Skin Disorders During Menopause

Abstract

Menopause is the cessation of menstrual periods due to the loss of ovarian function. Among the various phases of a woman's life, menopause has the greatest impact on health and has been one of the most neglected areas of research. Hormonal changes caused by menopause can lead to problems in the skin and its annexes, and despite the high frequency of dermatologic signs and symptoms, studies on this topic are limited. In this article, we review the skin disorders that result from the hormonal changes of menopause and other common dermatoses observed during this period and assess possible therapeutic approaches.

Full text

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Menopause is the cessation of menstrual periods
due to the loss of ovarian function. Among the
various phases of a woman’s life, menopause has
the greatest impact on health and has been one of
the most neglected areas of research. Hormonal
changes caused by menopause can lead to prob-
lems in the skin and its annexes, and despite the
high frequency of dermatologic signs and symp-
toms, studies on this topic are limited. In this arti-
cle, we review the skin disorders that result from
the hormonal changes of menopause and other
common dermatoses observed during this period
and assess possible therapeutic approaches.
Cutis. 2016;97:E16-E23.
In 1983 the Brazilian Ministry of Health launched
the Program for Integrated Women’s Health Care
following a worldwide trend to adopt multidisci-
plinary approaches that consider the complexity of
women’s health.1 Although menopause may have
the greatest impact on women’s health among all the
stages of life, research on this topic is limited.2 Due to
the aging general population, both the proportion of
women who are menopausal and the total population
of menopausal women have increased.2 On aver-
age, women in developed countries spend one-third
of their lives in menopause; thus, the physiology of
menopause has become a matter of public health. In a
survey of 87 women attending a specialist menopause
clinic, more than 64% reported prior skin problems.3
Despite the high frequency of dermatologic signs and
symptoms associated with menopause, few studies
have been conducted on the subject.3,4 In this article,
we review some of the common skin disorders that
occur during menopause and assess possible therapeu-
tic and preventive skin care approaches.
Stages of Menopause
During perimenopause, irregular menstrual cycles
and a series of clinical manifestations occur5 that
may precede menopause by 2 to 8 years.6 The term
menopausal transition is used by the World Health
Organization to describe the phase of perimenopause
prior to the end of menstrual periods.7 The World
Health Organization also suggests that the term
Skin Disorders During Menopause
Gleison V. Duarte, MD, PhD; Ana Cláudia Moura Trigo, MD; Mária de Fátima Paim de Oliveira, PhD
Drs. Duarte and Paim de Oliveira are from the Federal University of
Bahia, Brazil. Dr. Trigo is from Gynecology and Obstetrics Brazilian
Federation/Ministry of Education, Hospital do Servidor Público
Estadual of São Paulo, Brazil; Hospital Pérola Byington, São Paulo;
and the University of São Paulo.
Drs. Duarte and Paim de Oliveira are speakers for AbbVie Inc;
Janssen Global Services, LLC; and Pfizer Inc. Dr. Trigo reports no
conflict of interest.
Correspondence: Gleison V. Duarte, MD, PhD, Avenida Tancredo
Neves, 620, Sala 417, Salvador, Bahia, Brazil
(gleisonvduarte@yahoo.com.br).
PRACTICE POINTS
• Frontal fibrosing alopecia may respond to finasteride or dutasteride.
• Acute and chronic telogen effluvium may be associated with iron deficiency, mostly related to
malabsorption or chronic gastrointestinal bleeding, during perimenopause.
• Oral and topical isoflavones may reduce skin aging in menopausal women.
• The use of estrogens as hormone replacement therapy in menopausal women promotes an increase in
skin thickness and/or collagen content.
