Estrogen is a generic term for a class of steroid hormones that includes 17β-estradiol, estrone, and estriol. Estrogens are synthesized from the hormone testosterone by the enzyme aromatase. Although both men and women produce estrogens, women have more of the aromatase enzyme, so they produce much more estrogens than men. Estrogens are produced in the ovaries, testes, placenta, and the adrenal cortex. In men, estrogens synthesized from testosterone promote mating behavior and bone development.
In women, estrogens are produced in the ovaries in response to hormones released by the brain (luteinizing hormone and follicle-stimulating hormone). Estrogens and progestins (a related class of steroid hormones) are released by the ovaries of postpubertal and premenopausal women in a cyclic fashion. During the menstrual cycle, estrogens promote the maturation of an egg-containing follicle in the ovary, stimulate ovulation, and produce an environment in the female genitalia suitable for fertilization, implantation, and nourishment of an embryo. Estrogens are also involved in the development of female secondary sexual characteristics, female sexual behavior, and maternal behavior. Further, estrogens promote water retention, lipid and calcium metabolism, and bone growth. High levels of estrogens in women have been linked to improved memory function, particularly verbal memory function. Exogenous estrogens are used in oral contraceptives and in treatments for female hypogonadism, primary ovarian failure, and menopausal symptoms (see below). Because estrogens promote the growth of breast and uterine tissue, antiestrogen drugs such as tamoxifen or raloxifene are used to prevent and treat breast and uterine cancer. These drugs are termed “selective estrogen receptor modulators” (or SERMS) because they prevent the actions of estrogens in certain tissues (e.g., breast, uterus) while promoting estrogenic effects (e.g., on bone and lipid metabolism) elsewhere in the body.
Estrogens are also critically involved in early development. In female animals, an excess of estrogen just after birth can lead to male-like mating behaviors and cognitive function in adulthood. In women, the disorder, termed Turner syndrome, illustrates the importance of estrogens in normal development. Turner syndrome results from the congenital lack of the second X chromosome, which leads to an incomplete formation of the ovaries, a failure to produce estrogens and progestins, and infertility. Without estrogen therapy, girls with Turner’s syndrome fail to undergo puberty. A short stature, hearing loss, kidney dysfunction, and webbing of the neck are often observed in these patients. Turner syndrome patients are also deficient in visuospatial and verbal memory, deficits that can be reduced by long-term estrogen treatment.
As women age, levels of estrogens and progestins decline significantly, eventually leading to menopause (typically around age 50). Menopause is associated with a cessation of ovulation and menstrual cycling and a significant drop in estrogen and progestin levels, which results in symptoms such as hot flashes, mood swings, decreased sex drive, and vaginal dryness. Menopause is also associated with memory loss and increased risk of Alzheimer’s disease. Until recently, the hormone replacement therapy (either estrogens alone or estrogens plus progestins) prescribed to menopausal women was thought to prevent heart disease, osteoporosis, colon cancer, and memory loss. However, recent data from the large multicenter Women’s Health Initiative clinical trial indicate that 5 years of estrogen plus progestin replacement produces a small but significant increase in the incidence of heart disease, stroke, breast cancer, and memory loss (although it reduced the incidence of osteoporosis and colon cancer), and estrogen replacement alone increases the risk of stroke. These data have led to the recommendation that hormone replacement be used to relieve menopausal symptoms only for short durations and in low doses.
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