Effects of steroid hormones on lipid metabolism in sexual dimorphism: A Mendelian randomization study

Liang, Junzhi; Zhang, Bowen; Hu, Yannan; Na, Zhijing; Li, Da

doi:10.3389/fendo.2022.1119154

Cited by 9 publications

(4 citation statements)

References 52 publications

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“…Meanwhile, it had a protective effect on GC and increased the incidence of SC. [48] A two-sample MR analysis has proven a risk-increasing relationship between lipid-lowering drugs targeting (statins) and HCC, [49] while genetically proxied HMGCR inhibitors were significantly risk-decreasing related to BC. [50] Further RCTs are needed to demonstrate separate roles of HMGCR inhibitors (statins) in overall cancers.…”

Section: Discussionmentioning

confidence: 99%

Causal association between lipid-lowering drugs and cancers: A drug target Mendelian randomization study

Ding,

Chen,

Xia

et al. 2024

Medicine

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Accumulating evidences have indicated that lipid-lowering drugs have effect for the treatment of cancers. However, causal associations between lipid-lowering drugs and the risk of cancers are still unclear. In our study, we utilized single nucleotide polymorphisms of proprotein convertase subtilis kexin 9 (PCSK9) inhibitors and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors and performed a drug target Mendelian randomization to explore the causal association between lipid-lowering drugs and the risk of cancers. Five regression methods were carried out, including inverse variance weighted (IVW) method, MR Egger, weighted median, simple mode and weighted mode methods, of which IVW method was considered as the main analysis. Our outcome dataset contained the risk of breast cancer (BC), colorectal cancer, endometrial cancer, gastric cancer (GC), hepatocellular carcinoma (HCC), lung cancer, esophageal cancer, prostate cancer (PC), and skin cancer (SC). Our results demonstrated that PCSK9 inhibitors were significant associated with a decreased effect of GC [IVW: OR = 0.482, 95% CI: 0.264–0.879, P = .017]. Besides, genetic inhibitions of HMGCR were significant correlated with an increased effect of BC [IVW: OR = 1.421, 95% CI: 1.056–1.911, P = .020], PC [IVW: OR = 1.617, 95% CI: 1.234–2.120, P = .0005] and SC [IVW: OR = 1.266, 95% CI: 1.022–1.569, P = .031]. For GC [IVW: OR = 0.559, 95% CI: 0.382–0.820, P = .0029] and HCC [IVW: OR = 0.241, 95% CI: 0.085–0.686, P = .0077], HMGCR inhibitors had a protective risk. Our method suggested that PCSK9 inhibitors were significant associated with a protective effect of GC. Genetic inhibitions of HMGCR were significant correlated with an increased effect of BC, PC and SC. Meanwhile, HMGCR inhibitors had a protective risk of GC and HCC. Subsequent studies still needed to assess potential effects between lipid-lowering drugs and the risk of cancers with clinical trials.

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Section: Discussionmentioning

confidence: 99%

Causal association between lipid-lowering drugs and cancers: A drug target Mendelian randomization study

Ding,

Chen,

Xia

et al. 2024

Medicine

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“…PCOS is characterized by excessive androgen production [15,84]. In women, dehydroepiandrosterone negatively correlates with TC levels, whereas androstenedione is associated with lower TG and apoA levels [114]. A recent meta-analysis of 23 cohort studies found higher TC and lower HDL-C levels in women with PCOS compared to healthy controls [115].…”

Section: Female-specific Comorbiditiesmentioning

confidence: 99%

Sex aspects in lipoprotein metabolism, dyslipidemia, and lipid-lowering therapy: A comprehensive review

Zimodro,

Mucha,

Berthold

et al. 2024

Preprint

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Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

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“…This provides a reasonable explanation for PBF's greater protective effect among the older population. The TC*sex interactions may be related to sex-disparities in lipid metabolism, lifestyle patterns, pharmacological nonacceptance or therapeutic effects [32][33][34][35].…”

Section: Sensitivity Analysismentioning

confidence: 99%

Composite Lipid Parameters are Optimal in Predicting Chronic Kidney Disease Prognosis

Chen,

Xiao,

Chen

et al. 2023

Preprint

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Background Lipid management in clinic is critical to the prevention and treatment of CKD, while the manifestations of fat metabolism vary in type and have flexible correlations with CKD prognosis. Purpose Explore correlations between the widely used indicators of lipid metabolism in clinic and CKD prognosis; provide a reference for lipid management and treatment among non-dialysis CKD stages 3–5. Methods This is a retrospective cohort study utilizing the SMP-CKD database of 794 individuals with CKD stages 3–5. Variables with P < 0.10 in univariate Poisson models were induced to construct several timescale-based Poisson models with a stepwise regression according to lipid manifestation categories. We selected the best model via AIC, AUC and ROC and confirmed the independent relative exposures via RRs (95% CI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness. Results 255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.35 [48.50, 66.69] years with a median eGFR of 33.68 [17.55, 47.81] ml/min/1.73 m2. The fully adjusted category-based Poisson Model 4 in Dataset 5 had the largest AUC (0.717 [0.684, 0.751]) with P for ROC < 0.05. TC (1.158 [1.056, 1.271], P = 0.002) and PBF (0.948 [0.906, 0.992], P = 0.021) were significant factors of composite outcome and no manual measurements had any statistically significance. The

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Effects of steroid hormones on lipid metabolism in sexual dimorphism: A Mendelian randomization study

Cited by 9 publications

References 52 publications

Causal association between lipid-lowering drugs and cancers: A drug target Mendelian randomization study

Causal association between lipid-lowering drugs and cancers: A drug target Mendelian randomization study

Sex aspects in lipoprotein metabolism, dyslipidemia, and lipid-lowering therapy: A comprehensive review

Composite Lipid Parameters are Optimal in Predicting Chronic Kidney Disease Prognosis

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