Steroids structured as 4 carbon skeleton rings and 2 functional groups on each end differing locations and types of functional

groups are lipids

and hydrophobic, but different from fat functions: chemical signals, surround water in cells
A steroid is a type of organic compound that contains a specific arrangement of four cycloalkane rings that are joined to each otherExamples of steroids include the
dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatorydrug dexamethasone

The core of steroids is composed of seventeen carbon atoms bonded together that take the form of four fused rings: threecyclohexane rings (designated as rings A,
B, and C in the figure to the right) and one cyclopentane ring (the D ring). The steroids vary by the functional groups attached to this four ring core and by
theoxidation state of the rings. Sterols are special forms of steroids, with a hydroxyl group at position-3 and a skeleton derived fromcholestane.[1]

Hundreds of distinct steroids are found in plants, animals, andfungi. All steroids are made in cells either from the sterolslanosterol (animals and fungi) or
from cycloartenol (plants). Both lanosterol and cycloartenol are derived from the cyclization of thetriterpene squalene.[2]

Steroids are a class of organic compounds with a chemical structure that contains the core of gonane or a skeleton derived therefrom. Usually, methyl

groups are present at the carbons C-10 and C-13. At carbon C-17 an alkyl side chain may also be present.

Numbering of carbon atoms ingonane

The basic skeleton of a steroid, with standard stereo orientations. R is a side-chain.

Gonane is the simplest possible steroid and is composed of seventeen carbon atoms, bonded together to form four fused rings. The threecyclohexane rings

(designated as rings A, B, and C in the figure above right) form the skeleton of phenanthrene; ring D has a cyclopentanestructure. Hence, together they

are called cyclopentaphenanthrene.[3]

Commonly, steroids have a methyl group at the carbons C-10 and C-13 and an alkyl side chain at carbon C-17. Further, they vary by the configuration of the side

chain, the number of additional methyl groups and the functional groups attached to the rings. For example the hydroxyl group at position C-3 in sterols.

Cholesterol
Cholic acid
Medrogestone

Taxonomical/Functional

Some of the common categories of steroids:

Animal steroids,Insect steroids,Ecdysteroids such as ecdysterone,Vertebrate steroids,Steroid hormones

,Sex steroids are a subset of sex hormones that produce sex differences or support reproduction. They include androgens,estrogens,
and progestagens,,Corticosteroids include glucocorticoids and mineralocorticoids. Glucocorticoids regulate many aspects of metabolism andimmune function,
whereas mineralocorticoids help maintain blood volume and control renal excretion of electrolytes. Most medical 'steroid' drugs are corticosteroids.,Anabolic

steroids are a class of steroids that interact with androgen receptors to increase muscle and bone synthesis. There are natural and synthetic anabolic steroids.
In popular language, the word "steroids" usually refers to anabolic steroids.,Cholesterol, which modulates the fluidity of cell membranes and is the principal

constituent of the plaques implicated inatherosclerosis.,,Plant steroids,,,Phytosterols,,,Brassinosteroids,,,Fungus steroids,,,,Ergosterols

Structural

It is also possible to classify steroids based upon their chemical composition. One example of how MeSH performs this classification is available at the Wikipedia

MeSH catalog. Examples from this classification include:

Number of carbon
Class Examples
atoms

Cholestanes cholesterol 27

Cholanes cholic acid 24

Pregnanes progesterone 21

Androstane
testosterone 19
s

Estranes estradiol 18

Gonane (or steroid nucleus) is the parent (17-carbon tetracyclic) hydrocarbon molecule without any alkyl sidechains.[4]

[edit]Metabolism

Steroids include estrogen, cortisol, progesterone, and testosterone. Estrogen and progesterone are made primarily in the ovary and in theplacenta during

pregnancy, and testosterone in the testes. Testosterone is also converted into estrogen to regulate the supply of each, in the bodies of both females and males.

Certain neurons and glia in the central nervous system (CNS) express the enzymes that are required for the local synthesis of pregnane neurosteroids,

either de novo or from peripherally-derived sources. The rate-limiting step of steroid synthesis is the conversion of cholesterol to pregnenolone, which occurs

inside the mitochondrion.[5]

Simplified version of latter part of steroid synthesis pathway, where the intermediates isopentenyl pyrophosphate (IPP) and dimethylallyl
pyrophosphate (DMAPP) form geranyl pyrophosphate (GPP), squaleneand, finally, lanosterol, the first steroid in the pathways. Some
intermediates are omitted for clarity.

Steroid metabolism is the complete set of chemical reactions in organisms that produce, modify, and consume steroids. These metabolic pathways include:

 steroid synthesis – the manufacture of steroids from simpler precursors

 steroidogenesis – the interconversion of different types of steroids

 steroid degradation.
[edit]A. Steroid biosynthesis

Steroid biosynthesis is an anabolic metabolic pathway that produces steroids from simple precursors. This pathway is carried out in different ways in animals than

in many other organisms, making the pathway a common target for antibiotics and other anti-infective drugs. In addition, steroid metabolism in humans is the target

of cholesterol-lowering drugs such as statins.

It starts in the mevalonate pathway in humans, with Acetyl-CoA as building blocks, which form DMAPP and IPP.[6] In following steps, DMAPP and IPP

form lanosterol, the first steroid. Further modification belongs to the succeeding steroidogenesis.

[edit]Mevalonate pathway

Mevalonate pathway

Main article: Mevalonate pathway

The mevalonate pathway or HMG-CoA reductase pathway starts with and ends with dimethylallyl pyrophosphate (DMAPP) and isopentenyl
pyrophosphate (IPP).
[edit]Regulation and feedback

Several key enzymes can be activated through DNA transcriptionalregulation on activation of SREBP (Sterol Regulatory Element-Binding Protein-1 and -2). This

intracellular sensor detects low cholesterol levels and stimulates endogenous production by the HMG-CoA reductase pathway, as well as increasing lipoprotein

uptake by up-regulating the LDLreceptor. Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase

and phosphorylation.

