LITERATURE REVIEW

HORMONAL THERAPY IN SKIN AGING

Endang Tri Wahyuni, Khairuddin Djawad, Asnawi Madjid
Departement of Dermatovenereology Medical Faculty of Hasanuddin University / Wahidin
Sudirohusodo Hospital Makassar

ABSTRACT
Skin aging is a natural process and can affect in everyone. There are
several factors influenced of skin aging, there are genetic,
environmental and hormonal factors. The use of hormonal therapy in
some studies said to be useful to prevent some conditions that may
occur in postmenopausal women as urogenital atrophy, vasomotor
symptoms and osteoporosis but the hormonal effects on the skin itself
has not been report a lot of. In this article it explained about the
hormones which affect the decreased of skin aging.

keywords : normal therapy, skin aging.

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Hormonal Therapy in Skin Aging

Hormonal therapy on menopausal women,

showed the effects of changes in the basic
components of the skin as well as the
complex structure of the skin which can
slow the aging process. 2
In this paper will discuss some of the
hormones that play an important role in
the aging process, namely estrogen,
progesterone, growth hormone, Dehydroepiandrosterone (DHEA), melatonin, and
thyroid.

INTRODUCTION
Aging is a natural process that can
not be avoided by all living things, where
there is damage to both anatomically and
physiologically in all organs, from the
blood vessels and other organs until skin.1
The skin is the largest organ in the human
body, which will significantly affect the
process of aging and menopause, which
can affect the appearance someone.2
Aging of the skin that occurs is
influenced by several factors: genetic,
environmental, and hormonal factors. This
is a normal process in which the skin will
become thinner, atrophic, dry, skin
becomes brittle, and wrinkle.3
Aging of the skin consists of two
kinds of mechanisms that chronological
aging (intrinsic aging), is a universal
process, this process can not be avoided
and result in a complete of skin changes
with increasing age. Clinically visible skin
looks pale and smooth wrinkles. The
second phenomenon is extrinsic aging
(photoaging), is a process which is closely
related to long-term sun exposure. This is
not a comprehensive picture of aging more
evident areas face, ears, neck, back and
sides, arms and back of hands. Extrinsic
aging characteristics appear as coarse
wrinkles, loss elatisitas, and telangiektasis.4
One theory of aging is the decline in
several important hormones. Hormones
are special chemicals that circulate in
body fluids after it is created by a group of
cell / cell-specific groups. Hormones
regulate and coordinate the functions of
the cell / tissue of body.5
There are several hormones that
affect the skin aging process. In line with a
decline in the aging process of various
hormones. The use of hormonal therapy in
some studies said to be useful to prevent
some conditions that may occur in
postmenopausal women as urogenital
atrophy, vasomotor symptoms and osteoporosis but the hormonal effects on the
skin itself has not been report a lot of.6

Skin changes due to aging process

Changes due to aging processes
that occur on the skin can be divided into
changes in anatomical, physiological, and
chemical. Several anatomical changes can
be seen directly, such as loss of elasticity
and flexibility of the skin causing wrinkles
and wrinkles, reduced number of headhair, hyperpigmentation and skin tumors,
especially age 40 or older due to
prolonged exposure to sunlight, thickening
of the skin, the epidermis dry and cracked
, and changes in nail shape and hair.1
In histological and physiological aging of
the skin that is found: 1
- Skin becomes dry due to decreased
function of the skin oil glands
(sebaceous glands)
- Reduced water levels and drying of
skin collagen and elastin fibers due to
declining sex hormones.
- Decreased basal metabolic rate and
slowing the process of keratinization,
resulting in regeneration of epidermal
cells to slow.
The quality of the skin decreases
with age which is a synergistic effect of
chronological aging, photoaging, hormonal
deficiencies and environmental factors.6
(Table 1) Skin aging results from reduced
some
metabolic
activity.
Dermis
morphologic change, physical, and
chemical during aging. In total some
function of the skin will decrease with the
increase age.7

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Tabel 1. Seven types skin aging 6

Aging type
Chronologic
Genetic
Fotoaging

Factor
As time goes by
Inherited disease
UV radiation and infra
red
Food,alcohol,tobacco
and drugs
Chronic disease (eg.
Cancer)
Dysfunction
or
a
decrease
in
the
hormone system
gravitation

Behaviour
Catabolic
Endocrin

Gravitation

Mechanic
protection

Anatomic
correlation

Speculative clinical
consequences

Epidermal
Turn over

Basal
keratinocyte
(proliferative)
lessen
Reduced
vasculariza
tion

Poor wound healing

Barrier
function /
clearance of
the chemical

Sensoric
perception
Production of
vitamin D

Sensoris
nerve lessen
-

Immuno
surveillance

Decreased of
langerhans
and T cell

Inflamation
response

Decreased
perivascular
mast cell
Decreased of
flexus
superficial
area
Less Sweat
gland

Termoregulat
ion

Increase risk of
hypotermi

The skin is easily

torn
Tendency due to
pressure necrosis of
bony areas.

