Reduced hemostatic effects with drospirenone-based oral contraceptives containing estetrol vs. ethinyl estradiol.

OBJECTIVE: The effects of estetrol (E4), a natural fetal estrogen, combined with drospirenone (DRSP) were evaluated on plasma levels of sex hormone-binding globulin (SHBG), angiotensinogen and 12 hemostasis markers. STUDY DESIGN: Combinations of 3 mg DRSP with 5 or 10 mg E4 were compared with YAZ® (20 mcg ethinyl estradiol and 3 mg DRSP; EE/DRSP) in parallel groups of 15-18 healthy young women. Main outcome was the relative change from pretreatment to the end (day 24±1) of the third treatment cycle. RESULTS: All E4 combinations showed low estrogen impact compared to EE/DRSP. Effects on SHBG and angiotensinogen of 10 mg E4 combined with DRSP were 15%-20% that of EE/DRSP. Both E4/DRSP combinations reduced D-dimer level and the 5 mg E4/DRSP combination also decreased fragment 1+2. CONCLUSIONS: The reduction in coagulation markers suggests an anticoagulant effect from DRSP. The indications of a low thrombosis risk for E4 preparations should be validated in larger studies. IMPLICATION STATEMENT.

Effect of genome and environment on metabolic and inflammatory profiles.

Twin and family studies have established the contribution of genetic factors to variation in metabolic, hematologic and immunological parameters. The majority of these studies analyzed single or combined traits into pre-defined syndromes. In the present study, we explore an alternative multivariate approach in which a broad range of metabolic, hematologic, and immunological traits are analyzed simultaneously to determine the resemblance of monozygotic (MZ) twin pairs, twin-spouse pairs and unrelated, non-cohabiting individuals. A total of 517 participants from the Netherlands Twin Register, including 210 MZ twin pairs and 64 twin-spouse pairs, took part in the study. Data were collected on body composition, blood pressure, heart rate, and multiple biomarkers assessed in fasting blood samples, including lipid levels, glucose, insulin, liver enzymes, hematological measurements and cytokine levels. For all 51 measured traits, pair-wise Pearson correlations, correcting for family relatedness, were calculated across all the individuals in the cohort. Hierarchical clustering techniques were applied to group the measured traits into sub-clusters based on similarity. Sub-clusters were observed among metabolic traits and among inflammatory markers. We defined a phenotypic profile as the collection of all the traits measured for a given individual. Average within-pair similarity of phenotypic profiles was determined for the groups of MZ twin pairs, spouse pairs and pairs of unrelated individuals. The average similarity across the full phenotypic profile was higher for MZ twin pairs than for spouse pairs, and lowest for pairs of unrelated individuals. Cohabiting MZ twins were more similar in their phenotypic profile compared to MZ twins who no longer lived together. The correspondence in the phenotypic profile is therefore determined to a large degree by familial, mostly genetic, factors, while household factors contribute to a lesser degree to profile similarity.

Plasma cotinine levels in cigarette smokers: impact of mental health and other correlates.

BACKGROUND/AIMS: We examined in cigarette smokers whether cotinine was associated with depressive and/or anxiety disorders. METHODS: Data were derived from 1,026 smoking adults with and without depressive and/or anxiety disorders participating in the Netherlands Study of Depression and Anxiety (NESDA). Depressive and anxiety disorders were ascertained with the DSM-IV Composite International Diagnostic Interview. Cigarette consumption was inquired about during an interview. Cotinine was assessed in plasma. RESULTS: Currently depressed and/or anxious smokers (n=692) reported smoking a higher number of cigarettes per day (CPD) than smokers with a remitted disorder (n=190) and smokers with no lifetime disorder (n=144). After controlling for CPD and other covariates, depressed and/or anxious smokers had lower cotinine levels compared to smokers with no lifetime disorder (B=-56.0, p=0.001). In the full regression model, CPD was positively associated with cotinine levels, whereas current depression and/or anxiety and high body mass index were inversely associated with cotinine. CONCLUSION: After considering CPD, the presence of current depressive and/or anxiety disorders was associated with lower cotinine levels, which may point to a different smoking topography or a faster cotinine metabolism in individuals with affective disorders. The latter could help to explain the higher number of cigarettes smoked and poorer cessation rates among depressed or anxious patients.

The association of alcohol intake with γ-glutamyl transferase (GGT) levels: evidence for correlated genetic effects.

BACKGROUND: Blood levels of gamma-glutamyl transferase (GGT) are used as a marker for (heavy) alcohol use. The role of GGT in the anti-oxidant defense mechanism that is part of normal metabolism supposes a causal effect of alcohol intake on GGT. However, there is variability in the response of GGT to alcohol use, which may result from genetic differences between individuals. This study aimed to determine whether the epidemiological association between alcohol intake and GGT at the population level is necessarily a causal one or may also reflect effects of genetic pleiotropy (genes influencing multiple traits). METHODS: Data on alcohol intake (grams alcohol/day) and GGT, originating from twins, their siblings and parents (N=6465) were analyzed with structural equation models. Bivariate genetic models tested whether genetic and environmental factors influencing alcohol intake and GGT correlated significantly. Significant genetic and environmental correlations are consistent with a causal model. If only the genetic correlation is significant, this is evidence for genetic pleiotropy. RESULTS: Phenotypic correlations between alcohol intake and GGT were significant in men (r=.17) and women (r=.09). The genetic factors underlying alcohol intake correlated significantly with those for GGT, whereas the environmental factors were weakly correlated (explaining 4-7% vs. 1-2% of the variance in GGT respectively). CONCLUSIONS: In this healthy population sample, the epidemiological association of alcohol intake with GGT is at least partly explained by genetic pleiotropy. Future longitudinal twin studies should determine whether a causal mechanism underlying this association might be confined to heavy drinking populations.

Exposure to secondhand smoke and depression and anxiety: a report from two studies in the Netherlands.

OBJECTIVE: Previous population-based studies suggest that exposure to secondhand smoke (SHS) is related to increased depressive symptoms and poor mental health among non-smokers. We examined whether these associations could be replicated in two independent Dutch samples. METHODS: Non-smoking adults were selected from two studies: 1) the Netherlands Study of Depression and Anxiety (NESDA), comprising individuals with current and remitted depressive and/or anxiety disorders, and healthy controls and 2) the Netherlands Twin Register (NTR), comprising twin-family studies on health-related behaviors. In both studies, SHS exposure was assessed with plasma cotinine levels (1-14ng/ml vs. <1ng/ml). In NESDA, outcomes were current depressive and/or anxiety disorders, and depression and anxiety symptom severity scores. In NTR, the Adult Self Report derived DSM-subscales for depressive and anxiety problems, and anxious depressive scores were analyzed. RESULTS: In NESDA non-smokers (n=1757), increased plasma cotinine level (≥1ng/ml) was not related to current depressive and/or anxiety disorders [odds ratio (OR) 0.96, P=.77], nor to depression or anxiety severity indicators. Similarly, in NTR non-smokers (n=1088) cotinine levels ≥1ng/ml were not associated with the DSM-subscale for depressive problems [unstandardized regression coefficient (B) 0.04, P=.88], nor to other depression and anxiety measures. CONCLUSIONS: In non-smoking adults from patient and population samples, we found no evidence that plasma cotinine levels were related to either depressive and/or anxiety disorders, or to depressive and anxiety symptoms. This suggests that SHS exposure is not related to depression and anxiety in non-smoking adults.