Estradiol is the primary reproductive hormone in nonpregnant women.^2,3 This steroid hormone plays an important role in normal fetal development and in the development of secondary sexual characteristics in females. Estradiol influences the maturation and maintenance of the uterus during the normal menstrual cycle. Levels of estradiol steadily increase during the follicular phase of the menstrual cycle in association with the growth and development of the ovarian follicle. As the follicular phase proceeds, estradiol exerts a negative feedback control on the pituitary, resulting in a drop in FSH levels. Near the end of the follicular phase, there is a dramatic increase in estradiol levels. At this point, the feedback of estradiol on the hypothalamus becomes positive and produces the midcycle surge of LH which immediately precedes ovulation. After ovulation, estradiol levels initially fall abruptly, but then increase as the corpus luteum forms. At the end of the cycle, levels fall off in anticipation of the initiation of the next follicular phase. During pregnancy, the placenta produces estradiol. Estradiol levels are generally low in menopause due to diminished ovarian production.

A small amount of estradiol is produced by the male testes.^2,3 Elevated levels in males can lead to gynecomastia. Increased estradiol levels in males may be caused by increased body fat, resulting in enhanced peripheral aromatization of androgens. Levels in men can also be increased by excessive use of marijuana, alcohol, or prescribed drugs, including phenothiazines and spironolactone. Estradiol levels can also be dramatically elevated in germ cell tumors and tumors of a number of glands in both men and women.