[edit]Pharmacology

A number of drugs target the mevalonate pathway:

 Statins (used for elevated cholesterol levels)

 Bisphosphonates (used in treatment of various bone-degenerative diseases)

[edit]Plants and bacteria

In plants and bacteria, the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates.[7][8]
[edit]DMAPP to lanosterol

Isopentenyl pyrophosphate and dimethylallyl pyrophosphate donate isoprene units, which are assembled and modified to
form terpenes andisoprenoids,[8] which are a large class of lipids that include the carotenoids, and form the largest class of plant natural products.[9]

Here, the isoprene units are joined together to make squalene and then folded up and formed into a set of rings to make lanosterol.[10]Lanosterol can then

be converted into other steroids such as cholesterol and ergosterol.[10][11]

Human Steroidogenesis

[edit]B. Steroidogenesis

Steroidogenesis is the biological process by which steroids are generated from cholesterol and transformed into other steroids. The pathways of steroidogenesis

differ between different species, but the pathways of human steroidogenesis are shown in the figure.

Products of steroidogenesis include:

 androgens

 testosterone

 estrogens and progesterone

 corticoids

 cortisol

 aldosterone

Cholesterol is a waxy steroid metabolite found in the cell membranes and transported in theblood plasma of all animals.[2] It is an essential structural component of

mammalian cell membranes, where it is required to establish proper membrane permeability and fluidity. In addition, cholesterol is an important component for

the manufacture of bile acids, steroid hormones, and Vitamin D. Cholesterol is the principal sterol synthesized by animals, but small quantities are synthesized in

other eukaryotes, such as plants and fungi. It is almost completely absent among prokaryotes, which include bacteria.[3] Although cholesterol is an important and

necessary molecule for animals, a high level of serum cholesterol is an indicator for diseases such as heart disease.[4]

The name cholesterol originates from the Greek chole- (bile) and stereos (solid), and thechemical suffix -ol for an alcohol. François Poulletier de la Salle first

identified cholesterol in solid form in gallstones, in 1769. However, it was only in 1815 that chemist Eugène Chevreulnamed the compound "cholesterine".[5]

Cholesterol

IUPAC name[hide][hide]

(3β)-cholest-5-en-3-ol

Other names[hide][hide]

(10R,13R)-10,13-dimethyl-17-(6-methylheptan-2-yl)-2,3,4,7,8,9,11,12,14,15,16,17-

dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
 Properties

Molecular C27H46O

formula

Molar mass 386.65 g/mol

Appearance white crystalline powder[1]

Density 1.052 g/cm3

Melting point 148–150 °C[1]

Boiling point
360 °C (decomposes)

Solubility inw 0.095 mg/L (30 °C)

ater

Solubility soluble

in acetone, benzene,chloroform, ethanol, ether, hexa

ne,isopropyl myristate, methanol

F UNCTION

Cholesterol is required to build and maintain membranes; it modulates membrane fluidity over the range of physiological temperatures. The hydroxyl group on

cholesterol interacts with the polarhead groups of the membrane phospholipids and sphingolipids, while the bulky steroid and thehydrocarbon chain are embedded

in the membrane, alongside the nonpolar fatty acid chain of the other lipids. In this structural role, cholesterol reduces the permeability of the plasma membrane to

protons (positive hydrogen ions) and sodium ions.[7]

Within the cell membrane, cholesterol also functions in intracellular transport, cell signaling and nerve conduction. Cholesterol is essential for the structure and

function of invaginated caveolae and clathrin-coated pits, including caveola-dependent and clathrin-dependent endocytosis. In many neurons, a myelin sheath, rich

in cholesterol, since it is derived from compacted layers of Schwann cell membrane, provides insulation for more efficient conduction of impulses.[8]

Within cells, cholesterol is the precursor molecule in several biochemical pathways. In the liver, cholesterol is converted to bile, which is then stored in

the gallbladder. Bile contains bile salts, which solubilize fats in the digestive tract and aid in the intestinal absorption of fat molecules as well as the fat-soluble

vitamins, Vitamin A, Vitamin D, Vitamin E, and Vitamin K. Cholesterol is an important precursor molecule for the synthesis of Vitamin D and the steroid hormones,

including the adrenal gland hormones cortisol and aldosterone as well as the sex hormones progesterone, estrogens, and testosterone, and their derivatives.

Some research indicates that cholesterol may act as an antioxidant.[9

D IETARY SOURCES

Animal fats are complex mixtures of triglycerides, with lesser amounts of phospholipids and cholesterol. As a consequence, all foods containing animal fat contain

cholesterol to varying extents.[10] Major dietary sources of cholesterol include cheese, egg yolks, beef, pork,poultry, and shrimp.[11]

The amount of cholesterol present in plant-based food sources is generally much lower than animal based sources.[11][13] In addition, plant products such as flax

seeds and peanuts contain cholesterol-like compounds called phytosterols, which are suggested to help lower serumcholesterol levels.[14]

A change in diet in addition to other lifestyle modifications may help reduce blood cholesterol. Avoiding animal products may decrease the cholesterol levels in the

body not only by reducing the quantity of cholesterol consumed but also by reducing the quantity of cholesterol synthesized. Those wishing to reduce their

cholesterol through a change in diet should aim to consume less than 7% of their daily caloriesfrom saturated fat and fewer than 200 mg of cholesterol per day.[16]

