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Skin, the carotid artery and Skin, the carotid artery and intervertebral discs: intervertebral discs:
making the connectionmaking the connection
Mark P. Brincat
Estrogentherapy
Decreased skin thickness
(reversed)
Cerebral changes (Alzheimer’s decreased)
CVS effects (including carotids)
Genital organs(improved)
Bone loss (stopped and
reversed)
Connective tissue: different Connective tissue: different effectseffects
Cartilage
Extracellular matrixExtracellular matrix
• Glycoaminoglycans (GAGs)
• Proteins– Collagen– Elastin
Skin collagen changes with ageSkin collagen changes with age
120
115
110
105
100
20 30 40 50 60
Age (years)
Castelo-Branco C, et al. Maturitas 1992;15:113–19
150
200
250
0 5 10 15
Treated (59)
Untreated (148)
Years since menopause
Brincat M, et al. Br J Obstet Gynaecol 1985;92:256–9
Th
igh
co
llag
en c
on
ten
t (m
g/m
m2)
Thigh collagen with the number Thigh collagen with the number of years since the menopauseof years since the menopause
0 2 4 6 8 10 12
Months of treatment
Ski
n t
hic
knes
s (m
m)
*
***
***
* p < 0.05***p < 0.001
n = 40
Brincat M, et al. Obstet Gynecol 1987;70:840–5
Skin thickness in women onSkin thickness in women on100 mg estradiol implants100 mg estradiol implants
1.05
1.00
0.95
0.90
0.85
HRTNo HRT
Pierard-Franchimont C, et al. 1999
Scatterplot of tensile strength of Scatterplot of tensile strength of skin in menopausal womenskin in menopausal women
MD (mm)
Bio
log
ical
ela
stic
ity
(%)
90
80
70
60
50
40
30
20
10
01 2 3 4 5 6 7 8
Effects of menopause on the skinEffects of menopause on the skin
• Hot flushes, altered hot/cold sensation
• Dizzy spells, falling, fractures
• Skin collagen changes– Tensile properties of the skin– Wound healing
• Atrophic changes– Dry vulva, dry eyes– Hair– Incontinence– Dyspareunia– Psychosexual role of the skin, effect on relationships– Transdermal role
Brincat MP. HRT and the Skin, 2001
The collagen familyThe collagen family
Collagen class Types Tissue distribution
Fibril-forming I Most connective tissuesII Cartilage and vitreous humorIII Extensible connective tissues, skinV LungXI Tissues containing collagen I
Tissues containing collagen II
Fibril-associated IX Tissues containing collagen IIXII Tissues containing collagen IXIV Tissues containing collagen IXVI Many tissues
Network-forming IV Basal laminae
Anchoring filaments VII Attachments of basal laminae to underlying tissues
Brincat MP. HRT and the Skin, 2001
Carotid artery wall thicknessCarotid artery wall thickness
• The vessel wall is made up of three main layers which are affected by estrogen replacement– The intima– The media– The adventitia
• The effects of estrogens are:– Intima thickness – Externa thickness – Media thickness
24
25
26
27
28
29
30
31
32
33
34
Controls vs oral HRT p < 0.05Controls vs implants p < 0.005Oral HRT vs implants p = N.S.
