A small uncontrolled study on 45 men with MetS demonstrated that a 6-months metformin administration at a daily dose starting from 850 mg/day for the first week, gradually increased to 850 mg twice a day in the second week, and subsequently to 850 mg thrice a day, significantly reduced estradiol and SHBG, and increased LH, TT, and FT levels (26). The gene discussed is SHBG; the disease is metabolic syndrome.