Effect of hormone replacement therapy on intervertebral disc height.

OBJECTIVE: Intervertebral discs act as shock absorbers, thereby helping to reduce the risk of vertebral body fractures. Previous studies have shown that estrogen loss following menopause is associated with disc height reduction whereas treatment with hormone replacement therapy (HRT) helps to maintain disc height. This study reports the effect of HRT on disc height from a post hoc analysis of a prospective randomized clinical trial of the effect of HRT on bone density. METHODS: A total of 355 healthy postmenopausal women aged (mean ± standard deviation) 55.4 ± 4.8 years were randomized to HRT with oral 1 mg or 2 mg estradiol plus dydrogesterone or placebo. Dual-energy X-ray absorptiometry measurements (Lunar DPX) were obtained at baseline and following 2 years of treatment. Intervertebral disc height was measured in discs between T12 and L3 using the bone densitometer ruler. RESULTS: Compared with baseline, treatment with HRT resulted in a significant increase in total disc height with 1 mg estradiol (0.16 ± 0.65 cm, p = 0.015) and with 2 mg estradiol (0.21 ± 0.86 cm, p = 0.006) whilst there was no significant increase with placebo (0.13 ± 0.65 cm, p = 0.096). Between-group differences were not statistically significant. CONCLUSIONS: These results are consistent with previous findings of a beneficial effect of estrogen on discs. This may be in part responsible for the anti-fracture efficacy of HRT on vertebral fractures.

The urogenital system and the menopause.

The major cause of urogenital atrophy in menopausal women is estrogen loss. The symptoms are usually progressive in nature and deteriorate with time from the menopausal transition. The most prevalent urogenital symptoms are vaginal dryness, vaginal irritation and itching. The genitourinary syndrome of menopause includes vulvovaginal atrophy and the postmenopausal modifications of the lower urinary tract. Dyspareunia and vaginal bleeding from fragile atrophic skin are common problems. Other urogenital complaints include frequency, nocturia, urgency, stress urinary incontinence and urinary tract infections. Atrophic changes of the vulva, vagina and lower urinary tract can have a large impact on the quality of life of the menopausal woman. However, hormonal and non-hormonal treatments can provide patients with the solution to regain the previous level of function. Therefore, clinicians should sensitively question and examine menopausal women, in order to correctly identify the pattern of changes in urogenital atrophy and manage them appropriately.

Chemoprevention of breast cancer among women at elevated risk as defined by Gail Score.

The risk of an individual woman to develop breast cancer over a 5-year period can be estimated using the Gail Model. The risk factors included in this model effectively classify patients into two different subgroups. One subgroup comprises patients at increased risk because of increased exposure to estrogen. These women are more likely to benefit from endocrine chemopreventive therapies, namely selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). The second subgroup comprises women who have inherited genetic mutations that predispose them to breast cancer. Chemoprevention in these patients is more likely to be achieved by novel agents, such as lapatinib, gefitinib, fenretinide, rexinoids and poly(ADP-ribose) polymerase (PARP)-inhibitors.

Estrogens and the intervertebral disc.

Intervertebral discs are an integral part of the vertebral column. It has been shown that menopause has a negative effect on bone and on intervertebral discs. Estrogen has a beneficial effect of preserving the health of collagen-containing tissues, including the intervertebral disc. The intervertebral disc allows for mobility of the spine, and maintains a uniform stress distribution of the area of the vertebral endplates. Also, the disc influences spinal height. The disc tissue is adapted for this biomechanical function. The function of the spine is impaired if there is a loss of disc tissue. Narrowing of the disc space due to degeneration of intervertebral discs is associated with a significantly increased risk of vertebral fractures. Estrogen should be seen as the first-choice therapy for bones and other collagen-rich tissues, such as intervertebral discs, because it maintains homeostasis of the bone-remodelling unit. Unlike bisphosphonates, estrogen is unique in its ability to regenerate bone collagen after its disintegration, apart from suppressing osteoclastic activity. Besides, there is insufficient data on deterioration in bone qualities and micro-cracks in patients on long-term bisphosphonates.

Intervertebral disc height correlates with vertebral body T-scores in premenopausal and postmenopausal women.

