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Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Causal association between lipid-lowering drugs and female reproductive endocrine diseases: a drug-targeted Mendelian
Jing Zhao1, Runfang Wang2, Liyun Song1
1Department of Gynecology, Hebei General Hospital, Shijiazhuang, China.
Purpose:
The relationship between dyslipidemia and female reproductive endocrine diseases has been increasingly studied. The use of lipid-lowering drugs in treating various related diseases, including coronary heart disease, may affect female reproductive endocrine diseases. Therefore, our study aims to investigate the effects of lipid-lowering drugs on female reproductive endocrine diseases and provide a basis for the appropriate selection of drugs.
Methods:
In this study, we focused on three drug targets of statins, namely HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase kexin 9 (PCSK9) inhibitors, and Niemann-Pick C1-Like 1 (NPC1L1) inhibitors. To identify potential inhibitors for these targets, we collected single nucleotide polymorphisms (SNPs) associated with HMGCR, PCSK9, and NPC1L1 from published genome-wide association study statistics. Subsequently, we conducted a drug target Mendelian randomization (MR) analysis to investigate the effects of these inhibitors on reproductive endocrine diseases mediated by low-density lipoprotein cholesterol (LDL-C) levels. Alongside coronary heart disease as a positive control, our main outcomes of interest included the risk of polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), premenstrual syndrome (PMS), abnormal uterine bleeding (including menorrhagia and oligomenorrhea), and infertility.
Results:
PCSK9 inhibitors significantly increased the risk of infertility in patients (OR [95%CI] = 1.14 [1.06, 1.23], p<0.05). In contrast, HMGCR inhibitors significantly reduced the risk of menorrhagia in female patients (OR [95%CI] = 0.85 [0.75, 0.97], p<0.05), but had no statistical impact on patients with oligomenorrhea.
Conclusion:
The findings suggest that PCSK9 inhibitors may significantly increase the risk of infertility in patients. On the other hand, HMGCR inhibitors could potentially offer protection against menorrhagia in women. However, no effects of lipid-lowering drugs have been observed on other reproductive endocrine disorders, such as PCOS, POF, PMS and oligomenorrhea.
Insights
PCSK9 inhibitors may increase infertility risk, while HMGCR inhibitors may reduce menorrhagia. Lipid-lowering drugs showed no effect on PCOS, POI, PMS, or oligomenorrhea in this study.
Area of Science:
- Endocrinology
- Pharmacology
- Genetics
Background:
- Dyslipidemia is increasingly linked to female reproductive endocrine diseases.
- Lipid-lowering drugs used for conditions like coronary heart disease may impact female reproductive health.
- Understanding these drug effects is crucial for safe and effective treatment selection.
Purpose of the Study:
- To investigate the impact of specific lipid-lowering drug targets on female reproductive endocrine diseases.
- To provide evidence-based guidance for choosing appropriate lipid-lowering therapies in women.
- To analyze the effects of HMGCR, PCSK9, and NPC1L1 inhibitors on reproductive health outcomes.
Main Methods:
- Utilized Mendelian randomization (MR) analysis with genome-wide association study data.
- Focused on three key drug targets: HMGCR, PCSK9, and NPC1L1 inhibitors.
- Assessed the risk of polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), premenstrual syndrome (PMS), abnormal uterine bleeding (menorrhagia, oligomenorrhea), and infertility.
Main Results:
- PCSK9 inhibitors were associated with a significant increase in infertility risk (OR [95%CI] = 1.14 [1.06, 1.23]).
- HMGCR inhibitors significantly reduced the risk of menorrhagia (OR [95%CI] = 0.85 [0.75, 0.97]).
- No significant effects were observed for HMGCR inhibitors on oligomenorrhea or for any of the studied drugs on PCOS, POI, or PMS.
Conclusions:
- PCSK9 inhibitors may elevate infertility risk in women.
- HMGCR inhibitors show potential protective effects against menorrhagia.
- Current evidence does not support a link between these lipid-lowering drug targets and other major reproductive endocrine disorders like PCOS or POI.
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