Different effects of tibolone and continuous combined estrogen plus progestogen hormone therapy on sex hormone binding globulin and free testosterone levels – an association with mammographic density

Objective To compare the effects of tibolone and continuous combined hormone therapy on circulating sex steroids and their binding proteins and their relationship to mammographic density.

Study design A prospective, double-blind placebo-controlled study. A total of 166 postmenopausal women were equally randomized to receive tibolone 2.5?mg, estradiol 2?mg/norethisterone acetate 1?mg (E2/NETA) or placebo. Serum analyses of sex steroids, insulin-like growth factor (IGF-I) and binding proteins and assessment of mammographic breast density were performed at baseline and after 6 months of treatment.

Results Estrogens were markedly increased and androgens decreased by E2/NETA. In contrast, tibolone had only a minor influence on circulating estrogens. Sex hormone binding globulin (SHBG) levels were reduced by 50%, while levels of androgens increased. Baseline values of estrone sulfate (E1S), around 1.0–1.1?nmol/l, were increased to 44.7?nmol/l by E2/NETA and to only 1.7?nmol/l by tibolone (p?<?0.001). Mammographic breast density displayed a negative correlation with age and body mass index and a positive association with SHBG. After 6 months there was also a negative correlation with levels of free testosterone.

Conclusion We found that tibolone and E2/NETA caused distinct differences in estrogen/androgen status and blood levels of possible breast mitogens. The negative association between free testosterone and mammographic density could be a possible explanation for tibolone having less influence on the breast.     

Percutaneous administration of testosterone gel in postmenopausal women – a pharmacological study

We wished to investigate if a testosterone gel administered percutaneously to postmenopausal women could result in stable serum levels of the hormone and which dose was required to produce levels within the normal premenopausal range. Fifteen postmenopausal women, mean age 55.3 years (range 45–70 years), volunteered to participate in the study and were divided into three groups. They received 10, 20 or 30?mg of testosterone as a 1% testosterone hydroalcoholic gel at 09.00?hours daily for 14 days. The gel was applied in a thin layer on the outside of the thigh each morning, over an area of approximately 15?cm². Blood samples were collected hourly between 09.00 and 17.00?hours on days 1 and 14, and also at 08.00?hours on days 3, 5, 11, 12, 13 and finally day 16, i.e. 2 days after termination of treatment. The mean basal serum level of testosterone was 1.1?±?0.9?nmol/l and for 5α-dihydrotestosterone 208?±?143?pmol/l. There was a clear increase from the 10?mg to the 20?mg treatment (mean testosterone level during treatment 3.2 and 7.2?nmol/l, respectively) while serum testosterone values after 30?mg showed very little further increase (mean 7.5?nmol/l). Values for days 3–5 were quite similar to those for days 13–14. The present study suggests that adequate and acceptable serum levels of testosterone can be achieved with 10?mg testosterone applied transdermally.     

Iterative deconvolution of simultaneous 99mTc and 201Tl projection data measured on a CdZnTe-based cardiac SPECT scanner

We present a method of correcting self-scatter and crosstalk effects in simultaneous technetium-99m/thallium-201 stress/rest myocardial perfusion (single photon emission computed tomography) SPECT scans. The method, which is in essence a hybrid between the triple energy window method and scatter modelling, is based on a model of spatial and spectral distribution of projection counts in several selected energy windows. The parameters of the model are determined from measurements of thin rod sources in air when no in-object scatter or attenuation effects are present. The model equations are solved using the iterative maximum likelihood expectation maximization algorithm in the projection space to find estimates of the primary photopeak counts of both radionuclides. The method has been developed particularly for a novel dedicated cardiac camera based on CdZnTe pixellated detectors, although it can also be adapted to a conventional scintillator camera. The method has been validated in anthropomorphic phantom experiments. Significant improvement in defect contrast has been observed with only moderate increase in image noise. The application of the method to patient data is illustrated.     

Factors associated with failure to identify the culprit artery by the electrocardiogram in inferior ST-elevation myocardial infarction

Background

Right and left circumflex coronary artery occlusions cause inferior myocardial infarction. To improve the targeting of diagnostic and therapeutic measures individually, factors interfering with identification of the culprit artery by the electrocardiogram (ECG) were explored.

Methods

Patients with inferior preinfarction syndrome (n = 266) were included to the Danish Trial in Acute Myocardial Infarction-2 substudy. The culprit vessel was predicted by the ECG, and findings were correlated with angiography. Factors associated with false identification of the culprit artery by the ECG were examined.

Results

Electrocardiogram criteria for right coronary artery occlusion to predict coronary angiography findings had sensitivity, specificity, and positive and negative predictive values of 95%, 52%, 84%, and 81%. For left circumflex coronary artery occlusion, the corresponding values were 51%, 93%, 70%, and 85%, respectively. False ECG identification of the culprit artery was independently associated with left coronary dominance (P < .001; odds ratio [OR], 22.0; 95% confidence interval [CI], 7.2-67.0), multivessel disease (P = .035; OR, 2.2; 95% CI, 1.1-4.7), and absence of proximal occlusion pattern in the ECG (P = .003; OR, 4.0; 95% CI, 1.6-9.8).

Conclusions

Left coronary artery dominance, multivessel disease, and absence of ECG signs of proximal culprit lesion are associated with failure to predict the culprit artery of inferior myocardial infarction by the 12-lead ECG.