OBJECTIVE: To assess the correlation between vertebral body T-score and intervertebral disc height in premenopausal and postmenopausal women. METHODS: A total of 203 women were recruited from a large bone densitometer directory. The disc heights measured were those between the 12th thoracic and third lumbar vertebra. The discs were assigned the symbols D, whereby D1 applies for the disc between the 12th thoracic and first lumbar vertebra. The disc height of the group of women (n=38) with osteoporotic vertebral fractures was compared with the disc heights of hormone-treated women (n=47), untreated postmenopausal women (n=77) and another group of premenopausal women (n=41). Bone density measurements were taken by a Norland Bone Densitometer (DEXA 586). RESULTS: The lowest disc heights were found in the fracture group. The total disc height in the fracture group was 1.42+/-0.25 cm, significantly lower (P<0.0001) than the untreated group (1.82+/-0.3 cm), which in turn was significantly (P<0.0001) lower than the hormone-treated group (2.2+/-0.26 cm) and the premenopausal group (2.11+/-0.21 cm). The lowest T-scores were also noted in the vertebral fracture group (T-score=-3.1+/-0.3) (P<0.0001). The highest T-score recorded for the premenopausal group was -0.38+/-45, higher than that of the untreated menopausal -1.4+/-0.32 and hormone treated women -0.65+/-0.3, all three significantly higher than the fracture group (P<0.0001). The lowest T-scores were also noted in the vertebral fracture group (T-score=-3.1+/-0.3) (P<0.0001). The highest T-score recorded for the premenopausal group was -0.38+/-45, higher than that of the untreated menopausal -1.4+/-0.32 and hormone treated women -0.65+/-0.3, all three significantly higher than the fracture group (P<0.0001). Bone density across all groups revealed a correlation with disc height (R=0.29) (P<0.05). The group with vertebral osteoporotic fractures was the only group to show a negative correlation (-0.21) between disc height and vertebral bone density. Conversely, a significant correlation (R=0.47) (P<0.001) between the T-score and the total lumbar intervertebral disc height was noted in the premenopausal group of women. The menopausal group of untreated women also showed a significant correlation between the T-score and disc height (R=0.25 P<0.05); however, an insignificant positive correlation was found in the hormone-treated group. CONCLUSION: The fracture group was noted to have the lowest intervertebral disc height and lowest T-scores compared with the other three groups. The hormone-treated and the premenopausal women had the highest disc heights and T-scores recorded. Positive correlations between T-score and disc height were noted for all the groups except for the fracture group. These results suggest a coupling between the vertebral body and intervertebral disc, which if disrupted may lead to increased risk for fracture. The combination of both T-score and disc height may improve the screening sensitivity for vertebral body fracture risk.

Urogenital atrophy.

The major cause of urogenital atrophy in menopausal women is estrogen loss. The symptoms are usually progressive in nature and deteriorate with time from the menopausal transition. The most prevalent urogenital symptoms are vaginal dryness, vaginal irritation and itching. The classical changes in an atrophic vulva include loss of labial and vulvar fullness, with narrowing of the introitus and inflamed mucosal surfaces. Dyspareunia and vaginal bleeding from fragile atrophic skin are common problems. Other urogenital complaints include frequency, nocturia, urgency, incontinence and urinary tract infections. Atrophic changes of the vulva, vagina and lower urinary tract can have a large impact on the quality of life of the menopausal woman. However, hormonal and non-hormonal treatments can provide patients with the solution to regain previous level of function. Therefore, clinicians should sensitively question and examine menopausal women, in order to correctly identify the pattern of changes in urogenital atrophy and manage them appropriately.

The skin, carotid and intervertebral disc: making the connection!

