Difference between revisions of "Estrogen" - New World Encyclopedia
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[[Image:Oestradiol-2D-skeletal.png|thumb|[[Estradiol]]. Note one [[hydroxyl]] group in D ring. The 'di' refers both to this hydroxyl and the one on the A ring (leftmost).]] | [[Image:Oestradiol-2D-skeletal.png|thumb|[[Estradiol]]. Note one [[hydroxyl]] group in D ring. The 'di' refers both to this hydroxyl and the one on the A ring (leftmost).]] | ||
[[Image:Estrone.svg|thumb|[[Estrone]]. Note [[ketone]] (=O) group in D ring. ]] | [[Image:Estrone.svg|thumb|[[Estrone]]. Note [[ketone]] (=O) group in D ring. ]] | ||
| − | '''Estrogens''' (also '''oestrogens''') are a group of | + | '''Estrogens''' (also '''oestrogens''') are a group of steroid compounds, named for their importance in the [[Estrus cycle|oestrus]] cycle, that function as the primary female sex [[hormone]]. While estrogens are present in both men and women, they are usually present at significantly higher levels in women of reproductive age. They promote the development of female secondary sex characteristics, such as [[breast]]s, and are also involved in the thickening of the endometrium and other aspects of regulating the [[menstrual cycle]]. [[Follicle-stimulating hormone|Follicle stimulating hormone]] (FSH) and [[luteinizing hormone]] (LH) regulate the production of estrogen in ovulating women. Since estrogen circulating in the [[blood]] can [[negative feedback|feedback]] to reduce circulating levels of FSH and LH, some oral contraceptives contain estrogens. |
| − | The three major naturally occurring estrogens in women are | + | The three major naturally occurring estrogens in women are estradiol, estriol, and estrone. From menarche (woman's first menstrual period) to [[menopause]], the primary estrogen is estradiol 17beta. In the body these are all produced from [[androgen]]s through [[enzyme]] action. Estradiol is produced from [[testosterone]] and estrone from [[androstenedione]]. Estrone is weaker than estradiol, and in post-menopausal women more estrone is present than estradiol. |
| − | == Estrogen | + | ==Estrogen Production == |
| − | Estrogen is produced primarily by developing follicles in the | + | Estrogen is produced primarily by developing follicles in the ovaries, the corpus luteum and the placenta. Some estrogens are also produced in smaller amounts by other tissues such as the [[liver]], [[adrenal gland]]s and the [[breast]]s. These secondary sources of estrogen are especially important in post-[[menopause|menopausal]] women. Synthesis of oestrogenes starts in theca interna [[cell]]s 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]]. There is evidence that a testosterone supplement can support female sexual desire (Braunstein et al, 2005). Many studies of the role of sex steroid hormones on sexual desire have been done in naturally post-menopausal women or women who have had their ovaries surgically removed. Such studies have found better correlation between sexual desire and androgen levels than for estrogen levels (Warnock et al, 2005). A clinical study found that women aged 18 to 44 who reported low sexual desire tended to have low levels of dehydroepiandrosterone sulfate (Davis et al, 2005). Dehydroepiandrosterone is an abundant sex steroid in women and like other steroids is efficiently sulfated. Dehydroepiandrosterone (DHEA) is a precursor steroid that can be converted to estrogens (estradiol) and androgens such as testosterone and [[Dihydrotestosterone|5α-dihydrotestosterone]]<ref>{{cite book | chapterurl = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=dehydroepiandrosterone+AND+endocrin%5Bbook%5D+AND+233201%5Buid%5D&rid=endocrin.box.509 | chapter = Metabolism of androgens to estradiol | title = Endocrinology: An Integrated Approach | author = Stephen Nussey and Saffron Whitehead | year = 2001 | publisher = BIOS Scientific Publishers Ltd | id = ISBN 1-85996-252-1 }}</ref>. Estrogens can be produced by the enzyme [[aromatase]] which converts [[androgen]]s such as DHEA to estrogens, mainly estradiol and estrone. Estriol is the third major human estrogen. |
| − | == Properties of | + | ==Properties of Estrogen== |
| − | + | *Structural | |
| − | |||
- stimulate endometrial growth | - stimulate endometrial growth | ||
- maintanence of vessel and skin | - maintanence of vessel and skin | ||
