Effect of testosterone replacement therapy on lipids and lipoproteins in hypogonadal and elderly men.

We investigated the effects of long-term testosterone replacement in hypogonadal and elderly men on lipids and lipoproteins. Twenty-two men with initial serum testosterone concentrations below 3.5 ng/ml took part in the study: 11 with hypopituitarism (1st group) and 11 otherwise healthy elderly men with low testosterone levels (2nd group). Testosterone deficiency was replaced by intramuscular injections of testosterone enanthate 200 mg every second week. Plasma levels of sex hormones, gonadotropins, SHBG, lipids and lipoproteins were determined before the treatment and after 3, 6 and 12 months of treatment. During the treatment serum testosterone and estradiol increased significantly, reaching normal levels. This was associated with a decrease in total cholesterol (from 225 +/- 16.9 mg/dl to 202 +/- 13.6 mg/dl after 6 months and 198 +/- 12.8 mg/dl after 1 year of testosterone administration, P < 0.0001 in men with hypoandrogenism associated with aging and from 255 +/- 12.1 mg/dl to 214 +/- 10.6 mg/dl after 6 months and 206 +/- 9 mg/dl after 1 year of treatment, P < 0.0001 in men with hypopituitarism) and LDL-cholesterol concentrations (from 139 +/- 12.5 mg/dl to 126 +/- 10.7 mg/dl after 6 months and 118 +/- 9.8 mg/dl after 1 year of testosterone administration, P < 0.0001 in men with hypoandrogenism associated with aging and from 178 +/- 10.3 mg/dl to 149 +/- 10.2 mg/dl after 6 months and 140 +/- 7.3 mg/dl after 1 year of treatment, P < 0.001 in men with hypopituitarism). However, no significant decrease in HDL-cholesterol levels or HDL2- and HDL3-cholesterol subfractions was observed. The effects of testosterone replacement therapy on lipids and lipoproteins were similar in both groups with different aetiology of hypogonadism. No side effects on the prostate were observed. The results of this study indicate that testosterone replacement therapy in hypogonadal and elderly men may have a beneficial effect on lipid metabolism through decreasing total cholesterol and atherogenic fraction of LDL-cholesterol without significant alterations in HDL-cholesterol levels or its subfractions HDL2-C and HDL3-C.

Hyperinsulinaemia and decreased plasma levels of dehydroepiandrosterone sulfate in premenopausal women with coronary heart disease.

OBJECTIVES: The purpose of the study was to establish plasma levels of insulin, ovarian sex hormones and dehydroepiandrosterone sulfate (DHEA-S) and to evaluate their correlations with lipids in premenopausal women with angiographically demonstrated coronary stenosis. DESIGN: Differences in plasma levels of insulin, ovarian sex hormones, DHEA-S and lipids between groups were compared by analysis of variance. SETTING: From January 1993 until December 1993 patients were diagnosed in the Outpatient Clinic of the Department of Endocrinology Medical Centre for Postgraduate Education, Warsaw. SUBJECTS: Premenopausal women with normal oral glucose tolerance test (OGTT) results, with and without coronary stenosis were studied: 21 women after acute myocardial infarction with angiographically demonstrated coronary stenosis (women with CHD), and 14 women with chest pain, a positive exercise test without significant changes of coronary arteries on coronarography (women with normal coronarography, NC). The control group consisted of nine, healthy women with no risk factors for CHD. MAIN OUTCOME MEASURES: In premenopausal women with CHD, the decreased plasma level of DHEA-S and hyperinsulinaemia were anticipated. RESULTS: In women with CHD, the plasma levels of DHEA-S (926.5 +/- 83 ng mL-1) were significantly lower than those in women with NC (1375.7 +/- 181 ng mL-1) and in healthy controls (1984 +/- 127 ng mL-1), P < 0.02 and P < 0.001, respectively. The fasting insulin and insulin response to an OGTT in women with CHD and with NC was higher than in healthy subjects. A significant decrease of high-density lipoprotein (HDL) cholesterol, HDL-2 cholesterol and apolipoprotein A-I, and an increase of total cholesterol, low-density lipoprotein cholesterol C and apolipoprotein B levels in women with CHD compared to healthy controls were observed. A negative correlation between fasting insulin and the plasma levels of DHEA-S was established. CONCLUSION: In premenopausal women, hyperinsulinaemia and decreased DHEA-S levels may contribute to the development of coronary atherosclerosis.

Effects of transdermal 17 beta-oestradiol combined with oral progestogen on lipids and lipoproteins in hypercholesterolaemic postmenopausal women.

