It can cause burning of the skin.

Benefits and harms

Tazarotene versus vehicle cream:

We found one systematic review (search date 2002, 2 RCTs) and one additional RCT. One RCT identified by the review reported on improvement of other outcomes in the forearm but not improvement in facial wrinkles, and therefore the data were not analysed.

Wrinkle improvement

Tazarotene compared with placebo Tazarotene may improve the appearance of wrinkles at 24 weeks (low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in fine wrinkles

RCT
5-armed trial
349 people with moderate facial photodamage
In review
Physician-assessed improvement of fine facial wrinkling (6-point scale: 0 = none to 5 = very severe) 24 weeks
27/59 (46%) with tazarotene 0.01% (once-daily application for 24 weeks)
11/58 (19%) with vehicle cream (once-daily application for 24 weeks)

RR 2.41
95% CI 1.32 to 4.40
Moderate effect sizetazarotene 0.01%

RCT
5-armed trial
349 people with moderate facial photodamage
In review
Physician-assessed improvement of fine facial wrinkling (6-point scale: 0 = none to 5 = very severe) 24 weeks
20/58 (34%) with tazarotene 0.025% (once-daily application for 24 weeks)
11/58 (19%) with vehicle cream (once-daily application for 24 weeks)

RR 1.82
95% CI 0.96 to 3.45
Not significant

RCT
5-armed trial
349 people with moderate facial photodamage
In review
Physician-assessed improvement of fine facial wrinkling (6-point scale: 0 = none to 5 = very severe) 24 weeks
28/58 (48%) with tazarotene 0.05% (once-daily application for 24 weeks)
11/58 (19%) with vehicle cream (once-daily application for 24 weeks)

RR 2.55
95% CI 1.40 to 4.61
Moderate effect sizetazarotene 0.05%

RCT
5-armed trial
349 people with moderate facial photodamage
In review
Physician-assessed improvement of fine facial wrinkling (6-point scale: 0 = none to 5 = very severe) 24 weeks
32/58 (55%) with tazarotene 0.1% (once-daily application for 24 weeks)
11/58 (19%) with vehicle cream (once-daily application for 24 weeks)

RR 2.91
95% CI 1.63 to 5.20
Moderate effect sizetazarotene 0.1%

RCT
563 adults with Fitzpatrick skin types I–IV, double blind Proportion of people with improved fine wrinkling by at least 1 grade on a 5-point scale 24 weeks
about 42% with tazarotene 0.1% (applied once daily for 24 weeks)
about 18% with placebo cream (applied once daily for 24 weeks)
Absolute results reported graphically

P <0.001
Effect size not calculatedtazarotene 0.1%
Improvement in coarse wrinkles

RCT
563 adults with Fitzpatrick skin types I–IV, double blind Proportion of people with improved coarse wrinkling by at least 1 grade on a 5-point scale 24 weeks
about 15% with tazarotene 0.1% (applied once daily for 24 weeks)
about 8% with placebo cream (applied once daily for 24 weeks)
Absolute results reported graphically

P <0.001
Effect size not calculatedtazarotene 0.1%

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
5-armed trial
349 people with moderate facial photodamage
In review
Adverse effects
with tazarotene 0.01% (once-daily application for 24 weeks)
with tazarotene 0.025% (once-daily application for 24 weeks)
with tazarotene 0.05% (once-daily application for 24 weeks)
with tazarotene 0.1% (once-daily application for 24 weeks)
with vehicle cream (once-daily application for 24 weeks)

RCT
563 adults with Fitzpatrick skin types I–IV, double blind Desquamation
105/283 (37%) with tazarotene 0.1% (applied once daily for 24 weeks)
8/280 (3%) with placebo cream (applied once daily for 24 weeks)

P <0.001
Effect size not calculatedplacebo

RCT
563 adults with Fitzpatrick skin types I–IV, double blind Erythema
84/283 (30%) with tazarotene 0.1% (applied once daily for 24 weeks)
6/280 (2%) with placebo cream (applied once daily for 24 weeks)

P <0.001
Effect size not calculatedplacebo

RCT
563 adults with Fitzpatrick skin types I–IV, double blind Burning
82/283 (29%) with tazarotene 0.1% (applied once daily for 24 weeks)
1/280 (0.4%) with placebo cream (applied once daily for 24 weeks)

P <0.001
Effect size not calculatedplacebo

Tazarotene versus tretinoin:

We found one systematic review (search date 2002, 1 RCT) and one additional RCT, which both compared various concentrations of tazarotene versus 0.05% tretinoin.

Wrinkle improvement

Tazarotene compared with tretinoin We don't know how tazarotene and tretinoin compare at improving wrinkles (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in fine wrinkles

Systematic review
117 people with moderate skin photodamage
Data from 1 RCT
Proportion of people with improved fine facial wrinkles (physician-assessed using a 6-point scale: 0 = none to 5 = very severe) 24 weeks
27/59 (46%) with tazarotene 0.01% (applied once daily for 24 weeks)
32/58 (55%) with tretinoin 0.05% (applied once daily for 24 weeks)

RR 1.21
95% CI 0.84 to 1.73
Not significant

Systematic review
117 people with moderate skin photodamage
Data from 1 RCT
Proportion of people with improved fine facial wrinkles (physician-assessed using a 6-point scale: 0 = none to 5 = very severe) 24 weeks
20/58 (34%) with tazarotene 0.025% (applied once daily for 24 weeks)
32/58 (55%) with tretinoin 0.05% (applied once daily for 24 weeks)

RR 1.60
95% CI 1.05 to 2.44
Small effect sizetretinoin 0.05%

Systematic review
117 people with moderate skin photodamage
Data from 1 RCT
Proportion of people with improved fine facial wrinkles (physician-assessed using a 6-point scale: 0 = none to 5 = very severe) 24 weeks
28/58 (48%) with tazarotene 0.05% (applied once daily for 24 weeks)
32/58 (55%) with tretinoin 0.05% (applied once daily for 24 weeks)

RR 1.14
95% CI 0.80 to 1.63
Not significant

Systematic review
117 people with moderate skin photodamage
Data from 1 RCT
Proportion of people with improved fine facial wrinkles (physician-assessed using a 6-point scale: 0 = none to 5 = very severe) 24 weeks
32/58 (55%) with tazarotene 0.1% (applied once daily for 24 weeks)
32/58 (55%) with tretinoin 0.05% (applied once daily for 24 weeks)

RR 1.00
95% CI 0.72 to 1.39
Not significant

RCT
173 people, mean age 55 years, with Fitzpatrick skin types I–IV Proportion of people with improved fine wrinkling by at least 1 grade on a 5-point scale 24 weeks
70/88 (80%) with tazarotene 0.1% (applied once daily in the evening for 24 weeks)
53/85 (62%) with tretinoin 0.05% (applied once daily in the evening for 24 weeks)

P <0.01
Effect size not calculatedtazarotene 0.1%
Improvement in coarse wrinkles

RCT
173 people, mean age 55 years, with Fitzpatrick skin types I–IV Proportion of people with improved coarse wrinkling by at least 1 grade on a 5-point scale 24 weeks
34/88 (39%) with tazarotene 0.1% (applied once daily in the evening for 24 weeks)
29/85 (32%) with tretinoin 0.05% (applied once daily in the evening for 24 weeks)