| Line 18: | Line 17: | ||
- increase uterine growth | - increase uterine growth | ||
| − | + | *Protein synthesis | |
- increase hepatic production of binding proteins | - increase hepatic production of binding proteins | ||
| − | + | *Coagulation | |
- increase circulating level of factors 2,7,9,10, anti-thrombin III, plasminogen | - increase circulating level of factors 2,7,9,10, anti-thrombin III, plasminogen | ||
- increase platelet adhesiveness | - increase platelet adhesiveness | ||
| − | + | *Lipid | |
| − | - increase HDL, triglyceride, fat deposit | + | - increase HDL (good cholesterol), triglyceride, fat deposit |
| − | - decrease LDL | + | - decrease LDL (bad cholesterol) |
| − | + | *Fluid balance | |
- salt and water retention | - salt and water retention | ||
| − | GI | + | *Gastrointestinal (GI) |
- reduce bowel motility | - reduce bowel motility | ||
| − | - increase cholesterol in bile | + | - increase cholesterol in [[bile]] |
| − | ==Medical | + | ==Medical Applications== |
| − | A range of synthetic and natural substances have been identified that possess estrogenic activity. These include | + | A range of synthetic and natural substances have been identified that possess estrogenic activity. These include bisphenol-A, phthalate esters, and nonylphenol. |
| − | Estrogen replacement therapy has proven to be a very useful method of treating osteoporosis in postmenopausal women as well as the symptoms of menopause such as hot flushes, 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. | + | Estrogen replacement therapy has proven to be a very useful method of treating osteoporosis in postmenopausal women as well as the symptoms of menopause such as hot flushes, 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. Standard therapy is 0.625 mg/day of conjugated estrogens (such as is in Premarin), but the dose can range from 0.3 mg/day to 1.25 mg/day. Estrogen replacement therapy also has favorable effects on serum cholesterol levels and is claimed to dramatically reduce the incidence of cardiovascular disease. There are, however, risks associated with estrogen therapy. Among the older postmenopausal women studied as part of the Women's Health Initiative (WHI), an orally-administered estrogen supplement has been 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 Provera as ''Prempro'')[http://www.nih.gov/PHTindex.htm]. Research is underway to determine if risks of estrogen supplement use are the same for all estrogen supplement types. In particular, topically-applied estrogen may have a different spectrum of side-effects than does estrogen administered by the oral route[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16396517&query_hl=55&itool=pubmed_docsum]. |
| − | Another very popular medical application of estrogen is the combined administration of it with | + | Another very popular medical application of estrogen is the combined administration of it with progestins in the application of oral contraceptives. |
| − | Other uses include therapy involving vaginal atrophy, hypoestrogenism (as a result of hypogonadism, castration, or primary ovarian failure), amenorrhea, dysmenorrhea, and oligomenorrhea. | + | Other uses include therapy involving 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. |
| − | === Boxed Warning === | + | ===Boxed Warning=== |
| − | The labeling of estrogen-only products includes a | + | The labeling of estrogen-only products includes a black box warning that unopposed estrogen (without progestin) therapy increases the risk of endometrial cancer. |
| − | 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 | + | 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 0.625 mg of CEE with 2.5 mg of the progestin [[medroxyprogesterone acetate]] (MPA).<ref name=fdanewlabel>{{cite web |author=FDA |title=FDA Approves New Labels for Estrogen and Estrogen with Progestin Therapies for Postmenopausal Women Following Review of Women's Health Initiative Data |url=http://www.fda.gov/bbs/topics/NEWS/2003/NEW00863.html |date=1-8-2003 |accessdate=2006-09-20}}</ref><ref name="Medline"> |
{{cite web | {{cite web | ||
| last = | | last = | ||
| Line 75: | Line 74: | ||
</ref> | </ref> | ||
| − | ==Estrogen and | + | ==Estrogen and Lung Disease== |