The role of hormones in skin aging

Some of the important functions of
the skin looks depends on the hormone.
Sex hormones clearly have an important
role in the aging process as evidenced by
the decline in skin appearance gradually
begin during perimenopause. This change
has not been fully investigated, although
histologically have shown the existence of
estrogen and progesterone receptors in
the skin. 2

Table 2. Skin changes due to age and

clinical effect 8
Functional

Decreased of
vascularisatio
n
Decreased of
subcutaneous
lipid
Flat
Dermoepider
mal junction
Decreased of
subcutaneus
lipid

Increased risk of
Establishments /
ACD
Changes in response
to topical
medications
Increased risk of
trauma to press,
heat, chemical
Increased risk of
osteomalacia and
bone fracture
Decreased of
incidence and
intensity of delayed
hypersensitivity
recation , increased
risk of skin
cancer,increased of
risk herpes zoster
and other skin
infection

Synthesis of sex hormones and decline

during aging
Sex hormones are synthesized in
the adrenal glands and gonads. During
puberty, the gonads secrete testosterone
women and men. The prostate is a male
secondary sex organs can convert testosterone into a form that is more potent
dihydrotestosterone (DHT). Women during
the reproductive period, to produce
testosterone produced by the ovaries and
converted into estradiol that is physiologically active and contains a lot of
estrogen. Other forms of physiological
estrogen is estrone and estriol. Estrone is
the predominant estrogen after menopause, while estriol is synthesized by the
placenta during pregnancy. In the adrenal
gland estrogen and androgen precursor is
dehydroepiandrosterone (DHEA) which is
a derivative kolesterol.9
DHEA levels in men and women
will decline with age, at the age of 70 to 80
years of its concentration is only about 1020% of that found in the young age.9

Influenced allergic
process,iritant,and
skin infection,
Elongated period of
healing and
resolution of the
infection is slow
Increase risk of heat
stroke

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Menopause is the cessation of menstruation which occurs a reduction in

ovarian follicles, followed by a decrease in
the level serum estradiol. Men also have a
relationship between the decrease in
testosterone secretion with age is called
andropause, where a decline in androgen
levels associated with various symptoms,
such as sexual dysfunction, hypogonadism, and psychologic changes.9

stable molecule, synthesized from procollagen with the help of specific enzymes
and degraded by collagenase. By using
animal estrogen administration showed
degradation of collagen barriers. There are
complex relationships between regulatory
factors, receptors, and enzymes in
regulating the balance of collagen,
although the mechanism of estrogen on
collagen integrity itself is not known.11
Collagen is influenced by sex hormone
status and decline after menopause.
Women who did not receive hormone
therapy, the composition of the skin
collagen decreased during menopause.6
Enzymes associated with the
process of post translational collagen
decreased during aging. Amount of
hydroxyproline and hydroxylysine glycolsilated on type I collagen decreased
during aging.12 There is a reduction in the
number of fibroblasts that synthesize
collagen and blood vessels that supply the
skin this leads to wrinkle.12There is the
relationship between skin collagen loss
and menopause and estrogen deficiency.
Some 30% of skin collagen (type I and III)
are missing in the first five years after
menopause. Decrease in total collagen
decreased approximately 2.1% per
year.12,15
Women who are at the post
menopausal complaints usually have dry
skin, easy bruising, and skin wrinkles.
Aging of the skin especially on the face
can cause psychological stress in women.
Several studies showed thinning of the
skin and dermis collagen content and
density decrease with time after menopause as a result of hipoestogen.13
Decrease in skin connective tissue
resulting in sagging skin, loss of tonicity it
is accompanied by increased skin lines
and wrinkles. The relationship between the
hormone with increased content of
collagen and elastic tissue, suggesting
that the hormone can also reduce
wrinkle.14