A fairly consistent finding in work on the menopause and hormone replacement therapy is the positive effect of estrogen on connective tissue and its turnover. The menopause has been shown repeatedly to have a negative effect on the connective tissue in the dermis of the skin. Such an effect is prevented and in some cases reversed with estrogen therapy. This is similar to what happens in bone matrix. Similarly, the media in the carotid has been shown to undergo the same change with the menopause and with estrogen therapy as the dermis. The carotid artery media is increased in menopausal women on estrogen therapy and is thinner in untreated women. Recently, new information has revealed that the menopause, i.e. estrogen deprivation, has similar effects on the connective tissue of intervertebral discs. In aged intervertebral discs, the predominant collagen is type III, not type I, which is the predominant collagen in skin and bone, although skin has additional type III. These negative changes are once again prevented or reversed with estrogen therapy. This effect probably also extends to the extracellular non-collagenous matrix in all these systems, i.e. skin, carotid and intervertebral discs. The common thread is that estrogen has profound effects on connective tissue turnover, no matter the site. This has far-reaching implications not only in maintaining the structure and aesthetic appearance of tissue, but also the strength and stiffness of various tissues and the functioning of neighboring and surrounding organs.

Low intervertebral disc height in postmenopausal women with osteoporotic vertebral fractures compared to hormone-treated and untreated postmenopausal women and premenopausal women without fractures.

OBJECTIVE: To assess the intervertebral disc height in postmenopausal women with osteoporotic vertebral fractures. METHODS: A total of 203 women were recruited from a bone densitometer directory. The disc heights measured were those between the 12th thoracic and 3rd lumbar vertebrae. The discs were assigned the symbols D, whereby D(1) refers to the disc between the 12th thoracic and 1st lumbar vertebrae. The disc height of the group of women (n = 38) with osteoporotic vertebral fractures was compared to the disc heights of hormone-treated women (n = 47), untreated postmenopausal women (n = 77) and another group of premenopausal women (n = 41). RESULTS: The total disc height (D(1) - D(3)) (mean +/- standard deviation) in the fracture group was 1.58 +/- 0.1 cm, significantly lower (p < 0.0001) than in the untreated group (1.82 +/- 0.06 cm), which in turn was significantly (p < 0.0001) lower than in the hormone-treated group (2.15 +/- 0.08 cm) and in the premenopausal group (2.01 +/- 0.09 cm). CONCLUSION: The fracture group was noted to have the lowest intervertebral disc height compared to the other three groups. The hormone-treated and the premenopausal women had the highest disc heights recorded. These results may be due to the effect that the menopause and senescence have on the discal connective tissue components. This may lead to loss of the shock-absorbing properties of the intervertebral disc and an altered discoid shape, influencing the occurrence of osteoporotic vertebral body fractures.

Skin ageing.

Cutaneous ageing manifests itself as a progressive reduction in maximum function and reserve capacity of skin tissue. It is not a unique and uniform biological event. Skin comprises three layers: epidermis, dermis and subcutaneous tissue. Collagen atrophy is a major factor in skin ageing. There is a strong correlation between skin collagen loss and estrogen deficiency due to the menopause. Skin ageing, especially in the face, is associated with a progressive increase in extensibility and a reduction in elasticity. With increasing age, the skin also becomes more fragile and susceptible to trauma, leading to more lacerations and bruising. Furthermore, wound healing is impaired in older women. Estrogen use after the menopause increases collagen content, dermal thickness and elasticity, and it decreases the likelihood of senile dry skin. Large-scale clinical trials are necessary to help make informed recommendations regarding postmenopausal estrogen use and its role in the prevention of skin ageing.

Estrogens and the skin.

OBJECTIVE: A review of the medical literature concerning the effect of the menopause and its hormonal treatment on the skin. METHODS: An extensive Medline and Pubmed internet search utilizing the key words: collagen, elastin, estrogen, hormone replacement therapy, skin and aging. RESULTS: The literature review demonstrated a wide array of research ranging from basic science work to clinical implications of the effects of the menopause and its treatment on the skin. CONCLUSION: Estrogen loss at menopause has a profound influence on skin. Estrogen treatment in postmenopausal women has been repeatedly shown to increase collagen content, dermal thickness and elasticity, and data on the effect of estrogen on skin water content are also promising. Further, physiologic studies on estrogen and wound healing suggest that hormone replacement therapy (HRT) may play a beneficial role in cutaneous injury repair. Results on the effect of HRT on other physiologic characteristics of skin, such as elastin content, sebaceous secretions, wrinkling and blood flow, are discordant. Given the responsiveness of skin to estrogen, the effects of HRT on aging skin require further examination, and careful molecular studies will likely clarify estrogen's effects at the cellular level.

