Skin, the carotid artery and intervertebral discs: making the connection

1. Skin, the carotid artery and intervertebral discs: making the connection Mark P. Brincat

2. Connective tissue: different effects Genital organs(improved) Cerebral changes (Alzheimer’s decreased) Cartilage Decreased skin thickness (reversed) CVS effects (including carotids) Estrogentherapy Bone loss (stopped and reversed)

3. Extracellular matrix • Glycoaminoglycans (GAGs) • Proteins • Collagen • Elastin

4. Skin 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

5. Thigh collagen with the number of years since the menopause 250 200 Treated (59) Thigh collagen content (mg/mm2) 150 Untreated (148) 0 5 10 15 Years since menopause Brincat M, et al. Br J Obstet Gynaecol 1985;92:256–9

6. Skin thickness in women on100 mg estradiol implants 1.05 1.00 0.95 0.90 0.85 *** *** Skin thickness (mm) * 0 2 4 6 8 10 12 n = 40 Months of treatment * p < 0.05 ***p < 0.001 Brincat M, et al. Obstet Gynecol 1987;70:840–5

7. Scatterplot of tensile strength of skin in menopausal women HRT No HRT 90 80 70 60 50 40 30 20 10 0 Biological elasticity (%) 1 2 3 4 5 6 7 8 MD (mm) Pierard-Franchimont C, et al. 1999

8. Effects 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

9. The collagen family Collagen class Types Tissue distribution Fibril-forming I Most connective tissues II Cartilage and vitreous humor III Extensible connective tissues, skin V Lung XI Tissues containing collagen I Tissues containing collagen II Fibril-associated IX Tissues containing collagen II XII Tissues containing collagen I XIV Tissues containing collagen I XVI Many tissues Network-forming IV Basal laminae Anchoring filaments VII Attachments of basal laminae to underlying tissues Brincat MP. HRT and the Skin, 2001

10. Carotid 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

11. 34 33 32 31 30 29 28 27 26 25 24 Controls Oral HRT Implants n = 32 n = 51 n = 46 Effect of HRT on carotid artery wall in postmenopausal women (media) (mean ± SE) ** Carotid artery wall (media) thickness (mm) * Controls vs oral HRT p < 0.05 Controls vs implants p < 0.005 Oral HRT vs implants p = N.S. * ** Muscat Baron Y. Maturitas 1997;27:47–53

12. 1.30 1.25 1.20 1.15 1.10 1.05 1.00 0.95 0.90 0.85 Effect of HRT on carotid artery wall thickness in postmenopausal women(intima/media) (mean ± SE) Carotid artery wall thickness (intima/media) (mm) * * Controlsn = 51 Oral HRTn = 46 Implantsn = 32 Controls vs. oral HRT p < 0.05 Controls vs. implants p < 0.05 Oral HRT vs. implants p = NS * * Muscat Baron Y. Maturitas 1997;27:47–53

13. Normal intervertebral disc Collagen types II and IX– inner lamellae Collagen type II, IX, X Collagen type I outer lamellae Collagen types II and IV

14. Aged intervertebral disc Significant decreases in glycoaminoglycans and elastin Collagen types I, III, VI Early lesionscollagens II & IX Advanced lesions collagens III & VI

15. 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

16. Total intervertebral disc height in different groups of women D1 – D3 total length ** ** ** HRT/MENS vs MENO, CAL p < 0.05 Muscat Baron Y, Brincat MP, et al. Hum Reprod 2005;20:3566–70

17. Effect of HRT on disc thickness in postmenopausal women taking corticosteroids ** ** p < 0.01

18. Bone density, skin and disc thickness in postmenopausal women on HRT

19. Intervertebral disc space in normal women plotted as a function of age(n = 464) * * ** ** ** ** 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) *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. Intervertebral disc space in normal postmenopausal women (n = 312) plotted as a function of years since menopause * § † † *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

21. Intervertebral disc space in 3 groups of age- matched (47 years; n = 39 in each group) pre-, peri- and postmenopausal women * ** p < 0.001 by ANOVA p < 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

22. Scattergram of bone density index of femoral neck in menopausal women and skin biological elasticity 90 80 70 60 50 40 30 20 10 0 Biological elasticity (%) 0 0.2 0.4 0.6 0.8 1 Bone mass density index Pierard-Franchimont C, et al. 2001

23. Scattergram of Ward's triangle bone density vs. skin thickness 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Controls, n = 411 Fractures, n = 129 Ward's triangle density (g/cm2) 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 Skin thickness (mm) Sensitivity % Accuracy % Skin thickness 91.7 39.2 Ward’s triangle 100.0 50.9 Box Ward’s triangle 91.7 59.1 Brincat MP, Galea R, 2001

24. Conclusion • 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