Accepted: 31 October 2017

DOI: 10.1111/jocd.12508

REVIEW ARTICLE

A review of the role of estrogen in dermal aging and facial

attractiveness in women

Edwin D Lephart PhD

Department of Physiology and

Developmental Biology and The
Neuroscience Center, College of Life
Sciences, Brigham Young University, Provo,
UT, USA
Correspondence
Edwin D Lephart, Department of Physiology
and Developmental Biology and The
Neuroscience Center, College of Life
Sciences, Brigham Young University, Provo,
UT, USA.
Email: Edwin_Lephart@byu.edu
Funding information
The project was funded, in part, by a grant
from the TTO/Life Science College, # 19-
2215 at Brigham Young University.
Summary
Estrogens are known to have protective and favorable influences on skin health;
conversely, androgens oppose the actions of estrogens. Estrogen’s chemical mes-
sages are transmitted via the classical nuclear hormone estrogen receptors (ER)
alpha and beta and the rapid-acting G-coupled membrane estrogen receptor. Andro-
gens [both testosterone and 5a-dihydrotestosterone (5a-DHT)] bind the same
androgen receptor. Estrogen levels peak in the mid- to late 20s in women and then
decline by 50% by 50 years of age and dramatically decrease further after meno-
pause. The loss of estrogens with aging contributes to diminished dermal health,
whereas estrogen hormone therapy [eg, oral conjugated equine estrogens (CEE)]
restores skin health. Several reports suggest positive correlations between the levels
of circulating estrogens and: (1) perceived age, (2) attractiveness, (3) enhanced skin
health, and (4) facial coloration in women. Based upon a psychological dermato-
endocrine perspective, the positive correspondence of high estrogens levels with
perceived age and facial attractiveness in women especially with aging demonstrates
the importance of hormonal influences on observed dermal health and youthful
appearance.

KEYWORDS
aging, attractiveness, dermal, estrogen receptors, estrogens, human skin

1 | SKIN AGING: PERCEPTION IS REALITY 2 | BASIC SKIN COMPONENTS AND

—THE PROBLEM AT HAND CHANGES IN SKIN AGING

The aging of skin via intrinsic and extrinsic factors occurs in all indi-
viduals and is influenced by genetic, environmental, and hormonal
dynamics. It is clear that the goal in dermatological procedures or
cosmetic applications was to help people look better in order to feel
better about themselves.1 Regardless of the many influences con-
tributing to skin aging, it is known that estrogen plays a key role;
however, it is not evident how this correlates to the perception of
skin aging, facial appearance, and so forth. In this review, evidence is
presented for estrogen’s actions in determining skin aging, facial
attractiveness, and coloration from a basic science to a psychological
dermato-endocrine perspective, which has received little research
attention previously.
There are several reviews on aging skin in humans that adequately
cover this topic, which include free radicals, oxidative stress, antioxi-
dants, intrinsic (or chronological), and extrinsic (photo) aging, etc.1-5
In brief, the skin is commonly divided into three layers: the epider-
mis, the dermis, and the hypodermis (Figure 1).
General changes in the synthesis, abundance, and maintenance of
various skin structures during the aging process are well known.1,2,6
Up to age 20, the skin thickens then thins progressively during aging in
adults. All aspects of the skin layers change with aging as displayed in
Figure 2. This cartoon shows, in younger skin, normal thickness and
health of the epidermis, dermis, and hypodermis, which declines with
age.1,7 The epidermis decreases in thickness with the alterations in the

282 | © 2018 Wiley Periodicals, Inc. wileyonlinelibrary.com/journal/jocd J Cosmet Dermatol. 2018;17:282–288.