It is debatable that a diet, changed to reduce dietary fat and cholesterol, can lower blood cholesterol levels,[4] (and thus reduce the likelihood of development of,

among others, coronary artery disease leading to coronary heart disease), because any reduction to dietary cholesterol intake could be counteracted by the

organs compensating to try and keep blood cholesterol levels constant.[17] Also pointed out is the experimental discovery that in the diet, ingested animal protein can

raise blood cholesterol more than the ingested saturated fat or any cholesterol. [18]

[EDIT ]S IGNIFICANCE

[EDIT ]HYPERCHOLESTEROLEMIA

Main articles: hypercholesterolemia and lipid hypothesis

According to the lipid hypothesis, abnormal cholesterol levels (hypercholesterolemia)—that is, higher concentrations of LDL and lower concentrations of functional

HDL—are strongly associated with cardiovascular disease because these promote atheroma development in arteries (atherosclerosis). This disease process leads

to myocardial infarction (heart attack), stroke, and peripheral vascular disease. Since higher blood LDL, especially higher LDL particle concentrations and smaller

LDL particle size, contribute to this process more than the cholesterol content of the LDL particles,[31] LDL particles are often termed "bad cholesterol" because they

have been linked to atheroma formation. On the other hand, high concentrations of functional HDL, which can remove cholesterol from cells and atheroma, offer

protection and are sometimes referred to as "good cholesterol". These balances are mostly genetically determined but can be changed by body build,medications,

food choices, and other factors.[32]

Conditions with elevated concentrations of oxidized LDL particles, especially "small dense LDL" (sdLDL) particles, are associated withatheroma formation in the

walls of arteries, a condition known as atherosclerosis, which is the principal cause of coronary heart disease and other forms of cardiovascular disease. In contrast,

HDL particles (especially large HDL) have been identified as a mechanism by which cholesterol and inflammatory mediators can be removed from atheroma.

Increased concentrations of HDL correlate with lower rates of atheroma progressions and even regression. A 2007 study pooling data on almost 900,000 subjects in

61 cohorts demonstrated that blood total cholesterol levels have an exponential effect on cardiovascular and total mortality, with the association more pronounced in

younger subjects. Still, because cardiovascular disease is relatively rare in the younger population, the impact of high cholesterol on health is still larger in older

people.[33]
The 1987 report of National Cholesterol Education Program, Adult Treatment Panels suggest the total blood cholesterol level should be: < 200 mg/dL normal blood

cholesterol, 200–239 mg/dL borderline-high, > 240 mg/dL high cholesterol.[40] The American Heart Associationprovides a similar set of guidelines for total (fasting)

blood cholesterol levels and risk for heart disease:[41]

Level mg Level mm
Interpretation
/dL ol/L

Desirable level corresponding to lower risk for

< 200 < 5.0
heart disease

200–240 5.2–6.2 Borderline high risk

> 240 > 6.2 High risk

Given the well-recognized role of cholesterol in cardiovascular disease, it is surprising that some studies have shown an inverse correlation between cholesterol

levels and mortality. A 2009 study of patients with acute coronary syndromes found an association of hypercholesterolemia with better mortality outcomes.[44] In

the Framingham Heart Study, in subjects over 50 years of age they found an 11% increase overall and 14% increase in CVD mortality per 1 mg/dL per year drop in

total cholesterol levels. The researchers attributed this phenomenon to the fact that people with severe chronic diseases or cancer tend to have below-normal

cholesterol levels.[45] This explanation is not supported by the Vorarlberg Health Monitoring and Promotion Programme, in which men of all ages and women over 50

with very low cholesterol were increasingly likely to die of cancer, liver diseases, and mental diseases. This result indicates that the low-cholesterol effect occurs

even among younger respondents, contradicting the previous assessment among cohorts of older people that this is a proxy or marker for frailty occurring with age.
[46]

[EDIT ]HYPOCHOLESTEROLEMIA

Abnormally low levels of cholesterol are termed hypocholesterolemia. Research into the causes of this state is relatively limited, but some studies suggest a link

with depression, cancer, and cerebral hemorrhage. In general, the low cholesterol levels seem to be a consequence of an underlying illness, rather than a cause.[33]

E STROGEN

From Wikipedia, the free encyclopedia

Estriol. Note two hydroxyl (-OH) groups attached to the D ring (rightmost ring).
Estradiol. Note one hydroxyl group attached to the D ring. The 'di' refers both to this hydroxyl and the one on the A ring (leftmost).

Estrone. Note the ketone (=O) group attached to the D ring.

Estrogens (AmE), oestrogens (BE), or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals, and

functioning as the primary femalesex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal. Their name comes from

the Greek words estrus/οίστρος = sexual desire + gen/γόνο = to generate.

Estrogens are synthesized in all vertebrates[1] as well as some insects.[2] Their presence in both vertebrates and insects suggests that estrogenic sex hormones

have an ancient history.

Estrogens are used as part of some oral contraceptives, in estrogen replacement therapy forpostmenopausal women, and in hormone replacement

therapy for trans women.

Like all steroid hormones, estrogens readily diffuse across the cell membrane. Once inside the cell, they bind to and activate estrogen receptors which in

turn modulate the expression of many genes.[3]Additionally, estrogens have been shown to activate a G protein-coupled receptor, GPR30.[4]

T YPES

[EDIT ]STEROIDAL

The three major naturally occurring oestrogens in women are estrone (E1), estradiol (E2), and estriol (E3). Oestradiol (E2) is the predominant form in nonpregnant

females, estrone is produced during menopause, and estriol is the primary oestrogen of pregnancy. In the body these are all produced from androgens through

actions of enzymes.

 From menarche to menopause the primary oestrogen is 17β-estradiol. In postmenopausal women more estrone is present than oestradiol.

 Oestradiol is produced from testosterone and estrone from androstenedione by aromatase.

