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By reducing the number of LDL receptors (LDLR) on the surface of liver cells, PCSK9 leads to the accumulation of LDL-C, increasing the risk of CVDs

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Additionally, E2 is known to be able to signal through the insulin-like growth factor 1 receptor (IGF-1R) in the skin in a non-genomic manner and this process has been implicated in the regulation of cutaneous aging (Serizawa et al., 2017)

Not only does it make them less bioavailable, but they often come with gastrointestinal side effects such as stomach pain, diarrhea and vomiting