Does hormone therapy improve age-related skin changes in postmenopausal women?: A randomized, double-blind, double-dummy, placebo-controlled multicenter study assessing the effects of norethindrone acetate and ethinyl estradiol in the improvement of mild to moderate age-related skin changes in postmenopausal women

doi:10.1016/j.jaad.2008.05.009

Journal of the American Academy of Dermatology

Volume 59, Issue 3, September 2008, Pages 397-404.e3

https://doi.org/10.1016/j.jaad.2008.05.009 Get rights and content

Background

In postmenopausal women, declining estrogen levels are associated with a variety of skin changes, many of which are reportedly improved by estrogen supplementation.

Objective

A study was conducted to assess the effects of continuous combined norethindrone acetate (NA) and ethinyl estradiol (EE) in the control of mild to moderate age-related skin changes in postmenopausal women.

Methods

Four hundred eighty-five subjects were enrolled in this 48-week randomized, double-blind study. Subjects were randomized to one of three study arms: placebo group (165 subjects), 1 mg NA/5 μg EE group (162 subjects), or a 1 mg NA/10 μg EE group (158 subjects). The primary efficacy parameters of the study were investigator global assessment of coarse and fine facial wrinkling at week 48 and subjective self-assessment of changes in wrinkling from baseline at week 48. Secondary parameters included investigator global assessment of skin laxity/sagging at week 48, investigator global assessment of skin texture/dryness at week 48, patient self-assessment of laxity/sagging, texture/dryness, and wrinkle depth determined by image analysis of skin replicas of the periorbital (crow's feet) and jowl areas, and skin elasticity determined by timed deformation and recoil.

Results

There were similar scores in investigator global assessment in wrinkling and sagging modules at baseline across all three treatment groups. There were slight decreases in all parameters for all treatment groups for the primary subject end points, but there were no statistically significant differences between the NA/EE groups and placebo. For subject self-assessment of overall severity of skin wrinkling, there were no significant changes at weeks 24 and 48 compared to baseline. These data were unaffected by smoking status or alcohol consumption.

Limitations

This study assessed the effects of 48 weeks of low-dose estrogen upon facial skin in women who were, on average, 5 years postmenopausal. The effects of higher estrogen doses, longer treatment duration, or effects upon perimenopausal women cannot be extrapolated from this study.

Conclusion

Low-dose hormone therapy for 48 weeks in postmenopausal women did not significantly alter mild to moderate age-related facial skin changes.

Introduction

Deterioration of the skin with age results from a combination of factors. These include genetic and environmental factors, particularly sun exposure and smoking. For postmenopausal women, decreasing estrogen levels may play a role in skin aging. With menopause, there is declining expression of cutaneous estrogen receptors.1, 2, 3 Estrogen therapy may be prescribed to control some of the undesirable symptoms of menopause, such as vasomotor symptoms and vaginal atrophy. Common skin changes associated with menopause include atrophy, dryness, fine wrinkling, laxity, and poor wound healing. Some authors have reported that that estrogen supplementation, usually in high doses, may ameliorate some of the skin changes seen after menopause.4, 5, 6, 7, 8, 9, 10, 11, 12, 13 Others, however, were unable to confirm some of these effects.14, 15, 16 The objective of the current study was to assess the effects of 48 weeks of two low-dosage combinations of norethindrone acetate (NA) and ethinyl estradiol (EE) (1 mg NA/5μg EE and 1 mg NA/10 μg EE) compared with placebo on skin aging in postmenopausal women with mild to moderate age-related skin changes.

Section snippets

Methods

The study was randomized, double blind, double dummy, placebo controlled, and multicenter. Institutional review board approval was obtained for the study, and all patients gave their informed consent to participate. A central training program was used to standardize clinical assessments from center to center and investigator to investigator. This consisted of a full day of training in clinical assessment of photoaging in live subjects. Investigator to investigator as well as within investigator

Results

Overall, 485 subjects were enrolled in the study, 165 in the placebo group, 162 in the 1/5 NA/EE group, and 158 in the 1/10 NA/EE group. In general, subject characteristics at screening baseline appeared similar across the treatment groups (Table I). The subjects were, on average, 53.6 years old and approximately 5 years postmenopausal. Approximately 95% were white and the average body mass index was 26.3. The average follicle-stimulating hormone level at baseline was 97.3 mIU/mL, and the

Discussion

In women, declining estrogen levels are associated with a variety of skin changes, many of which are reportedly reversed or improved by estrogen supplementation. These include decreased skin thickness, collagen content and elasticity,11, 12, 13, 14, 15, 16, 17 increased fine wrinkling and skin dryness, 4, 5, 6, 7, 8, 9, 10, 11, 12 and impaired wound healing.¹⁰

This study is the first large prospective randomized controlled trial evaluating the effects of HT on facial skin aging. Surprisingly,

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: Supported by a grant from Pfizer, Inc.

: Disclosure: Dr Symons was employed in the Clinical Research Department at Pfizer Inc at the time this study was conducted. He was a member of the Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, when the manuscript was written. Dr Phillips is on the Scientific Advisory Board of Hygeia Therapeutics.

: Reprints not available from the authors.

^∗: A list of the members of the HT Study Group may be found online as Appendix 1 at www.eblue.org.

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Background

Objective

Methods

Results

Limitations

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Am J Obstet Gynecol

Maturitas

Maturitas

Am J Pathol

Maturitas

Maturitas

Skin changes in menopause Maturitas

Maturitas

Maturitas

Int J Gynecol Obstet

Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptor α and β

Endocrinology

Demonstration of estrogen receptors in the skin

J Endocrinol Invest

Sequence and expression of human estrogen receptor complementary DNA

Science

Does hormonal skin aging exist?

Dermatology