LEPHART
F I G U R E 1 Human Skin Layers. This
cartoon displays the epidermis, dermis, and
hypodermis along with the cellular
components and extracellular matrix
elements. Redrawn, in part, with
permission via Elsevier1
epidermis
dermis
F I G U R E 2 Human Characteristics in
Younger versus Older Skin. The cartoon
displays the decreases in the structural
dermis
components and changes in all three skin
hypo-
layers with aging. Diagram redrawn, in
part, from data in Farage et al7, 2007, with
permission from Informa Healthcare
shape of the keratinocytes, and the epidermal-dermal junction flattens.
Also, the number and size of pores increase with aging along with the
7
appearance of age spots (Figure 2). The dermis also decreases in
thickness due to the loss of collagen, elastin, and hyaluronic acid.1,7 A
feature of aged human skin includes fragmentation of collagen fibers
by the action of matrix metalloproteinases such as MMP 1 and
increased mitochondrial oxidative stress that results in common dele-
tions of mitochondrial DNA via the c-Jun/AP-1 pathway in dermal
8-10
fibroblasts. In this regard, the normal age-associated loss of colla-
gen and elastin in skin results in increased distensibility and loss of
tonicity with the progression of deepening facial creases and wrin-
kles.1,2,11 For instance, collagen type I and collagen type III are thought
to decrease by as much as 30% in the first 5 years after menopause
along with a decrease in skin thickness, which correlates with estrogen
deficiency.2,6 Moreover, the structure of the sweat glands becomes
distorted along with a decrease in the number of blood vessels (Fig-
ure 2).7 Finally, the overall volume of the hypodermis decreases,
where alterations in the distribution of subcutaneous fat occur.1,2
3 | THE HORMONAL PUZZLE FROM
RECEPTORS TO FACIAL APPEARANCE IN
DERMAL HEALTH
3.1 | Estrogens
Estrogens play an essential function in most cells and tissues in the
12,13
body. In particular, many studies have shown that estrogens
| 283
age spots appear
epidermis decreases:
junction flattens
elastin fibers
dermis decreases:
collagen fibers
↓collagen, elastin
& hyaluronic acid
hypodermis decreases:
fat diminishes with age
Younger Skin Older Skin
have several important beneficial/protective roles in skin physiol-
ogy.6,14,15 Estrogen levels peak in the mid- to late 20s in women and
then decline by 50% by 50 years of age and dramatically decrease
further after menopause.1 Figure 3 displays the pattern of estrogen
biosynthesis and estrogen levels during reproductive transitions. Fur-
thermore, as shown in Figure 4, estrogens are known to: (1) increase
collagen, elastin, blood flow, and skin thickness,6,14,15 (2) be natural
modulators of matrix metalloproteinases (MMPs), where they inhibit
MMPs that are known to break down collagen,1,6,7 (3) increase mois-
ture and skin turgor,6,11,13,14 (4) increase the rate and quality of
6,11,14
wound healing and (5) increase fibroblast viability and stimu-
late the proliferation of keratinocytes (see Figure 3).11,16 Finally,
estrogens stimulate the hair follicle for scalp hair growth6,11,14 and
act as natural antioxidants, where they protect against oxidative
stress and inflammation.1,12
3.2 | Estrogen receptors (ER) alpha (a), beta (b), and
g-coupled membrane estrogen receptors
Estrogen receptors, ERa & ERb, are members of the superfamily
family of nuclear hormone receptors.17 The “classical” estrogen
receptor (ERa) was discovered by Elwood Jensen in 1958 and cloned
in 1986, while ERb was reported 10 years later in 1996.17 Human
ERb is homologous to ERa, particularly in the DNA-binding domain
(97% amino acid identity) and in the ligand-binding domain (54%
amino acid identity), but share little homology in other domains.1-5
Based upon the dissimilar amino acid homology in the ligand-binding
284 | LEPHART

Menarche Final Menstrual Period

Reproductive Transitions & Estrogen Levels
Reproductive Menopausal Transition Postmenopause
Terms: Early Peak Late Early Late Early Late
Premenopause Perimenopause CEE therapy No HT
Dura on Un l
of Stage:
Variable Variable 1 yr 4 yr Demise

Amenorrhea
Regular Variable cycle > 2 skipped

12 months
Menstrual Variable to length ( > 7 days cycles &
Cycles Length Decreases different from
None
regular “Normal” amenorrhea
~ 2 days normal) (250 days)

Estrogen Ovarian (follicle) & corpus luteum (cl) P450 ↓ Ovarian P450 arom Mainly peripheral
Biosynthesis arom converts C-19 androgens to estrogens and ↑ peripheral conversion of C-19
via Phase of Cycle conversion of C-19 androgens to estrogens
(P450 arom) Follicular Preovulatory Luteal androgens to estrogens estrone > estradiol
Estrone 50 pg/ml 125 pg/ml 70 pg/ml Decline by 50 % 40 pg/ml
17β-Estradiol 65 pg/ml 250 pg/ml 125 pg/ml by age 50 < 15 pg/ml
Age in yrs 9-15 18 - 25 30 - 39 40 - 45 46 - 49 50-52 55 > 60