P <0.05
Effect size not calculatedtazarotene 0.1%

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

Systematic review
117 people with moderate skin photodamage
Data from 1 RCT
Adverse effects (overall)
2/58 (3%) with tazarotene 0.01% (applied once daily for 24 weeks)
3/58 (5%) with tretinoin 0.05% (applied once daily for 24 weeks)

RR 1.50
95% CI 0.26 to 8.65
Not significant

Systematic review
117 people with moderate skin photodamage
Data from 1 RCT
Adverse effects
0/58 (0%) with tazarotene 0.025% (applied once daily for 24 weeks)
3/58 (5%) with tretinoin 0.05% (applied once daily for 24 weeks)

RR 7.0
95% CI 0.37 to 132.56
Not significant

Systematic review
117 people with moderate skin photodamage
Data from 1 RCT
Adverse effects
2/58 (3%) with tazarotene 0.05% (applied once daily for 24 weeks)
3/58 (5%) with tretinoin 0.05% (applied once daily for 24 weeks)

RR 1.50
95% CI 0.26 to 8.65
Not significant

Systematic review
117 people with moderate skin photodamage
Data from 1 RCT
Adverse effects
2/58 (3%) with tazarotene 0.1% (applied once daily for 24 weeks)
3/58 (5%) with tretinoin 0.05% (applied once daily for 24 weeks)

RR 1.50
95% CI 0.26 to 8.65
Not significant

RCT
173 people, mean age 55 years, with Fitzpatrick skin types I–IV Sensation of burning on the skin
15% with tazarotene 0.1% (applied once daily in the evening for 24 weeks)
0% with tretinoin 0.05% (applied once daily in the evening for 24 weeks)
Absolute numbers not reported

Reported as significant
P value not reported
Effect size not calculatedtretinoin

RCT
173 people, mean age 55 years, with Fitzpatrick skin types I–IV Irritation
21% with tazarotene 0.1% (applied once daily in the evening for 24 weeks)
35% with tretinoin 0.05% (applied once daily in the evening for 24 weeks)
Absolute numbers not reported

Reported as not significant
P value not reported
Not significant

RCT
173 people, mean age 55 years, with Fitzpatrick skin types I–IV Dryness
9% with tazarotene 0.1% (applied once daily in the evening for 24 weeks)
15% with tretinoin 0.05% (applied once daily in the evening for 24 weeks)
Absolute numbers not reported

Reported as not significant
P value not reported
Not significant

RCT
173 people, mean age 55 years, with Fitzpatrick skin types I–IV Peeling
12% with tazarotene 0.1% (applied once daily in the evening for 24 weeks)
11% with tretinoin 0.05% (applied once daily in the evening for 24 weeks)
Absolute numbers not reported

Reported as not significant
P value not reported
Not significant

RCT
173 people, mean age 55 years, with Fitzpatrick skin types I–IV Redness
10% with tazarotene 0.1% (applied once daily in the evening for 24 weeks)
7% with tretinoin 0.05% (applied once daily in the evening for 24 weeks)
Absolute numbers not reported

Reported as not significant
P value not reported
Not significant

RCT
173 people, mean age 55 years, with Fitzpatrick skin types I–IV Erythema
3% with tazarotene 0.1% (applied once daily in the evening for 24 weeks)
4% with tretinoin 0.05% (applied once daily in the evening for 24 weeks)
Absolute numbers not reported

Reported as not significant
P value not reported
Not significant

RCT
173 people, mean age 55 years, with Fitzpatrick skin types I–IV Stinging
3% with tazarotene 0.1% (applied once daily in the evening for 24 weeks)
6% with tretinoin 0.05% (applied once daily in the evening for 24 weeks)
Absolute numbers not reported

Reported as not significant
P value not reported
Not significant

RCT
173 people, mean age 55 years, with Fitzpatrick skin types I–IV Itching
3% with tazarotene 0.1% (applied once daily in the evening for 24 weeks)
4% with tretinoin 0.05% (applied once daily in the evening for 24 weeks)
Absolute numbers not reported

Reported as not significant
P value not reported
Not significant

Further information on studies

Comment

None.

Substantive changes

2008; 2008: 1711.
Published online 2008 December 16.

Tretinoin

Summary

Topical tretinoin improves fine wrinkles compared with placebo cream in people with mild to moderate photodamage, but its effect on coarse wrinkles is unclear.

Topical tretinoin may cause itching, burning, erythema, and skin peeling.

Benefits and harms

Tretinoin versus placebo:

We found one systematic review (search date 2002, 12 RCTs), which separately compared the effects of various concentrations of tretinoin (0.1%, 0.05%, 0.025%, 0.02%, 0.01%, and 0.001%) versus placebo. We also found one subsequent RCT.

Wrinkle improvement

Tretinoin compared with placebo Daily application of tretinoin at concentrations above 0.02% may be more effective than placebo at improving facial fine and coarse wrinkles at 16 to 48 weeks in people with mild to moderate and moderate to severe photodamage. However, daily application of tretinoin at concentrations lower than 0.02% (0.001%–0.01%) may be no more effective than placebo at improving wrinkles (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in fine wrinkles (tretinoin 0.001%)

Systematic review
147 people with mild to moderate photodamage
Data from 1 RCT
Proportion of people with improved fine facial wrinkles (physician-assessed) 24 weeks
20/75 (27%) with topical tretinoin 0.001% (once daily for 24 weeks)
28/72 (39%) with vehicle cream (once daily for 24 weeks)

RR 0.69
95% CI 0.43 to 1.10
RCTs identified by review had methodological limitations; see further information on studies for full details
Not significant
Improvement in fine wrinkles (tretinoin 0.01%)

Systematic review
345 people with mild to moderate photodamage
3 RCTs in this analysis
Proportion of people with improved fine facial wrinkles (physician-assessed) 24 weeks
93/174 (53%) with topical tretinoin 0.01% (once daily for 24 weeks)
63/171 (37%) with vehicle cream (once daily for 24 weeks)

RR 1.57
95% CI 0.91 to 2.71
RCTs identified by review had methodological limitations; see further information on studies for full details
Not significant

Systematic review
34 people with mild to moderate photodamage of the face and forearms
Data from 1 RCT
Proportion of people with improved fine forearm wrinkles (physician-assessed) 24 weeks
24/34 (71%) with topical tretinoin 0.01% (once daily for 24 weeks)
1/34 (3%) with vehicle cream (once daily for 24 weeks)

P <0.01
RCTs identified by review had methodological limitations; see further information on studies for full details
Effect size not calculatedtretinoin 0.01%
Improvement in fine wrinkles (tretinoin 0.02%)

Systematic review
328 people with moderate to severe photodamage
2 RCTs in this analysis
Proportion of people with improved fine facial wrinkles (physician-assessed) 24 weeks
98/159 (62%) with topical tretinoin 0.02% (once daily for 24 weeks)
65/169 (39%) with vehicle cream (once daily for 24 weeks)

RR 1.60
95% CI 1.28 to 2.01
RCTs identified by review had methodological limitations; see further information on studies for full details
Small effect sizetretinoin 0.02%
Improvement in fine wrinkles (tretinoin 0.025%)

Systematic review
67 people with moderate to severe photodamage
Data from 1 RCT
Mean improvement in fine facial wrinkle score (physician-assessed using a 10-point scale) 48 weeks
1.3 with topical tretinoin 0.025% (once daily for 48 weeks)
0.6 with vehicle cream (once daily for 48 weeks)

