PRF1 and hyperandrogenism: Furthermore, the expansion of the cytotoxic CD4+CD28null T cell subpopulation in PCOS and the association of perforin/granzyme-B levels with hyperandrogenism in PCOS strongly suggest a high risk of immune-mediated CVD and kidney dysfunction in PCOS [94], similar to patients with acute coronary syndrome, atherosclerosis, renal diseases, and CVD [35,42,47,67,84,85,94,106,121,122].