Estrogen and androgen receptors in

the skin
The skin is a target organ for various
hormones,
including
estrogen
and
estrogen receptors.
The highest estrogen receptors are
found in women than in men.3 Steroid
hormones such as estradiol and testosterone, biological activity through
binding to nuclear receptors that begins
with transcription and translation. Several
studies have shown that ER- is the major
estrogen receptor in human skin and are
most widely in the epidermis, blood
vessels, dermal fibroblasts, and the outer
portion of the hair root follicle.9 ER-
receptors and androgen (which can bind to
testosterone or DHT) only in cells in the
hair follicle dermal papilla. These three
receptors are also found in the sebaceous
glands. ER- is also present in most of the
sweat glands ekrin androgen and
progesterone receptors which are found
much less. Thus it seems clear that sex
hormones are involved in proliferation,
differentiation, function of the skin and
adnexal structures such as lipid.9
Effects of estrogen on collagen
Skin is comprised mostly of collagen.
Human skin consists of 14 types of
collagen, of which 80% were found skin
collagen is collagen type I, while 15%
were type III. Type I collagen is responsible for skin firmness, while type III
collagen play a role in elatisitas. Type I
collagen in the reticular dermis and type III
collagen in the papillary dermis.3, 10 The
relatively collagen in the dermis form a

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Skin thickness increases until it

reaches a peak at age 35-49 years and
then began to thin out in accordance with
age. Skin thickness decreased by 1.13%
for each year after menopause. Thirty
percent of collagen disappeared in the first
five years after menopause.14 Reduction of
collagen, glycosaminoglycan and content
of the water can cause skin thinning effect.
The epidermis showed thinning and
disappearance of the rete ridge. Several
studies have shown estrogen causes an
increase in skin thickness. 14

essential for skin health. There is a rich

network of capillaries in the papillary
dermis will, in charge of the flush
menopause.12, 18 Flushing is a typical
symptom of menopause. This is caused by
vasodilatation deep papilla dermis and
subcutaneous, mainly found on the face,
neck, chest, palms and feet. Present in
75% of women during perimenopause.
The prevalence during early menopause
can occur due to loss of peripheral
vascular deficiency associated with
estrogen.19

Effects of estrogen on skin moisture

Effects of estrogen on the secretion of

sebaceous glands
Activity of sebaceous glands in the
skin regulated by circulating hormone
levels. Estrogen decreases the amount
and size of sebaceous glands, sebum
production as well, which works the
opposite of stimulating androgen secretion
of gland.14
Effects of estrogen on wound healing

Healthy skin contains a substance of

water, which is determined by evaporation
and skin hydration. Transepidermal water
flux decreases with increasing age. In the
dermis there is a small amount of
glycosaminoglycans, which is related to
skin collagen. Glycoaminoglycans has a
high ability to bind water and hydration is
essential for normal skin.
Glycosaminoglycans decreased with
age. Collagen and glycosaminoglycans
interact to produce changes in collagen
associated with age. This allows the
hydration of the dermis is affected by
glycosaminoglycans.12, 15
Dry skin is a condition most often
occurs in older women. An epidemiological
survey on 3875 postmenopausal women
aged over 40 years found that 36.2% were
dry. Use of estrogen in decreasing
significance in the skin of elderly people.
This positive effect may be related to
estrogen, which stimulates an increase in
mucopolysaccharide and hyaluronic acid
in the skin, where it is associated with
increasing water composition in the
dermis. This increase may also increase
the thickness kulit.12, 16.17

With age the skin becomes more

fragile and susceptible to trauma, leading
to more frequent lacerations and bruises.
Elderly woman who looks less good
wound healing, probably because the level
of transforming growth factor (TGF)- is
low .14
Healing of skin wounds including
vascularization, granulation, collagen deposition, and reepitelisasi. Effects of
estrogen on wound healing process is still
not clear.14 Study in humans, found that
estrogen can increase the secretion of
TGF- by fibroblast dermis, and this can
improve the quality of wound healing.20
Progesterone
Progesterone is the dominant hormone during pregnancy. This hormone is
made in the ovary, these hormones also
made by the placenta during pregnancy.
Small portion of progesterone is made by
adrenal gland and testis of men.
Progesterone is made from the saponification of steroids. Function of this

Effects of estrogen on blood flow

Dermis and epidermis are nutrited by
the arteries and capillaries that are above
the subcutaneous layer. Structural integrity
and function of capillary blood vessels

