Long-acting progestin-only contraceptives impair endometrial vasculature by inhibiting uterine vascular smooth muscle cell survival

Over a million unintended pregnancies occur in the United States each year because of either discontinuation or misuse of contraceptives. The major reason for discontinuation of long-acting progestin-only contraceptives (LAPCs) is the occurrence of abnormal uterine bleeding (AUB). Uncovering the mechanisms underlying LAPC-induced AUB is essential to prevent their discontinuation. We found that LAPCs reduce proliferation of human and guinea pig endometrial vascular smooth muscle cells (VSMCs), resulting in production of thin-walled hyperdilated fragile microvessels. In cultured VSMCs, chemokine (C-C motif) ligand 2 reverses LAPC-mediated inhibition of VSMC proliferation, suggesting that LAPCs impair endometrial vascular integrity and that chemokine ligand 2 administration may prevent LAPC-induced AUB.