Gender, Contraceptives and Individual Metabolic Predisposition Shape a Healthy Plasma Lipidome.
ABSTRACT: Lipidomics of human blood plasma is an emerging biomarker discovery approach that compares lipid profiles under pathological and physiologically normal conditions, but how a healthy lipidome varies within the population is poorly understood. By quantifying 281 molecular species from 27 major lipid classes in the plasma of 71 healthy young Caucasians whose 35 clinical blood test and anthropometric indices matched the medical norm, we provided a comprehensive, expandable and clinically relevant resource of reference molar concentrations of individual lipids. We established that gender is a major lipidomic factor, whose impact is strongly enhanced by hormonal contraceptives and mediated by sex hormone-binding globulin. In lipidomics epidemiological studies should avoid mixed-gender cohorts and females taking hormonal contraceptives should be considered as a separate sub-cohort. Within a gender-restricted cohort lipidomics revealed a compositional signature that indicates the predisposition towards an early development of metabolic syndrome in ca. 25% of healthy male individuals suggesting a healthy plasma lipidome as resource for early biomarker discovery.
Project description:Plasma metabolomics and lipidomics have been commonly used for biomarker discovery. Studies in white and Japanese populations suggested that gender and age can affect circulating plasma metabolite profiles; however, the metabolomics characteristics in Chinese population has not been surveyed. In our study, we applied liquid chromatography-mass spectrometry-based approach to analyze Chinese plasma metabolome and lipidome in a cohort of 534 healthy adults (aging from 15 to 79). Fatty-acid metabolism was found to be gender- and age-dependent in Chinese, similar with metabolomics characteristics in Japanese and white populations. Differently, lipids, such as TGs and DGs, were found to be gender-independent in Chinese population. Moreover, nicotinate and nicotinamide metabolism was found to be specifically age-related in Chinese. The application of plasma metabolome and lipidome for renal cell carcinoma diagnosis (143 RCC patients and 34 benign kidney tumor patients) showed good accuracy, with an area under the curve (AUC) of 0.971 for distinction from healthy control, and 0.839 for distinction from the benign. Bile acid metabolism was found to be related to RCC probably combination with intestinal microflora. Definition of the variation and characteristics of Chinese normal plasma metabolome and lipidome might provide a basis for disease biomarker analysis.
Project description:<h4>Objective</h4>To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals.<h4>Design</h4>Systematic review of the published literature.<h4>Methods</h4>We searched PubMed, POPLINE, and EMBASE for peer-reviewed publications of studies (in any language) from inception to 21 September 2015. We included studies of women using hormonal contraceptives and antiretrovirals concurrently. Outcomes of interest were effectiveness of either therapy, toxicity, or pharmacokinetics. We used standard abstraction forms to summarize and assess strengths and weaknesses.<h4>Results</h4>Fifty reports from 46 studies were included. Most antiretrovirals whether used for therapy or prevention, have limited interactions with hormonal contraceptive methods, with the exception of efavirenz. Although depot medroxyprogesterone acetate is not affected, limited data on implants and combined oral contraceptive pills suggest that efavirenz-containing combination antiretroviral therapy may compromise contraceptive effectiveness of these methods. However, implants remain very effective despite such drug interactions. Antiretroviral plasma concentrations and effectiveness are generally not affected by hormonal contraceptives.<h4>Conclusion</h4>Women taking antiretrovirals, for treatment or prevention, should not be denied access to the full range of hormonal contraceptive options, but should be counseled on the expected rates of unplanned pregnancy associated with all contraceptive methods, in order to make their own informed choices.
Project description:OBJECTIVES:Sex steroid hormones may explain known gender-related variations in asthma prevalence and clinical manifestation. We investigated the relationship between use of hormonal contraceptives and asthma in women, and assessed evidence of biological interaction between use of hormonal contraceptives and body mass index in this relationship. DESIGN:Population-based analysis using data from serial (i.e. 2003, 2008 and 2010) Scottish Health Surveys. SETTING:Random samples of the Scottish general population. PARTICIPANTS:A total of 3257 non-pregnant, 16-45-year-old women. EXPOSURE:Current use of hormonal contraceptives. MAIN OUTCOME MEASURES:Self-reported current physician-diagnosed asthma, current wheezing symptoms, wheezing attacks and treatment for asthma or wheeze. RESULTS:Women comprising 30.9% (95% confidence interval 29.3-32.5) were currently using any hormonal contraceptive and current physician-diagnosed asthma was present in 6.5% (95% confidence interval 5.7-7.4). Use of any hormonal contraceptive was associated with reduced risk of current physician-diagnosed asthma (odds ratio 0.68; 95% confidence interval 0.47-0.98) and receiving ?3 asthma care episodes (odds ratio 0.45; 95% confidence interval 0.25-0.82), but the evidence was equivocal for wheezing attacks. Use of hormonal contraceptives among overweight or obese women was non-statistically significantly associated with asthma, but there was 42-135% increased risk in overweight and obese non-contraceptive using women. CONCLUSIONS:Use of hormonal contraceptives may reduce asthma exacerbations and number of care episodes. Overweight and obese non-contraceptive-using women may be at increased risk of asthma. Prospective studies are now needed to confirm these findings. Both oestrogen and progesterone may stimulate smooth airway muscle function and inhibit the activities of TH2 responses. Future studies should investigate these underlying mechanisms.