 Oestrone is weaker than estradiol.

Premarin, a commonly prescribed estrogenic drug, contains the steroidal oestrogens equilin and equilenin. There are oestradiol skin patches such as Estraderm

(the original brand, introduced in the late 1980s) that offer a completely natural alternative. (A skin patch rather than pill also has the advantage of direct

transmission into the blood stream without going through the liver.)

N ONSTEROIDAL

A range of synthetic and natural substances have been identified that also possess estrogenic activity.[6]

 Synthetic substances of this kind are known as xenoestrogens.

 Plant products with estrogenic activity are called phytoestrogens.

 Those produced by fungi are known as mycoestrogens.

Unlike estrogens produced by mammals, these substances are not necessarily steroids.
[edit]

B IOSYNTHESIS

Steroidogenesis, showing estrogens at bottom right as in pink triangle.

Oestrogens are produced primarily by developing folliclesin the ovaries, the corpus luteum, and the placenta.Luteinizing hormone (LH) stimulates the production of

estrogen in the ovaries. Some oestrogens are also produced in smaller amounts by other tissues such as theliver, adrenal glands, and the breasts. These

secondary sources of oestrogens are especially important in postmenopausal women. Fat cells also produce oestrogen,[7] potentially being the reason

why underweightor overweight are risk factors for infertility.[8]

In females, synthesis of oestrogens starts in theca internacells in the ovary, by the synthesis of androstenedionefrom cholesterol. Androstenedione is a substance

of moderate androgenic activity. This compound crosses thebasal membrane into the surrounding granulosa cells, where it is converted to oestrone or oestradiol,

either immediately or through testosterone. The conversion of testosterone to oestradiol, and of androstenedione to oestrone, is catalyzed by the

enzyme aromatase.

Oestradiol levels vary through the menstrual cycle, with levels highest just before ovulation.

[EDIT ]FUNCTION

The actions of estrogen are mediated by the Estrogen receptor (ER), a dimeric nuclear protein that binds to DNA and controls gene expression. Like other steroid

hormones, estrogen enters passively into the cell where it binds to and activates the estrogen receptor. The estrogen:ER complex binds to specific DNA sequences

called a Hormone response element to activate the transcription of some 137 ER-regulated genes, of which 89 are direct target genes. [9] Since estrogen enters all

cells, its action are dependent on the presence of the ER in the cell. The ER is expressed in specific tissues including the ovary, uterus and breast.

While oestrogens 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 sexual characteristics, such as breasts, and are also involved in the thickening of theendometrium and other aspects of

regulating the menstrual cycle. In males, oestrogen regulates certain functions of the reproductive systemimportant to the maturation of sperm[10][11][12] and may be

necessary for a healthy libido.[13][14] Furthermore, there are several other structural changes induced by oestrogen in addition to other functions.

 Structural

 promote formation of female secondary sex characteristics

 accelerate metabolism

 reduce muscle mass

  increase fat stores

 stimulate endometrial growth

 increase uterine growth

 increase vaginal lubrication

 thicken the vaginal wall

 maintenance of vessel and skin

 reduce bone resorption, increase bone formation

 morphic change (endomorphic -> mesomorphic -> ectomorphic)

 protein synthesis

 increase hepatic production of binding proteins

 coagulation

 increase circulating level of factors 2, 7, 9, 10, plasminogen

 decrease antithrombin III

 increase platelet adhesiveness

 Lipid

 increase HDL, triglyceride

 decrease LDL, fat deposition

 Fluid balance

 salt (sodium) and water retention

 increase cortisol, SHBG

 Gastrointestinal tract

 reduce bowel motility

 increase cholesterol in bile

 Melanin

 increase pheomelanin, reduce eumelanin

 Cancer

 support hormone-sensitive breast cancers (see section below)

 Lung function

 promotes lung function by supporting alveoli (in rodents but probably in humans).[15]

Sexual desire is dependent on androgen levels rather than estrogen levels.[16]

[EDIT ]FETAL DEVELOPMENT

In humans, the masculinizing effects of prenatal androgens on behavior (and other tissues, with the possible exception of effects on bone) appear to act exclusively

through the androgen receptor.[19] As a result, the utility of rodent models for studying human psychosexual differentiation has been questioned.[20]
[EDIT ]MENTAL HEALTH

Oestrogen is considered to play a significant role in women’s mental health. Sudden estrogen withdrawal, fluctuating estrogen, and periods of sustained oestrogen

low levels correlates with significant mood lowering. Clinical recovery from postpartum, perimenopause, andpostmenopause depression has been shown to be

effective after levels of oestrogen were stabilized and/or restored.[21][22]aromatase deficiency is ultimately suspected which is involved in the synthesis of oestrogen in

humans and has therapeutic implications in humans having obsessive-compulsive disorder.[23]

[EDIT ]MEDICAL APPLICATIONS

[EDIT ]O RAL CONTRACEPTIVES

Since oestrogen circulating in the blood can negatively feed-back to reduce circulating levels of FSH and LH, most oral contraceptives contain a synthetic

oestrogen, along with a synthetic progestin. Even in men, the major hormone involved in LH feedback is estradiol, nottestosterone.

[EDIT ]B REAST CANCER

About 80% of breast cancers, once established, rely on supplies of the hormone estrogen to grow: they are known as hormone-sensitive or hormone-receptor-

positive cancers. Suppression of production of estrogen in the body is a treatment for these cancers.

