The major estrogen secreted by the ovary is 17β-estradiol; this is converted to estrone in the blood. Estriol is the principal estrogen formed by the placenta during pregnancy. These three compounds, 17β-estradiol, estrone, and estriol, account for most of the estrogenic activity in humans.
The ability of estrogens to suppress secretion of follicle-stimulating hormone (FSH) by the pituitary gland and thereby inhibit ovulation makes estrogen and estrogenlike compounds major components in oral contraceptives. Estrogen replacement therapy (ERT) uses synthetic estrogen (e.g., Premarin), typically given with progestins (e.g., Provera) to treat the physical changes of menopause, including hot flashes and vaginal dryness. ERT also retards the development of osteoporosis in postmenopausal women but increases the risk of breast cancer, heart attack (see infarction), stroke, and, when not given with progestins, uterine cancer. Estrogens are also used to treat prostate cancer.
Any of a class of hormones that primarily influence the female reproductive system's development, maturation, and function. The three major estrogens—estradiol, estrone, and estriol—are produced mainly by the ovaries and placenta; the adrenal glands and the testes secrete smaller amounts. Estrogens affect the ovaries, vagina, fallopian tubes, uterus, and mammary glands and play crucial roles in puberty, menstruation, pregnancy, and parturition (labour). They also influence the structural differences between female and male bodies. In experimental animals, loss of estrogens diminishes mating desires and other behavioral patterns.
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Like all steroid hormones, estrogens readily diffuse across the cell membrane; inside the cell, they interact with estrogen receptors. Additionally, estrogens have been shown to activate a G protein-coupled receptor, GPR30.
Premarin, a commonly prescribed estrogenic drug, contains the steroidal estrogens equilin and equilenin, in addition to estrone sulfate. A range of synthetic and natural substances have been identified that also possess estrogenic activity. Synthetic substances of this kind are known as xenoestrogens, plant products with estrogenic activity are called phytoestrogens, and those produced by fungi are known as mycoestrogens. Unlike estrogens produced by mammals, these substances are not necessarily steroids.
Estrogen is produced primarily by developing follicles in the ovaries, the corpus luteum, and the placenta. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) stimulate the production of estrogen in the ovaries. Some estrogens are also produced in smaller amounts by other tissues such as the liver, adrenal glands, and the breasts. These secondary sources of estrogen are especially important in postmenopausal women.
Synthesis of estrogens starts in theca interna cells in the ovary, by the synthesis of androstenedione from cholesterol. Androstenedione is a substance of moderate androgenic activity. This compound crosses the basal membrane into the surrounding granulosa cells, where it is converted to estrone or estradiol, either immediately or through testosterone. The conversion of testosterone to estradiol, and of androstenedione to estrone, is catalyzed by the enzyme aromatase.
Estradiol levels vary through the menstrual cycle, with levels highest just before ovulation.
As more fully discussed in the article on Hormone replacement therapy, estrogen and other hormones are given to postmenopausal women in order to prevent osteoporosis as well as treat the symptoms of menopause such as hot flashes, vaginal dryness, urinary stress incontinence, chilly sensations, dizziness, fatigue, irritability, and sweating. Fractures of the spine, wrist, and hips decrease by 50-70% and spinal bone density increases by ~5% in those women treated with estrogen within 3 years of the onset of menopause and for 5-10 years thereafter.
Before the specific dangers of conjugated equine estrogens were well understood, standard therapy was 0.625 mg/day of conjugated equine estrogens (such as Premarin). There are, however, risks associated with conjugated equine estrogen therapy. Among the older postmenopausal women studied as part of the Women's Health Initiative (WHI), an orally-administered conjugated equine estrogen supplement was found to be associated with an increased risk of dangerous blood clotting. The WHI studies used one type of estrogen supplement, a high oral dose of conjugated equine estrogens (Premarin alone and with medroxyprogesterone acetate as PremPro).
In a study by the NIH, esterified estrogens were not proven to pose the same risks to health as conjugated equine estrogens. Hormone replacement therapy has favorable effects on serum cholesterol levels, and when initiated immediately upon menopause reduces the incidence of cardiovascular disease. Estrogen has a protector effect on atherosclerosis : it lowers LDL and triglycerides, it raises HDL levels and has endothelial vasodilatation properties plus an anti-inflammatory component.
