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Biomedical subjects

G M Prelevic

Publications and source records attributed to G M Prelevic.

At least 19 recordsLinked to original sources
PubMed2005

Increased circulating levels of matrix metalloproteinase-2 and -9 in women with the polycystic ovary syndrome.

INTRODUCTION: Matrix metalloproteinases (MMPs) have been implicated in various pathological processes including inflammatory response, cardiovascular disease, and recently also in ovarian dysfunction. Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age and is characterized by chronic anovulation, insulin resistance, and increased prevalence of cardiovascular risk factors. Circulating levels of MMPs and their tissue inhibitors (TIMPs) so far have not been assessed in the PCOS. MATERIALS AND METHODS: Serum levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured in 23 women with PCOS [age (mean +/- sd), 30.5 +/- 6.7 yr; body mass index, 35.8 +/- 7.5 kg/m2] and 22 healthy, regularly menstruating women (age, 29.4 +/- 5.6; body mass index, 31.7 +/- 9.2 kg/m2). RESULTS: Women with PCOS had significantly higher concentrations of MMP-2 (999.8 +/- 155 vs. 521.8 +/- 242 ng/ml; P < 0.001), MMP-9 (592.4 +/- 279 vs. 345 +/- 309; P = 0.007), and TIMP-1 levels (823.8 +/- 145 vs. 692 +/- 210 ng/ml; P = 0.02) than control healthy women. There was no difference in TIMP-2 levels (47.3 +/- 30 vs. 44.4 +/- 39.7 ng/ml; P = 0.21) between women with PCOS and controls. CONCLUSIONS: Obese women with PCOS have elevated serum concentrations of MMP-2 and -9. It might be hypothesized that elevated MMP concentrations may be related to increased cardiovascular risk in PCOS and/or menstrual irregularities associated with this syndrome.

Adult↗
PubMed2005

Hormone replacement therapy in postmenopausal women.

From the endocrine point of view, menopause is considered a deficiency state and menopausal hormone replacement therapy (HRT) regarded as restoring the premenopausal endocrine milieu. Millions of healthy postmenopausal women were taking HRT in late 1990's many in the absence of menopausal symptoms. The major benefit from HRT was considered to be cardiovascular protection and also protection against osteoporosis and Alzheimer's Disease. The Women's Health Initiative (WHI) trial and other studies published since 2002 fundamentally changed our understanding of risks and benefits associated with HRT. This review discusses the effects of HRT on menopausal symptoms, cognitive function, cardiovascular disease, osteoporosis and also breast and bowel cancer.

Alzheimer Disease↗
PubMed2004

Polycystic ovary syndrome, diabetes and cardiovascular disease: risks and risk factors.

Polycystic ovary syndrome is one of the most common endocrine disorders in the human, affecting approximately 10% of women of reproductive age. Although originally considered a gynaecological disorder, the syndrome is associated with a wide range of endocrine and metabolic abnormalities, including insulin resistance. Affected women are at an increased risk of developing gestational and non-insulin dependent diabetes and there is an association with cardiovascular risk factors including obesity, hypertension, dyslipidaemia, hyperhomocysteinaemia, increased intima media thickness and impaired vascular elasticity. The effect on cardiovascular mortality is currently unclear. However, in view of the proven links with diabetes and the cardiovascular risk markers, this condition should be considered within the province of physicians as well as gynaecologists.

Adult↗
PubMed2001

Effects of physical activity and menopausal hormone replacement therapy on postural stability in postmenopausal women--a cross-sectional study.

OBJECTIVES: Poor postural stability and muscular strength in postmenopausal women are associated with increased risk of falls and fractures. This study examined whether these risk factors for falls differed according to habitual physical activity and menopausal hormone replacement therapy (HRT) use. METHODS: Subjects were 117 postmenopausal women (mean age 65.3+/-6.0 years); of whom 70 had taken HRT for at least 5 years (42 tibolone and 28 transdermal oestradiol), whilst 47 had not received HRT. Duration of physical activity was assessed with monitors worn on a waist belt. Subjects were grouped into low (LPA; < or = 15 min day(-1)) or high (HPA; >15 min day(-1)) physical activity. Postural stability was assessed using a swaymeter which measured displacement at the waist. Maximal isometric strength of knee flexors was determined in 23 of the tibolone group, 26 of the oestrogen group and 12 of the no therapy group. RESULTS: Stature and body mass did not differ according to physical activity participation or HRT use, although the more active women were on average 2.5 years younger than the less active women. Body sway was lower in more physically active women in three of the four measurement conditions (P<0.05) and this effect persisted after inclusion of age as covariate. Body sway tended to be highest in the no therapy group, although not significantly so. Mean knee extensor strength was higher in women taking tibolone and oestrogen than in those not on therapy (115.3 (5.2), 118.2 (7.2) and 97.6 (9.3) Nm, respectively), although again this difference was not statistically significant. CONCLUSIONS: The more physically active postmenopausal women had significantly better postural stability than less active women, whilst HRT had no significant effect. Physical activity might thus have a role in reducing the risk of fracture through reducing the risk of falling.