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hormone is to regulate the menstrual

cycle, preparing the uterus to accept the
fetus if pregnancy occurs. Production in
normal women begins 14 days before
menstruation. Its function is to prevent premenstrual syndrome, discomfort, breast
pain, and headaches by balancing the
hormone estrogen. 5

In the blood circulation by binding

of GH binding protein (BP), which consists
of two kinds, namely the high-affinity BP of
GH (85-90%) and low affinity BP.
Suspected liver is the main organ that
produces HGH-BP. GH is not a direct
stimulator of growth but indirectly through
a factor called serum somatomedin or
insulin-like growth factor (IGF). There are
two known types of the somatomedin
somatomedin A and somatomedin C.
Somatomedin C or IGF-1 is a major
growth stimulator produced mainly by the
liver, and a small part by muscle, bone,
cartilage, kidney and skin. Levels of GH
and IGF-1 also influenced by gonadal
hormones are exogenous and endogenous. Estradiol levels and high
testostron at the age of puberty also
increases GH secretion. GH deficient
patients were divided into two groups:
patients with low levels of GH/IGF-1 because the hypothalamic-pituitary disease
and healthy patients with low levels of
GH/IGF-1 due aging process.22
HGH levels in humans after the age
of 21 to 31 years declined by about 14%
perdekade, thus the average total
production of HGH for 24 hours reduced
by half at the age of 60 years. Everyday
we produce about 500 micrograms at age
20 years, 200 micrograms at age 40 years
and 45 micrograms at age 80 years old.21

Effects of progesterone against skin

aging
Progesterone
may
significantly
improve the symptoms of menopause.
Progesterone deficiency will make the skin
of the face, hands and feet dry. Facial
muscles tense as people seem depressed.
In postmenopausal women who received
ERT (Estrogen Replacement Therapy) is
usually necessary to add progesterone to
reduce the likelihood of uterine cancer.15
Growth Hormone Secretion of Human
Growth Hormone (HGH)
Human Growth Hormone (HGH)
released by the pituitary gland located in
the center of the brain. Pituitary cell
(called somatotrop) that make up the
HGH, which is also known as somatotropin.21
GH secretion is mainly regulated
by the hypothalamus that produce GH
releasing hormone (GHRH) that functions
to stimulate secretion and function of
somatostatin inhibits secretion. GH is
secreted in the circulation in pulsatif with
average levels are low in the blood and
has a half-life of 20-30 minutes. GH
secretion is also increased after exercise.
Secretion decreased in a state of obesity,
depression, and hyperglycemia. Women of
reproductive age are known to secrete GH
is higher than men of similar age. The
stimulation by GHRH depends on calcium
and is mediated by cyclic adenosine
monophospate (cAMP). GH response to
GHRH decreased at the age above 40
years, so a decline in GH secretion by
14% and decreased half-life of 6% per
dekade.22

Effects of Human Growth Hormone

(HGH) to skin aging
Human growth hormone is the most
important hormone to combat aging. GH is
considered as the leader of other
hormones. GH can tighten the skin,
thicken hair, prevent and reduce wrinkles
on the skin. This hormone deficiency in
adults will lead to thinning hair, brittle,
eyelids down, lips shrink, face to fall down,
the gums shrink. Face will wrinkled, dry
skin, dehydration, muscular shoulders and
buttocks .5
Some evidence suggests that growth
hormone may directly or indirectly regulate
the growth of skin and skin structure.

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levels less than 7 nM / L referred to as

hypogonadism and approximately 5% of
men over the age of 60 years experience
anything like this that can give effect
include decreased libido, mass, and
muscle strength, bone mass, and etc. 28,29
DHEA is a steroid hormone in the
body the most. DHEA levels decline with
age, parallel with the decrease in GH
(Growth Hormone). DHEA is an important
ingredient in the formation of the
hormones testosterone, estrogen, progesterone, and cortisone / cortisol. This
hormone is made by adrenal gland (kidney
son). Deficiency of this hormone will cause
dry skin and weak.5