Research is underway to determine if risks of estrogen supplement use are the same for all methods of delivery. In particular, estrogen applied topically may have a different spectrum of side-effects than when administered orally, and transdermal oestrogens do not affect clotting as they are absorbed directly into the systemic circulation, avoiding first-pass metabolism in the liver. This route of administration is thus preferred in women with a history of thrombo-embolic disease.
Estrogen is also used in the therapy of vaginal atrophy, hypoestrogenism (as a result of hypogonadism, castration, or primary ovarian failure), amenorrhea, dysmenorrhea, and oligomenorrhea. Estrogens can also be used to suppress lactation after child birth.
Hormone-receptor-positive breast cancers are treated with drugs which suppress production in the body of estrogen. This technique, in the context of treatment of breast cancer, is known variously as hormonal therapy, hormone therapy, or anti-estrogen therapy (not to be confused with hormone replacement therapy). Certain foods such as soy may also suppress the proliferative effects of estrogen and are used as an alternative to hormone therapy.
In humans and mice, estrogen promotes wound healing.
At one time, estrogen was used to induce growth attenuation in tall girls. Recently, estrogen-induced growth attenuation was used as part of the controversial Ashley Treatment to keep a developmentally disabled girl from growing to adult size.
Under certain circumstances, estrogen may also be used in males for treatment of prostate cancer.
Most recently, estrogen has been used in experimental research as a way to treat patients suffering from bulimia nervosa, in addition to Cognitive Behavioral Therapy, which is the established standard for treatment in bulimia cases. The estrogen research hypothesizes that the disease may be linked to a hormonal imbalance in the brain.
Estrogen has also been used in studies which indicate that it may be an effective drug for use in the treatment of traumatic liver injury.
Based on a review of data from the WHI, on January 8, 2003 the FDA changed the labeling of all estrogen and estrogen with progestin products for use by postmenopausal women to include a new boxed warning about cardiovascular and other risks. The estrogen-alone substudy of the WHI reported an increased risk of stroke and deep vein thrombosis (DVT) in postmenopausal women 50 years of age or older and an increased risk of dementia in postmenopausal women 65 years of age or older using 0.625 mg of Premarin conjugated equine estrogens (CEE). The estrogen-plus-progestin substudy of the WHI reported an increased risk of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli and DVT in postmenopausal women 50 years of age or older and an increased risk of dementia in postmenopausal women 65 years of age or older using PremPro, which is 0.625 mg of CEE with 2.5 mg of the progestin medroxyprogesterone acetate (MPA).
On September 9, 1993, the FDA determined that not all topically-applied hormone-containing drug products for OTC human use are generally recognized as safe and effective and are misbranded. An accompanying proposed rule deals with cosmetics, concluding that any use of natural estrogens in a cosmetic product makes the product an unapproved new drug and that any cosmetic using the term "hormone" in the text of its labeling or in its ingredient statement makes an implied drug claim, subjecting such a product to regulatory action.
In addition to being considered misbranded drugs, products claiming to contain placental extract may also be deemed to be misbranded cosmetics if the extract has been prepared from placentas from which the hormones and other biologically active substances have been removed and the extracted substance consists principally of protein. The FDA recommends that this substance be identified by a name other than "placental extract" and describing its composition more accurately because consumers associate the name "placental extract" with a therapeutic use of some biological activity.
The “first orally effective estrogen”, Emmenin, derived from the late-pregnancy urine of Canadian women, was introduced in 1930 by Collip and Ayerst Laboratories. Estrogens are not water-soluble and cannot be given orally, but the urine was found to contain estriol glucuronide which is water soluble and becomes active in the body after hydrolization.
Scientists continued to search for new sources of estrogen because of concerns associated with the practicality of introducing the drug into the market. At the same time, a German pharmaceutical drug company, formulated a similar product as Emmenin that was introduced to German women to treat menopausal symptoms.
In 1938, British scientists obtained a patent on a newly formulated nonsteroidal estrogen, Diethylstilbestrol (DES), that was cheaper and more powerful than the previously manufactured estrogens. Soon after, concerns over the side effects of DES were raised in scientific journals while the drug manufacturers came together to lobby for governmental approval of DES. It was only until 1941 when estrogen therapy was finally approved by the Food and Drug Administration (FDA) for the treatment of menopausal symptoms.
Estrogen metabolism and the diet-cancer connection: rationale for assessing the ratio of urinary hydroxylated estrogen metabolites. (Estrogen Metabolism/ Cancer Review).
Apr 01, 2002; Abstract Estrogens are known for their proliferative effects on Estrogen-sensitive tissues resulting in...