WMD 0.75
95% CI 0.22 to 1.28
RCTs identified by review had methodological limitations; see further information on studies for full details
Effect size not calculatedtretinoin 0.025%
Improvement in fine wrinkles (tretinoin 0.05%)

Systematic review
593 people with mild to moderate photodamage
5 RCTs in this analysis
Proportion of people with improved fine facial wrinkles 24 weeks
186/298 (62%) with topical tretinoin 0.05% (once daily for 24 weeks)
102/295 (35%) with vehicle cream (once daily for 24 weeks)

RR 1.76
95% CI 1.47 to 2.12
RCTs identified by review had methodological limitations; see further information on studies for full details
Small effect sizetretinoin 0.05%

Systematic review
125 people with mild to moderate photodamage
Data from 1 RCT
Proportion of people with improved fine forearm wrinkles (physician-assessed) 24 weeks
32/62 (52%) with topical tretinoin 0.05% (once daily for 24 weeks)
22/63 (35%) with vehicle cream (once daily for 24 weeks)

RR 1.48
95% CI 0.98 to 2.24
RCTs identified by review had methodological limitations; see further information on studies for full details
Not significant
Improvement in fine wrinkles (tretinoin 0.1%)

Systematic review
30 people with photodamage of the face and forearms
Data from 1 RCT
Proportion of people with improved fine facial wrinkles (physician-assessed) 16 weeks
14/15 (93%) with topical tretinoin 0.1% (once daily for 16 weeks)
0/15 (0%) with vehicle cream (once daily for 16 weeks)

RR 29.00
95% CI 1.89 to 445.86
RCTs identified by review had methodological limitations; see further information on studies for full details
Large effect sizetretinoin 0.1%

Systematic review
30 people
Data from 1 RCT
Proportion of people with improved fine forearm wrinkles 16 weeks
30/30 (100%) with topical tretinoin 0.1% (once daily for 16 weeks)
0/30 (0%) with vehicle cream (once daily for 16 weeks)

P <0.001
RCTs identified by review had methodological limitations; see further information on studies for full details
Effect size not calculatedtretinoin 0.1%

RCT
45 people with moderate to severe facial photodamage Proportion of people with improved fine facial wrinkles (physician- and patient-assessed) 6 months
94% with tretinoin 0.1% (microsphere gel preparation; applied once daily for 6 months)
23% with vehicle gel (applied once daily for 6 months)
Absolute numbers not reported

P <0.0001
Method of randomisation and allocation concealment were unclear
Effect size not calculatedtretinoin 0.1%
Improvement in coarse wrinkles (tretinoin 0.01%)

Systematic review
34 people with mild to moderate photodamage of the face and forearms
Data from 1 RCT
Proportion of people with improved coarse facial wrinkles (physician-assessed) 24 weeks
7/17 (41%) with topical tretinoin 0.01% (once daily for 24 weeks)
1/17 (6%) with vehicle cream (once daily for 24 weeks)

RR 7.00
95% CI 0.96 to 50.93
RCTs identified by review had methodological limitations; see further information on studies for full details
Not significant
Improvement in coarse wrinkles (tretinoin 0.02%)

Systematic review
328 people with moderate to severe photodamage
2 RCTs in this analysis
Proportion of people with improved coarse facial wrinkles (physician-assessed) 24 weeks
64/159 (40%) with topical tretinoin 0.02% (once daily for 24 weeks)
40/169 (24%) with vehicle cream (once daily for 24 weeks)

RR 1.70
95% CI 1.22 to 2.37
RCTs identified by review had methodological limitations; see further information on studies for full details
Small effect sizetretinoin 0.02%
Improvement in coarse wrinkles (tretinoin 0.05%)

Systematic review
162 people with mild to moderate photodamage
2 RCTs in this analysis
Proportion of people with improved coarse facial wrinkles (physician-assessed) 24 weeks
41/79 (52%) with topical tretinoin 0.05% (once daily for 24 weeks)
25/83 (30%) with vehicle cream (once daily for 24 weeks)

RR 1.68
95% CI 1.17 to 2.42
RCTs identified by review had methodological limitations; see further information on studies for full details
Small effect sizetretinoin 0.05%
Improvement in coarse wrinkles (tretinoin 0.1%)

Systematic review
30 people with mild to moderate photodamage of the face and forearms
Data from 1 RCT
Proportion of people with improved coarse facial wrinkles (physician-assessed) 16 weeks
6/15 (40%) with topical tretinoin 0.1% (once daily for 16 weeks)
0/15 (0%) with vehicle cream (once daily for 16 weeks)

RR 13.0
95% CI 0.80 to 212.02
RCTs identified by review had methodological limitations; see further information on studies for full details
Not significant

Systematic review
30 people
Data from 1 RCT
Proportion of people with improved coarse forearm wrinkles 16 weeks
9/30 (30%) with topical tretinoin 0.1% (once daily for 16 weeks)
0/30 (0%) with vehicle cream (once daily for 16 weeks)

P <0.01
RCTs identified by review had methodological limitations; see further information on studies for full details
Effect size not calculatedtretinoin 0.1%

RCT
45 people with moderate to severe facial photodamage Proportion of people with improved coarse facial wrinkles (physician- and patient-assessed) 6 months
22% with tretinoin 0.1% (microsphere gel preparation; applied once daily for 6 months)
5% with vehicle gel (applied once daily for 6 months)
Absolute numbers not reported

P = 0.1
Method of randomisation and allocation concealment were unclear
Not significant
Improvement in wrinkles (global; tretinoin 0.1%)

RCT
45 people with moderate to severe facial photodamage Global assessment score (investigators and participants scored signs of photodamage and skin irritation, using a scale from 0–9 [0 = none, 1–3 = mild, 4–6 = moderate, 7–9 = severe]) 6 months
with tretinoin 0.1% (microsphere gel preparation; applied once daily for 6 months)
with vehicle gel (applied once daily for 6 months)
Absolute results reported graphically

P <0.0003
Method of randomisation and allocation concealment were unclear
Effect size not calculatedtretinoin 0.1%

RCT
45 people with moderate to severe facial photodamage Proportion of people with improved facial tactile roughness (physician- and patient-assessed) 6 months
83% with tretinoin 0.1% (microsphere gel preparation; applied once daily for 6 months)
91% with vehicle gel (applied once daily for 6 months)
Absolute numbers not reported

P = 0.53
Method of randomisation and allocation concealment were unclear
Not significant

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects (tretinoin 0.01%)

Systematic review
344 people with mild to moderate photodamage
2 RCTs in this analysis
Burning or stinging 24 weeks
36/173 (21%) with topical tretinoin 0.01% (once daily for 24 weeks)
18/171 (11%) with vehicle cream (once daily for 24 weeks)

RR 1.99
95% CI 1.20 to 3.32
Small effect sizevehicle cream
Adverse effects (tretinoin 0.05%)

Systematic review
349 people
2 RCTs in this analysis
Erythema 24 weeks
60/178 (34%) with topical tretinoin 0.05% (once daily for 24 weeks)
16/171 (9%) with vehicle cream (once daily for 24 weeks)

