Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome

Thirty-two women with polycystic ovary syndrome (PCOS) wereallocated to two antiandrogen treatment regimens; 28 women completedthe trial. Twenty women were treated with ethinyloestradioland cyproterone acetate (EO-CA) cyclically for 6 months andeight women were treated with the gonadotrophin releasing hormone(GnRH) analogue, goserelin for 6 months. Effects on hirsutism,insulin sensitivity (estimated by glucose clamp technique),blood lipids and hormones were measured. Women treated withEO-CA showed a reduction in hirsutism (P <0.05), and decreasedserum androgen concentrations (P <0.001) as well as reducedinsulin sensitivity (P <0.05). In women treated with goserelin,serum androgen concentrations also decreased (P <0.001),but there was no significant reduction of hirsutism. This group,however, showed an improved insulin sensitivity (P <0.05)despite an unchanged body mass index. Bone mineral density wasunaltered in both treatment groups. The reduction in androgenconcentrations caused by EO-CA was not paralleled by increasedinsulin sensitivity, most probably due to the effect of ethinyloestradiolper se. In contrast, the reduction in androgen concentrationsby goserelin was accompanied by an improved insulin sensitivity.     

Loss of total body potassium during rapid weight loss does not depend on the decrease of potassium concentration in muscles. Different methods to evaluate body composition during a low energy diet

OBJECTIVE: The aim of the study was to elucidate whether combustion of skeletal muscle glycogen during a very low calorie diet (VLCD) was associated with decreased muscle potassium content. A comparison between different methods was also performed to evaluate body composition during a VLCD and a low calorie diet (LCD). DESIGN: Dietary treatment of obese women by VLCD and LCD. Measurements after 1 and 2 weeks of VLCD and 6 months of LCD. SUBJECTS: Fifteen perimenopausal obese women aged 46.5+/-1.3 y and 15 of 48.0+/-0.7 y of age. MEASUREMENTS: Skeletal muscle biopsies under local anaesthesia. Body composition measurements by means of deal-energy X-ray absorptiometry (DEXA), and measurements of total body potassium (40K) and total body nitrogen (TBN). Measurements of electrolytes and glycogen concentration in muscle samples. RESULTS: In the first study (1 week of VLCD) skeletal muscle glycogen decreased (P<0.01), but muscle potassium increased (P<0.01). Muscle sodium decreased (P<0.01), while muscle magnesium was unaltered. Body weight decreased by 2.9+/-0.5 kg and 40K decreased. Fat-free mass (FFM) calculated from 40K and DEXA decreased by 2.7 vs 1.9 kg (P<0.001). Body fat measured with DEXA decreased by 1.1 kg (P<0.01), but not body fat calculated from 40K. TBN decreased by 0.03+/-0.01 kg (P<0.05) and FFM calculated from TBN by 2.9+/-0.5 kg (P<0.002). In the second study, 6 months on the LCD resulted in 17.0+/-2.0 kg weight reduction and this was mainly due to reduced body fat, 14. 0+/-2.0 kg measured with DEXA and from 40K (P<0.001). The decrease in FFM was slight. CONCLUSION: One week of VLCD resulted in muscle glycogen depletion but increased muscle potassium content in spite of decreased total body potassium. FFM contributed to the main part of body weight loss during short periods of severe energy restriction, but remained unchanged during long-term dietary treatment. Body fat became mostly responsible for the body weight loss during long-term LCD. Calculations of changes of FFM from 40K and TBN seem to overestimate the FFM decrease associated with short-term VLCD. International Journal of Obesity (2000)24, 101-107     

Thyroid hormones in the pathogenesis and treatment of obesity

Thyroid hormones (TH) are potent modulators of adaptive thermogenesis and can potentially contribute to development of obesity. The decrease of T₃ in association with reduction of calorie intake is centrally regulated via decreases in leptin and melanocortin concentrations and peripherally via a decrease in deiodinase activity, all aimed at protein and energy sparing. The use of TH in the treatment of obesity is hardly justified except in cases of elevated thyrotropin (TSH) with low/normal T₃ and T₄ and/or a low T₃ or T′₃/T₄ or a high TSH/T₃ ratio. TH treatment with small doses of T₃ can also be exceptionally applied in obese patients resistant to dietary therapy who are taking β-adrenergic blockers or with obesity developed after cessation of cigarette smoking and with hyperlipidemia and a concomitant high thryrotropin/T₃ ratio. Supplementation with Se²⁺ and Zn²⁺ may be tried along with more severe calorie restriction to prevent decline of T₃.     