OBJECTIVES: The purpose of the study was to evaluate the effect of transdermal 17 beta-oestradiol with oral progestogen on the plasma levels of lipids, lipoproteins and apolipoproteins in hypercholesterolaemic postmenopausal women. DESIGN: During 6 months of replacement therapy with transdermal 17 beta-oestradiol combined with oral progestogen, plasma lipids, lipoproteins and apolipoproteins after 3 and 6 months were measured and compared with pretreatment values by Student's t-test. SETTING: From January 1992 until September 1992 patients were diagnosed and treated in an out-patient clinic of the Department of Endocrinology Medical Centre for Postgraduate Education, Warsaw. SUBJECTS: The patients studied were 11 non-obese postmenopausal women with hypercholesterolaemia based on the World Health Organization criteria. INTERVENTIONS: Venous blood samples were obtained before and 3 and 6 months after the beginning of cyclic replacement therapy with transdermal 17 beta-oestradiol (E2 100 micrograms day-1 combined with oral chlormadinone acetate (2 mg day-1 for 7 days in each cycle). MAIN OUTCOME MEASURES: The antiatherogenic effect of transdermal oestrogen replacement therapy exerted by increased levels of high-density lipoprotein subfraction 2 cholesterol (HDL2-C) leading to the decrease of the total cholesterol level was anticipated. RESULTS: After 6 months of the treatment the concentrations of HDL2 cholesterol (HDL2-C) increased from 0.45 +/- 0.07 mmol l-1 to 0.73 +/- 0.03 mol l-1 (P < 0.05) but the levels of HDL3 cholesterol (HDL3-C) decreased from 1.15 +/- 0.06 mmol l-1 to 0.89 +/- 0.07 mmol l-1 (P < 0.05). The concentrations of total cholesterol decreased from 6.9 +/- 0.13 mmol l-1 to 6.2 +/- 0.2 mmol l-1 (P < 0.05). No changes were observed in the plasma levels of total triglycerides, HDL cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, VLDL triglycerides, apolipoproteins A-I and B. CONCLUSIONS: In hypercholesterolaemic postmenopausal women, transdermally administered 17 beta-oestradiol 100 micrograms daily in combination with oral chlormadinone acetate has a beneficial effect through raising the level of the antiatherogenic HDL2-C subfraction and decreasing the level of total cholesterol.

[Assessment of outcome in treatment of cardiac shock after myocardial infarction with intravenous streptokinase]. / Ocena wyników leczenia wstrzasu zawalowego dozylnym wlewem streptokinazy.

In 1986 a prospective randomized study coordinated by the Institute of Cardiology in Warsaw was started in 10 teaching cardiology hospitals in Poland for assessment of the results of treatment with intravenous streptokinase infusion in acute myocardial infarction. The studied population comprised 927 patients admitted to intensive treatment units within 6 hours after the onset of infarction pain. For the groups treated with streptokinase or heparin 752 patients were selected at random. In 175 cases the administration of streptokinase was contraindicated. These patients received conventional treatment and served as controls. The age of the patients was from 38 to 70 years, mean age 57.6 +/- 9.3 years. In 105 out of 927 cases cardiac shock was diagnosed. In the groups of early shock during hospitalization the death rate was 82%. No statistically significant difference was found in the death rates between patients with cardiac shock treated with heparin or with streptokinase.

[Aneurysms in acute myocardial infarction (multicenter studies)]. / Tetniaki w ostrym zawale serca. (Badania wieloosrodkowe).

The authors present outcomes concerning frequency of appearance and clinical course of aneurysms after acute myocardial infarction. The study population consisted of 730 patients (mean age 54 +/- 9 years) with acute myocardial infarction, including 579 men and 151 women. The diagnosis was based on the following criteria: 1) coronary artery disease history, 2) physical examination, 3) ECG, 4) 2-dimensional echocardiography, 5) biochemical data. Post-infarction aneurysm was revealed in 42 patients (5.8%, 33 men and 9 women); antero-lateral aneurysm--in 36 patients (85.7%), and inferior-posterior aneurysm--in 6 patients (14.3%). Ventricular arrhythmias in the first day of infarction had a high frequency in both groups; with aneurysm--92.9%, without aneurysm--82.2%. The frequency of arrhythmia in 21-st day of infarction decreased similarly in both groups with aneurysm--40.5%, without aneurysm--38.9%. There was no statistically significant difference among both groups. There was no correlation between localisation of aneurysms and degree of contractility disturbances of the heart muscle (dyskinesis, akinesis). Heart failure--class III and IVK (Killip-Kimball classification) occurred in 19.0% of patients with aneurysm and in 10.4% of patients without aneurysm. That was no essential correlation between localisation of aneurysms and advancement of the heart failure.

Transdermal 17 beta-estradiol combined with oral progestogen increases plasma levels of insulin-like growth factor-I in postmenopausal women.

