Oral contraceptives in adolescents: a retrospective population-based study on blood pressure and metabolic dysregulation.

PURPOSE: This study aimed to explore the relationship between oral contraceptive use and blood pressure values and in a national cohort of women adolescents and to investigate the level of coexistence of the high blood pressure levels, dyslipidemia or insulin resistance. METHODS: This is a retrospective cohort study that evaluated data form 14,299 adolescents aged 14 to 17 years. Crude and race-and age-adjusted analyses were performed using Poisson regression to estimate the prevalence ratios. Data clustering analysis was performed using machine learning approaches supported by an unsupervised neural network of self-organizing maps. RESULTS: We found that 14.5% (n = 2076) of the women adolescents use oral contraceptives. Moreover, an increased prevalence of high blood pressure, dyslipidemia, and insulin resistance (all P < 0.001) was observed among adolescents who use oral contraceptives as compared to those who do not. Our analysis also showed that 2.3% of adolescents using oral contraceptives had both high blood pressure levels and dyslipidemia, whereas 3.2% had high blood pressure levels combined with insulin resistance (all P < 0.001). The algorithmic investigative approach demonstrated that total cholesterol, LDLc, HDLc, insulin, and HOMA-IR were the most predicted variables to assist classificatory association in the context of oral contraceptive use among women adolescents with high blood pressure. CONCLUSIONS: These findings suggest that oral contraceptives were associated with an increased prevalence of high blood pressure, dyslipidemia, and insulin resistance among women adolescents. Although the indication of this therapy is adequate to avoid unintended pregnancies, their use must be based on rigorous individual evaluation and under constant control of the cardiometabolic risk factors.

High uric acid levels in overweight and obese children and their relationship with cardiometabolic risk factors: what is missing in this puzzle?

OBJECTIVES: The prevalence of hyperuricemia, a common disorder, has been increasing. Moreover, the association between obesity, serum uric acid levels, and cardiometabolic markers in children is unclear. Therefore, this study aimed to analyze the inter-relationships between these factors in a sample of children aged 6-12 years. METHODS: We evaluated 764 children and stratified them according to their body mass index (BMI). Blood pressure and uric acid, creatinine, lipid, and glycemic profiles were evaluated, and the estimated glomerular filtration rate (eGFR) and the homeostatic model assessment for insulin resistance (HOMA-IR) index were calculated. RESULTS: There was a significant linear trend of increasing systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), total cholesterol, low-density lipoprotein cholesterol (LDLc), uric acid, insulin levels, and HOMA-IR index values corresponding with overweight and obese groups; however, high-density lipoprotein cholesterol (HDLc) levels decreased with increasing obesity. The mean creatinine level and eGFR were similar across all BMI groups. Uric acid levels were significantly correlated with BMI (r=0.527), waist circumference (r=0.580), SBP (r=0.497), DBP (r=0.362), TG (r=0.534), total cholesterol (r=0.416), LDLc (r=0.286), HDLc (r=-0.248), insulin (r=0.613), and HOMA-IR index (r=0.607). Multiple regression analyses showed that BMI (B=0.071; SE=0.012; p<0.001), TG (B=0.004; SE=0.001; p<0.001), LDLc (B=0.003; SE=0.001; p=0.006), and insulin (B=0.066; SE=0.007; p<0.001) (R2=0.460) were significant predictors of increased uric acid levels and explained 46% of the variability in uric acid in these children. CONCLUSIONS: Our findings suggest that overweight or obese children are more likely to have higher uric acid levels. Moreover, several cardiometabolic risk factors were strongly associated with high uric acid levels.

Treatment with Standard and Low Dose of Conjugated Equine Estrogen Differentially Modulates Estrogen Receptor Expression and Response to Angiotensin II in Mesenteric Venular Bed of Surgically Postmenopausal Hypertensive Rats.

Standard hormone therapy for menopausal women [conjugated equine estrogen (CEE) 0.625 mg] has been associated with increased risk of venous thrombosis. Regimens containing a lower CEE dose (0.30 mg) have been used clinically to decrease side effects of supraphysiologic doses of estrogen. In this study, we determined the effects of standard (SD) and low dose (LD) of CEE on venular function in ovariectomized (OVX) spontaneously hypertensive rats (SHR). Contractions by angiotensin-II (Ang-II 10 µM) in perfused mesenteric venular bed were markedly increased in OVX (21.5 ± 1.3 mmHg) compared with Sham (14.7 ± 1.1 mm Hg, P < 0.05). CEE-SD did not modify Ang-II responses in OVX, whereas CEE-LD restored Ang-II contraction to Sham levels. Endothelial nitric oxide synthase (eNOS) inhibition by L-NAME increased Ang-II contractions in Sham and CEE-LD and was without effect in venules of OVX SHR and CEE-SD. In OVX there was decreased NO generation in association with diminished eNOS phosphorylation and increased O2- generation in the venular wall. CEE-LD reverted the deleterious effects of ovariectomy. Although CEE-SD augmented eNOS phosphorylation in OVX, it was unable to increase NO levels, probably owing to its inability to reduce O2- Distinct effects by CEE-SD and CEE-LD parallel the differential modulation of Ang-II and estrogen receptors. Compared with Sham, CEE-LD increases Ang II receptor type 2, whereas CEE-SD modified ERß expression in the venous bed. Interestingly, both CEE doses increased G protein-coupled estrogen receptor in OVX. Our data suggest that estrogen dose is an important factor for venous function. Although CEE-LD reversed deleterious effects of OVX, CEE-SD showed null effects despite its ability to increase eNOS activity.