Several studies have shown that the

growth hormone receptor (GHR) mRNA
and protein expression was present in the
fetal period in human development.
Growth hormone receptor (GHR) were
seen on staining pieces of fetal skin in the
epidermis, sebaceous glands, sweat
glands, blood vessels, and dermis
fibroblast consider that the role of growth
hormone in regulating the function of
keratinocytes and fibroblast.24
The study of the provision of HGH in
older people has been conducted by
Daniel Rudman, in a study conducted for 6
months an increase in skin thickness as
much as 7.1%. More research is also
carried out giving HGH for six months
showed improved skin texture, skin
thickness, and elasticity skin.25
HGH can also increase the synthesis
of proteins that are under the skin. Studies
in experimental animals showed an
increase in strength and composition of
skin collagen. Collagen and elastin are
located below the epidermis foundation.
HGH restore skin turgor the skin is
characteristic of the young people.21 In
animal studies of GH administration
increases collagen, elastin and improve
turgor skin.22
A recent study states that the
reduction in the expression of connective
tissue growth factor (CTGF), with a
reduction in transforming growth factor
(TGF)- is responsible for the loss of
dermal collagen in progresif.26

Effects of DHEA
(Dehydroepiandrosterone) on skin
aging
Researchers have identified several
mechanisms of the skin of the role of
DHEA, a hormone is to protect the skin
against the aging process, and maintain
skin health. A study showed that DHEA is
applied topically effectiveness is 85-90%
higher than orally, because the hormone
can be absorbed directly and give effect to
the skin. 30 In addition, DHEA is declared
to have antioxidant capacity against the
free radicals. Protection against free
radicals is associated with the ability of
DHEA to prevent skin cancer in mice. 5
Melatonin
Melatonin is a hormone synthesized
by the pituitary gland. Pituitary gland is
located behind the center of the third
ventricle of the brain. Gland consists of
two types of cells, namely pinealosit and
neuroglia. Tues pinealosit is the dominant
cell that produces indolamin (mostly
melatonin) and peptides. 31
The hormone melatonin from
serotonin is formed with the help of some
enzim.31 Synthesis and release of
melatonin is stimulated by darkness and
inhibited by light. Bright environments but
does not cause affecting the circadian
rhythm. Light has two effects on melatonin

DHEA (Dehydroepiandrosterone)
The aging process associated with
significant changes in body composition in
both men and women, characterized by
increased body fat, decreased muscle
mass and strength. 27 Changes in body
composition was followed by decreased
secretion of adrenal androgen DHEA. With
decreasing levels of DHEA mean conversion to testosterone also declined.
Since the age of 30 years testosterone
levels continued to decline slowly with an
average of 1-2% per year. Testosterone

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Hormonal Therapy in Skin Aging

prostaglandins and leukotrienes resulting

in the formation of erythema suppresed.34
Since 1993 melatonin is known as
the potent destruction of free radicals that
poten.34 The action does not seem as
radical destruction mediated by receptors.
To get the required concentration of the
antioxidant effects of melatonin are higher
than the peak concentrations at night. This
suggests that the antioxidant effects of
melatonin occur only at concentrations
farmakologic of melatonin.31 Melatonin
destroy a wide range of reactive oxygen
species (ROS) and reactive nitrogen.
Melatonin as an antioxidant thought to
initiate action when there is stimulation of
SOD, glutathione peroxidase, glutathione
reductase, G6PDH, and inhibition of nitric
oxide sintase.35 Melatonin present in the
cell membrane lipid bilayer and can be
worked locally as a free radical destruction.33 At the end of melatonin can
stabilize the cell membrane making it more
resistant to oxidative attack. The cells
protected from oxidative damage.35

secretion and synthesis, the first is a bright

light on the cycle - the dark will affect the
secretion, the second is light with a certain
intensity and duration will suppress
melatonin synthesis. In normal people with
a certain dose of light exposure inhibits the
secretion of melatonin. 31
Melatonin is a lipophilic hormone
that can cross the blood brain.31 hormone
secretion is increased after dark with peak
levels at 2-4 o'clock in the morning, then
decreased melatonin secretion slowly.31 In
infants aged <3 months of very little.
Meanwhile, at the age of 1-3 years to
increase and become sikardian achieve
the highest levels (median 326 pg / ml),
after which it decreases with old levels 31
Daily melatonin in young adults the
average and peak levels of melatonin at
night in a row is 10 and 60 pg / ml. 31
Melatonin works on melatonin
receptors in the suprachiasmatic nuclei
(SCN) of the hypothalamus, to affect the
rhythm of work sikardian.32 information
transmitted light from the retina through
the SCN to pituitary gland and central
nervous system. Photos will be releasing
norepinephrine receptors in the onset of
darkness, thus activating the system, and
a number of alpha 1 adrenergic receptor
and beta 1 in the gland increases.
Increased activity of NAT enzymes initiate
synthesis and release of this enzyme
activity melatonin.31 rhythm that regulates
the daily rhythms of melatonin, the low
levels throughout the day and rose sharply
in the evening day.32

