These major factors have direct effects on anestrus but also interact with one or more other factors to control postpartum anestrus. Physiological mechanisms associated with anestrus involve blockage of the GnRH "pulse generator" in the hypothalamus, but other pathways also must be involved because bypassing the pulse generator is not an effective treatment for all cows. The primary cause of anestrus probably is different for different stages of anestrus. The mediating mechanisms for anestrus are not involved with prolactin, oxytocin, the adrenal or direct neural input from the mammary gland but are at least partially involved with blood glucose and the endogenous opioid peptide system. Management options to decrease the impact of anestrus and infertility include: 1) restrict breeding season to less than or equal to 45 d; 2) manage nutrition so body condition score is 5 to 7 before calving; 3) minimize effects of dystocia and stimulate estrous activity with a sterile bull and estrous synchronization; and 4) judicious use of complete, partial or short-term weaning.