To answer this question, Hoeger randomized 43 adolescent girls with PCOS to either lifestyle intervention, estrogen-progestin (ethinyl estradiol + desogestrel) combination pills, metformin (1700 mg daily), or placebo for a six-month period, and demonstrated that groups randomized to lifestyle intervention and the combination pills (but not metformin) had increases in SHBG levels and reductions in free androgen index and in PAI-1 [133] despite only non-significant changes in weight in all groups. The gene discussed is SERPINE1; the disease is polycystic ovary syndrome.