Thyroid
Thyroid is made by the thyroid gland
which is located at the front of the neck,
below the Adam's apple (Adam's apple).
This hormone is released thyroxine T4
(90%) and triodothyronine T3 (10%). The
pituitary gland regulates the production of
thyroid involved by issuing TSH (thyroid
stimulating hormone). Most of thyroxine
would be converted into T3 in the liver, this
form is active in the metabolism of body.5
Thyroid
function
speeds
up
metabolism and weight control, shrink the
face and body, improve blood circulation,
thereby increasing the energy supply,
oxygen, water and other hormones
throughout the body. Thyroid hormones
provide energy to every cell and form heat
to the body by stimulating the mitochondria are a source of energy every
cell.5

Melatonin effects on skin aging

Melatonin is known to have activity
antioksidan.33 Bangha et al demonstrated
the effect of melatonin suppression by
topically to the ultra violet -induced erythema.34 Melatonin is shown to inhibit the
formation of ultraviolet-induced erythema.
The possibility that melatonin prevents
damage from ultraviolet to affect the
metabolism of arachidonic acid, resulting
in decreased local concentrations of

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given premenopause.13 Small dose given

as possible. For preparations containing
conjugated estrogen dose is 0.3 to 1.25
mg or 0.01-0.02 mg per day for ethinyl
estradiol. Cyclic therapy should be done
for 21-25 days each month under
supervision. The addition of progesterone
include medroksi progestrin acetate 10 mg
/ day on days 10-14 endomatrium can
reduce the risk of carcinoma. Estradiol
tablets given 1-2 mg/day.36
Estrogen side effects that often arise
are nausea and vomiting. Frequency of
nausea allegedly aligned with the potential
estrogenic, so some preparations cause
less nausea than the other. With oral
estrogen therapy should not be administered in patients with thrombo-embolism,
thrombophlebitis, severe hypertension,
liver dysfunction, chronic hemolytic anemia, hyperlipidemia, breast or genital
cancer, varicose veins, migraine, and
earned heart.36

Effects of thyroid hormones in aging

skin
Thyroid hormones play a role in
controlling metabolic activity in all tissues,
so regulate metabolism throughout the
body. Although thyroid hormone levels
usually decrease with age, but doctors
often assume that hypothyroidism is
common in the elderly. Thyroid deficiency
is usually caused autoimun.5
Thyroid hormone deficiency (hypothyroidism) can cause swelling of the body
and face, the face becomes pale, thick
lips, thin hair, rare and fragile, the skin
becomes dry, cold hands, and constipation. 5
Hormone replacement therapy
HRT (hormone replacement therapy)
is an important component in the
treatment of anti aging.5 Hormone replacement therapy helps the body return
to hormonal composition when young, the
record does not cross the line so that
normal physiological levels can reverse or
delay the aging process. By regulating
hormones in the physiological levels would
not occur side effects of unwanted or
harmful to body .5
There are several hormones that are
often used in hormone replacement
therapy. The number and dosage according to the presence of the more recent
discoveries. For each hormone necessary
to know the various types of preparations
are available, how to use and dose.13

Oral Estrogen - progesterone

combination
Estrogen together with progesterone
administered sequentially or continuously.
Sequential estrogen alone is given on the
first day until day 28. Combined estrogenprogesterone preparations include Diane
(containing 2 mg cyproterone acetate +
0.035 mg ethinylestradiol) and Yasmin
(drospirenone 3 mg contains 0.03 mg
ethinylestradiol +) .36
Topical Estrogen
One study showed topical estrogen
to maintain the thickness of the skin and
increase collagen and glycosaminoglycan
content of the skin such as that produced
by hormonal therapy oral.9,36 Some of the
topical estrogen available include: 37

Oral estrogen
There are two types of estrogen that
is available is synthetic and natural.
Synthetic estrogens have a potent estrogen activity but are structurally differs by
estrogen produced by the ovaries. Some
of them are ethinylestradiol, mestranol and
stilbestrol. Among natural estrogens
including estradiol, estrone, and estriol will
increase estrogen levels in the plasma
which is identical to the estrogen produced
by the ovaries at the dose of estrogen

A. Estradiol gel (Oestrogel)

Applied to the abdomen and upper
thigh area and left a few minutes to dry
before using the clothes. This preparation