RR 3.58
95% CI 1.99 to 6.46
Moderate effect sizevehicle cream

Systematic review
349 people
2 RCTs in this analysis
Scaling/dryness 24 weeks
115/178 (65%) with topical tretinoin 0.05% (once daily for 24 weeks)
49/171 (29%) with vehicle cream (once daily for 24 weeks)

RR 2.23
95% CI 1.72 to 2.88
Moderate effect sizevehicle cream

Systematic review
349 people
2 RCTs in this analysis
Burning and stinging 24 weeks
69/178 (39%) with topical tretinoin 0.05% (once daily for 24 weeks)
18/171 (11%) with vehicle cream (once daily for 24 weeks)

RR 3.75
95% CI 2.35 to 5.98
Moderate effect sizevehicle cream
Adverse effects (tretinoin 0.1%)

Systematic review
76 people with moderate to severe photodamage of the face and forearms
Data from 1 RCT
Erythema 48 weeks
16/36 (44%) with topical tretinoin 0.1% (once daily for 48 weeks)
0/40 (0%) with vehicle cream (once daily for 48 weeks)

RR 36.57
95% CI 2.27 to 588.35
Large effect sizevehicle cream

RCT
45 people with moderate to severe facial photodamage Skin erythema 1 month
with tretinoin 0.1% (microsphere gel preparation; applied once daily for 6 months)
with vehicle gel (applied once daily for 6 months)
Absolute results not reported

P = 0.0005
Method of randomisation and allocation concealment were unclear
Effect size not calculatedvehicle gel

RCT
45 people with moderate to severe facial photodamage Peeling 1 month
with tretinoin 0.1% (microsphere gel preparation; applied once daily for 6 months)
with vehicle gel (applied once daily for 6 months)
Absolute results not reported

P <0.0001
Method of randomisation and allocation concealment were unclear
Effect size not calculatedvehicle gel

RCT
45 people with moderate to severe facial photodamage Dryness 1 month
with tretinoin 0.1% (microsphere gel preparation; applied once daily for 6 months)
with vehicle gel (applied once daily for 6 months)
Absolute results not reported

P <0.0001
Method of randomisation and allocation concealment were unclear
Effect size not calculatedvehicle gel

RCT
45 people with moderate to severe facial photodamage Itching 1 month
with tretinoin 0.1% (microsphere gel preparation; applied once daily for 6 months)
with vehicle gel (applied once daily for 6 months)
Absolute results not reported

P = 0.0005
Method of randomisation and allocation concealment were unclear
Effect size not calculatedvehicle gel

RCT
45 people with moderate to severe facial photodamage Burning/stinging 1 month
with tretinoin 0.1% (microsphere gel preparation; applied once daily for 6 months)
with vehicle gel (applied once daily for 6 months)
Absolute results not reported

P <0.0001
Method of randomisation and allocation concealment were unclear
Effect size not calculatedvehicle gel

RCT
45 people with moderate to severe facial photodamage Peeling 6 months
with tretinoin 0.1% (microsphere gel preparation; applied once daily for 6 months)
with vehicle gel (applied once daily for 6 months)
Absolute results not reported

P = 0.001
Method of randomisation and allocation concealment were unclear
Effect size not calculatedvehicle gel

RCT
45 people with moderate to severe facial photodamage Dryness 6 months
with tretinoin 0.1% (microsphere gel preparation; applied once daily for 6 months)
with vehicle gel (applied once daily for 6 months)
Absolute results not reported

P = 0.007
Method of randomisation and allocation concealment were unclear
Effect size not calculatedvehicle gel

Tretinoin versus tazarotene:

See option on tazarotene.

Further information on studies

Methodological limitations The RCTs included in the systematic review are limited by their small sample sizes, short duration, and inconsistencies among investigator and participant assessments. The methods of randomisation and allocation concealment were unclear in most RCTs in the systematic review. Adverse effects of tretinoin The systematic review found that all strengths of tretinoin were associated with adverse effects. The most common adverse effects were itching, burning/stinging, dryness, and erythema, which peaked during the first 2 weeks and decreased with time.

Comment

We found individual case reports of congenital defects associated with topical tretinoin used during the first trimester of pregnancy. We found one observational study that identified 215 case histories of women who used tretinoin cream for acne during the first trimester of pregnancy, and compared them with 430 age-matched, non-exposed women who delivered infants at the same hospital. The study found no significant difference in the incidence of major congenital disorders (1.9% with tretinoin v 2.6% with control; RR 0.7, 95% CI 0.2 to 2.3).

Substantive changes

Tretinoin One RCT added comparing tretinoin versus placebo cream in people with sun-damaged skin. It found that tretinoin increased the proportion of people with improved fine wrinkles at 6 months compared with placebo, but also increased skin erythema, peeling, burning, dryness, and itching. Categorisation changed (Trade-off between benefits and harms).

2008; 2008: 1711.
Published online 2008 December 16.

Isotretinoin

Summary

Isotretinoin cream improves fine and coarse wrinkles compared with vehicle cream in people with mild to severe photodamage, but causes severe irritation of the face in 5–10% of people.

Isotretinoin is associated with increased facial erythema, scaling/dryness, and burning/stinging compared with placebo cream.

Benefits and harms

Isotretinoin versus placebo:

We found one systematic review (search date 2002), which included one RCT comparing isotretinoin versus placebo. We also found one additional RCT.

Wrinkle improvement

Isotretinoin compared with placebo Isotretinoin cream (0.1%) may be more effective than placebo at improving facial fine and coarse wrinkles and forearm wrinkles after 36 weeks in people with moderate to severe photodamage (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in fine wrinkles

Systematic review
681 people with moderate to severe facial photodamage, and mild to severe photodamage of arms and hands
Data from 1 RCT
Improvement in fine facial wrinkles 36 weeks
with topical isotretinoin 0.1% (0.5 g) (applied once daily for 36 weeks)
with vehicle cream (applied once daily for 36 weeks)

WMD 4.90
95% CI 3.79 to 6.01
Effect size not calculatedisotretinoin 0.1%

Systematic review
681 people with moderate to severe facial photodamage, and mild to severe photodamage of arms and hands
Data from 1 RCT
Improvement in fine wrinkles of the forearm 36 weeks
with topical isotretinoin 0.1% (0.5 g) (applied once daily for 36 weeks)
with vehicle cream (applied once daily for 36 weeks)

WMD 3.0
95% CI 2.17 to 3.83
Effect size not calculatedisotretinoin 0.1%

RCT
776 people in 17 US centres, aged 20–76 years, with mild to moderate facial photodamage Physician-assessed improvement of fine facial wrinkling (change from baseline measured on 100 mm VAS: –50 = worse, 0 = no change, +50 = better) 36 weeks
+7.4 with topical isotretinoin 0.05% (applied once daily for 12 weeks), followed by isotretinoin 0.01% (applied for the next 24 weeks)
+5.3 with vehicle cream (applied for 36 weeks)

P <0.01
Effect size not calculatedisotretinoin

RCT
776 people in 17 US centres, aged 20–76 years, with mild to moderate facial photodamage Participant-assessed improvement of fine facial wrinkling (change from baseline measured on 100 mm VAS: –50 = worse, 0 = no change, +50 = better) 36 weeks
+11.7 with topical isotretinoin 0.05% (applied once daily for 12 weeks), followed by isotretinoin 0.01% (applied daily for the next 24 weeks)
+7.9 with vehicle cream (applied for 36 weeks)