Immunomodulatory activity of cucurbitacin E isolated from Ecballium elaterium.

The immunomodulatory effect of cucurbitacin E, extracted from Ecballium elaterium, was tested on peripheral human lymphocytes. These lymphocytes were co-cultured with cancer cells and an interesting lymphocyte-mediated cytotoxicity was observed.

Hormone replacement therapy and the skin.

Estrogens have a profound influence on skin. The hypoestrogenism occurring after the menopause leads to measured deterioration in the skin. Estrogen receptors have been identified in the skin and the concentration of these receptors varies in the different parts of the body. Estrogen improves skin in more than one way, the collagen content and quality is improved, skin thickness is increased, while vascularisation is enhanced. The extracellular matrix responsible for the tone and appearance of the skin is also improved. It is not just the skin that shows an improvement with estrogen therapy but also skin appendages, such as hair. Estrogens have been shown to increase the hair follicle life cycle. Skin aging is not totally estrogen dependent because the ravages of age and the external environment play very important roles. The effects of estrogen on skin need further elucidation and with the emergence of newer techniques it is now possible to study more clearly the changes occurring at the cellular level. Estrogen replacement reverses the deleterious effect of estrogen deprivation on the skin, which is thus yet another organ that benefits from hormone replacement therapy.

Increased reduction in bone density and skin thickness in postmenopausal women taking long-term corticosteroid therapy: a suggested role for estrogen add-back therapy.

BACKGROUND: Long-term corticosteroid therapy is complicated by osteoporosis and generalized thinning of the skin. These two complications of such therapy were routinely assessed at the Menopause Clinic of St. Luke's Hospital Medical School, University of Malta. METHODS: A cross-sectional study was performed on 64 postmenopausal women who had been taking long-term corticosteroids. Each woman had her skin thickness measured using high-resolution ultrasound (22 MHz) and her bone density measured by dual-energy X-ray absorptiometry (DEXA). These measurements were compared with those of a control group (n = 557), a group of women who had sustained osteoporotic fractures (n = 180) and a group of women taking hormone replacement therapy (HRT) (n = 399). A longitudinal study of 29 postmenopausal women taking corticosteroids was also performed. This study compared results for women who, in addition to their corticosteroids, were taking HRT and for those who were taking corticosteroids alone. RESULTS: The cross-sectional study showed that corticosteroid therapy was associated with the lowest mean skin thickness measurement (0.83 mm). Similarly, low mean bone density measurements for the lumbar spine (0.805 g/cm2) and left hip (0.715 g/cm2) were obtained for this group. The mean skin thicknesses in the control group and the HRT group were 0.93 mm and 0.935 mm, respectively, while that in the osteoporotic fracture group was 0.88 mm. The bone density of the fracture group was similar to that of the group of women taking long-term corticosteroids, with the lumbar spine having a mean density of 0.805 g/cm2 and 0.81 g/cm2, and the left hip having a density of 0.705 g/cm2 and 0.715 g/cm2, respectively. Bone densities were similar for the control group and the HRT group, and higher than that of the corticosteroid or fracture group. The lumbar spine had a mean density of 0.925 g/cm2 in the control group and 0.93 g/cm2 in the hormonally treated group. Both the treated and control groups had similar bone densities of the left hip at about 0.82 g/cm2. The small longitudinal study compared postmenopausal women on long-term corticosteroid therapy taking HRT with another group who were not taking HRT. This 4-year study revealed mean total increases in skin thickness of 6.1% and bone density of 5.5% (left hip) and 14.6% (lumbar spine) in the HRT group, since the start of the study. Conversely, the control group registered reductions over 4 years in both skin thickness (2.8%) and bone density (lumbar spine 4.5% and hip 5.0%). CONCLUSION: In postmenopausal women taking long-term corticosteroids, skin thickness and bone density were both decreased, but the addition of HRT as add-back improved the situation dramatically. Skin thickness and bone density in women taking long-term corticosteroids were comparable to those in women who had sustained osteoporotic fractures. It is therefore suggested that HRT be used as add-back therapy in postmenopausal women taking long-term corticosteroid therapy.