Although it is premature to conclude that estrogen plus progestin use is unassociated with ovarian cancer risk, particularly given the conflicting findings, research on ovulating macaques suggests that progesterone offsets the effect of unopposed estrogen use by increasing apoptosis in the ovary (Rodriguez et al, 1998), possibly by altering levels of TGF-β, a regulator of apoptosis (Rodriguez et al, 2002). This evidence concerns the gene TGFB1 and ovarian carcinoma.