| − | Among people over 70 who have never smoked, women make up 85 percent of those with [[chronic obstructive pulmonary disease]] (COPD). Mice studies suggest the possibility that COPD incidence may be tied to decreases in estrogen as women age. | + | Among people over 70 who have never smoked, women make up 85 percent of those with [[chronic obstructive pulmonary disease]] (COPD). Mice studies suggest the possibility that COPD incidence may be tied to decreases in estrogen as women age. Female mice that had their ovaries removed to deprive them of estrogen lost 45 percent of their working [[alveoli]] from their lungs. Upon receiving estrogen, the mice recovered full lung function. |
| − | Two [[protein]]s that are activated by estrogen play distinct roles in breathing. | + | Two [[protein]]s that are activated by estrogen play distinct roles in breathing. One protein builds new alveoli and the other stimulates the alveoli to expel [[carbon dioxide]]. Loss of estrogen hampered both functions in the test mice. (Massaro & Massaro, 2004) |
| − | == Notes == | + | ==Notes== |
<references/> | <references/> | ||
Revision as of 00:47, 25 October 2006
Estrogens (also oestrogens) are a group of steroid compounds, named for their importance in the oestrus cycle, that function as the primary female sex hormone. While estrogens are present in both men and women, they are usually present at significantly higher levels in women of reproductive age. They promote the development of female secondary sex characteristics, such as breasts, and are also involved in the thickening of the endometrium and other aspects of regulating the menstrual cycle. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) regulate the production of estrogen in ovulating women. Since estrogen circulating in the blood can feedback to reduce circulating levels of FSH and LH, some oral contraceptives contain estrogens.
The three major naturally occurring estrogens in women are estradiol, estriol, and estrone. From menarche (woman's first menstrual period) to menopause, the primary estrogen is estradiol 17beta. In the body these are all produced from androgens through enzyme action. Estradiol is produced from testosterone and estrone from androstenedione. Estrone is weaker than estradiol, and in post-menopausal women more estrone is present than estradiol.
Estrogen Production
Estrogen is produced primarily by developing follicles in the ovaries, the corpus luteum and the placenta. 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 post-menopausal women. Synthesis of oestrogenes 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. There is evidence that a testosterone supplement can support female sexual desire (Braunstein et al, 2005). Many studies of the role of sex steroid hormones on sexual desire have been done in naturally post-menopausal women or women who have had their ovaries surgically removed. Such studies have found better correlation between sexual desire and androgen levels than for estrogen levels (Warnock et al, 2005). A clinical study found that women aged 18 to 44 who reported low sexual desire tended to have low levels of dehydroepiandrosterone sulfate (Davis et al, 2005). Dehydroepiandrosterone is an abundant sex steroid in women and like other steroids is efficiently sulfated. Dehydroepiandrosterone (DHEA) is a precursor steroid that can be converted to estrogens (estradiol) and androgens such as testosterone and 5α-dihydrotestosterone[1]. Estrogens can be produced by the enzyme aromatase which converts androgens such as DHEA to estrogens, mainly estradiol and estrone. Estriol is the third major human estrogen.
Properties of Estrogen
- Structural
- stimulate endometrial growth - maintanence of vessel and skin - reduce bone resorption, increase bone formation - increase uterine growth
- Protein synthesis
- increase hepatic production of binding proteins
- Coagulation
- increase circulating level of factors 2,7,9,10, anti-thrombin III, plasminogen - increase platelet adhesiveness
- Lipid
- increase HDL (good cholesterol), triglyceride, fat deposit - decrease LDL (bad cholesterol)
- Fluid balance
- salt and water retention
- Gastrointestinal (GI)
- reduce bowel motility - increase cholesterol in bile
Medical Applications
A range of synthetic and natural substances have been identified that possess estrogenic activity. These include bisphenol-A, phthalate esters, and nonylphenol.
