Estrogens, Progestins, and Specific Estrogen Receptor Modulators (SERMs)

Biologically important natural estrogens and progestins include estradiol, estrone, estriol, and progesterone. Estradiol-17 is the most potent estrogen that is found naturally in women. Estrone is one-tenth as biologically active as estradiol, and estriol is the weakest of the three. Estriol is synthesized by the placenta and is excreted at high levels in the urine of pregnant women. Progesterone is the most important naturally occurring progestin. The ovary is the major site of estrogen and progestin biosynthesis in nonpregnant premenopausal women. In pregnant women, the fetoplacental unit is the major source of estrogens and progestins. Peripheral sites of estrogen synthesis include the liver, kidney, brain, adipose tissue, skeletal muscle, and testes. Progesterone is secreted in small amounts by the testes and adrenal gland.The combined estrogen and progestin production by all of these peripheral sites amounts to 10% or less of ovarian synthesis in normal premenopausal women. In postmenopausal women, ovarian steroid synthesis declines and peripheral estrogen biosynthesis accounts for all estrogen produced, both in postmenopausal women and in males. The naturally occurring estrogens and progestins are not orally active because they are rapidly metabolically inactivated. The major site of estrogen and progestin metabolism is the liver. Both are subject to firstD R U G L I S T Estrogens, Progestins, and Specific Estrogen Receptor Modulators (SERMs)