E Steels, B Richert

Department of Dermatology

University Hospitals Brugmann, St Pierre and

Children’s Hospital Reine Fabiola

Université Libre de Bruxelles

Summary

• Structural skin changes, skin aging factors

• Effects of estrogen on structural and physicalchanges

• Place of hormone replacement therapy (HRT)

• Future treatments

Skin aging factors Intrinsic factors: geneticaly determined

• Ethnicity: pigmentation, lipid content

• Anatomical variations

• Hormonal changes

Extrinsic factors

• Exposure to UV light (photoaging)

• Tobacco use

• Lifestyle influence: nutrition, ambient conditions, medication

• Mechanical aging

M.A. Farage et al. Intrinsec and extrinsec factors in skin aging: a review. Int J Cosm Science, 2008.30,87-95.

Structural changes in aged skinSkin structure Observed effect of aging

Stratum corneum Lipid content decreases

Epidermis Decrease in thikness (atrophy)

Flattening of dermal-epidermal junction

Number of active melanocytes decreases

Number of Langerhan’s cells decreases

Dermis Decrease in thickness

Cellularity decrease: collagen and hyaluronic acid content

Decrease in collagen synthesis (fibroblast activity)

Changes in structure and function of sweat glands

Elastic fibers degrade

Decrease in number of blood vessels

Hypodermis Change in distibution of subcutaneous fat

Appendages Hair thins and loses pigment

Abnormal nail plates

Estrogen: mechanism of action Cellular aging:

• Oxidative damage : free radicals. E = direct antioxydant and indirect inducer of

antioxydant enzymes

• Senescence : E = prevention of telomere shortening

Genomic signaling

• ER α and ER β, intacellular, nuclear receptors

• Often co-localized, working antagonistically or synergistically

• Expression is tissue dependent

Non-genomic signaling

• Cell membrane forms of receptor, rapid response

• « ANGELS »S Stevenson, J Thornton. Effect of estrogens on skin aging and the potential role of SERMs. Clin Interv in Aging 2007 2(3):283-297.

Estrogen: effects on skinFactors complicating understanding:

•Few randomised trials (observational studies)

•≠ E preparation and doses, +/- progest or testost : isolated effect of E ?

•Assessment measures: subjective, objective withevaluator variation

•Moment of starting HRT, duration

•Risks associated with long term HRTS Stevenson, J Thornton. Effect of estrogens on skin aging and the potential role of SERMs. Clin Interv in Aging 2007 2(3):283-297.

Estrogen: effects on skinstructural components

Collagen content

Elastin fibers

Water content

Sebaceous secretions

Estrogen: effects on skinstructural components

Collagen content

Elastin fibers

Water content

Sebaceous secretions

Collagen content

• Exact mechanism of E on collagen integrity not known

• 30% of skin collagen is lost in the first 5 years

• Correlates with age-related decrease in bone mineral density

• Most of studies: beneficial effect of SC, topical or oral E

treatment BUT often not comparable

M.P. Brincat et al. Estrogens and the skin. Climacteric 2005;8:110-123.J Calleja-Agius et al. Skin aging. Menop Intern 2007;13:60-64.

Estrogen: effects on skinstructural components

Collagen content

Elastin fibers

Water content

Sebaceous secretions

Elastin fibers

• Controversial clinical studies

• Histological study: Improvement with topical E

• Clinical studies: no improvement from baseline

with HRT, BUT small sample, short treatment,

early after menopause onset

M.P. Brincat et al. Estrogens and the skin. Climacteric 2005;8:110-123.J Calleja-Agius et al. Skin aging. Menop Intern 2007;13:60-64.

Estrogen: effects on skinstructural components

Collagen content

Elastin fibers

Water content

Sebaceous secretions

Water content

• Dry skin is one of the commonest dermatological condition in older women

• Xerosis: decreased hydratation of the upper layers of the SC, weakening of the barrier function

• Mucopolysaccharides and hyaluronic acid levels increasewith E stimulation dermal water content skin

thickness

• Controversial studies

Piérard-Franchimont et al. Skin water-holding capacity and transdermal estrogen therapy for menopause:a pilot study. Maturitas 1995;22:151-4.