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Hormonal Therapy in Skin Aging

levels are also maintained a more

constant compared to oral administration where there are fluctuating
levels of estradiol and the ratio of
estradiol / estrone daily. Side effects
that may result is systemic side
effects such as those caused by oral
estrogen that breast pain, headaches,
fluid retention, weight gain, nausea.
The most common side effect is skin
irritation, redness, itching, and skin
discoloration patches affixed in place.
Research on topical estrogen has
been
reported
to
result
in
improvement and skin elasticity and
firmness. The depth of wrinkles and
skin pore size also decreased as
much as 62-100%. Estrogen given in
the form of topical 0.01% estradiol
and estriol 0.3% cream, administered
at a dose of 1 g was applied every
day for 6 months on the face and neck
using the applicator. 38

is reported to be effective in treating

vasomotor symptoms and vaginal atrophy
that occurs in postmenopausal women.2.
1.

Estrogen in a cream (Estrace,

Ogen)
Use is applied to the vagina. Has
proven efficacy in the treatment of
vaginal atrophy. The absorbtion vary
depending on the type, dose estrogen
and vehikulum used.3.

2.

Vaginal ring
Vaginal ring is placed on the upper
third of the vagina and the position will
be maintained by the pressure of the
vaginal wall. Systemic absorption
through the vaginal epithelium depends on the surface area of the
vaginal ring. Estradiol levels may
persist and be maintained until approximately three months.4

3.

Estradiol vaginal tablets (Vagifen,

Premarin, Ovestin, Orthogynest)
Inserted into the vagina and has been
proven effective in treating vaginal
atrophy. Twice weekly doses reported
to be effective and not cause systemic
effects and effects on the endometrium.5.

4.

5.

Progesterone
Topical progesterone dose (intradermal) is 20 mg / day. Several studies
using up to 200 mg a day. Progesterone
levels are safe when the body does not
exceed the physiological levels at a young
age. Side effects of progesterone include
increased LDL cholesterol, and lowers
HDL cholesterol, making facial swelling,
breast tenderness, depression, and mood
disorders. 5

Estradiol implants
Implanted subcutaneously in the
abdomen or buttocks. Implant raises
circulating estradiol levels relatively
stable for 4-12 months.6.

HGH (Human Growth Hormone)

Transdermal
estrogen
patches
(TTS)
TTS consists of a reservoir patch
(Estraderm TTS 50) and matrix patch
(Climara) with daily doses of 50-100
mg of 17b-estradiol. Matrix patch
placed on the chest or abdomen once
a week while the Estraderm patch
affixed to two times a week. The
advantage of using this patch is not
pass the first-pass metabolism and in
the liver and in circulating estradiol

Human Growth Hormone (HGH) as

an anti-aging benefit to enhance the
vitality and energy, increased muscle
mass, skin thickening, improve sleep
quality, bone growth and maintain and
improve the quality of life.21
Human Growh Hormone (HGH) has
been made in the laboratory through
genetic engineering method that produces
a protein that is identical to the HGH that
is created naturally in the body. There are
some names of HGH depends on the plant

59

IJDV

Vol.1 No.1 2012

that produces it, such as Protropin and

Nutropin (Genentech), Humatrope (Eli
Lily),
Gentropin
(Pharmacia-Upjohn),
Norditropin (Novo Nordisk) and Serostim
(Serano Laboratories) .21
Injection using a small needle used
to inject as insulin and subcutaneous
injections performed (under the skin). The
recommended dose is between 2 and 8 IU
per week (1 mg = 3IU). Some anti-aging
specialist endocrine dividing the daily dose
to twice daily, a dose in the morning and
one dose at night, to better resemble the
human growth hormone released by the
body.21
GH therapy should be started with a
low dose is 3-4 mg / kg / day. Human
maintenance dose required age> 35 years
typically <1 mg / day. Dose may be
increased as needed to a maximum of
1.75 mg / day for patients aged <35 years
and 0.875 mg / day for age> 35 years.
Lovino et al provide intravenous GHRH
injection interval of the day for 12 days
and get the conclusion that the increased
GH response in elderly men that GH levels
similar to adult males, with elevated levels
of IGF-1. The same response obtained in
GHRH administration in women aged
menopause.22
Side effects of HGH are commonly
reported joint pain, stiffness and swelling
of the extremities. This occurs because
HGH effects on water retention and can be
treated by lowering dose.21

