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Objective : Analyze the serum levels of DHEA (prasterone) and its metabolites after daily intravaginal 0.50% (6.5 mg) DHEA in postmenopausal women with vulvovaginal atrophy (VVA). Methods : Serum samples were obtained at baseline and after 12, 26 and 52 weeks of treatment. The serum levels of DHEA, DHEA-sulfate (DHEA-S), androstene-3β, 17β-diol (5-diol), androstenedione (4-dione), testosterone, dihydrotestosterone (DHT), estrone (E 1 ), estradiol (E 2 ), E 1 -sulfate (E 1 -S), androsterone glucuronide (ADT-G) and androstane-3α,17β-diol 17-glucuronide (3α-diol-17G) were measured by validated liquid chromatography-tandem mass spectrometry. Results : A total of 435 women were exposed for 52 weeks. All serum steroids remained within normal values with no significant differences between lengths of treatment. For the most relevant estrogen-related compounds, namely E 1 , E 2 , and E 1 -S, a reliable marker of total estrogen exposure, the values in the DHEA-treated group at 52 weeks were –3.4%, –9.1% and +1.8%, respectively, compared to the normal postmenopausal values, thus clearly confirming the absence of significant systemic estrogen exposure. Conclusion : While confirming that all serum sex steroids originating exclusively from DHEA after menopause are maintained within the normal postmenopausal values, the present data show that the dose of intravaginal DHEA used is free from systemic exposure with no detectable change in metabolism up to 52 weeks of treatment.

Background: Metabolic syndrome (MetS) consists of a constellation of metabolic abnormalities that confer increased risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Endothelial dysfunction is one of the key components of MetS which is caused by imbalance between vasodilatory substances like nitric oxide (NO) and vaso-constrictive substances like endothelin and prothrombotic factors like plasminogen activator inhibitor-1 (PAI-1). Objective: To study the markers of endothelial dysfunction (NO and endothelin) and prothrombotic markers (PAI-1) among the study subjects. Materials and methods: We enrolled 50 diagnosed cases of MetS as per International Diabetes Federation (IDF) criteria and 50 healthy volunteers as controls. Clinical evaluation included anthropometric, routine biochemical, hematological, serum insulin, NO, endothelin and PAI-1 measurements. Results: Subjects with MetS had higher insulin, endothelin and PAI-1 levels and low NO levels as compared to controls and the difference was found to be significant. The serum insulin levels were positively correlated with PAI-1 and endothelin, and negatively correlated with NO. Conclusion: Endothelial functional status as reflected by decreased NO and increased serum endothelin levels along with insulin resistance is seen in MetS. Moreover, higher serum level of PAI-1 also tilts towards a more prothrombotic milieu in the vascular endothelium. Hence endothelial dysfunction and prothrombotic markers may be used to guide for early diagnosis of cardiovascular disease and type 2 diabetes in patients with MetS.

Inflammatory breast carcinoma (IBC) is a special type of breast cancer with a poor survival rate. Though several IBC cell lines have been established, recently a first IMC cell line was established. The aims of this study were: (1) to validate a highly sensitive, reliable, accurate and direct amplified enzyme immunoassay (EIA) to measure several cell-secreted steroid hormones: progesterone (P4), androstenedione (A4), testosterone (T), 17β-estradiol (E2) and estrone sulfate (SO4E1) in the culture medium. (2) To assess whether hormone production profile by IPC-366 cells validates the IMC model for human IBC. We validated a non-competitive amplified EIA for inflammatory breast cancer cell lines based on the results of accuracy, precision, sensitivity and parallelism. The low detection limits of the technique were: P4=13.2 pg/well, A4=2.3 pg/well, T=11.4 pg/well, E2=1.9 pg/well and SO4E1=4.5 pg/well. Intra- and inter-assay coefficient of variation percentages were <10%. The mean recovery rate of hormone added to the culture medium was >90%. In all hormones studied SUM149 have higher levels (1.4 times, but not significant) than IPC-366, and the correlation index between SUM149 and IPC-366 concentrations were >97%. We can coclude that cells of both cell lines, IPC-366 and SUM149, are capable to produce steroid hormone in culture media. The presented EIA methodology is very valuable for the detection of steroid production in culture media and could be used in hormone regulation studies and therapeutic agents in cell lines of inflammatory and non-inflammatory mammary carcinoma or other cancer cell lines in preclinical studies.