Recently researchers have discovered that the common table mushroom has anti-aromatase[26] properties and therefore possible anti-estrogen activity. Clinical trials

have begun in the United States looking into whether the table mushroom can prevent breast cancer in people.[27] A recent study has highlighted the importance of

this research. In 2009, a case-control study of the eating habits of 2,018 women, revealed that women who consumed mushrooms had an approximately 50% lower

incidence of breast cancer. Women who consumed mushrooms and green tea had a 90% lower incidence of breast cancer.[28]

Hormone-receptor-positive breast cancers are treated with drugs which suppress production of estrogen in the body.[29] 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.[30]

[EDIT ]P ROSTATE CANCER

Under certain circumstances, estrogen may also be used in males for treatment of prostate cancer.[31]

[EDIT ]MISCELLANEOUS

In humans estrogen promotes wound healing.[32]

At one time, estrogen was used to induce growth attenuation in tall girls.[33] 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.[34]

Most recently, estrogen has been used in experimental research as a way to treat patients suffering from bulimia nervosa, in addition toCognitive 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.[35]

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.[36]
[EDIT ]HEALTH RISKS AND WARNING LABELS

Hyperestrogenemia (elevated levels of estrogen) may be a result of exogenous administration of estrogen or estrogen-like substances, or may be a result of

physiologic conditions such as pregnancy. Any of these causes is linked with an increase in the risk of thrombosis.[37]

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 progestinmedroxyprogesterone acetate (MPA).[38][39][40]

The labeling of estrogen-only products in the U.S. includes a boxed warning that unopposed estrogen (without progestagen) 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.

[EDIT ]COSMETICS

Some hair shampoos on the market include estrogens and placental extracts; others contain phytoestrogens. There are case reports of young children developing

breasts after exposure to these shampoos.[41] 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.[42]

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.[42]

[EDIT ]E NVIRONMENTAL EFFECTS

Estrogens are among the wide range of endocrine-disrupting compounds (EDCs) because they have high estrogenic potency. When this specific EDC makes its

way into the environment it may cause male reproductive dysfunction to wildlife.
[edit]

T ESTOSTERONE

From Wikipedia, the free encyclopedia

For the film, see Testosterone (film).

Testosterone

Systematic (IUPAC) name

(8R,9S,10R,13S,14S,17S)- 17-hydroxy-10,13-dimethyl-

1,2,6,7,8,9,11,12,14,15,16,17-

dodecahydrocyclopenta[a]phenanthren-3-one
 Formula C19H28O2

Mol. mass 288.42

SMILES eMolecules & PubChem

InChI[show][show]

Physical data

Melt. point 155–156 °C (311–313 °F)

Spec. rot +110,2°

SEC Combust −11080 kJ/mol

Pharmacokinetic data

Bioavailability low (due to extensive first pass metabolism)

Metabolism Liver, Testis and Prostate

Half-life 2-4 hours

Excretion Urine (90%), feces (6%)

Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles,[1] birds,[2] and other vertebrates. In mammals, testosterone is

primarily secreted in thetestes of males and the ovaries of females, although small amounts are also secreted by theadrenal glands. It is the

principal male sex hormone and an anabolic steroid.

In men, testosterone plays a key role in the development of male reproductive tissues such as the testis and prostate as well as promoting secondary sexual

characteristics such as increased muscle, bone mass and the growth of body-hair.[3] In addition, testosterone is essential for health and well-being[4] as well as the

prevention of osteoporosis.[5]

On average, an adult human male body produces about ten times more testosterone than an adult human female body, but females are more sensitive to the

hormone.[6]

PHYSIOLOGICAL EFFECTS

In general, androgens promote protein synthesis and growth of those tissues with androgen receptors. Testosterone effects can be classified

as virilizing and anabolic, although the distinction is somewhat artificial, as many of the effects can be considered both. Testosterone is anabolic, meaning it builds

up bone and muscle mass.

 Anabolic effects include growth of muscle mass and strength, increased bone density and strength, and stimulation of linear growth and bone maturation.

 Androgenic effects include maturation of the sex organs, particularly the penis and the formation of the scrotum in the fetus, and after birth (usually at puberty)

a deepening of the voice, growth of the beard and axillary hair. Many of these fall into the category of malesecondary sex characteristics.

Testosterone effects can also be classified by the age of usual occurrence. For postnatal effects in both males and females, these are mostly dependent on the

levels and duration of circulating free testosterone.

[EDIT ]PRE- PERIPUBERTAL

Pre- Peripubertal effects are the first observable effects of rising androgen levels at the end of childhood, occurring in both boys and girls.[vague]

 Adult-type body odour

 Increased oiliness of skin and hair, acne

 Pubarche (appearance of pubic hair)

 Axillary hair

 Growth spurt, accelerated bone maturation

 Hair on upper lip and sideburns.

[EDIT ]P UBERTAL

Pubertal effects begin to occur when androgen has been higher than normal adult female levels for months or years. In males, these are usual late pubertal effects,

and occur in women after prolonged periods of heightened levels of free testosterone in the blood.
 Enlargement of sebaceous glands. This might cause acne.

 Phallic enlargement or clitoromegaly

 Increased libido and frequency of erection or clitoral engorgement

 Pubic hair extends to thighs and up toward umbilicus

 Facial hair (sideburns, beard, moustache)

 Loss of scalp hair (Androgenetic alopecia)

 Chest hair, periareolar hair, perianal hair

 Leg hair

 Axillary hair

 Subcutaneous fat in face decreases

 Increased muscle strength and mass[15]

 Deepening of voice

 Growth of the Adam's apple

 Growth of spermatogenic tissue in testicles, male fertility

 Growth of jaw, brow, chin, nose, and remodeling of facial bone contours

 Shoulders become broader and rib cage expands

 Completion of bone maturation and termination of growth. This occurs indirectly via estradiol metabolites and hence more gradually in men than women.

 Testosterone is necessary for normal sperm development. It activates genes in Sertoli cells, which promote differentiation ofspermatogonia.

