A randomized trial on the effect of oral combined estradiol and drospirenone on glucose and insulin metabolism in healthy menopausal women with a normal oral glucose tolerance test.

BACKGROUND: Menopause is often associated with a central accumulation of body fat. This provokes insulin resistance. The resulting hyperinsulinemia may increase the risk of diabetes, cardiovascular disease and breast cancer. Long-term studies indicate that menopausal hormone therapy (MHT) reduces insulin resistance. To broaden knowledge of the mechanisms behind the influence of MHT on glucose homeostasis we focused on the direct short-term effects of MHT with oral combined estradiol and drospirenone on glucose and insulin metabolism in healthy postmenopausal women. METHODS: This randomized, placebo-controlled study recruited 80 healthy postmenopausal women. Women were randomized to treatment with estradiol 1 mg continuously combined with drospirenone 2 mg or placebo for 6-8 weeks. All participants underwent an oral glucose tolerance test (OGTT) before and after the treatment period. Glucose, insulin, fructosamine and C-peptide levels were measured in serum before and 30, 60, 90, 120 and 150 min after a 75-gram oral glucose challenge. RESULTS: After intervention, significantly higher glucose levels at 120 min (p < 0.024) and 150 min (p < 0.030) were observed in the MHT group compared with the placebo group. These glucose levels remained within the normal range. A significantly lower insulin peak serum level (p < 0.040) and a non-significantly smaller area under the curve (AUC) for insulin levels (p = 0.192) was observed in the MHT group at the end of the study period relative to baseline. No significant change in the insulin AUC in the placebo group was observed. There were no significant differences in fructosamine, HOMA-IR and C-peptide levels between the MHT group and the placebo group. CONCLUSION: This double-blind randomized study (EC/2008/694) indicates that treating healthy, postmenopausal women with 1 mg estradiol continuously combined with 2 mg drospirenone significantly decreases peak insulin levels and increases peak glucose levels during an OGTT compared to placebo. These glucose levels remained within the normal range.

Use of a liquid ionization chamber for stereotactic radiotherapy dosimetry.

Liquid ionization chambers (LICs) offer an interesting tool in the field of small beam dosimetry, allowing better spatial resolution and reduced perturbation effects. However, some aspects remain to be addressed, such as the higher recombination and the effects from the materials of the detector. Our aim was to investigate these issues and their impact. The first step was the evaluation of the recombination effects. Measurements were performed at different SSDs to vary the dose per pulse, and the collection efficiency was obtained. The BEAMnrc code was then used to model the Cyberknife head. Finally, the liquid ionization chamber itself was modelled using the EGSnrc-based code Cavity allowing the evaluation of the influence of the volume and the chamber materials. The liquid ionization charge collection efficiency is approximately 0.98 at 1.5 mGy pulse(-1), the highest dose per pulse that we have measured. Its impact on the accuracy of output factors is less than half a per cent. The detector modelling showed a significant contribution from the graphite electrode, up to 6% for the 5 mm collimator. The dependence of the average electronic mass collision stopping power of iso-octane with beam collimation is negligible and thus has no influence on output factor measurements. Finally, the volume effect reaches 5% for the small 5 mm collimator and becomes much smaller (<0.5%) for diameters above 10 mm. LICs can effectively be used for small beam relative dosimetry as long as adequate correction factors are applied, especially for the electrode and volume effects.