Inhibitory effect of shark liver oil on cutaneous angiogenesis induced in Balb/c mice by syngeneic sarcoma L-1, human urinary bladder and human kidney tumour cells.

The effect of shark liver oil on cutaneous angiogenesis induced in mice by intradermal grafting of tumour cells was evaluated. It was shown that this substance (Ecomer) suppressed neovascular response in mice grafted with sarcoma L-1 syngeneic cells, human kidney cancer and human urinary bladder cancer cells. In addition, strong stimulatory effect of this drug on mice blood granulocyte number and their metabolic activity was observed.     

Muscle adaptations and glucose control after physical training in insulin-dependent diabetes mellitus

Summary. Six men and three women with insulin-dependent diabetes (without complications) participated in physical training three times a week for 20 weeks. Physical training did not change the concentration of fasting blood-glucose, glucose excretion in urine or glucosylated haemoglobin (Hb_A1). However, the glucose disposal rate during euglycaemic clamp increased after training. In two patients a minor reduction of insulin dosage was necessary to alleviate slight hypoglycaemic episodes. The training resulted in significant increases in quadriceps isometric and dynamic strength and endurance. Maximal oxygen uptake increased by 8%, the activity of glycolytic enzymes in vastus lateralis muscle by 47% for hexokinase, and 30% for tri-osephosphate dehydrogenase and 25% for lactic dehydrogenase, the activity of oxidative enzymes by 42% for citrate synthase and 46% for 3-hydroxy-acyl-CoA-dehydrogenase. The glycogen concentration in the vastus lateralis muscle did not change significantly. Lipoprotein lipase activity did not change in muscle, nor in adipose tissue. The mean muscle fibre area increased by 25% and the area of FTa fibres by 30%. The new formation of capillaries around different muscle fibres was significant for FTb fibres (26%). The proliferation of capillaries, however, appeared to be insufficient to cope with the increased area of muscle fibres. As a result, the mean area of muscle fibre supplied by one capillary (a measure of diffusion distance) significantly increased after training for FTa fibres. It is concluded that with the exception of deficient proliferation of capillaries, patients with insulin-dependent diabetes mellitus show a normal central and peripheral adaptation to physical training. Physical training does not apparently improve blood glucose control in most cases, despite an increased insulin sensitivity.     

Muscle morphology,enzyme activity and muscle strength in elderly men and women

Summary. The quadriceps muscle were investigated with respect to isometric and isokinetic muscle strength, morphology and as regards some enzymes and metabolites of importance for the contractile processes. The material comprises 52 men (66–76 years) and 13 women (61–71 years) without clinical symptoms. Some participants used antihypertensive and/or heart-regulating medicine but were symptom-free. None of the subjects participated in any systematic training. All of them except for one physically inactive woman carried out moderate physical activities for at least 4 hweek. The body cell mass was higher in the men than in the women, and was highly correlated to muscle strength in both sexes. The fibre distribution was similar in both sexes with an average of 48 % Type I fibres in the men and 54 % Type I fibres in the women. The women had fewer Type II B fibres (4%) than the men (18 %). The average Type I fibre area did not differ between the sexes. The average Type II fibre area and the mean fibre area were smaller in women than in men, so that the ratio between the mean Type II and Type I fibre area was smaller in the women (0–76) than in the men (0–95). Signs of denervation/reinnervation, such as type grouping and an increase number of enclosed fibres, were observed very rarely and no great number of atrophic fibres indicating neuropathy was found. In both sexes, there was a reduction in the Type II fibre size, specially in relation to Type I fibre size, compared with young people. There was no difference between the enzymatic (Mg²⁺ATPase, MK and LDH) and the phosphagen (ATP and CP) content values between the sexes and no correlation between these variables and muscle strength. The capillarization was similar in the men and the women.     

High blood pressure and muscle morphology/metabolism – causal relationship or only associated factors?