P <0.01
Effect size not calculatedisotretinoin
Improvement in coarse wrinkles

Systematic review
681 people with moderate to severe facial photodamage, and mild to severe photodamage of arms and hands
Data from 1 RCT
Improvement in coarse facial wrinkles 36 weeks
with topical isotretinoin 0.1% (0.5 g) (applied once daily for 36 weeks)
with vehicle cream (applied once daily for 36 weeks)

WMD 3.0
95% CI 2.17 to 3.83
Effect size not calculatedisotretinoin 0.1%
Improvement in wrinkles (global)

RCT
776 people in 17 US centres, aged 20–76 years, with mild to moderate facial photodamage Physician-assessed overall skin appearance (change from baseline measured on 100 mm VAS: –50 = worse, 0 = no change, +50 = better) 36 weeks
+8.3 with topical isotretinoin 0.05% (applied once daily for 12 weeks), followed by isotretinoin 0.01% (applied for the next 24 weeks)
+6.4 with vehicle cream (applied for 36 weeks)

P <0.01
Effect size not calculatedisotretinoin

RCT
776 people in 17 US centres, aged 20–76 years, with mild to moderate facial photodamage Participant-assessed overall skin appearance (change from baseline measured on 100 mm VAS: –50 = worse, 0 = no change, +50 = better) 36 weeks
with topical isotretinoin 0.05% (applied once daily for 12 weeks), followed by isotretinoin 0.01% (applied for the next 24 weeks)
with vehicle cream (appled for 36 weeks)

Reported as not significant
P value not reported
Not significant

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

Systematic review
681 people with moderate to severe facial photodamage, and mild to severe photodamage of arms and hands
Data from 1 RCT
Withdrawal because of adverse effects
25/323 (8%) with topical isotretinoin 0.1% (0.5 g) (applied once daily for 36 weeks)
9/353 (3%) with vehicle cream (applied once daily for 36 weeks)

Significance not assessed

Systematic review
681 people with moderate to severe facial photodamage, and mild to severe photodamage of arms and hands
Data from 1 RCT
Erythema
210/323 (65%) with topical isotretinoin 0.1% (0.5 g; applied once daily for 36 weeks)
90/358 (25%) with vehicle cream (applied once daily for 36 weeks)

RR 2.59
95% CI 2.13 to 3.15
Moderate effect sizevehicle cream

Systematic review
681 people with moderate to severe facial photodamage, and mild to severe photodamage of arms and hands
Data from 1 RCT
Scaling/dryness
175/323 (54%) with topical isotretinoin 0.1% (0.5 g; applied once daily for 36 weeks)
30/358 (8%) with vehicle cream (applied once daily for 36 weeks)

RR 6.47
95% CI 4.52 to 9.24
Large effect sizevehicle cream

Systematic review
681 people with moderate to severe facial photodamage, and mild to severe photodamage of arms and hands
Data from 1 RCT
Burning/stinging
214/323 (66%) with topical isotretinoin 0.1% (0.5 g; applied once daily for 36 weeks)
55/358 (15%) with vehicle cream (applied once daily for 36 weeks)

RR 4.31
95% CI 3.34 to 5.57
Moderate effect sizevehicle cream

RCT
776 people in 17 US centres, aged 20–76 years, with mild to moderate facial photodamage Withdrawal because of adverse effects
5/307 (1.6%) with topical isotretinoin 0.05% (applied once daily for 12 weeks), followed by isotretinoin 0.01% (applied for the next 24 weeks)
1/306 (0.3%) with vehicle cream (applied for 36 weeks)

Significance not assessed

Further information on studies

Five dermatologists assessed pre- and post-treatment photographs. The RCT reported that all dermatologists found that isotretinoin significantly improved fine wrinkles compared with vehicle cream (P <0.05).

Comment

The RCTs provide limited evidence on the effectiveness of isotretinoin 0.1% in the treatment of wrinkles, and so more studies are needed to confirm these findings.

Substantive changes

No new evidence

2008; 2008: 1711.
Published online 2008 December 16.

Alpha and beta hydroxyl acids

Summary

We don't know whether alpha or beta hydroxyl acids are beneficial.

Benefits and harms

Glycolic acid versus vehicle cream:

We found one systematic review (search date 2002, 2 RCTs, 149 people with mild to moderate photodamage). The systematic review did not perform a meta-analysis.

Wrinkle improvement

Glycolic acid compared with placebo Glycolic acid 8% may be more effective than placebo at improving fine wrinkles after 12 to 22 weeks (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in fine wrinkles

Systematic review
75 people
Data from 1 RCT
Improvement in fine wrinkles 12 weeks
with glycolic acid 5% (applied for 12 weeks)
with vehicle cream (applied for 12 weeks)

WMD –0.42
95% CI –1.68 to +0.84
Not significant

RCT
3-armed trial
74 women
In review
Physician-assessed improvement of fine facial wrinkling (measured on a 10-point scale: 0 = none and 9 = severe) 22 weeks
22% with glycolic acid 8% (applied twice daily)
15% with vehicle cream (applied twice daily)

P <0.05
Effect size not calculatedglycolic acid 8%

RCT
3-armed trial
74 women
In review
Mean grade change of physician-assessed fine facial wrinkling (measured on a 10-point scale: 0 = none and 9 = severe) 22 weeks
–1.14 with glycolic acid 8% (applied twice daily)
–0.86 with vehicle cream (applied twice daily)

P <0.05
Effect size not calculatedglycolic acid 8%

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

Systematic review
75 people
Data from 1 RCT
Adverse effects
with glycolic acid 5% (applied twice daily)
with vehicle cream (applied twice daily)

RCT
3-armed trial
74 women
In review
Adverse effects
with glycolic acid 8% (applied twice daily)
with lactic acid 8% (applied twice daily)
with vehicle cream (applied twice daily)

Lactic acid versus vehicle cream:

We found one systematic review (search date 2002, 2 RCTs, 149 people with mild to moderate photodamage). The review identified one RCT assessing lactic acid.

Wrinkle improvement

Lactic acid compared with placebo Lactic acid 8% may be more effective than placebo at improving fine wrinkles after 22 weeks (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in fine wrinkles

RCT
3-armed trial
74 women
In review
Physician-assessed improvement of fine facial wrinkling (measured on a 10-point scale: 0 = none and 9 = severe) 22 weeks
22% with lactic acid 8% (applied twice daily)
15% with vehicle cream (applied twice daily)

P <0.05
Effect size not calculatedlactic acid 8%

RCT
3-armed trial
74 women
In review
Mean grade change of physician-assessed fine facial wrinkling (measured on a 10-point scale: 0 = none and 9 = severe) 22 weeks
–1.04 with lactic acid 8% (applied twice daily)
–0.86 with vehicle cream (applied twice daily)

P <0.05
Effect size not calculatedlactic acid 8%

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
3-armed trial
74 women
In review
Adverse effects
with glycolic acid 8% (applied twice daily)
with lactic acid 8% (applied twice daily)
with vehicle cream (applied twice daily)

Comment

The effectiveness of glycolic acid and lactic acid in the treatment of wrinkles is based on data from RCTs that reported the mean change in grade as an outcome. However, whether the mean grade change results in a clinically important improvement is not clear.

Substantive changes

No new evidence

2008; 2008: 1711.
Published online 2008 December 16.