F I G U R E 3 The Reproductive Transitions of Premenopause, Perimenopause, and Postmenopause Along with Estrogen Biosynthesis and
Estrogens Levels for Each Interval. The diagram displays the duration of the stage, menstrual cycles, endocrine changes for cytochrome P450
aromatase (P450arom) expression, and estrogen values for estrone and 17b-estradiol with aging. The premenopause and postmenopause
estrogens levels are from Stanczyk FZ.49 The lack of estrogen is associated with vertical wrinkles of the upper lip in women after menopause
(see bottom right-hand portion of Figure 3). Photograph insert: http://www.etopical.com/skin/get-rid-wrinkles/lip-lines-wrinkles-get-rid-best-
cream-lip-fillers-treatment/

region, one may predict 17b-estradiol would display different affini-
ties for the ERs, but surprisingly, 17b-estradiol has almost equal high
affinity for ERa with a Kd = 0.13 nmol/L and for ERb with a Kd =
0.15 nmol/L.18 Due to this high affinity for the ERs, 17b-estradiol is
the most potent naturally circulating sex steroid hormone in the
body and the most potent estrogen among estrone and estriol in
order of nuclear steroid receptor affinity.19
Evidence exists that selective ERb agonistic actions provide pro-
tective mechanisms in breast cancer and prostate health, which may
be suggested for dermal applications as well.20-22 Several studies
using immunohistochemistry reported that ERb was the predominant
ER in adult human scalp skin (especially in the layers of the epider-
mis) and in the hair follicle.23-25 Conversely, more recent studies
demonstrated that ERa and ERb are present in human skin, and an
immunohistochemical study showed that while there is no difference
in the expression of ERa and ERb between male and female human
skin, the expression of ERb is significantly decreased in the epider-
26,27
mis after 50 years of age.
Also, it is now apparent that many cells express
nongenomic, G protein-coupled membrane ER termed GPR30 or
GPER1 by cytosolic signal transduction proteins via signaling cas-
cades.6,26,28 Most notably, GPER1 has been identified recently in
keratinocytes and dermal fibroblasts, where the distribution of
these rapid-acting G protein-coupled receptors appears to be com-
parable.26
3.3 | Androgens
In brief, androgens oppose the positive actions of estrogens in skin
(Figure 4).25,29,30 In this case, testosterone can be converted to the
more potent androgen, 5a-dihydrotestosterone (5a-DHT), by the 5a-
reductase type I enzyme in human skin.23,30,31
3.4 | Androgen receptor
Remarkably, both androgens (testosterone and 5a-DHT) bind the
same nuclear androgen receptor (AR) (Figure 4).31 The 5a-reductase
enzyme is predominant in sebaceous and sweat glands with lower
a activity in epidermal cells, fibroblasts, and hair follicles.23-25 AR is
present in epidermal and follicular keratinocytes, sebocytes, sweat
LEPHART | 285

Estrogen Testosterone 5α-DHT

5α-reductase enzyme

17β-Estradiol Testosterone 5α-DHT

Estrogens Androgens
2.5X to
COLLAGEN, ELASTIN, BLOOD
FLOW & SKIN THICKNESS ⬆ ⬇ 5X MORE
POTENT
MMPs
(breaks down collagen) ⬇ ⬆
MOISTURE & TURGOR of SKIN
(supple & robust) ⬆ ⬇
WOUND HEALING
(rate and quality) ⬆ ⬇ Androgen
Receptor
FIBROBLAST (viability) ⬆ ⬇