Estrogen replacement therapy has proven to be a very useful method of treating osteoporosis in postmenopausal women as well as the symptoms of menopause such as hot flushes, 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. Standard therapy is 0.625 mg/day of conjugated estrogens (such as is in Premarin), but the dose can range from 0.3 mg/day to 1.25 mg/day. Estrogen replacement therapy also has favorable effects on serum cholesterol levels and is claimed to dramatically reduce the incidence of cardiovascular disease. There are, however, risks associated with estrogen therapy. Among the older postmenopausal women studied as part of the Women's Health Initiative (WHI), an orally-administered estrogen supplement has been 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 Provera as Prempro)[1]. Research is underway to determine if risks of estrogen supplement use are the same for all estrogen supplement types. In particular, topically-applied estrogen may have a different spectrum of side-effects than does estrogen administered by the oral route[2].
Another very popular medical application of estrogen is the combined administration of it with progestins in the application of oral contraceptives.
Other uses include therapy involving 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.
Boxed Warning
The labeling of estrogen-only products includes a black box warning that unopposed estrogen (without progestin) therapy increases the risk of endometrial cancer.
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 0.625 mg of CEE with 2.5 mg of the progestin medroxyprogesterone acetate (MPA).[2][3][4]
Estrogen and Lung Disease
Among people over 70 who have never smoked, women make up 85 percent of those with chronic obstructive pulmonary disease (COPD). Mice studies suggest the possibility that COPD incidence may be tied to decreases in estrogen as women age. Female mice that had their ovaries removed to deprive them of estrogen lost 45 percent of their working alveoli from their lungs. Upon receiving estrogen, the mice recovered full lung function.
Two proteins that are activated by estrogen play distinct roles in breathing. One protein builds new alveoli and the other stimulates the alveoli to expel carbon dioxide. Loss of estrogen hampered both functions in the test mice. (Massaro & Massaro, 2004)
Notes
- ↑ Stephen Nussey and Saffron Whitehead (2001). "Metabolism of androgens to estradiol", Endocrinology: An Integrated Approach. BIOS Scientific Publishers Ltd. ISBN 1-85996-252-1.
- ↑ FDA (1-8-2003). FDA Approves New Labels for Estrogen and Estrogen with Progestin Therapies for Postmenopausal Women Following Review of Women's Health Initiative Data. Retrieved 2006-09-20.
- ↑ IMPORTANT WARNING. MedlinePlus. Retrieved 9-18-2006.
- ↑ Kolata, Gina (1-9-2003). F.D.A. Orders Warning on All Estrogen Labels. The New York Times. Retrieved 9-18-2006.
ReferencesISBN links support NWE through referral fees
- Braunstein GD, Sundwall DA, Katz M, Shifren JL, Buster JE, Simon JA, Bachman G, Aguirre OA, Lucas JD, Rodenberg C, Buch A, Watts NB. (2005). Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Archives of Internal Medicine 165 (14): 1582-9. PMID 16043675.
- Davis SR, Davison SL, Donath S, Bell RJ. (2005). Circulating androgen levels and self-reported sexual function in women. Journal of the American Medical Association 294 (1): 91-6. (Full text requires registration)
- Massaro D, Massaro GD (2004). Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice. American Journal of Physiology. Lung Cellular and Molecular Physiology 287 (6): L1154-9. PMID 15298854.
- Warnock JK, Swanson SG, Borel RW, Zipfel LM, Brennan JJ. (2005). Combined esterified estrogens and methyltestosterone versus esterified estrogens alone in the treatment of loss of sexual interest in surgically menopausal women. Menopause 12 (4): 374-84. PMID 16037752.
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