As muscle tissue constitutes a main target organ for glucose metabolism and is responsible for the development of insulin resistance, it seems plausible to elucidate the relationship between blood pressure and muscle morphology and metabolism. The association between blood pressure and capillarization/morphology of the vastus lateralis muscle and metabolic variables was evaluated in 24 perimenopausal obese women [body mass index (BMI) 34·9 ± 1·1; waist–hip ratio (WHR) 0·90 ± 0·02]. The muscle enzyme activity of lipoprotein lipase (LPL), citrate synthase and glycogen synthase was determined. There was a significant negative correlation between the percentage of type I fibres and relative fibre area of type I on the one hand and systolic and diastolic blood pressure on the other. There was a negative correlation between the capillary density (i.e. number of capillaries/muscle fibre) and a positive correlation between the diffusion distance (fibre area supplied by one capillary) and diastolic blood pressure. The activities of LPL and citrate synthase were positively correlated with the percentage of type I and negatively correlated with the percentage of type II muscle fibres. The activity of LPL was also negatively correlated with plasma glucose and the insulin/C-peptide ratio. The insulin/C-peptide ratio was positively correlated with the percentage of type II muscle fibres. In stepwise multiple regression analyses, 20–30% of the variation in systolic and diastolic blood pressure could be explained by the variables of muscle fibre distribution. Excluding muscle morphological variables from the regression model, the insulin/C-peptide ratio accounted for 13% of the variation in systolic and diastolic blood pressure. The results of the study show the close association between muscle morphology and blood pressure. It remains to be elucidated whether this association indicates a causal relationship.     

Prevention of muscle soreness by pretreatment with antioxidants

A free radical-scavenging preparation (pollen extract) or the corresponding placebo was given to 50 volunteers over a period of 4 weeks to test the hypothesis that muscle soreness is associated with the generation of free radicals. The increase in malonyldialdehyde and lactate immediately after exercise both in blood and in muscle tissue was significantly lower after treatment with the scavenging preparation. The same was true for the prolonged post-exercise increase in creatine kinase over a 5-day period. The post-exercise glycogen content of muscle was higher in the pollen extract group, as were the subjective feelings of pain, oedema, discomfort and tension in the working muscle. We conclude that the beneficial preventive effect of pollen extract on post-exercise muscle soreness and lowering of the concentration of lipid peroxides indicate that free radicals are probably involved in the development of muscle soreness.     

Energy expenditure and body composition during weight reduction in hyperplastic obese women

The energy expenditure and body composition changes in out-patients during a long-term weight reduction with a diet recommended to provide 1100 kcal were studied in eight hyperplastic obese women. The study was focused on finding plausible explanations for the decreasing weight loss rate after several weeks of successful weight reduction. Using a heart rate monitoring method, the energy expenditure was measured four times at selected intervals during the study. Then, the energy intake was calculated on the basis of three dietary recordings lasting from 4 to 7 days. The recorded energy intake increased at the end of the weight reduction, but no changes in daily energy expenditure were found. The oxygen consumption during standardized cycling, walking, and domestic work decreased, but when the patient was at rest, no changes occurred during the weight reduction. The weight loss predicted from the energy balance and body composition changes was considerably greater than the actually determined weight loss. Large discrepancies were found after 5 weeks on the weight reducing regimen between the recorded dietary intake and what could be calculated from urinary nitrogen losses. With the available methods for determining energy intake and expenditure, it was considered impossible to fully explain the reason for the weight plateau observed after long-term weight reduction in out-patients.     

Regional adipose tissue cellularity in relation to metabolism in young and middle-aged women

Body composition and total number of fat cells were investigated in 31 randomly selected women 52 yr of age and in 13 young women (mean age 22 yr) whose body weights were within ±10% of the ideal weight. Two of the 52-yr-old women were obviously obese and excluded. Regional determinations of adipose tissue thickness, fat cell size, and number were also determined. Middleaged women had more body fat (BF) but a lower body cell mass (BCM) than the younger group. The increased BF in the middle-aged women was exclusively explained by larger fat cells, since the younger women had a significantly higher total number of fat cells. This increase was also found when differences in height, body weight, and body fat were matched out. Local fat cell number was also increased in the younger group. Local fat cell size was increased in all regions investigated in the middle-aged women, but the increase was particularly pronounced in the abdominal region. The highest degrees of correlation between fat cell sizes of different regions were found between the epigastric and hypogastric regions and between femoral and gluteal regions. Furthermore, the plasma insulin levels correlated with the fat cell sizes of the abdominal region but not with those of the femoral or gluteal regions.In conclusion, the data might indicate that the fat cells of the abdominal region are more sensitive to nutritional and/or hormonal factors than those of other regions. This may in turn indicate the existence of different fat cell populations.