Carbon dioxide laser

Summary

We don't know whether carbon dioxide laser is better than no active treatment in people with wrinkles, as we found no direct evidence.

We don't know whether carbon dioxide laser is more effective than dermabrasion, chemical peel, erbium:YAG laser or carbon dioxide laser plus variable pulse erbium:YAG laser at improving wrinkles, as studies have given inconclusive results.

Adverse effects are common with carbon dioxide laser, especially erythema.

Benefits and harms

Carbon dioxide laser versus placebo/no treatment:

We found no systematic reviews or RCTs.

Carbon dioxide laser versus dermabrasion:

We found one systematic review (search date 2002, 3 RCTs, 55 women with wrinkles) comparing carbon dioxide laser versus dermabrasion.

Wrinkle improvement

Carbon dioxide laser compared with dermabrasion We don't know how carbon dioxide laser treatment and dermabrasion compare at improving wrinkles (low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement of wrinkles

Systematic review
55 women with wrinkles
3 RCTs in this analysis
Wrinkle score (on a 0–5 scale)
with carbon dioxide laser
with dermabrasion

WMD –0.10
95% CI –0.35 to +0.16
Not significant

Quality of life

No data from the following reference on this outcome.

Adverse effects

Compared with dermabrasion Carbon dioxide laser may worsen postoperative erythema and drainage (low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

Systematic review
55 women with wrinkles
3 RCTs in this analysis
Erythema 1 month
with carbon dioxide laser
with dermabrasion

WMD 0.31
95% CI 0.15 to 0.47
Effect size not calculateddermabrasion

RCT
20 women with wrinkles
In review
Hypertrophic scar
with carbon dioxide laser
with dermabrasion

RCT
20 women with wrinkles
In review
Herpetic lesions
with carbon dioxide laser
with dermabrasion

RCT
20 women with wrinkles
In review
Proportion of people reporting worse "post-treatment drainage" with each intervention
10/20 (50%) with carbon dioxide laser
2/20 (10%) with dermabrasion

P = 0.002
Effect size not calculateddermabrasion

Carbon dioxide laser versus chemical peel:

We found one systematic review (search date 2002, 1 RCT, 20 women) and one additional RCT.

Wrinkle improvement

Carbon dioxide laser compared with chemical peel We don't know how carbon dioxide laser treatment and chemical peel compare at improving wrinkles (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in wrinkles

RCT
20 women, aged 51–71 years, with Fitzpatrick skin type I–III and with wrinkles on upper lip
In review
Average change in upper lip wrinkle score (6-point scale: 0 = none to 5 = severe) baseline to 6 months
from 4.30 to 1.11 with carbon dioxide laser
from 4.20 to 0.47 with baker's phenol chemical peel

P <0.03
Effect size not calculatedbaker's phenol chemical peel

RCT
24 men and women, aged 43–73 years, with Fitzpatrick skin types I–III Severity of periorbital wrinkles (6-point scale: 0 = none to 5 = severe) baseline to 6 months
from 4.00 to 1.75 with carbon dioxide laser
from 4.13 to 3.29 with trichloroacetic acid chemical peel

P <0.001
Effect size not calculatedcarbon dioxide laser

Quality of life

No data from the following reference on this outcome.

Adverse effects

Carbon dioxide laser compared with chemical peel We don't know whether carbon dioxide laser is associated with an increased risk of adverse effects, including erythema, scarring, herpes simplex infection, contact dermatitis, hypopigmentation, or whitehead formation (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
20 women, aged 51–71 years, with Fitzpatrick skin type I–III and with wrinkles on upper lip
In review
Erythema
with carbon dioxide laser
with baker's phenol chemical peel

RCT
20 women, aged 51–71 years, with Fitzpatrick skin type I–III and with wrinkles on upper lip
In review
Hypertrophic scar
with carbon dioxide laser
with baker's phenol chemical peel

RCT
20 women, aged 51–71 years, with Fitzpatrick skin type I–III and with wrinkles on upper lip
In review
Herpes simplex infection
with carbon dioxide laser
with baker's phenol chemical peel

RCT
24 men and women, aged 43–73 years, with Fitzpatrick skin types I–III Mean length of erythema duration
4.5 months with carbon dioxide laser
2.5 months with trichloroacetic acid chemical peel

RCT
24 men and women, aged 43–73 years, with Fitzpatrick skin types I–III Scarring
13/24 (52%) with carbon dioxide laser
3/24 (13%) with trichloroacetic acid chemical peel

RCT
24 men and women, aged 43–73 years, with Fitzpatrick skin types I–III Contact dermatitis to bacitracin–polymyxin B ointment
with carbon dioxide laser
with trichloroacetic acid chemical peel

RCT
24 men and women, aged 43–73 years, with Fitzpatrick skin types I–III Hypopigmentation
with carbon dioxide laser
with trichloroacetic acid chemical peel

RCT
24 men and women, aged 43–73 years, with Fitzpatrick skin types I–III Whitehead formation
with carbon dioxide laser
with trichloroacetic acid chemical peel

No data from the following reference on this outcome.

Carbon dioxide laser versus erbium:YAG laser:

We found one systematic review (3 RCTs, 55 people). The results of these studies were not combined because of the variability in outcomes.

Wrinkle improvement

Carbon dioxide laser compared with erbium:YAG laser Carbon dioxide laser may be more effective than erbium:YAG laser (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in wrinkles

RCT
21 women, aged 39–74 years, with upper lip wrinkles, Fitzpatrick skin types I–IV
In review
Overall wrinkle improvement (not defined) 2 months
63% with carbon dioxide laser
54% with variable pulse erbium:YAG laser

Significance not assessed
Results should be interpreted with caution because the participants and investigators were not blinded to treatment allocation

RCT
12 women and 1 man, aged 30–80 years, with perioral or periorbital wrinkles, Fitzpatrick skin types I–III
In review
Average improvement in wrinkle score (assessed from photographs; 9-point scale: 0 = absent to 8 = severe)
1–2 points with pulsed carbon dioxide laser (one pass)
1–2 points with erbium:YAG laser (four passes)

Reported as not significant
P value not reported
The RCT may have been too small to exclude a clinically important difference
Results should be interpreted with caution because the participants and investigators were not blinded to treatment allocation
Not significant

RCT
19 women and 2 men, aged 18–90 years, with perioral or periorbital wrinkles, Fitzpatrick skin types I–III
In review
Wrinkle improvement (measured by aggregate of investigators', participants', and panel's assessments [photographs]) 6 months
with carbon dioxide laser
with variable pulse erbium:YAG laser
Absolute results not reported

P <0.03
Results should be interpreted with caution because the participants and investigators were not blinded to treatment allocation
Effect size not calculatedcarbon dioxide laser

Quality of life

No data from the following reference on this outcome.

