The fact that cell culture experiments (80), rat experiments (48–51), clinical observations of human patients undergoing sex-change therapies also demonstrate E2-concentration-dependent INS resistance or diabetes (27–29), third-trimester pregnancy (1–11), OHSS (16, 17), or PCOS (30–39, 47) are in the same concentration ranges as the in vitro effects suggests that the in vitro data can be extrapolated to in vivo cases. This evidence concerns the gene INS and diabetes mellitus.