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ObjectivesThe primary objective was to assess the efficacy, cycle control and tolerability of a monophasic combined oral contraceptive (COC) containing nomegestrol acetate (NOMAC) and 17β-oestradiol (E2). Effects on acne were evaluated as a secondary objective. Results were compared to those of a COC containing drospirenone (DRSP) and ethinylestradiol (EE).MethodsWomen (aged 18-50 years) were randomised to receive NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n = 1591) or DRSP/EE (3 mg/30 μg) in a 21/7-day regimen (n = 535) for 13 cycles.ResultsEstimated Pearl Indices for NOMAC/E2 and DRSP/EE were 0.38 and 0.81 in women aged ≤ 35 years and 0.31 and 0.66 for all women (18–50 years), respectively. Scheduled withdrawal bleedings were shorter and lighter among users of NOMAC/E2 and were sometimes absent altogether. Intracyclic bleeding/spotting was infrequent in both groups, and decreased over time. Type and frequency of adverse events were similar to those typically reported for COCs.ConclusionsThese data show that NOMAC/E2 provides high contraceptive efficacy with acceptable cycle control as well as an overall adverse event profile similar to that of DRSP/EE.

This paper is available online at http://dmd.aspetjournals.org ABSTRACT:In vivo metabolism of tibolone was studied in three healthy postmenopausal volunteers after daily oral administration of 2.5 mg of tibolone for 5 days and a single dose of 2.5 mg Х 555 kBq of Tibolone [(7␣,17␣)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one] is a tissue-specific compound with favorable effects on bone, vagina, climacteric symptoms, mood, and sexual well being in postmenopausal women. It has not been observed to stimulate the endometrium (Moore, 1999) or the breast, as demonstrated by the lower incidence of breast tenderness and lower mammographic density (Valdivia and Ortega, 2000). Therefore, in some tissues, tibolone has different effects than estrogens.The metabolism of tibolone has been studied in female rats, rabbits, and dogs. A considerable number of metabolites were identified in this study using 1 H NMR and mass spectroscopy, and qualitative and quantitative differences between species were observed (Jacobs et al., 1992;Verhoeven et al., 2002). Major phase I metabolic routes were the reduction of 3-keto to 3␣-or 3␤-hydroxy moieties, and the major phase II metabolic route was sulfate conjugation of the hydroxy groups at C3 and C17. Profiling of the target organs showed a tissue-specific distribution of metabolites. The majority of these metabolites existed as sulfate conjugates. These data in animals indicate that tibolone exerts its tissue-specific activities, at least partly, due to its tissue-specific metabolism and distribution. In addition, the presence of local sulfatases may convert inactive sulfated metabolites to active forms.The linearity of the pharmacokinetic profile of tibolone was studied in three groups of nine healthy female volunteers using 1.25, 2.5, and 5 mg of tibolone, respectively. The pharmacokinetic profile was mainly based on the primary phase I plasma metabolites (i.e., tibolone, 3␣-hydroxy tibolone, 3␤-hydroxy tibolone, and ⌬ 4 -tibolone). The steady state was attained by day 5 in all three dose groups. Since in most cases the plasma concentration of tibolone and ⌬ 4 -tibolone was below the detection limit, their elimination half-life could not reliably be determined. The geometric mean value of the elimination half-life of 3␣-hydroxy tibolone for the three dose levels ranged from 7.2 to 8.5 h. The very low plasma concentrations of the parent compound and the even lower concentrations of the ⌬ 4 -isomer, in combination with the considerably higher concentrations of the 3␣-and 3␤-hydroxy metabolites, indicated that tibolone is extensively metabolized, predominantly by hydroxylation at C3.Human biotransformation pathways need to be identified, and the possibility of metabolic or pharmacokinetic interactions occurring with coadministered compounds need to be addressed during the development of a drug. In vitro approaches are usually used to study these issues and to evaluate their potential clinical relevance. These in vitro studies generally focus on cytochrome P450, which is a collecti...

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Cycle control with vaginal ring was excellent and superior to that of a COC containing 30 mug EE.

Background: Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage.Objectives: This study was primarily designed to investigate the effect of a low-fat spread with added PSs on brachial artery endothelial function as measured by flow-mediated dilation (FMD). Second, effects on arterial stiffness, blood pressure, serum lipids, and plasma PS concentrations were investigated. We hypothesized that PSs would not worsen FMD but would rather modestly improve FMD.Design: This study had a double-blind, randomized, placebo-controlled, parallel design. After a 4-wk run-in period, 240 hypercholesterolemic but otherwise healthy men and women consumed 20 g/d of low-fat spread without (control) or with added PSs (3 g/d) during 12 wk. Pre- and postintervention, vascular function measurements and blood sampling were performed.Results: In total, 232 participants completed the study period. For the primary endpoint FMD, 199 participants were included in the statistical analysis. PS intake did not affect FMD (+0.01 percentage points; 95% CI: −0.73, 0.75) compared with control. Measures of arterial stiffness (pulse wave velocity and augmentation index) and blood pressure were also not significantly changed compared with control. After PS intervention, LDL cholesterol significantly decreased on average by 0.26 mmol/L (95% CI: −0.40, −0.12) or 6.7% compared with control. Plasma sitosterol and campesterol concentrations significantly increased in the PS group up to on average 11.5 μmol/L and 13.9 μmol/L (expressed as geometric means), respectively.Conclusions: The intake of a low-fat spread with added PSs neither improved nor worsened FMD or other vascular function markers in hypercholesterolemic men and women. As expected, serum LDL cholesterol decreased, whereas plasma PSs increased after PS intake. This study was registered at clinicaltrials.gov as NCT01803178.

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