Accidental Falls↗
PubMed2000

The influence of physical activity on the response of bone mineral density to 5 years tibolone.

OBJECTIVES: Menopausal hormone replacement therapy (HRT) maintains bone mineral density (BMD) and reduces risk of fracture in postmenopausal women. It has been suggested that sex steroids and loading may have synergistic effects on bone. We therefore investigated whether habitual physical activity influences the response of BMD to tibolone in postmenopausal women. METHODS: The subjects were 42 postmenopausal women aged mean (SE) 65.8+/-6.2 year who had taken tibolone for prevention/ treatment of osteoporosis over 5 years. Bone mineral density was measured annually by dual X-ray absorptiometry and physical activity was assessed using accelerometers after 5 years therapy. RESULTS: Twenty-six women were classified as having low physical activity (LPA; <15 min day(-1)) and sixteen as high physical activity (HPA; >15 min day(-1)). Spine BMD did not differ significantly between groups at baseline and increased significantly by 2 years of treatment with further increase to 5 years. The magnitude of increase did not differ between groups. Hip BMD at baseline was 7.3% higher in HPA women (P=0.07). Hip BMD increased over 2 years tibolone treatment in LPA women (+5.6%, P<0.01) whilst no significant change occurred in the HPA group (-0.5%). This difference in response between groups was statistically significant (P=0.002) and persisted after adjustment for age and body mass (P=0.002). Hip BMD was maintained in both groups over the subsequent 3 years of treatment. CONCLUSIONS: Spine BMD increased significantly in response to tibolone irrespective of physical activity participation. The more physically active women had higher hip BMD at baseline but the response to tibolone was greater in the less physically active women. The difference in response between groups may be due to physically active women having lower resorption at the hip and hence reduced response to anti-resorptive effects of HRT.

Absorptiometry, Photon↗
PubMed1999

Effect of estrogen replacement therapy on cardiac function in postmenopausal women with and without flushes.

Left ventricular heart function and its response to long-term estrogen replacement therapy was assessed in 30 postmenopausal women, 20 of whom had modest to severe hot flushes and 10 of whom had never had them. Continuous transdermal estradiol was given to women who had surgically induced menopause, and a combination of transdermal estradiol and sequential medroxyprogesterone acetate was given to those who had spontaneous menopause. Left ventricular systolic and diastolic function was evaluated by complete two-dimensional M-mode and pulsed Doppler echocardiography before and after 6 and 12 months of therapy. The parameters assessed were: systolic and diastolic blood pressure, heart rate, cardiac septal and posterior wall dimensions, left ventricular end-systolic and end-diastolic dimensions and volumes, ejection fraction (EF), ejection time, peak left ventricular outflow velocity (PFV), flow velocity integral (FVI), acceleration time (AT), mean acceleration of systolic flow (MA), duration of early and late filling phase, peak velocity of the early (E) and late (A) mitral flow, and A/E velocity ratio. Although no difference in chamber and wall dimensions between flushers and non-flushers was found, women with hot flushes had lower (not significantly) EF, PFV, FVI, MA, blood pressure and heart rate before therapy. Twelve-month estrogen replacement therapy significantly reduced cardiac wall dimensions and improved systolic function in both flushers and non-flushers. However, stroke volume, EF and MA were increased whereas systolic blood pressure and heart rate were decreased more in flushers. Also, the increase in E mitral flow and decrease in A/E were more pronounced in flushers. Thus, although estrogen replacement therapy significantly improves heart function in healthy postmenopausal women, there appears to be some minor differences in response between flushers and non-flushers.

Administration, Cutaneous↗
PubMed1998

The effect of hormone replacement therapy on diastolic left ventricular function in hypertensive and normotensive postmenopausal women.