Adverse effects

Carbon dioxide laser compared with erbium:YAG laser Carbon dioxide laser may be associated with a increased risk of hyperpigmentation, hypopigmentation, and prolonged erythema (low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
21 women, aged 39–74 years, with upper lip wrinkles, Fitzpatrick skin types I–IV
In review
Postoperative erythema
with carbon dioxide laser
with variable pulse erbium:YAG laser

Reported as not significant
P value not reported
Not significant

RCT
21 women, aged 39–74 years, with upper lip wrinkles, Fitzpatrick skin types I–IV
In review
Hyperpigmentation
with carbon dioxide laser
with variable pulse erbium:YAG laser

RCT
12 women and 1 man, aged 30–80 years, with perioral or periorbital wrinkles, Fitzpatrick skin types I–III
In review
Postoperative erythema 2 weeks
with pulsed carbon dioxide laser (one pass)
with erbium:YAG laser (four passes)

P <0.04
Effect size not calculatedcarbon dioxide laser

RCT
12 women and 1 man, aged 30–80 years, with perioral or periorbital wrinkles, Fitzpatrick skin types I–III
In review
Postoperative erythema 2 and 6 months
with pulsed carbon dioxide laser (one pass)
with erbium:YAG laser (four passes)

RCT
12 women and 1 man, aged 30–80 years, with perioral or periorbital wrinkles, Fitzpatrick skin types I–III
In review
Hyperpigmentation
with pulsed carbon dioxide laser (one pass)
with erbium:YAG laser (four passes)

Reported as not significant
P value not reported
Not significant

RCT
19 women and 2 men, aged 18–90 years, with perioral or periorbital wrinkles, Fitzpatrick skin types I–III
In review
Erythema 2 weeks
95% with carbon dioxide laser
67% with variable pulse erbium:YAG laser

RCT
19 women and 2 men, aged 18–90 years, with perioral or periorbital wrinkles, Fitzpatrick skin types I–III
In review
Erythema 2 months
62% with carbon dioxide laser
24% with variable pulse erbium:YAG laser

RCT
19 women and 2 men, aged 18–90 years, with perioral or periorbital wrinkles, Fitzpatrick skin types I–III
In review
Mild erythema 6 months
10% with carbon dioxide laser
0% with variable pulse erbium:YAG laser

RCT
19 women and 2 men, aged 18–90 years, with perioral or periorbital wrinkles, Fitzpatrick skin types I–III
In review
Hypopigmentation
43% with carbon dioxide laser
5% with variable pulse erbium:YAG laser

P <0.05
Effect size not calculatedvariable pulse erbium:YAG laser

RCT
19 women and 2 men, aged 18–90 years, with perioral or periorbital wrinkles, Fitzpatrick skin types I–III
In review
Hyperpigmentation
29% with carbon dioxide laser
24% with variable pulse erbium:YAG laser

No data from the following reference on this outcome.

Carbon dioxide laser versus carbon dioxide laser plus variable pulse erbium:YAG laser:

We found one systematic review (1 double blind RCT, 20 women).

Wrinkle improvement

Carbon dioxide laser compared with carbon dioxide laser plus variable pulse erbium:YAG laser We don't know how carbon dioxide laser and carbon dioxide laser plus variable pulse erbium:YAG laser compare at improving wrinkles (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in wrinkles

Systematic review
20 women, aged 42–72 years, with Fitzpatrick skin types I–III on the upper lip
Data from 1 RCT
Wrinkle improvement 4 months
67% with carbon dioxide laser alone
68% with carbon dioxide laser plus variable pulse erbium:YAG laser

Reported as not significant
P value not reported
Not significant

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

Systematic review
20 women, aged 42–72 years, with Fitzpatrick skin types I–III on the upper lip
Data from 1 RCT
Erythema
with carbon dioxide laser alone
with carbon dioxide laser plus variable pulse erbium:YAG laser

Reported as not significant
P value not reported
Not significant

Systematic review
20 women, aged 42–72 years, with Fitzpatrick skin types I–III on the upper lip
Data from 1 RCT
Pain
with carbon dioxide laser alone
with carbon dioxide laser plus variable pulse erbium:YAG laser

Reported as not significant
P value not reported
Not significant

Further information on studies

Carbon dioxide laser versus dermabrasion: Two of the RCTs included in the review reported withdrawal rates of 1/20 (5%) and 1/15 (7%). The third RCT gave no information on withdrawal rates.

Carbon dioxide laser versus dermabrasion: In the RCT identified by the review, 85% of women (20 women in RCT) had erythema on the upper lip (similar for both groups) 1 month after treatment. In 10% of people, erythema was reported to be worse on the laser-treated side, and in 5%, on the dermabrasion-treated side. The average duration of erythema was 2.5 months for both treatments. Pain, oedema, eczema, and whiteheads resolved either spontaneously or with minimal treatment.

Comment

The effects of chemical peels and CO2 lasers are likely to be dependent on the technique of the dermatological surgeon; therefore, results may not generalise to different populations. The available evidence is too weak to define the effects of CO2 laser on wrinkles.

Substantive changes

No new evidence

2008; 2008: 1711.
Published online 2008 December 16.

Chemical peel

Summary

We don't know whether chemical peels are beneficial.

Benefits and harms

Chemical peel versus placebo/no treatment:

We found no systematic review or RCTs.

Chemical peel versus carbon dioxide laser:

See option on carbon dioxide laser.

Comment

Chemical peel versus carbon dioxide laser:

See comment on carbon dioxide laser.

Substantive changes

No new evidence

2008; 2008: 1711.
Published online 2008 December 16.

Dermabrasion

Summary

We found no direct information about whether dermabrasion is better than no active treatment.

We don't know whether dermabrasion is more effective at improving wrinkles compared with carbon dioxide laser treatment, as studies have given inconclusive results, but adverse effects are common with both treatments, especially erythema.

Benefits and harms

Dermabrasion versus placebo/control:

We found no systematic reviews or RCTs.

Dermabrasion versus carbon dioxide laser:

See option on carbon dioxide laser.

Comment

None.

Substantive changes

No new evidence

2008; 2008: 1711.
Published online 2008 December 16.

Facelift

Summary

We don't know whether facelifts improve wrinkles, as we found no direct information about their effects on wrinkles.

Benefits and harms

Facelift:

We found no systematic review and no RCTs.

Comment

Clinical guide:

The effectiveness and safety of facelift surgery is likely to depend on the technique of the surgeon.

Substantive changes

No new evidence

2008; 2008: 1711.
Published online 2008 December 16.

Oral natural cartilage polysaccharides

Summary

We don't know whether oral natural cartilage polysaccharides are beneficial.

Benefits and harms

Oral natural cartilage polysaccharides versus placebo:

We found one systematic review (search date 2002, 1 RCT) and one additional RCT.

Wrinkle improvement

Oral natural cartilage polysaccharides compared with placebo We don't know whether an oral preparation of cartilage polysaccharide is more effective at 3 months (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in fine wrinkles

RCT
30 women, aged 40–60 years, with moderate to severe wrinkles
In review
Proportion of women with improved facial fine wrinkles 90 days
10/15 (67%) with oral cartilage polysaccharide preparation (Vivida® 500 mg/day)
0/15 (0%) with placebo

RR 21.0, 95% CI 1.34 to 328.86
The RCT was small, and the possibility of publication bias cannot be excluded
Large effect sizeoral natural cartilage polysaccharide

RCT
144 people, aged 35–50 years, with Fitzpatrick skin type II or III and mild to moderate photoaging Improvement in face or eye wrinkles (physician assessed and participant assessed using a 10 cm visual analogue scale, dermatologist assessed using photographs) 3 months
with cartilage polysaccharide preparation (Imedeen® 400 or 200 mg/day for 3 months)
with placebo (for 3 months)

Reported as not significant
P value not reported
Not significant

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
144 people, aged 35–50 years, with Fitzpatrick skin type II or III and mild to moderate photoaging Adverse effects
23/96 [24%] with cartilage polysaccharide preparation (Imedeen® 400 or 200 mg/day for 3 months)
10/48 [21%] with placebo (for 3 months)

P >0.05
Not significant

No data from the following reference on this outcome.