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climacterium should be substituted for perimenopause
in the period ranging from just before the onset of
menopause to 1 year after menopause. Climacterium
is the period of transition between the last years
of the reproductive stage and postreproductive
life, which begins with the gradual disappearance of
ovarian function.8
Menopause is the cessation of menstrual periods
due to the loss of ovarian function and is a normal
physiologic process in women when it occurs after
the fifth decade of life. The mean age at menopause
is 51 years, and the clinical criterion used to estab-
lish the diagnosis is complete absence of menstrual
periods for 12 months.6
Throughout a woman’s life, the total num-
ber of primordial ovarian follicles decreases and
most become refractory to the actions of pituitary
gonadotropins. As a result, the circulating level of
estradiol progressively decreases and progesterone
production by the corpus luteum becomes irregular
and subsequently ceases.8 Increased production of
follicle-stimulating hormone and luteinizing hor-
mone occurs as a consequence. Conversely, the
changes in circulating androgens are more complex
and controversial.9 It has been documented that
testosterone production is lower in postmenopausal
patients and that sex hormone–binding globulin
decreases and the free androgen index increases.
Dehydroepiandrosterone sulfate linearly declines as
a function of age, but it lacks an obvious relationship
with ovarian function.10
The Importance of Hormones on the Skin
Ovarian failure and the resulting hormonal changes
during menopause affect almost all aspects of wom-
en’s health and may present with signs and symptoms
in nearly every body system.5 Symptoms are experi-
enced differently according to ethnic, educational,
and sociocultural variability. Asian American women
report a low frequency of physical, psychological,
and psychosomatic symptoms compared with black
women.11 Brazilian women have a higher prevalence
of vasomotor symptoms compared to women in other
developed Western countries.12 Also, medications
used during perimenopause to prevent and treat
osteoporosis are capable of inducing hot flashes.13
Estrogens are essential for skin hydration because
they increase production of glycosaminoglycans,
promote an increased production of sebum, increase
water retention, improve barrier function of the
stratum corneum, and optimize the surface area of
corneocytes. As a result, concerns about dry skin are
more frequent among menopausal women who are
not taking hormone replacement therapy (HRT).2
Decreased estrogen reduces the polymerization of
glycosaminoglycans, while elastin experiences gran-
ular degeneration and fragmentation, forming cystic
spaces. In addition, there is a reduction in the micro-
vasculature and thinning of the epidermis.14,15
Albright et al16 noted that the skin of menopausal
women with osteoporosis showed considerable atro-
phy, a finding subsequently supported by a study from
Brincat et al.17 In menopausal women, the decrease
in estrogen promotes a reduction in type I and
type III collagen and a reduction in the type III
collagen to type I collagen ratio compared with
nonmenopausal women.18 Healthy skin is made up
of type I collagen (80%, responsible for strength) to
type III collagen (15%, responsible for elasticity).2
However, a decrease in androgens is partially respon-
sible for the reduction in sebum secretion, xerosis,
and skin thinning or atrophy, accompanied by a
reduction in blood vessels, oxygenation, and nutri-
tion of the skin, as well as increased transepidermal
water loss.19,20 Regarding skin annexes, the decrease
in estrogen causes a reduction in axillary and pubic
hair. The reduction in elastic fibers results in a loss
of firmness and elasticity. Moreover, with a relative
predominance of androgenic hormones, vellus hair
may be replaced by thicker hair.21
Anagen hairs have estrogen receptors in both
sexes. In contrast to the α-receptor, the β-receptor
largely is expressed in the papillary dermis and the
hair’s bulb region; this expression could account for
the occurrence of androgenetic alopecia in meno-
pausal women. These receptors are not expressed in
telogen hairs, and their role in regulating the hair
cycle is unknown.20 The aging of the follicular unit,
resulting from the reduction of active melanocytes,
promotes the appearance of gray hair. It is estimated
that in 50% of men and women, half of their hair
will be gray by 50 years of age.21 The age of onset
for graying hair appears to be influenced by heredity
and ethnicity. Unlike the skin, hair aging is more
affected by intrinsic than extrinsic factors.22,23
In women, hormonal changes during menopause
are the main source of alterations in hair character-
istics.24 The identification of high concentrations of
hydrogen peroxide and low levels of catalase in the
stems of gray hairs have shed light on the biochem-
istry of hair whitening and opened new possibilities
for its prevention and treatment. A change in the
