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Hyperandrogenism sensitizes leukocytes to hyperglycemia to promote oxidative stress in lean reproductive-age women.

ABSTRACT: Hyperandrogenism and oxidative stress are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate oxidative stress.The purpose of this study was to determine the effect of oral androgen administration on fasting and glucose-stimulated leukocytic reactive oxygen species (ROS) generation, reduced nicotinamide adenine dinucleotide phosphate oxidase p47(phox) subunit gene expression, and plasma thiobarbituric acid-reactive substances (TBARS) in lean healthy reproductive-age women.Sixteen lean healthy ovulatory reproductive-age women were treated with 130 mg dehydroepiandrosterone (DHEA) or placebo (n = 8 each) for 5 d in this randomized, controlled, double-blind study that was performed at an an academic medical center.Leukocytic ROS generation, p47(phox) gene expression, and plasma TBARS were quantified in the fasting state and 2 h after glucose ingestion, before and after treatment.Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens or any prooxidant markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-sulfate, increased the percent change in glucose-challenged p47(phox) RNA content, and increased the percent change in fasting and glucose-challenged ROS generation from mononuclear cells and polymorphonuclear cells, p47(phox) protein content, and plasma TBARS.Elevation of circulating androgens comparable to what is present in PCOS increases leukocytic ROS generation, p47(phox) gene expression, and plasma TBARS to promote oxidative stress in lean healthy reproductive-age women. Thus, hyperandrogenemia activates and sensitizes leukocytes to glucose in this population.

SUBMITTER: Gonzalez F

PROVIDER: S-EPMC3410256 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Hyperandrogenism sensitizes leukocytes to hyperglycemia to promote oxidative stress in lean reproductive-age women.

González Frank F Nair K Sreekumaran KS Daniels Janice K JK Basal Eati E Schimke Jill M JM Blair Hilary E HE

The Journal of clinical endocrinology and metabolism 20120508 8

<h4>Context</h4>Hyperandrogenism and oxidative stress are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate oxidative stress.<h4>Objective</h4>The purpose of this study was to determine the effect of oral androgen administration on fasting and glucose-stimulated leukocytic reactive oxygen species (ROS) generation, reduced nicotinamide adenine dinucleotide phosphate oxidase p47(phox) subunit gene expression, and plasma thiobarbituric acid-reacti ...[more]

PMID: 22569241

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Project description:Potentially teratogenic medications are frequently prescribed without provision of contraceptive counseling.To evaluate whether computerized clinical decision support (CDS) can increase primary care providers' (PCPs') provision of family planning services when prescribing potentially teratogenic medications.Cluster-randomized trial conducted in one academic and one community-based practice between October of 2008 and April of 2010.Forty-one PCPs were randomized to receive one of two types of CDS which alerted them to risks of medication-induced birth defects when ordering potentially teratogenic medications for women who may become pregnant. The 'simple' CDS provided a cautionary alert; the 'multifaceted' CDS provided tailored information and links to a structured order set designed to facilitate safe prescribing. Both CDS systems alerted PCPs about medication risk only once per encounter.We assessed change in documented provision of family planning services using data from 35,110 encounters and mixed-effects models. PCPs completed surveys before and after the CDS systems were implemented, allowing assessment of change in PCP-reported counseling about the risks of medication-induced birth defects and contraception.Both CDS systems were associated with slight increases in provision of family planning services when potential teratogens were prescribed, without a significant difference in improvement by CDS complexity (p = 0.87). Because CDS was not repeated, 13% of the times that PCPs received CDS they substituted another potential teratogen. PCPs reported significant improvements in several counseling and prescribing practices. The multifaceted group reported a greater increase in the number of times per month they discussed the risks of medication use during pregnancy (multifaceted: +4.9 ± 7.0 vs. simple: +0.8 ± 3.2, p = 0.03). The simple CDS system was associated with greater clinician satisfaction.CDS systems hold promise for increasing provision of family planning services when fertile women are prescribed potentially teratogenic medications, but further refinement of these systems is needed.

Project description:The human salivary microbial community plays a crucial role in local and systemic diseases. Biological and lifestyle factors such as menstrual cycle, oral hygiene, and smoking have been documented to impact this community. However, while hormonal contraceptives are the most prescribed drug in healthy women and intimate partners play key roles in microbial exchange between humans, their impact on the salivary microbiome of women of reproductive age have been understudied. Additionally, the role of other lifestyle factors such as diet, allergies, age, and stress on the saliva microbiome of the general population is not well understood. Here, we studied the salivary microbiome of 255 healthy women of reproductive age using self-sampling kits and 16S rRNA amplicon sequencing combined with questionnaires on lifestyle and host-related parameters. A preserved salivary bacterial community of 12 genera (Actinobacillus, Actinomyces, Alloprevotella, Campylobacter, Fusobacterium, Gemella, Granulicatella, Leptotrichia, Neisseria, Prevotella, Streptococcus, and Veillonella) was identified. Contrary to what we expected, the number of intimate partners or specific contraceptive use did not have a major impact on these bacterial communities. However, recent use of oral antibiotics was associated with a significant decrease in richness at genus level and increase in mean relative abundances of several taxa. Being stressed or nervous was associated with a significantly increased richness of the salivary microbiome at the level of amplicon sequencing variants . Nevertheless, these associations with host-related and lifestyle variables only appeared to be subtle, suggesting that the salivary microbiome is mainly driven by the buccal environment and health status of an individual. IMPORTANCE The salivary microbiome has been proven to play a crucial role in local and systemic diseases. Moreover, the effects of biological and lifestyle factors such as oral hygiene and smoking on this microbial community have already been explored. However, what was not yet well understood was the natural variation of the saliva microbiome in healthy women and how this is associated with specific use of hormonal contraception and with the number of different sexual partners with whom microbiome exchange is expected regularly. In this paper, we characterized the salivary microbiome of 255 healthy women of reproductive age using an in-depth questionnaire and self-sampling kits. Using the large metadata set, we were able to investigate the associations of several host-related and lifestyle variables with the salivary microbiome profiles. Our study shows a high preservation between individuals.

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Hyperandrogenism sensitizes leukocytes to hyperglycemia to promote oxidative stress in lean reproductive-age women.

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Hyperandrogenism sensitizes leukocytes to hyperglycemia to promote oxidative stress in lean reproductive-age women.

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