F I G U R E 4 Estrogen and Androgen Steroid Characteristics in Human Skin. 17b-Estradiol binds two nuclear steroid receptors: estrogen
receptor a and estrogen receptor b with almost equal affinity.18 Testosterone can be converted to the more potent androgen, 5a-
dihydrotestosterone (5a-DHT), via the 5a-reductase enzyme.31 Both testosterone and 5a-DHT bind the same nuclear steroid receptor, the
androgen receptor (AR).31 However, 5a-DHT is thought to be 2.5 to 5.0 times more potent as compared to testosterone for AR binding
affinity and biological actions.32 Using a western cowboy theme, the black hat displays negative effects while the white hat displays positive
effects in dermal health

glands, dermal papilla cells, dermal fibroblasts, and endothelial
cells.23-26
The differences between testosterone and 5a-DHT are demon-
strated by their binding characteristics for the AR.32 In general, 5a-
DHT is thought to be 2.5 to 5 times more potent than testosterone
(Figure 4). Finally, androgens are known to: increase MMPs and free
radical production, suppress epidermal barrier function, depress
immune function and impair wound healing, decrease fibroblast via-
bility, inhibit scalp hair growth, enhance sebaceous gland enlarge-
ment and production of sebum, and stimulate comedogenesis and
1,16,25,29,30
inflammation.
3.5 | Hormone therapy during menopause
The distinguished clinician/researcher in reproductive endocrinology,
Fred Naftolin, noted “estrogen is the main architect of the reproduc-
tive phenotype of women,” and in reference to menopause, “humans
are now the only species to regularly live to twice their reproductive
age.”12 This perspective on reproduction and menopause is profound
with the most frequently reported symptoms during menopause
being: hot flashes, irritability, reduced concentration and coordina-
tion, sleep disturbances, vasomotor disorders (sweating), and bone
mobilization (osteoporosis).33-35 Because estrogens are powerful
antioxidants along with widespread positive effects throughout the
body, they may slow the progress of aging including their influences
1,6,12,14,15
on the skin. This notion is supported by a recent
assessment of the menopausal transition in approximately 2500
women in the United States, where Khoudary et al36 reported that
changes in sex steroids (particularly estrogens) potentially explain the
greater limitation in physical functioning (performing daily activities)
in women that had experienced menopause.
In this regard, the physiological changes in skin associated with
aging and menopause include alterations in barrier function, declina-
tion of sensory and pain perception, decreased thermoregulation,
impairment in response to injury (wound healing), decreased immune
function, and decreased vitamin D production.2,6,25 Thus, the decli-
nation and loss of estrogen have a profound impact on skin health
either through chronological aging or via surgery-induced meno-
pause.33,37 The hallmark of estrogen declination is the appearance of
vertical lines in the upper lip of postmenopausal women (see Fig-
ure 3).
Hormone therapy for menopausal women has demonstrated the
powerful influence of estrogens on the skin (eg, topical gels,
0.625 mg/d of CEE, 2 mg/d estradiol valerate, implants) (see Fig-
ure 3).6,14,15,38 As mention previously, it is well established that the
main component of skin atrophy with aging is the 30% loss in colla-
gen deposition during the first 5 years associated with menopause,
which can be prevented or reversed in many cases with estrogen
hormone therapy.2,6,7,14 Epidermal thickness is also improved with
estrogen hormone therapy during the perimenopausal transition
along with improvements in elasticity and skin laxity (in women who
did not smoke).15 However, the observation that hormone
286 | LEPHART
replacement therapy did not improve skin wrinkling in women who
were 5 years postmenopausal was consistent with previous
reports.15,34
4 | AGING, ATTRACTIVENESS, FACIAL
APPEARANCE, AND COLORATION
CORRESPOND TO CHANGES IN WOMEN’S
ESTROGEN LEVELS
The first report to demonstrate that blood 17b-estradiol levels
accurately predicted the estimation in age in women was by Wildt
and Petermann in 1999.39 One hundred perimenopausal women
were in this study, where Wildt and Petermann estimated the age
of women, when they entered their outpatient clinic and found a
correspondence between perceived age and serum 17b-estradiol
concentrations.39 The results showed that the age of women was
overestimated when serum 17b-estradiol levels were low and
underestimated when levels 17b-estradiol were high.39
However, this study did not take into account whether the
women tested were smokers (vs. nonsmokers), which is known to
enhance facial dermal aging especially around the perioral region
not only in the relatively young, but also among the aged popula-
tion.40,41
Another study to directly test whether facial attractiveness in
women (n = 59; mean age = 20.4 years of age) as a reflection of