balance of oxidation/reduction reactions may lead to
DNA damage and melanocyte apoptosis.22,25
Osteoporosis and Vitamin D
Concerns about the worsening of or induction of
osteoporosis after menopause due to the excessive
use of sunscreens and vitamin D (VD) deficiency are
controversial. Middle-aged women with low serum
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25-hydroxyvitamin D levels (<20 ng/mL) have an
increased risk of fracture during menopausal tran-
sition.26 A study that measured the UV index in
São Paulo, Brazil, demonstrated that environmental
levels ensure sufficient production of VD from unin-
tentional sun exposure throughout the course of the
year.27 Thus, concerns about the use of sunscreen
affecting VD levels are not justified.27,28
In a study that specifically focused on postmeno-
pausal women in Recife, Brazil (which is located
10º south of the equator), a considerable prevalence
of VD deficiency was found, ranging from 30% to
83% depending on age. Despite the abundance of
sunlight, the researchers emphasized that the VD
prevalence rates found in the study were similar to
those observed in nontropical countries, such as the
United States and Canada; however, the period of
intentional exposure to the sun was not assessed.29
Moreover, the lack of consensus on the appropriate
levels of sun exposure makes it difficult to compare
different countries, and thus it is recommended that
minimum normal limits be regionally established.29,30
Although it has been suggested that the use of
sun protection factor 15 could, in theory, promote a
99% reduction in the synthesis of VD, other studies
have failed to identify such an insufficiency.31,32 In
practice, the disparity may be explained by the large
variation in the amount of sunscreen applied, by the
body areas to which it is applied, and by the fact
that duration of sun exposure usually is greater when
using sunscreen.31
Considering all the evidence and taking into
account that the safe limit for sun exposure that
allows maximum synthesis of VD without an
increased risk for skin cancer remains unknown,
the American Academy of Dermatology states that
intentional exposure to the sun should not be con-
sidered a main source of sun exposure and the use
of sunscreen should not be discouraged. Instead,
the Academy recommends using dietary sources of
VD or artificial VD supplementation at doses that
vary by age: between 1 and 70 years, a dose of
600 IU daily is recommended; older than 70 years,
800 IU daily.33
Primary Skin Disorders of Menopause
Pruritus—Pruritus is the primary skin concern in
women older than 65 years. Given that xerosis is
the most prominent cause of pruritus, consider the
possible role of menopause-related transepidermal
water loss.19,34 Regardless of the underlying cause,
however, some general measures are recommended
for managing pruritus in menopausal women such
as using low-pH moisturizers daily, preferably after
bathing; keeping nails short; wearing loose and
light clothing; maintaining a comfortable ambient
temperature; using humidifiers or air-conditioning
devices; restricting bathing time; and avoiding hot
water and high-pH sanitizers.34
Hyperhidrosis—Night sweats, hyperhidrosis,
and hot flashes (flushing) are common con-
cerns in 35% to 50% of perimenopausal women
and in 30% to 80% of postmenopausal women.
Menopausal hyperhidrosis is classified as secondary
hyperhidrosis, the symptoms of which may be allevi-
ated by HRT, suggesting that the cause is decreasing
levels of estrogen.35
In addition to HRT, other treatments such as gab-
apentin, serotonin-norepinephrine reuptake inhibi-
tors, and acupuncture are used to treat menopausal
hyperhidrosis. One study evaluated the use of oxybu-
tynin for 3 months in 21 patients with menopausal
hyperhidrosis, and the authors concluded that the
drug was effective and well tolerated in women who
were nonresponsive to HRT.36
Senile Alopecia—Starting at 50 years of age, scalp
hairs show varying degrees of change in pigmenta-
tion, growth, and diameter. Despite the normal ratio
of telogen to anagen hair, there may be a consider-
able reduction in follicular density. The clinical dis-
tinction between senile alopecia and androgenetic
alopecia can be challenging, and the conditions
may coexist.24
Androgenetic Alopecia—Up to 50% of women
experience androgenetic alopecia, or female pat-
tern hair loss (FPHL), during their lives.24 It is the
main cause of hair loss in women, and women in
perimenopause are the most affected. Hair regrowth
is difficult when treatment is not instituted early in
perimenopausal FPHL.24 The pathogenesis involves
a progressive reduction in the hair cycle, result-
ing in shrinkage of the hair follicles.37 Unlike
the pathogenesis of androgenetic alopecia in men,
little is known about the role of androgens in
FPHL.37 The measurement of androgen levels is not
recommended in the absence of symptoms of viriliza-
tion or in the absence of abnormal clinical patterns
or progression.24
Three clinical forms of FPHL have been described:
(1) Ludwig classification (diffuse central thinning
concentrated in the parieto-occipital region with
the frontal hairline intact), (2) Olsen classifica-
tion (thinning of the central line and a consequent
Christmas tree pattern), and (3) Hamilton classifi-
cation (frontotemporal or vertex recession, which
is seen less often than the other 2 forms). Female
pattern hair loss primarily is treated with a 2% to
5% minoxidil solution,38 which is able to interrupt
hair loss or induce mild to moderate regrowth in
60% of patients with FPHL.37 The effectiveness of
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the treatment should only be assessed after 1 year of
use.37 Contact dermatitis is the main adverse effect,
but its incidence may be reduced by up to 82% by
using vehicles that do not contain propylene glycol.39
If the use of minoxidil solution is not possible, good
results also have been reported with antiandrogen
medications, such as spironolactone.40 These drugs
are especially useful in cases of hyperandrogenism.37
Conventional doses of finasteride 1 mg daily, as
used in men, have shown discrepant results in meno-
pausal women.41-45 Improvement of FPHL has been
shown in studies using doses of 2.5 mg or higher for
a minimum of 12 months.42-45 The use of dutasteride,
an inhibitor of 5α-reductases I and II, promotes
greater inhibition (100%) of dihydrotestosterone
activity than finasteride (70%) in men; however, it
has not yet been approved by the US Food and Drug
Administration for treatment in women.46
Impaired Wound Healing—Wound healing also
is affected by aging. Delays in healing may be more
closely related to the decrease in estrogen levels
than to intrinsic aging. A comparison between
the expression of genes associated with healing in
young and elderly men showed that most of the
genes are regulated exclusively by estrogen, which
could explain the higher incidence of chronic ulcers
in elderly men compared to women.47 However,
menopausal women also are at risk for development
of chronic ulcers.48 Ashcroft et al49 showed that the
use of topical estrogen accelerates the healing of
acute incisional wounds by increasing transforming
growth factor β.
Healing of the oral mucosa is associated with a
higher rate of complications and longer recovery
time in women than in men. Estrogens produce
anti-inflammatory effects, whereas progesterone
demonstrates a proinflammatory effect. Testosterone
has anti-inflammatory effects and is able to modify
the proinflammatory state in the oral mucosae of
menopausal women. Wound healing in menopausal
women who are not receiving HRT tends to be
slower than in those who are receiving HRT. Age is
not necessarily an important factor in wound heal-
ing. Premenopausal and younger women have shown
no notable differences in healing. Nevertheless, after
menopause, differences in wound healing have been
found, indicating that hormonal status may be more
crucial to wound healing than age.50
Common Dermatoses With No
Hormonal Associations
Brittle Nail Syndrome—Brittle nail syndrome (BNS)
affects 20% of the population with a female-to-male
ratio of 2:1.The pathogenesis of BNS involves fac-
tors that affect the adhesion of corneocytes to the
nail plate and alter nail formation from its matrix;
the former process produces onychoschizia, whereas
the latter leads to onychorrhexis.51
The normal nail contains approximately
18% water, and nails with less than 16% water
content are more likely to develop weakness.52 Nail
water content appears to be negatively influenced
by repetitive occupational exposure to water, and
its increase is proportional to the frequency of
moisturizer use. The use of certain nail polishes
and cuticle removers is considered one of the
main reasons for nail weakness in those who have
frequent manicures.53
Management of BNS requires the correction
of the precipitating cause by hydration of the nail
blade, cuticle, and proximal nail folds, preferably
under occlusion. Supplementation with biotin is
considered highly effective by many researchers.54,55
In a retrospective study, the use of biotin for
6 months improved BNS in 63% (22/35) of patients.56
Recommended doses generally are more than
2.5 mg daily.57 The use of 10% urea in nail pol-
ish once or twice daily showed that both regimens
improved the morphology, consistency, and reflec-
tiveness of the nail plate.52
The use of nail polish containing hydroxypropyl
chitosan, Equisetum arvense extract, and methylsul-
fonylmethane has been reported as a treatment of
dystrophic and fragile fingernails. The treatment
was evaluated in patients with nail psoriasis and it
was shown to be effective in decreasing dystrophy.58
Although women are affected twice as frequently
as men,51 there are no known studies comparing the
prevalence of BNS in premenopausal versus meno-
pausal women, despite the fact that the ratio of
women to men affected has been shown to increase
with age.51,52 In our clinical practice, BNS pre-
dominates among menopausal women. We believe
that low estrogen levels may lead to dehydration of
thenailplate.