In order to evaluate the effect of postmenopausal estrogen replacement therapy on the plasma levels of the insulin-like growth factor-I (IGF-I) 12 postmenopausal women aged 44 to 59 years were studied. The control group consisted of 15 healthy premenopausal women aged 20-44 years. In the postmenopausal women the plasma levels of IGF-I, gonadotrophins and sex hormones were determined before and after 3 and 6 months cyclic replacement therapy with transdermal 17 beta-estradiol (E2 100 micrograms patches applied twice weekly) combined with oral chlormadinone acetate (2 mg daily for 7 days in each cycle). Basal levels of estradiol (E2), IGF-I, dehydroepiandrosterone sulphate (DHEA-S), testosterone and androstenedione were lower, but gonadotropin levels were higher in postmenopausal than in premenopausal women. In all the women studied age was inversely correlated with IGF-I levels (r = -0.793, p less than 0.001) and with DHEA-S concentrations (r = -0.435, p less than 0.02). In postmenopausal women transdermal estradiol administration restored the circulating E2 levels to the early follicular range and increased the IGF-I levels (from 76.4 +/- 9.2 micrograms/l to 141.8 +/- 20.8 micrograms/l; p less than 0.01). Transdermal estradiol decreased gonadotrophin levels without changes in concentration of DHEA-S, testosterone, androstenedione and SHBG. In postmenopausal women before and during replacement therapy a positive correlation was found between estradiol and IGF-I concentrations (r = -0.439, p less than 0.01). These results suggest that cyclic replacement therapy with transdermal 17 beta-estradiol in combination with chlormadinone acetate given orally increase the plasma levels of IGF-I in postmenopausal women.

The role of hyperinsulinemia in the development of lipid disturbances in nonobese and obese women with the polycystic ovary syndrome.

In order to establish the role of insulin in the pathogenesis of lipid abnormalities in hyperandrogenic women with the polycystic ovary syndrome (PCO) 49 women aged 18 to 35 yr with a normal glucose tolerance test were studied. They were divided into two groups: 27 women with PCO (9 obese and 18 nonobese), and 22 healthy women (12 with simple obesity and 10 with normal body weight). In the PCO group, the fasting insulin levels and the insulin response to oral glucose load were higher than in the matched controls. Significantly lower levels of HDL2-cholesterol and higher levels of apolipoprotein B were observed in obese and non nonobese PCO patients. In obese women with PCO this was associated with lower levels of HDL-cholesterol and apolipoprotein A-I (Apo A-I), whereas the levels of total triglycerides and VLDL-triglycerides (VLDL-TG) were increased. Multiple regression analysis in PCO women, after adjustment for age, body mass index and the levels of insulin and sex hormones, showed a strong positive correlation between the fasting insulin levels and total triglycerides and VLDL-TG, while a negative correlation was found between fasting insulin levels and apo A-I. These results indicate that hyperinsulinemia may play a role in the development of lipid disturbances in women with the PCO.

[Sex hormones in men with coronary arteriosclerosis]. / Hormony plciowe u mezczyzn z miazdzyca tetnic wiencowych.

Testosterone and estradiol levels were determined in 85 male patients aged between 23 and 52 years with: coronographically diagnosed coronary arteriosclerosis (20 with the instable and 37 with stable coronary disease), and in 28 healthy volunteers serving as a control group. Testosterone concentrations in the instable coronary disease (13.6 +/- 1.7 nM/l) were significantly lower than in the stable form of the disease (18.56 +/- 1.1 nM/l) and in healthy volunteers 20.9 +/- 1.0 nM/l, p less than 0.02 and p less than 0.001 respectively. Estradiol concentrations in male patients with instable coronary disease (228.3 +/- 22.8 pM/l) and with stable form of the disease (157.0 +/- 12.6 pM/l) were significantly higher than in healthy volunteers, p less than 0.02 and p less than 0.001 respectively. The obtained results indicate gonadal disorders in male patients with coronary arteriosclerosis.

Decreased plasma dehydroepiandrosterone sulfate and dihydrotestosterone concentrations in young men after myocardial infarction.

Plasma levels of dehydroepiandrosterone sulfate (DHEA-S), testosterone, dihydrotestosterone (DHT) androstenedione, sex hormone-binding globulin (SHBG), lipoproteins, apolipoproteins and high density lipoprotein (HDL) subfraction were measured in 32 men aged 26-40 years after myocardial infarction (MI) suffered at least 3-4 months prior to the study, who were normocholesterolemic and had angiographically demonstrated coronary occlusion. The control group consisted of 76 healthy men aged 25-40 years. Blood samples were obtained in the morning from fasting subjects. A significant decrease in plasma DHEA-S and DHT levels were found in MI patients. Also, a significant decrease in HDL-cholesterol, HDL2-cholesterol (HDL2-C) and apolipoprotein A-I, an increase in apolipoprotein B and LDL-cholesterol (LDL-C) levels were observed in those patients as compared with healthy men. However, there were no differences in testosterone, androstenedione and SHBG concentrations between the groups. Significant correlations between testosterone and HDL2-C (r = 0.46, P less than 0.01), as well as between DHEA-S and HDL3-C (r = 0.39, P less than 0.05) levels in MI patients were observed. These results suggest that decreased levels of plasma DHEA-S and DHT may promote the development of coronary atherosclerosis in men.

[Activitrax--a pacemaker with a regulated rhythm rate]. / Activitrax--stymulator z regulowana czestoscia rytmu.

In 10 patients: 7--with the complete atrioventricular block and 3 with the sick sinus syndrome the rate responsive activity sensing pacemaker--Activitrax was implanted. Significant increase of rheographically measured cardiac output in a course of rate responsive pacing in comparison with on demand constant frequency rate stimulation was stated during treadmill exercise tests performed 6 and 12 weeks after a pulse generator implantation.