Project description:Family planning options, including hormonal contraceptives, are essential for improving reproductive health among the more than 17 million women living with HIV worldwide. For these women, prevention of unintended pregnancy decreases maternal and child mortality, as well as reduces the risk of perinatal HIV transmission. Similarly, treatment of HIV with antiretroviral therapy (ART) is essential for reducing morbidity and mortality among HIV-positive individuals, as well as preventing HIV transmission between sexual partners or from mother to child. Importantly, despite the benefits of hormonal contraceptives, barriers to effective family planning methods exist for HIV-positive women. Specifically, drug-drug interactions can occur between some antiretroviral medications and some hormonal contraceptives, which may influence both contraceptive efficacy and tolerability. In addition, safety concerns have been raised about the impact of hormonal contraceptives on HIV disease progression, tolerability, and the risk of female-to-male HIV transmission. This review article summarizes the potential for drug-drug interactions, tolerability, and contraceptive effectiveness when hormonal contraceptives are combined with ART. In addition, the evidence surrounding the influence of hormonal contraceptives on HIV transmission and HIV disease progression in women living with HIV are summarized.
Project description:OBJECTIVE:To examine the use of hormonal contraceptives among immigrant and native women in Norway. DESIGN:Nationwide registry-based study based on merged data from the Norwegian Prescription Database, the Norwegian Population Registry, the Regular General Practitioner Database and the Medical Birth Registry. SETTING:Norway. SAMPLE:All women born abroad to two foreign-born parents (immigrants), or born in Norway to two Norwegian-born parents (natives) aged 16-45 years, who lived in Norway in 2008. METHODS:Data on all collected supplies of hormonal contraceptives in 2008 were merged with demographic, socio-economic and immigration data, information on any delivery and women's general practitioners. MAIN OUTCOME MEASURES:User rates of hormonal contraception and predictors of contraceptive use. RESULTS:A total of 893,073 women were included, of whom 130,080 were immigrants. More native women (38%) used hormonal contraceptives compared with all immigrant groups (15-24%). The odds ratios for any use of hormonal contraceptives for immigrants compared with Norwegian-born women were; Nordic countries 0.53, South and Central America 0.53, Western countries 0.39, Asia 0.30, Eastern Europe 0.29, Africa 0.29. Work, education, long stay in Norway and young age of immigration predicted the use of hormonal contraceptives among immigrants. CONCLUSIONS:The use of hormonal contraceptives varies between natives and immigrant groups. Further work is needed to ascertain whether these differences can be explained by higher desires for fertility, preferential use of non-hormonal contraceptives or other reasons identified through qualitative research.
Project description:It is widely accepted that free radicals in tobacco smoke lead to oxidative stress and generate the popular lipid peroxidation biomarker 8-iso-prostaglandin F2? (8-iso-PGF2?). However, 8-iso-PGF2? can simultaneously be produced in vivo by the prostaglandin-endoperoxide synthases (PGHS) induced by inflammation. This inflammation-dependent mechanism has never been considered as a source of elevated 8-iso-PGF2? in tobacco smokers. The goal of this study is to quantify the distribution of chemical- and PGHS-dependent 8-iso-PGF2? formation in the plasma of tobacco smokers and non-smokers. The influences of gender and hormonal contraceptive use were accounted for. The distribution was determined by measuring the 8-iso-PGF2?/prostaglandin F2? (PGF2?) ratio. When comparing smokers (n = 28) against non-smokers (n = 30), there was a statistically significant increase in the 8-iso-PGF2? concentration. The source of this increased 8-iso-PGF2? was primarily from PGHS. When stratifying for gender, the increase in 8-iso-PGF2? in male smokers (n = 9) was primarily from PGHS. Interestingly, female smokers on hormonal contraceptives had increased 8-iso-PGF2? in both pathways, whereas those not on hormonal contraceptives did not have increased 8-iso-PGF2?. In conclusion, increased plasma 8-iso-PGF2? in tobacco smokers has complex origins, with PGHS-dependent formation as the primary source. Accounting for both pathways provides a definitive measurement of both oxidative stress and inflammation.