estrogen levels was conducted by Law-Smith et al42 in 2006. They
assayed urinary metabolites of estrogen and progesterone to investi-
gate the relationship between sex steroid levels and ratings of femi-
ninity, attractiveness, and apparent health of women’s faces. The
major finding of this study was that women (not using makeup) with
higher levels of late follicular estrogen had more feminine, attractive,
and healthy-looking faces than those with lower estrogen levels. The
authors concluded that estrogen levels (more so than progesterone)
predicted facial appearance that has implications for the evolutionary
approach to facial attractiveness.42
Women’s attractiveness changing with sex steroid hormone levels
across the menstrual cycle has also been reported (in 202 normal-
cycling women in the United States) by Puts et al,43 where increased
attractiveness occurred during peak fertility periods and implicated
that sex steroid hormones were driving these associations.
In an investigation by Maestriperi et al44 in 2014, facial attrac-
tiveness was studied in two groups of women of pre- and post-
menopausal ages (35 to 50 years and 51 to 65 years, respectively)
along with age-matched men. The major outcome of this study had
an evolutionary perspective on facial attractiveness, where middle-
aged women had the highest ratings, while postmenopausal women
experienced a greater age-related decline in facial attractiveness as
compared to same-aged men.44
In another study by Gunn et al45 in 2016 entitled, “Mortality is
Written on the Face,” examined 187 Danish twin pairs, where ten
nurses rated the perceived age of each twin from photographs and
selected which twin had survived the other twin. The conclusions of
this study suggested that facial cues, but not hair or clothing cues,
drive a link between perceived age and survival.
Moreover, facial coloration and human physical attractiveness
were tested in two studies. One study in Britain by Fink et al46 evalu-
ated via a set of three-dimensional shape-standardized stimulus faces
(photographs of women ages 11 to 76 years, mean = 37.4 years)
where varying only skin color distribution due to variation in biological
age and cumulative photodamage was rated by a panel of na€ıve judges
for endpoints that included age, health, and beauty. The authors con-
cluded that skin color distribution plays a role in the perception of age,
attractiveness, and health of female faces.46
Finally, a study by Jones et al47 in 2015 tested two independent
groups of white women in the United Kingdom (n = 50, mean age
20.9 years; and n = 66, mean age 21.5 years) to determine whether
a direct link between salivary estradiol levels and female facial red-
ness provided cues for attractiveness. The results of this study
showed a direct relationship between salivary estradiol levels and
facial redness in the two independent groups of women where the
authors suggested that women’s facial redness tracks changes with
estradiol levels.47 Thus, the correspondence between estrogen levels
and facial attractiveness leads to good dermal health with the added
benefit of an alluring youthful appearance.48,49
5 | CONCLUSIONS
In this review, data are presented that changes in estrogen levels are
associated with facial attractiveness and coloration while the declination
of estrogen is detrimental for skin health before menopause, and espe-
cially associated with poor dermal well-being during perimenopause
and the postmenopausal intervals. The positive influence of estrogen
hormone therapy during perimenopause includes skin, bone, and vaso-
motor symptoms, which are mediated by ER alpha and beta. The posi-
tive correspondence of high estrogen levels with perceived age and
facial attractiveness in women with aging has been reported that sup-
port the hormonal actions of estrogens. However, hormonal therapy
may present problems for many women particularly for those where
drawbacks associated with estrogen declination, menopause, and cancer
conditions exist. Thus, further research is warranted to clarify how
estrogens protect against skin aging, enhance facial appearance, and
potentially link these actions to good dermal and enhanced general
health through selective estrogen receptor mechanisms. One such
group of compounds may be selective estrogen receptor modulators
(SERMs) such as dietary isoflavonoids which possess estrogen’s positive
actions and at the same time inhibit androgen’s negative impact on der-
mal health without the downside of estrogenic complications associated
with neoplastic growth and the postmenopausal interval.1,16,22
CONFLICT OF INTERESTS
The author declares no conflict of interest in the data/research pre-
sented in this review and regarding the publication of this manu-
script.
LEPHART
AUTHOR CONTRIBUTIONS
Edwin D. Lephart contributed to the concept, research, and writing
of this article.
ORCID
Edwin D Lephart http://orcid.org/0000-0003-2027-9187
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