OBJECTIVES: To evaluate the effect of hormone replacement therapy (HRT) on left ventricular diastolic function in a group of hypertensive and normotensive postmenopausal women. METHODS: Left ventricular diastolic function at rest was evaluated by M-mode, two-dimensional and Doppler echocardiography in 19 postmenopausal women with normal blood pressure and 11 postmenopausal women with mild hypertension, before treatment and during 12 months of HRT. Transdermal estradiol was used in women with a surgical menopause and a sequential regimen of transdermal estradiol and peroral medroxyprogesterone acetate in women with a spontaneous menopause. The parameters assessed were: body mass index, heart rate, ejection fraction of the left ventricle (EF), septal (SW) and posterior wall (PW) dimensions, left ventricular end-systolic (LVsd) and end-diastolic (LVdd) dimensions and volumes (ESV, EDV), total diastolic time (DT), duration of the early (Ei) and of the late (Ai) filling phase, peak velocity of the early (E) and late mitral flow (A), A/E velocity ratio and systolic and diastolic blood pressure. Quantitative data were analyzed using unpaired t-test, MANOVA and multiple regression analysis where appropriate. RESULTS: Hypertensive postmenopausal women had significantly higher SW (P < 0.05), PW (P < 0.05), A/E (P < 0.05) and A (P < 0.001) than normotensive postmenopausal women, before therapy. After 12 months of HRT a significant decrease in SW, PW, LVsd, ESV and increase in EF, DT, Ei and E was observed in both hypertensive and normotensive postmenopausal women. Heart rate slowed and systolic pressure decreased significantly only in normotensive postmenopausal women on HRT. CONCLUSION: HRT of 12 months' duration does not deteriorate left ventricular diastolic function of both hypertensive and normotensive postmenopausal women. Improvement in some parameters of diastolic function could be partially explained by the decrease in heart rate and systolic pressure, induced by therapy.

Administration, Cutaneous↗
PubMed1998

Metabolic effects of tibolone in postmenopausal women with non-insulin dependent diabetes mellitus.

OBJECTIVE: Postmenopausal women with non-insulin dependent diabetes (NIDDM) are frequently obese, hypertensive and hyperlipidaemic and hence at particular risk of coronary heart disease (CHD). They might therefore benefit from menopausal therapy. In view of the improvement in insulin sensitivity and the reduction in triglyceride levels induced by tibolone in healthy postmenopausal women we evaluated the effects of 12 months of tibolone on glycaemic control, serum insulin and lipid levels in postmenopausal women with NIDDM. DESIGN: A prospective 12 months before/after intervention study. PATIENTS: Fourteen postmenopausal women (mean age 58.14 +/- 1.25 years; mean duration of menopause 121.21 +/- 13.42 months; mean BMI: 26.55 +/- 0.97) with NIDDM (mean duration of diabetes 113.79 +/- 13.89 months). MEASUREMENTS: Fasting and postprandial blood glucose levels were assessed monthly, serum fructosamine, fasting and postprandial insulin every 3 months and serum lipids (total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol) every 6 months. RESULTS: Changes in blood glucose, both fasting and postprandial, were not statistically significant during the treatment period. Serum fructosamine concentration increased significantly after 9 months. A significant decrease in fasting and postprandial insulin concentrations was observed after 9 months. A non-significant decrease was observed in total cholesterol, LDL cholesterol and triglyceride but no change in HDL cholesterol. Body weight did not change during the period of observation. CONCLUSION: A slight deterioration in glycaemic control, a fall in insulin concentration and no change in serum lipids were observed in women with NIDDM during 12 months treatment with tibolone.

Anabolic Agents↗
PubMed1997

The effect of tibolone on cardiac flow in postmenopausal women with non-insulin dependent diabetes mellitus.