Project description:Perception of emotional valence and emotional memory performance vary across the menstrual cycle. However, the consequences of altered ovarian hormone levels due to the intake of hormonal contraceptives on these emotional and cognitive processes remain to be established. In the present study, which included 2169 healthy young females, we show that hormonal contraceptives (HC) users rated emotional pictures as more emotional than HC-non-users and outperformed non-users in terms of better memory recall of emotional pictures. The observed association between HC-status and memory performance was partially mediated by the perception of emotional picture valence, indicating that increased valence ratings of emotional pictures in HC-users led to their better emotional memory performance. These findings extend the knowledge about the relation of HC-intake with emotional valence perception and emotional memory performance. Further, the findings might stimulate further research investigating the interrelation of enhanced memory for emotional events and the increased risk for anxiety-related psychiatric disorders in women.
Project description:Recent advances in mass spectrometry-based techniques have inspired research into lipidomics, a subfield of '-omics', which aims to identify and quantify large numbers of lipids in biological extracts. Although lipidomics is becoming increasingly popular as a screening tool for understanding disease mechanisms, it is largely unknown how the lipidome naturally varies by age and sex in healthy individuals. We aimed to identify cross-sectional associations of the human lipidome with 'physiological' ageing, using plasma from 100 subjects with an apolipoprotein E (APOE) E3/E3 genotype, and aged between 56 to 100 years. Untargeted analysis was performed by liquid chromatography coupled-mass spectrometry (LC-MS/MS) and data processing using LipidSearch software. Regression analyses confirmed a strong negative association of age with the levels of various lipid, which was stronger in males than females. Sex-related differences include higher LDL-C, HDL-C, total cholesterol, particular sphingomyelins (SM), and docosahexaenoic acid (DHA)-containing phospholipid levels in females. Surprisingly, we found a minimal relationship between lipid levels and body mass index (BMI). In conclusion, our results suggest substantial age and sex-related variation in the plasma lipidome of healthy individuals during the second half of the human lifespan. In particular, globally low levels of blood lipids in the 'oldest old' subjects over 95 years could signify a unique lipidome associated with extreme longevity.
Project description:Women are at substantially greater risk for anterior cruciate ligament (ACL) injuries than are men.To conduct a systematic review and meta-analysis of the literature to clarify the effect of the menstrual cycle and contraceptives on the laxity of and noncontact injuries to the ACL.Systematic review; Level of evidence, 4.Searches were conducted using MEDLINE (1946-August 2016), the Cochrane Library Database, clinical trial registries, and related reference lists. Search terms included athletic injuries, knee injuries, ligaments, joint instability, menstrual cycle, ovulation, hormones, and contraceptives. Investigators independently dually abstracted and reviewed study details and quality using predefined criteria and evaluated overall strength of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria.Twenty-one studies totaling 68,758 participants were included: 5 on the menstrual cycle and ACL injury, 7 on hormonal contraceptives and ACL injury, as well as 13 on menstrual cycle and ligament laxity. Four of 5 studies of women not using hormonal contraception indicated that the luteal phase was the least associated with ACL injuries. The 2 largest and highest quality studies on hormonal contraceptives suggested that hormonal contraceptives may be protective against ACL injury. Six of 12 studies on ACL laxity provided quantitative data for meta-analysis, finding significantly increased laxity during the ovulatory phase compared with the follicular phase.The literature suggests an association between hormonal fluctuations and ACL injury. Recent studies have suggested that oral contraceptives may offer up to a 20% reduction in risk of injury. The literature on ACL injuries and the menstrual cycle has more than doubled over the past decade, permitting quantitative analysis for the first time. However, the overall strength of this evidence is low. Promising potential directions for future research include long-term observational studies with ongoing hormonal assays and large interventional trials of follicular suppression, including newer hormonal methods.
Project description:Although the transcriptome, proteome, and interactome of several eukaryotic model organisms have been described in detail, lipidomes remain relatively uncharacterized. Using Saccharomyces cerevisiae as an example, we demonstrate that automated shotgun lipidomics analysis enabled lipidome-wide absolute quantification of individual molecular lipid species by streamlined processing of a single sample of only 2 million yeast cells. By comparative lipidomics, we achieved the absolute quantification of 250 molecular lipid species covering 21 major lipid classes. This analysis provided approximately 95% coverage of the yeast lipidome achieved with 125-fold improvement in sensitivity compared with previous approaches. Comparative lipidomics demonstrated that growth temperature and defects in lipid biosynthesis induce ripple effects throughout the molecular composition of the yeast lipidome. This work serves as a resource for molecular characterization of eukaryotic lipidomes, and establishes shotgun lipidomics as a powerful platform for complementing biochemical studies and other systems-level approaches.