Supplement capsule / tablet usually

contains 5, 10, 25 or 50 mg DHEA, DHEA
dosage forms are also found in cream
other references .5 explain DHEA dose
used ranged from 25-150 mg, but should
start with low doses of approximately 2550 mg /day.39
Melatonin
Synthetic melatonin preparations are
available in the form of gelatine capsules
with a dosage of 1 mg and 5 mg. The use
of low doses resulted in serum melatonin
concentrations 10-100 times higher than
peak levels daily, within one hour after
drinking.
While the use of very low doses (from 0.1
to 0.3 mg) resulted in peak concentrations
within the normal range. Have never
reported any serious side effects or risks
associated with the use of oral melatonin
preparations.31
Thyroid
The state of hypothyroidism should
be given therapy. Dose of thyroid hormone
administration in each patient is different
because it must be tailored to each
condition. Thyroid can react with other
drugs, and should be very cautious in
patients with heart disease. Supplements
Fe (iron) for the blood booster can also
disturb the absorption of the thyroid, so the
administration should be separated 2
hours. Soy milk and some foods also
disturb the absorption of the thyroid in
baby.5

DHEA
Arlt et al state that DHEA replacement therapy may be administered in
women with adrenal insufficiency. The
resulting state of adrenal insufficiency
DHEA deficiency conditions. Giving with
DHEA at a dose of 50 mg / day for 4
months, it can increase serum concentrations of DHEA in the normal range
accompanied by an increase in sexuality.30
Some people use DHEA is an
alternative to HGH because cheap.39 The
exactly doses of DHEA not determinate
yet.5 Daily doses used between 5-25 mg.

Conclusion
Aging skin is a synergistic effect of
chronological aging, photoaging, environmental factors, and hormonal deficiencies.
Several hormones that affect the skin
decreased with age, namely estrogen,
progesterone, growth hormone, DHEA,
melatonin and thyroid. Several studies
have shown that administration of these
hormones can improve the structure

60

Endang Tri Wahyuni

Hormonal Therapy in Skin Aging

14. Brincat MP, baron YM, Galea R. Estrogen

and the skin. Climacteric 2005; 8: 110-23.
15. Castelo-Branco C. Skin kolagen changes
related to age, menopause and hormone
replacement therapy. Maturitas 1992; 15:
113-19.
16. Waller JM, Maibach HI. Age and skin
structure and function a quantitative
approach (II): protein, glycosaminoglycan,
water, and lipid content and structure.
Skin Res technol 2006; 12: 145-54.
17. Roberts WE. Dermatologic problems of
older women. Dermatol clin 2006; 24:
271-80.
18. Haenggi W, Linder HR, Birkhauser MH,
Schneider H. Microscopic findings of the
nail-fold capillaries dependence on
menopausal
status
and
hormone
replacement therapy. Maturitas 1995; 22:
37-46.
19. Ginsburg J, Hardiman P, OReilly B.
Peripheral blood flow in menopausel
women who have not flushes and in those
who do not. BMJ 1989; 298(6686): 148890.
20. Ashcroft GS, Dodsworth J, Van Boxtel E,
et al. Estrogen accelates cutaneous
wound healing associated with an
increase in TGF-beta 1 levels. Nat med
1997; 3: 1209-15.
21. Klatz RM. HGH The master hormone of
youth. In Newest HGH Research Ten
weeks to a younger you. Chicago: Sports
tech Lab, Inc. 1999; 31-79.
22. Nasution EJ, Pusponegoro Erdina HD.
Terapi Human Growth Hormone Untuk
Proses Penuaan. MDVI 2004; 31/4: 199207.
23. Klaus AA, Chien AJ, Olerud JE. Diabetes
and other endocrine disease, Growth
Hormone. In Wolf K, Goldsmith LA, Katz
SI, Gilchrest BA, Paller AS, Leffell DJ,
Fitzpatrick
dermatology
in general
th
medicine. 7 ed. Vol 1 &2. Mc Graw Hill
New York, 2008: 1482.
24. Wanke R, et al. Overgrowth of Skin In
Growth Hormone Transgenic Mice
Depend in The Presence of Male Gonads.
J Invest Dermatol 1999; 113: 967-971.
25. D Rudman, et al. Effects of Human
Growth Hormone in Men Over 60 year
old. N Engl J med 1990; 323(1): 1-6.
26. Oliver N, Sternlicht M, Gerritsen K, and
Goldschmeding R. Could aging human
skin use a connective tissue growth factor

of skin aging with age. For this reason the

use of hormone therapy, either oral,
topical or injection may be useful to
prevent skin changes that occur due to the
aging process.

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