 Regulates acute HPA (Hypothalamic–pituitary–adrenal axis) response under dominance challenge[16]

 Mental and physical energy

 Maintenance of muscle trophism

 Testosterone regulates the population of thromboxane A2 receptors on megakaryocytes and platelets and hence platelet aggregation in humans[17][18]

 Libido as evinced in clitoral engorgement/penile erection frequency[citation needed]

 Testosterone does not cause or produce deleterious effects on prostate cancer. In people who have undergone testosterone deprivation therapy, testosterone

increases beyond the castrate level have been shown to increase the rate of spread of an existing prostate cancer.[19][20][21]

 Recent studies have shown conflicting results concerning the importance of testosterone in maintaining cardiovascular health.[22][23]Nevertheless, maintaining

normal testosterone levels in elderly men has been shown to improve many parameters which are thought to reduce cardiovascular disease risk, such as

increased lean body mass, decreased visceral fat mass, decreased total cholesterol, and glycemic control.[24]

 Under dominance challenge, may play a role in the regulation of the fight-or-flight response[25]

 Falling in love decreases men's testosterone levels while increasing women's testosterone levels. It is speculated that these changes in testosterone result in

the temporary reduction of differences in behavior between the sexes.[26] It has been found that when the testosterone and endorphins in the ejaculated semen

meet the cervical wall after sexual intercourse, females receive a spike in testosterone, endorphin, and oxytocin levels, and males after orgasm during

copulation experience an increase in endorphins and a marked increase in oxytocin levels. This adds to the hospitable physiological environment in the female
 internal reproductive tract for conceiving, and later for nurturing the conceptus in the pre-embryonic stages, and stimulates feelings of love, desire, and

paternal care in the male (this is the only time male oxytocin levels rival a female's).[citation needed]

 Recent studies suggest that testosterone level plays a major role in risk-taking during financial decisions.[27][28]

 Fatherhood also decreases testosterone levels in men, suggesting that the resulting emotional and behavioral changes promote paternal care.[29]

 In animals (grouse and sand lizards), higher testosterone levels have been linked to a reduced immune system activity. Testosterone seems to have become

part of the honest signaling system between potential mates in the course of evolution.[30][31]

[EDIT ]BRAIN

As testosterone affects the entire body (often by enlarging; men have bigger hearts, lungs, liver, etc.), the brain is also affected by this "sexual" differentiation;
[10]
the enzyme aromatase converts testosterone into estradiol that is responsible for masculinization of the brain in male mice. In humans, masculinization of the

fetal brain appears, by observation of gender preference in patients with congenital diseases of androgen formation or androgen receptor function, to be associated

with functional androgen receptors.[32]

There are some differences between a male and female brain (possibly the result of different testosterone levels), one of them being size: the male human brain is,

on average, larger.[33] In a Danish study from 2003, men were found to have a total myelinated fiber length of 176,000 km at the age of 20, whereas in women the

total length was 149,000 km.[34] However, women have more dendritic connections between brain cells.[35]

A study conducted in 1996 found no immediate short term effects on mood or behavior from the administration of supraphysiologic doses of testosterone for 10

weeks on 43 healthy men.[15] Another study found a correlation between testosterone and risk tolerance in career choice among women.[36]

Literature suggests that attention, memory, and spatial ability are key cognitive functions affected by testosterone in humans. Preliminary evidence suggests that

low testosterone levels may be a risk factor for cognitive decline and possibly for dementia of the Alzheimer’s type,[37][38] a key argument in life extension medicine

for the use of testosterone in anti-aging therapies. Much of the literature, however, suggests a curvilinear or even quadratic relationship between spatial

performance and circulating testosterone,[39] where both hypo- and hypersecretion (deficient- and excessive-secretion) of circulating androgens have negative

effects on cognition and cognitively modulated aggressivity, as detailed above.

Contrary to what has been postulated in outdated studies and by certain sections of the media, aggressive behaviour is not typically seen in hypogonadal men who

have their testosterone replaced adequately to the eugonadal/normal range. In fact, aggressive behaviour has been associated with hypogonadism and low

testosterone levels and it would seem as though supraphysiological and low levels of testosterone and hypogonadism cause mood

disorders and aggressive behaviour, with eugondal/normal testosterone levels being important for mental well-being. Testosterone depletion is a normal

consequence of aging in men. One possible consequence of this could be an increased risk for the development of Alzheimer’s disease.[40][41]

Human steroidogenesis, showing testosterone near bottom.

[EDIT ]REGULATION
Environmental factors affecting testosterone levels include:

 Loss of status or dominance in men may result in a decreased testosterone level.[25]

 Implicit power motivation predicts an increased testosterone release in men.[47]

 Aging reduces testosterone release.[48]

 Hypogonadism

 Sleep (REM dream) increases nocturnal testosterone levels.[49]

 Resistance training increases testosterone levels,[50] however, in older men, that increase can be avoided by protein ingestion.[51]

 Zinc deficiency lowers testosterone levels[52] but over supplementation has no effect on serum testosterone.[53]

 Licorice. The active ingredient in licorice root, glycyrrhizinic acid has been linked to small, clinically non-significant decreases in testosterone levels.[54] In

contrast, a more recent study found that licorice administration produced a substantial testosterone decrease in a small, female-only sample.[55]

 Natural or man-made antiandrogens including spearmint tea reduce testosterone levels.[56][57][58]

Vial of testosterone for intramuscular injection

There are many routes of administration for testosterone. Forms of testosterone for human administration currently available include injectable (such as

testosterone cypionate or testosterone enanthate in oil), oral,[65]buccal,[66] transdermal skin patches, and transdermal creams or gels.[67]

Roll-on methods and nasal sprays are currently under development.