Estrogen: effects on skinstructural components

Collagen content

Elastin fibers

Water content

Sebaceous secretion

Sebaceous secretion

• Large interindividual differences

• E reduce size and number of sebaceous glands

and thus production of sebum

• ERT alone = sebum-suppressive action

• E+P = increase in skin surface lipidsSator et al. The influence of HRT on skin ageing: a pilot study. Maturitas 2001;39:43-55.Callens et al. Does hormonal skin aging exist? A study of the influence of diif HT regimens on the skin of

postmenopausal women using non-invasive measurement techniques. Dermatology 1996;193:289-94.

Estrogen: effects on skinphysical characteristics

Skin thickness

Elasticity and distensibility

Wrinkles

Estrogen: effects on skinphysical characteristics

Skin thickness

Elasticity and distensibility

Wrinkles

Skin thickness• Thining comes from decreasing of collagen,

GAG, water content

• Numerous studies with systemic or topical

treament: global positive effect of HRT

• Observable benefits are inversely proportional to

initial thickness value

G Hall, T Phillips.J Am Acad Dermatol 2005;53(4):555-68.

Estrogen: effects on skinphysical characteristics

Skin thickness

Elasticity and distensibility

Wrinkles

Elasticity and distensibility

• In absence of HRT, elasticity decreases and

distensibility increases

• Assessment by non-invasive computerized

devices

• HRT can mitigate age-related changes in tensile

properties

G Hall, T Phillips.J Am Acad Dermatol 2005;53(4):555-68.

Estrogen: effects on skinphysical characteristics

Skin thickness

Elasticity and distensibility

Wrinkles

Wrinkles

• Few clinical studies

• Technical challenges in quantitating facial

wrinkles

• Results are unconclusive

G Hall, T Phillips.J Am Acad Dermatol 2005;53(4):555-68.

E Emmerson, M Hardman. The role of estrogen deficiency in skin ageing and wound healing. Biogerontology 2011.

Estrogen: effect on wound healing

Emmerson, Hardman. The role of estrogen deficiency in skin aging and wound healing. Biogerontology March 2011.

• Systemic HRT improves healing in post-

menopaused women

• Topical E treament improves healing in elderly

men and women

Estrogen: effects on hairs

• Lack of standard treatment in most of hair

diseases

• Postmenopausal women have an increased

frequency of androgenic alopecia

• Facial hair density increases with age

• Body hair density decreases with ageChen et al. Hair loss in elderly women. Eur J Dermatol 2010;20(2):145-51.

• Androgenic alopecia:

worsening after menopause

efficacy of antiandrogens ?

Remain controversial

Estrogen: effects on mucosa

• Menopause: atrophy of the vaginal mucosa, atrophicvulvo-vaginitis, genital dryness

• Assessment of the vulvar skin around menopause: no significant changes in hydratation, elasticity,

permeability in comparison to skin

• Chronic vulvar and perineal dermatitis comes fromincontinence

M A Farage, H I Maibach. Morphology and physiological changes of genital skin and mucosa.Curr Probl Dermatol. 2011;40:9-19.

HRT : summary• Short term use

• In early phase of menopause

• Indications = treatment of symptoms (hot flushes, sweating, insomnia, fatigue, depressed mood, urogenital atrophy),

osteoporosis prevention

• Prevention of skin aging = additional benefit

« HRT cannot be recommended today to treat skin aging »

Topical hormonal treatment

• Estradiol, estriol is safer (lower affinity for ER)CEE :greater estrogenic potency, effects on vaginal mucosa

no systemic effects

effective as systemic treatment

• Progesterone 2% (Holzer et al, Br J Dermatol 2005)

• Phytoestrogen (Isoflavone): secondary effects ?

Future : SERMs• Either estrogenic or antiestrogenic effects, depending on the

tissue

• In vitro studies: tamoxifen and raloxifen increase fibroblast

proliferation (but don’t promote migration)

• Preliminary clinical studies:

Raloxifen: increases elasticity and collagen content

Genistein: increases dermal vascularisation and epidermal

thikness

Topical tamoxifen: improvement in keloid appearanceS Stevenson, J Thornton. Effect of estrogens on skin aging and the potential role of SERMs.Clin Interv in Aging 2007;2(3):283-297.

Conclusion

• Topical hormonal treatments

• Development of SERMs, selective ligands for

ERα and Erβ, ANGELS

• Numerous cosmetic alternatives (topical

treatment, botulic toxin, collagen and

hyaluronic acid, lasers…)

Thank you !