The reason estradiol has such modest effects in women is unclear. One possible explanation is that the age-related increase in body weight that occurs in both men and women obscures the influence of menopause on body weight. That is, weight may have already increased when the inhibitory effect of estradiol declines at menopause.

An important aspect of the association between estradiol levels and eating in both animals and women is that increases in estradiol secretion precede the decrease in eating by 1 to 3 days. Peripheral estradiol replacement in oophorectomized animals requires a similar period to inhibit eating. Presumably, increases in estradiol elicit a physiologic cascade of events that requires this amount of time to affect eating. A similar phenomenon occurs with estradiol-induced sexual receptivity in oophorectomized rats. Estradiol binding in the ventromedial hypothalamic area, where estradiol acts to induce sexual receptivity, peaks 1 to 2 hours after peripheral estradiol treatment in oophorectomized rats, but sexual receptivity does not increase for at least 24 hours.[13] Part of the challenge in understanding estradiol's effects on eating is to determine the cellular events that bridge this period.

Meal size is usually the predominant determinant of total food intake, and estradiol selectively reduces meal size in animals. Therefore, the treatment of women who suffer from abnormal eating behaviors requires an understanding of the physiology of eating, particularly the control of meal size.