Frontal Fibrosing Alopecia—Frontal fibrosing alo-
pecia has a tendency to affect menopausal women.59
Frontal fibrosing alopecia is a slow, progressive,
lymphocytic cicatricial alopecia that produces sym-
metrical frontal or temporal recession but rarely
affects other areas of the scalp. It often is associated
with nonscarring alopecia of body hair or eyebrows.
The cicatricial area is atrophic, pale, and sur-
rounded by hyperpigmented skin due to long-term
sun damage.60,61
Many investigators believe it is a variant of
lichen planopilaris.62,63 Others suggest the possibil-
ity that hormonal changes characteristic of peri-
menopause contribute to triggering the disease.
Some cases show a partial response to finasteride or
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dutasteride.64 Furthermore, the lymphocytic inflam-
matory component of the disorder has been treated
with immunomodulators, topical and intralesional
corticosteroids, and hydroxychloroquine.60,63
Telogen Effluvium—Telogen effluvium (TE) is the
premature transformation of hair from the anagen
phase to the telogen phase. Considered a symptom
of an underlying condition (eg, endocrine, nutri-
tional, and autoimmune disorders) rather than a full
diagnosis in itself,65 TE is characterized by diffuse
hair loss confirmed by a pull test in which more than
5 hairs are removed from the scalp on tugging a sec-
tion of 25 to 50 hairs.66 If there is concurrent TE in
women with androgenetic alopecia, more severe hair
loss has been reported.24,66 There may be concerns of
dysesthesia of the scalp (trichodynia), especially in
patients with emotional stress.66
Most often diagnosed in women, TE in its acute
form is even more common in menopausal women
and lasts less than 6 months.24 The acute form of
TE is secondary to hemorrhage, high fever, surgery,
drug use, systemic diseases, diet, or great psycho-
logical stress and typically occurs 1 to 3 months
after the primary event.24,66 The most common
cause of iron deficiency at menopausal transition is
malabsorption or chronic gastrointestinal bleeding.
Ferritin levels below 40 µg/L are associated with
hair loss with a 98% specificity and sensitivity.24 Low
serum levels of vitamin B12 or VD also are considered
important factors.24,65,66
Chronic TE (ie, lasting more than 6 months)
predominantly occurs in women aged 40 to 60 years,
and its onset is abrupt. Chronic TE is considered a
diagnosis of exclusion.24 In 30% of cases of chronic
diffuse hair loss lasting longer than 6 months, the
cause is unknown.67 The pathogenesis is poorly
understood, though it is assumed to result from a
reduced duration of the anagen growth phase in the
absence of shrinking hair follicles.37,68
Patient education is the most important aspect
of TE management. The aim of treatment is to
reduce hair loss and correct the precipitating fac-
tors. Even if the underlying cause is corrected, hair
loss may continue for up to 6 months with the
desired cosmetic regrowth occurring after only 12 to
18 months.37,65 In acute secondary TE, the course
of the disease is self-limited, and correction of the
causal factor is sufficient. In chronic diffuse loss,
identification of causal factors is more difficult and
treatment involves adequate nutrition (ie, at least
1200 calories daily including 9.8 mg/kg body weight
of protein) and multivitamin supplementation, min-
oxidil, and even antiandrogen medications.37,65-67
Trichotillomania—Trichotillomania is the com-
pulsive behavior of plucking strands of hair and is
considered to be a poor adaptive response to stress.