Oral natural cartilage polysaccharides versus each other:

We found one systematic review (1 RCT, 30 women) comparing two commercial preparations.

Wrinkle improvement

Different oral natural cartilage polysaccharides compared with each other The Vivida® brand may be more effective than the Imedeen® brand at improving wrinkles (low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in fine wrinkles

Systematic review
30 women, aged 40–60 years, with moderate to severe wrinkles
Data from 1 RCT
Improvement in fine wrinkles 90 days
10/15 [66%] with Vivida® 500 mg daily for 90 days
3/15 [20%] with Imedeen® 380 mg daily for 90 days

RR 3.33
95% CI 1.14 to 9.75
Moderate effect sizeVivida® 500 mg

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

Systematic review
30 women, aged 40–60 years, with moderate to severe wrinkles
Data from 1 RCT
Adverse effects
with Vivida® 500 mg daily for 90 days
with Imedeen® 380 mg daily for 90 days

Further information on studies

Comment

The available evidence is inadequate to assess accurately the effects of oral cartilage preparations.

Substantive changes

No new evidence

2008; 2008: 1711.
Published online 2008 December 16.

Retinyl esters

Summary

We don't know whether retinyl esters are beneficial.

Benefits and harms

Retinyl esters:

We found no systematic reviews or RCTs.

Further information on studies

Comment

None.

Substantive changes

No new evidence

2008; 2008: 1711.
Published online 2008 December 16.

Topical natural cartilage polysaccharides

Summary

We don't know whether topical natural cartilage polysaccharides are beneficial.

Benefits and harms

Topical natural cartilage polysaccharides versus placebo:

We found one systematic review (search date 2002, 1 RCT).

Wrinkle improvement

Topical natural cartilage polysaccharides compared with placebo A topical preparation of cartilage polysaccharide may be more effective than placebo at reducing fine and coarse wrinkles at 120 days (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in fine wrinkles

RCT
30 women, aged 40–60 years, with moderate to severe facial wrinkles
In review
Proportion of women with no shallow wrinkles (less than 1 mm) 120 days
30/30 (100%) with topical cartilage polysaccharide 1% (twice daily for 120 days)
0/30 (0%) with placebo (twice daily for 120 days)

P <0.001
The clinical importance of this result is unclear; the RCT is limited by its small sample size and by potential difficulties with concealment of allocation
Application of creams to each side of the face may result in contamination
Effect size not calculatedtopical cartilage polysaccharide

RCT
30 women, aged 40–60 years, with moderate to severe facial wrinkles
In review
Proportion of women with no moderate wrinkles (1 mm) 120 days
27/30 (90%) with topical cartilage polysaccharide 1% (twice daily for 120 days)
0/30 (0%) with placebo (twice daily for 120 days)

P <0.001
The clinical importance of this result is unclear; the RCT is limited by its small sample size and by potential difficulties with concealment of allocation
Application of creams to each side of the face may result in contamination
Effect size not calculatedtopical cartilage polysaccharide
Improvement in coarse wrinkles

RCT
30 women, aged 40–60 years, with moderate to severe facial wrinkles
In review
Proportion of women with no deep wrinkles (greater than 1 mm) 120 days
5/30 (17%) with topical cartilage polysaccharide 1% (twice daily for 120 days)
2/30 (7%) with placebo (twice daily for 120 days)

P <0.001
The clinical importance of this result is unclear; the RCT is limited by its small sample size and by potential difficulties with concealment of allocation
Application of creams to each side of the face may result in contamination
Effect size not calculatedtopical cartilage polysaccharide

Quality of life

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Comment

None.

Substantive changes

No new evidence

2008; 2008: 1711.
Published online 2008 December 16.

Variable pulse erbium:YAG laser

Summary

We found no direct information from RCTs about whether erbium:YAG laser is better than no active treatment.

We don't know whether erbium:YAG laser is more effective than carbon dioxide laser at improving wrinkles, as studies have given inconclusive results.

Benefits and harms

Variable pulse erbium:YAG laser versus placebo/no treatment:

We found no systematic review or RCTs.

Variable pulse erbium:YAG laser versus carbon dioxide laser:

See option on carbon dioxide laser.

Comment

Variable pulse erbium:YAG laser versus carbon dioxide laser:

See comment on carbon dioxide laser.

Substantive changes

No new evidence

2008; 2008: 1711.
Published online 2008 December 16.

Vitamin C or E (topical)

Summary

We don't know whether topical vitamin C improves the appearance of wrinkles, as studies have been small.

We found no direct information about whether topical vitamin E is better than no active treatment.

These vitamins may cause stinging and erythema.

Benefits and harms

Vitamin C versus placebo:

We found one systematic review (search date 2002), which included one double blind RCT.

Wrinkle improvement

Vitamin C compared with placebo We don't know whether topical vitamin C is more effective than placebo at improving fine and coarse facial wrinkles (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Improvement in fine wrinkles

RCT
28 people, age 36–72 years, with mild to moderate photodamage
In review
Physician-assessed improvement in fine wrinkles (using photographs; graded as "much improved", "improved", "no change", or "worse") 12 weeks
16/19 (84%) with topical ascorbic acid (0.5 mL) in a vehicle cream (applied once daily for 12 weeks)
3/19 (16%) with vehicle cream alone (applied once daily for 12 weeks)

P = 0.002
The RCT is limited by its small sample size, short duration and high withdrawal rate, which compromises the validity of the results
Effect size not calculatedascorbic acid
Improvement in coarse wrinkles

RCT
28 people, age 36–72 years, with mild to moderate photodamage
In review
Physician-assessed improvement in fine wrinkles (using photographs; graded as "much improved", "improved", "no change", or "worse") 12 weeks
13/19 (68%) with topical ascorbic acid (0.5 mL) in a vehicle cream (applied once daily for 12 weeks)
3/19 (16%) with vehicle cream alone (applied once daily for 12 weeks)

P = 0.01
The RCT is limited by its small sample size, short duration and high withdrawal rate, which compromises the validity of the results
Effect size not calculatedascorbic acid
Improvement in wrinkles (global)

RCT
28 people, age 36–72 years, with mild to moderate photodamage
In review
Physician-assessed improvement in fine wrinkles (using photographs; graded as "much improved", "improved", "no change", or "worse") 12 weeks
16/19 (84%) with topical ascorbic acid (0.5 mL) in a vehicle cream (applied once daily for 12 weeks)
3/19 (16%) with vehicle cream alone (applied once daily for 12 weeks)

RR 5.33
95% CI 1.85 to 15.34
The RCT is limited by its small sample size, short duration and high withdrawal rate, which compromises the validity of the results
Large effect sizeascorbic acid

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
28 people, age 36–72 years, with mild to moderate photodamage
In review
Adverse effects
with topical ascorbic acid (0.5 mL) in a vehicle cream (applied once daily for 12 weeks)
with vehicle cream alone (applied once daily for 12 weeks)

Vitamin E:

We found no systematic reviews or RCTs.

Comment

None.

Substantive changes

No new evidence


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