OBJECTIVE: Postmenopausal women with non-insulin dependent diabetes (NIDDM) are frequently obese, hypertensive and hyperlipidaemic and hence at particular risk of coronary heart disease (CHD). They might therefore benefit from menopausal therapy. In view of the fact that oestrogen replacement increases cardiac flow but not limb flow whilst tibolone dilates forearm flow in healthy postmenopausal women, a study was undertaken to evaluate the effects of tibolone on cardiac flow in postmenopausal women with NIDDM. DESIGN: A prospective 12 months before/after intervention study. PATIENTS: 15 postmenopausal women (mean age 58.36 +/- 1.25 years; mean duration of menopause 115.20 +/- 13.97 months; mean BMI: 26.22 +/- 1.02) with NIDDM (mean duration of diabetes 106.07 +/- 15.66 months). MEASUREMENTS: Cardiac flow was measured every 6 months for 1 year by pulsed Doppler echocardiography. The parameters assessed were: stroke volume (SV), cardiac output (CO), ejection fraction (EF), pre-ejection time (PEP), ejection time (ET), peak systolic flow velocity (PFV), acceleration time (AT), flow velocity integral (FVI), mean acceleration (MA), early diastolic filling time (Ei), atrial filling time interval (Ai), peak velocity of the early diastolic filling (E) and peak velocity of the early atrial filling (A). Blood pressure was also recorded during Doppler echocardiography. RESULTS: Stroke volume, cardiac output and ejection fraction increased significantly after 6 months. There was also a significant increase in peak flow velocity (PFV), flow velocity integral (FVI) and mean acceleration (MA) together with a significant increase in early diastolic filling time (Ei) and peak velocity of the early diastolic filling (E). Blood pressure was unchanged throughout the 12-month study period. CONCLUSION: The significant increase in stroke volume, cardiac output and flow velocity over the aortic valve parallel the effects of oestrogens in healthy postmenopausal women. The fact that tibolone improved left ventricular relaxation suggests the drug might help prevent or at least defer the development of cardiac dysfunction in diabetic women.

Anabolic Agents↗
PubMed1997

Menopause and post-menopause.

From the endocrine point of view, menopause is considered a deficiency state and oestrogen therapy regarded as restoring the pre-menopausal endocrine milieu. Oestrogen therapy alleviates acute climacteric symptoms and also reduces the risk of cardiovascular disease, osteoporosis and Alzheimer's disease. Cardiovascular protection seems to be the major benefit of oestrogen replacement: it reduces morbidity and mortality from coronary heart disease by approximately 50%. The mechanisms are complex and not fully under-stood. In this review we discuss currently available data on the effects of hormone replacement therapy on serum lipids and lipoproteins, the vessel wall (endothelium dependent and endothelium independent), blood flow, cardiac function, blood pressure, haemostasis, insulin sensitivity and direct anti-atherosclerotic effect as possible mechanisms of cardioprotection. Oestrogen therapy reduces the rate of post-menopausal bone loss, increases bone mineral density (BMD) and decreases fracture rate. Recent evidence suggests that initiation of oestrogen therapy in older women produces larger increases in BMD which might provide a significant protective effect at the time when fracture is common. The incidence of Alzheimer's disease is reduced by 50% in post-menopausal women taking oestrogen replacement. Limited clinical trials of oestrogen treatment in women with this disease have documented beneficial effects on cognitive function. The results of epidemiological studies of the effects of oestrogens on breast cancer risk are conflicting but recent evidence suggests that the risk is increased in current users after 5 years of use and among older women. In contrast, increase in the risk of venous thromboembolism is most significant within the first 12 months of therapy, strongly suggesting the importance of individual susceptibility.

Adult↗
PubMed1997

Insulin resistance in polycystic ovary syndrome.

Hyperinsulinaemia is found in 30% of slim and 75% of obese women with polycystic ovary syndrome. Despite resistance to insulin action in terms of glucose transport, increased insulin levels may cause hyperandrogenaemia by enhancement of androgen production in the ovaries where insulin acts as co-gonadotrophin. Recent interest in insulin resistance results from the recognition that it predisposes to various metabolic abnormalities, and could be involved in the pathogenesis of atherosclerosis. Women with polycystic ovary syndrome frequently have metabolic disturbances associated with insulin resistance, and recent long-term follow-up studies have indicated that they also have a higher incidence of diabetes and hypertension later in life compared with control populations. This review describes the association of hyperinsulinaemia with hyperandrogenism, metabolic and circulatory changes in women with polycystic ovary syndrome. Special emphasis is placed on recent studies of molecular mechanisms of insulin resistance in polycystic ovary syndrome and clinical implications of hyperinsulinaemia in these women.

Androgens↗
PubMed1997

New developments in postmenopausal hormone replacement therapy.

In this review we summarize background data that have steadily accumulated to help explain the beneficial actions of oestrogen replacement treatment on cardiovascular disease. The range of beneficial actions on the cardiovascular system is extraordinary, and goes far beyond the widely acknowledged effects on lipoprotein action. We also review recent reports on the beneficial actions of oestrogen treatment on Alzheimer's disease and colorectal cancer. The emphasis throughout is on understanding the mechanisms of benefit.

Alzheimer Disease↗