Car
oti
d a
rter
y w
all
(med
ia)
thic
kne
ss (
mm
)
**
*
***
Controls Oral HRT Implants
n = 51 n = 46 n = 32
Muscat Baron Y. Maturitas 1997;27:47–53
Effect of HRT on carotid artery Effect of HRT on carotid artery wall wall
in postmenopausal women in postmenopausal women (media) (mean ± SE)(media) (mean ± SE)
0.85
0.90
0.95
1.00
1.05
1.10
1.15
1.20
1.25
1.30
Controls vs. oral HRT p < 0.05Controls vs. implants p < 0.05Oral HRT vs. implants p = NS
Car
oti
d a
rter
y w
all
thic
knes
s (
inti
ma
/med
ia)
(mm
)
**
Controlsn = 51
Oral HRTn = 46
Implantsn = 32
**
Muscat Baron Y. Maturitas 1997;27:47–53
Effect of HRT on carotid artery wall Effect of HRT on carotid artery wall thickness in postmenopausal womenthickness in postmenopausal women
(intima/media) (mean ± SE)(intima/media) (mean ± SE)
Normal intervertebral discNormal intervertebral disc
Collagen types II and IX– inner lamellae
Collagen type I outer lamellae
Collagen type II, IX, X
Collagentypes II and IV
Aged intervertebral discAged intervertebral disc
Collagen types I, III, VI
Early lesionscollagens II & IX Advanced lesions
collagens III & VI
Significant decreases in glycoaminoglycans and
elastin
Functions of intervertebral discs Functions of intervertebral discs
• Intervertebral discs are responsible for 20% of the spinal column height
• Allow flexion and extension of the spine
• Also act as ‘shock absorbers’ of the spinal column
• This may have an impact on osteoporotic compression fracture
1
1.2
1.4
1.6
1.8
2
2.2
2.4
2.6
2.8
3
Calcium Biphos Menop Menstr HRT
(cm
)
****
** HRT/MENS vs MENO, CAL p < 0.05
D1 – D3 total length
Muscat Baron Y, Brincat MP, et al. Hum Reprod 2005;20:3566–70
Total intervertebral disc height in Total intervertebral disc height in different groups of women different groups of women
**
** p < 0.01
Effect of HRT on disc thickness in Effect of HRT on disc thickness in postmenopausal women taking postmenopausal women taking
corticosteroidscorticosteroids
0.4
0.45
0.5
0.55
0.6
0.65
0.7
0.75
0.8
1 2 3 4 5 6 7
Years since menopause
(cm
) HRT
Untreated
Bone density, skin and disc thickness Bone density, skin and disc thickness in postmenopausal women on HRTin postmenopausal women on HRT
0.4
0.5
0.6
0.7
0.8
0.9
1
1 2 3 4 5 6 7
Years
Disc thickness
Skin
Bone density
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
2.2
(cm
)Intervertebral disc space in normal Intervertebral disc space in normal women plotted as a function of agewomen plotted as a function of age
((n n = 464)= 464)
**
** ** ****
*p < 0.05 vs. younger age groups** p < 0.05 vs. younger age groups by Fisher test
Gambacciani M, et al. Climacteric 2007;10:298–305
20–25 26–30 31–35 36–40 40–45 46–50 51–55 56–60 61–65 65–70 71–75 >75
Age (years)
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years since menopause
(cm
)
*p < 0.05 vs. other groups† p < 0.05 vs. preceding groups§ p < 0.05 vs. preceding groups by Fisher test
Gambacciani M, et al. Climacteric 2007;10:298–305
Intervertebral disc space in normal Intervertebral disc space in normal postmenopausal women (postmenopausal women (n n = 312) plotted as = 312) plotted as
a function of years since menopausea function of years since menopause
† †
* §
1.84
1.65
1.38
0
0.5
1
1.5
2
2.5
(cm
)
Premenopause
Perimenopause
Postmenopause
***
Intervertebral disc space inIntervertebral disc space in 3 groups of age- 3 groups of age- matched (47 years; matched (47 years; n n = 39 in each group) pre-, = 39 in each group) pre-,
peri- and postmenopausal women peri- and postmenopausal women
p < 0.001 by ANOVAp < 0.002 vs. premenopausal group** p < 0.0001 vs. premenopausal and perimenopausal groups by Fisher test
Gambacciani M, et al. Climacteric 2007;10:298–305
Scattergram of bone density index of Scattergram of bone density index of femoral neck in menopausal women femoral neck in menopausal women
and skin biological elasticityand skin biological elasticity
Pierard-Franchimont C, et al. 2001
Bone mass density index
Bio
log
ical
ela
stic
ity
(%)
90
80
70
60
50
40
30
20
10
00 0.2 0.4 0.6 0.8 1
War
d's
tri
ang
le d
ensi
ty (
g/c
m2)
Skin thickness (mm)
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
00.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3
Fractures, n = 129
Controls, n = 411
Sensitivity % Accuracy %Skin thickness 91.7 39.2Ward’s triangle 100.0 50.9Box Ward’s triangle 91.7 59.1 Brincat MP, Galea R, 2001
Scattergram of Ward's triangle Scattergram of Ward's triangle bone density vs. skin thicknessbone density vs. skin thickness
ConclusionConclusion
• Menopause has been shown to directly or indirectly increase symptoms and signs of aging in the skin
• Hormone replacement therapy (HRT) has a positive effect on skin connective tissue parameters, both directly and indirectly
• This is in keeping with the general improvement demonstrated in several connective tissue sites such as blood vessels, bone and cartilage as a result of HRT in postmenopausal women