Finally, MVMR of fasting insulin, SHBG, BMI and testosterone and their effect on endometrial cancer, attenuated the significance of association (P > 0.5) of fasting insulin and bioavailable testosterone with the outcome, while SHBG and BMI remained significant, but with a modest decrease in effect size (ORMVMR = 0.61, PMVMR = 0.02 and ORMVMR = 1.65, PMVMR = 6.37 × 10−5). Hence this suggests that bioavailable testosterone and fasting insulin do not have an independent effect on endometrial cancer risk and the associations are likely to be mediated, at least in part, through SHBG and BMI. The gene discussed is INS; the disease is endometrial cancer.