[EDIT ]INDICATIONS

The original and primary use of testosterone is for the treatment of males who have too little or no natural endogenous testosterone production—males

with hypogonadism. Appropriate use for this purpose is legitimate hormone replacement therapy (testosterone replacement therapy [TRT]), which maintains serum

testosterone levels in the normal range.

However, over the years, as with every hormone, testosterone or other anabolic steroids has also been given for many other conditions and purposes besides

replacement, with variable success but higher rates of side effects or problems. Examples include reducing infertility, correcting lack of libido or erectile dysfunction,

correcting osteoporosis, encouraging penile enlargement, encouraging height growth, encouraging bone marrow stimulation and reversing the effects of anemia,

and even appetite stimulation. By the late 1940s testosterone was being touted as an anti-aging wonder drug (e.g., see Paul de Kruif's The Male Hormone).
[68]
Decline of testosterone production with age has led to interest inandrogen replacement therapy.[69]

To take advantage of its virilizing effects, testosterone is often administered to transsexual men as part of the hormone replacement therapy, with a "target level" of

the normal male testosterone level. Like-wise, transsexual women are sometimes prescribed anti-androgens to decrease the level of testosterone in the body and

allow for the effects of estrogen to develop.

Testosterone patches are effective at treating low libido in post-menopausal women.[70] Low libido may also occur as a symptom or outcome of hormonal

contraceptive use. Women may also use testosterone therapies to treat or prevent loss of bone density, muscle mass and to treat certain kinds of depression and

low energy state. Women on testosterone therapies may experience an increase in weight without an increase in body fat due to changes in bone and muscle

density. Most undesired effects of testosterone therapy in women may be controlled by hair-reduction strategies, acne prevention, etc. There is a theoretical risk

that testosterone therapy may increase the risk of breast or gynaecological cancers, and further research is needed to define any such risks more clearly.[70]

[EDIT ]ADVERSE EFFECTS

Exogenous testosterone supplementation comes with a number of health risks. Fluoxymesterone and methyltestosterone are synthetic derivatives of testosterone.

Methyltestosterone and Fluoxymesterone are no longer prescribed by physicians given their poor safety record, and testosterone replacement in men does have a

very good safety record as evidenced by over sixty years of medical use in hypogonadal men.

A 2006 article in Official Journal of the American Urological Association - The Journal of Urology pointed out that: Prostate cancer may become clinically apparent

within months to a few years after the initiation of testosterone treatment. [...] Physicians prescribing testosterone supplementation and patients receiving it should

be cognizant of this risk, and serum PSA testing and digital rectal examination should be performed frequently during treatment.

[EDIT ]A THLETIC USE

Testosterone may be used by an athlete in order to improve performance, and is considered to be a form of doping in most sports. There are several application

methods for testosterone, including intramuscular injections, transdermal gels and patches, and implantable pellets.

Anabolic steroids (including testosterone) have also been taken to enhance muscle development, strength, or endurance. They do so directly by increasing the

muscles' protein synthesis. As a result, muscle fibers become larger and repair faster than the average person's. After a series of scandals and publicity in the

1980s (such as Ben Johnson's improved performance at the 1988 Summer Olympics), prohibitions of anabolic steroid use were renewed or strengthened by many

sports organizations. Testosterone and other anabolic steroids were designated a "controlled substance" by the United States Congress in 1990, with the Anabolic

Steroid Control Act.[78] The use is seen as being a seriously problematic issue in modern sport, particularly given the lengths to which athletes and professional

laboratories go to in trying to conceal such abuse from sports regulators. Steroid abuse once again came into the spotlight recently as a result of the Chris

Benoit double murder-suicide in 2007, and the media frenzy surrounding it - however, there has been no evidence indicating steroid use as a contributing factor.

They believe it to be that he had over 15 concussions throughout his career in professional Wrestling

[EDIT ]DETECTION OF ABUSE

A number of methods for detecting testosterone use by athletes have been employed, most based on a urine test. These include the

testosterone/epitestosterone ratio (normally less than 6), the testosterone/luteinizing hormone ratio and the carbon-13 / carbon-12 ratio (pharmaceutical

testosterone contains less carbon-13 than endogenous testosterone). In some testing programs, an individual's own historical results may serve as a reference

interval for interpretation of a suspicious finding. Another approach being investigated is the detection of the administered form of testosterone, usually an ester, in

hair.[79][80][81][82]
[EDIT ]S YNTHETIC ANALOGS

A number of synthetic analogs of testosterone have been developed with improved bioavailability and metabolic half life relative to testosterone. Many of these

analogs have an alkyl group introduced at the C-17 position in order to prevent conjugation and hence improve oral bioavailability. These are the so-called “17-aa”

(17-alkyl androgen) family of androgens such as fluoxymesterone and methyltestosterone.

[EDIT ]RELATED DRUGS

Some drugs indirectly target testosterone as a way of treating certain conditions. For example, 5-alpha-reductase inhibitors such asfinasteride inhibits the

conversion of testosterone into dihydrotestosterone (DHT), a metabolite which is more potent than testosterone.[83]These 5-alpha-reductase inhibitors have been

used to treat various conditions associated with androgens, such as androgenetic alopecia(male-pattern baldness), hirsutism, benign prostatic hyperplasia (BPH),

and prostate cancer.[83] Alternatively GnRH antagonists bind toGnRH receptors in the pituitary gland, blocking the release of luteinising hormone (LH) and follicle-

stimulating hormone (FSH) from the pituitary.[84] In men, the reduction in LH subsequently leads to rapid suppression of testosterone release from the testes. GnRH

antagonists have been used for the treatment of prostate cancer.