Although trichotillomania most commonly occurs
in children, adolescents, and young adults, in older
adults it is more often associated with psychopathol-
ogy and is markedly more common in women.69 The
condition usually is refractory to treatment, and
although the scalp usually is the primary focus of
the behavior, eventually patients may pluck body
hair. Menopausal women also may present with
trichoteiromania in which hair loss is secondary to
repeated friction that has fractured the hair shaft; this
condition often is associated with scalp dysesthesia.24
Trichotillomania is considered an obsessive-compulsive
disorder, whereas trichoteiromania needs further inves-
tigation because it can occur secondary to many
psychiatric disorders. The specific psychotherapeutic
and pharmacologic treatments likely will depend on
the underlying cause of the disease.70
Treatment of Skin Disorders in
Menopausal Women
Classic HRT—Several studies have used histologic
analysis or ultrasonography to show that estrogens
used in HRT thicken the skin or increase collagen
content, whether given orally, topically, or transder-
mally.71-75 In a randomized, double-blind study com-
paring topical estrogen versus glycolic acid, 6 months
of estrogen use on only one side of the face promoted
a 23% increase in epidermal thickness (P=.00458),
and the use of glycolic acid stimulated a 27% increase
(P=.00467). The combined use of estrogen and
glycolic acid prompted a 38% increase in epidermal
thickness (P=.000181), with significant differences
observed for all groups compared with the controls
for the reversal of histologic markers of skin aging.76
Finally, collagen synthesis also is increased as
inferred by the increase in procollagen type I and II
terminal peptides.75 Hormone replacement therapy
also affects the skin’s ability to retain water and
leads to a reduction in skin wrinkling; however, the
effects of HRT on dyschromic alterations have not
been well studied.77 The numerous adverse effects of
HRT, such as an increased incidence of cancer and
cardiovascular morbidity, limit its use.
Isoflavones—Estrogen use is capable of causing
morphologic changes in the aged skin of meno-
pausal women.19,77 Given that HRT is contrain-
dicated for some women and can cause adverse
effects or pose unacceptable risks for others,
Accorsi-Neto et al15 studied the possibility of achiev-
ing the beneficial effects of estrogen with plant hor-
mones. Oral isoflavones given to rats that had been
irradiated with UV light inhibited the increased
expression of UV-induced metalloproteinases, reduc-
ing collagen degradation.78
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Among the phytoestrogens, genistein, an iso-
flavone, is notable for its selectivity, with a high
affinity for estrogen receptor β and low affinity for
estrogen receptor α, which is found in the uterus and
breasts. Accorsi-Neto et al15 assessed whether soy
isoflavones also would reduce skin aging in women,
as observed in the aforementioned rat study. After
6 months of using 100 mg of concentrated soy
extract daily, the investigators noted increased
thickness of the dermis and epidermis, increased
dermal vasculature, an increased number of
collagen and elastic fibers, and an increased papil-
lary index. In rats, genistein increases antioxidant
enzymes, such as superoxide dismutase, catalase,
and glutathione.78,79 Topical phytoestrogens also
were evaluated, with promising results for increased
skin thickness. In animals, the use of isoflavones
also offers protection against carcinogenesis in
sun-damaged skin.15
Some investigators believe that a better under-
standing of the mechanism of action and possible
side effects of phytoestrogens is essential to allow
their use as a promising antiaging alternative.80
There is no evidence that estrogens (eg, HRT)
possess antioxidant or photoprotective properties.78
Moreover, it is possible that new selective estro-
gen receptor modulators will specifically affect the
skin without the expected systemic effects of exist-
ing estrogens.80
Conclusion
Although often overlooked, skin disorders are quite
common during menopause. Understanding the
physiology of this important period in a woman’s
life is essential for developing an early and effective
preventive therapeutic approach. Use of sunscreens
has been questioned due to a concern about osteo-
porosis, but studies have not shown a connection
between sunscreen use and reduced VD levels.
Intentional sun exposure should not be considered a
source of VD; instead, recommend dietary or artifi-
cial supplementation. Although studies have shown
HRT to positively affect wound healing, reduce
signs of aging, increase hydration, and yield other
benefits, its use is not recommended for treating skin
disorders. Isoflavones could be promising alterna-
tives to estrogen; however, further studies are needed
before their use can be recommended.
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