Induction of collagen by estradiol: difference between sun-protected and photodamaged human skin in vivo

Arch Dermatol. 2008 Sep;144(9):1129-40. doi: 10.1001/archderm.144.9.1129.


Objective: To evaluate the effectiveness of topical estradiol in stimulating collagen I and III production in naturally aged and photoaged human skin of postmenopausal women and age-matched men.

Design: Vehicle-controlled treatment followed by biochemical and immunohistochemical analyses of skin biopsy specimens.

Setting: Academic referral center.

Participants: Seventy healthy volunteers (40 postmenopausal women with a mean age of 75 years, and 30 men with a mean age of 75 years) with photodamaged skin. Interventions Topical application of estradiol, 0.01%, 0.1%, 1%, or 2.5% or vehicle on aged or photoaged skin, with biopsy specimens taken after last treatment.

Main outcome measures: De novo synthesis of collagen by quantitative polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay.

Results: Topical estradiol increased procollagen I and III messenger RNA and collagen I protein levels in sun-protected aged hip skin in postmenopausal women and, to a lesser extent, in age-matched men. Surprisingly, no significant changes in production were observed in women or men after 2-week estradiol treatment of photoaged forearm or face skin, despite similar expression of estrogen receptors (ER-alpha, ER-beta, and GPR30) in aged and photoaged skin. Estradiol treatment induced the estrogen-responsive gene GREB1, indicating that penetration of topical estradiol and genomic response to estrogen were similar in the 3 anatomic sites.

Conclusions: Two-week topical estradiol treatment stimulates collagen production in sun-protected hip skin, but not in photoaged forearm or face skin, in postmenopausal women and aged-matched men. These findings suggest that menopause-associated estrogen decline is involved in reduced collagen production in sun-protected skin. Interestingly, alterations induced by long-term sun exposure hinder the ability of topical 2-week estradiol to stimulate collagen production in aged skin.

Trial registration: Identifier: NCT00113100.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Aged
  • Aged, 80 and over
  • Collagen Type I / biosynthesis*
  • Collagen Type III / biosynthesis*
  • Drug Administration Schedule
  • Environmental Exposure
  • Estradiol / administration & dosage*
  • Estradiol / pharmacology
  • Face
  • Female
  • Forearm
  • Gene Expression Regulation / drug effects
  • Hip
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Postmenopause
  • Procollagen / biosynthesis
  • Radiation Protection
  • Receptors, Estrogen / metabolism
  • Skin / drug effects*
  • Skin / metabolism*
  • Skin Aging
  • Sunlight
  • Time Factors
  • Transcription, Genetic / drug effects


  • Collagen Type I
  • Collagen Type III
  • GREB1 protein, human
  • Neoplasm Proteins
  • Procollagen
  • Receptors, Estrogen
  • Estradiol

Associated data