A NDROGEN
Androgen is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of masculine
characteristics in vertebrates by binding to androgen receptors. This includes the activity of the accessory male sex organs and development of male secondary sex characteristics.
Androgens, which were first discovered in 1936, are also called androgenic hormones or testoids. Androgens are also the original anabolic steroids. They are also the precursor of
all estrogens, the female sex hormones. The primary and most well-known androgen is testosterone.

T YPES OF ANDROGENS

Steroidogenesis, showing the relation between several androgens at bottom left. (Estrone and estradiol, in contrast, are estrogens.

A subset of androgens, adrenal androgens, includes any of the 19-carbon steroids synthesized by the adrenal cortex, the outer portion of the adrenal gland(zonula reticularis -
innermost region of the adrenal cortex), that function as weak steroids or steroid precursors, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S),
and androstenedione.
Besides testosterone, other androgens include:
 • Dehydroepiandrosterone (DHEA): a steroid hormone produced in the adrenal cortex from cholesterol. It is the primary precursor of
natural estrogens. DHEA is also called dehydroisoandrosterone or dehydroandrosterone.
• Androstenedione (Andro): an androgenic steroid produced by the testes, adrenal cortex, and ovaries. While androstenediones are
converted metabolically to testosterone and other androgens, they are also the parent structure of estrone. Use of androstenedione as
an athletic or body building supplement has been banned by the International Olympic Committee as well as other sporting
organizations.
• Androstenediol: the steroid metabolite that is thought to act as the main regulator of gonadotropin secretion.
• Androsterone: a chemical by-product created during the breakdown of androgens, or derived from progesterone, that also exerts
minor masculinising effects, but with one-seventh the intensity of testosterone. It is found in approximately equal amounts in
the plasma and urine of both males and females.
• Dihydrotestosterone (DHT): a metabolite of testosterone, and a more potent androgen than testosterone in that it binds more strongly
to androgen receptors. It is produced in the adrenal cortex.

A NDROGEN FUNCTIONS

DEVELOPMENT OF THE MALE

T ES TES FO RM ATIO N

During mammalian development, the gonads are at first capable of becoming either ovaries or testes.[1] In humans, starting at about week 4 the gonadal rudiments are present within
the intermediate mesoderm adjacent to the developing kidneys. At about week 6, epithelial sex cords develop within the forming testes and incorporate the germ cells as they
migrate into the gonads. In males, certain Y chromosome genes, particularly SRY, control development of the male phenotype, including conversion of the early bipotential gonad
into testes. In males, the sex cords fully invade the developing gonads.

A N DROGEN PRO DUCTIO N

The mesoderm-derived epithelial cells of the sex cords in developing testes become the Sertoli cells which will function to support sperm cell formation. A minor population of non-
epithelial cells appear between the tubules by week 8 of human fetal development. These are Leydig cells. Soon after they differentiate, Leydig cells begin to produce androgens.

A N DROGEN EFFECTS

The androgens function as paracrine hormones required by the Sertoli cells in order to support sperm production. They are also required for masculinization of the developing male
fetus (including penis and scrotum formation). Under the influence of androgens, remnants of the mesonephron, the Wolffian ducts, develop into the epididymis, vas deferens and
seminal vesicles. This action of androgens is supported by a hormone from Sertoli cells, AMH, which prevents the embryonic Müllerian ducts from developing into fallopian tubes
and other female reproductive tract tissues in male embryos. AMH and androgens cooperate to allow for the normal movement of testes into the scrotum.

E ARL Y REGULATIO N

Before the production of the pituitary hormone LH by the embryo starting at about weeks 11-12, human chorionic gonadotrophin (hCG) promotes the differentiation of Leydig cells
and their production of androgens. Androgen action in target tissues often involves conversion of testosterone to 5α-dihydrotestosterone (DHT).
S PERMATOGENESIS
During puberty, androgen, LH and FSH production increase and the sex cords hollow out, forming the seminiferous tubules, and the germ cells start to differentiate into sperm.
Throughout adulthood, androgens and FSH cooperatively act on Sertoli cells in the testes to support sperm production.[2] Exogenous androgen supplements can be used as a male
contraceptive. Elevated androgen levels caused by use of androgen supplements can inhibit production of LH and block production of endogenous androgens by Leydig cells.
Without the locally high levels of androgens in testes due to androgen production by Leydig cells, the seminiferous tubules can degenerate resulting in infertility. For this reason,
many transdermal androgen patches are applied to the scrotum.
I NHIBITION OF FAT DEPOSITION

Males typically have less adipose tissue than females. Recent results indicate that androgens inhibit the ability of some fat cells to store lipids by blocking a signal transduction
pathway that normally supports adipocyte function.[3] Also, androgens, but not estrogens, increase beta adrenergic receptors while decreasing alpha adrenargic receptors- which
results in increased levels of epinephrine/ norepinephrine due to lack of alpha-2 receptor negative feedback and decreased fat accumulation due to epinephrine/ norepinephrine then
acting on lipolysis-inducing beta receptors.
M USCLE MASS

Males typically have more skeletal muscle mass than females. Androgens promote the enlargement of skeletal muscle cells and probably act in a coordinated manner to enhance
muscle function by acting on several cell types in skeletal muscle tissue.[4] One type of cell that conveys hormone signals to generating muscle is the myoblast. Higher androgen
levels lead to increased expression of androgen receptor. Fusion of myoblasts generates myotubes, in a process that is linked to androgen receptor levels.[5]
B RAIN
Circulating levels of androgens can influence human behavior because some neurons are sensitive to steroid hormones. Androgen levels have been implicated in the regulation of
human aggression[6] and libido.

I NSENSITIVITY TO ANDROGEN IN HUMANS

Reduced ability of a XY karyotype fetus to respond to androgens can result in one of several problems, including infertility and several forms of intersexconditions. See
androgen insensitivity syndrome (AIS)