Progesterone (; P4) is an
endogenous
Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell.
For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...
steroid
A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration.
Steroids have two principal biological functions: as important components of cell membranes t ...
and
progestogen
Progestogens, also sometimes written progestins, progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestoge ...
sex hormone
Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects a ...
involved in the
menstrual cycle
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eg ...
,
pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
, and
embryogenesis
An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male ...
of humans and other species.
It belongs to a group of steroid hormones called the
progestogen
Progestogens, also sometimes written progestins, progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestoge ...
s
and is the major progestogen in the body. Progesterone has a variety of important functions in the body. It is also a crucial
metabolic intermediate
Metabolic intermediates are compounds produced during the conversion of substrates (starting molecules) into final products in biochemical reactions within cells.
Although these intermediates are of relatively minor direct importance to cell ...
in the production of other endogenous
steroid
A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration.
Steroids have two principal biological functions: as important components of cell membranes t ...
s, including the
sex hormone
Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects a ...
s and the
corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...
s, and plays an important role in brain function as a
neurosteroid.
In addition to its role as a natural hormone, progesterone is also used as a medication, such as in combination with
estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
for
contraception
Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth control only be ...
, to reduce the risk of
uterine or
cervical cancer
Cervical cancer is a cancer arising from the cervix or in any layer of the wall of the cervix. It is due to the abnormal growth of cells that can invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later sympt ...
, in
hormone replacement therapy
Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such ...
, and in
feminizing hormone therapy
Feminizing hormone therapy, also known as transfeminine hormone therapy, is a form of Transgender_health_care#Gender-affirming_care , gender-affirming care and a gender-affirming hormone therapy , gender-affirming hormone therapy to change t ...
.
It was first prescribed in 1934.
Biological activity
Progesterone is the most important progestogen in the body. As a potent
agonist
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
of the
nuclear progesterone receptor (nPR) (with an
affinity
Affinity may refer to:
Commerce, finance and law
* Affinity (law), kinship by marriage
* Affinity analysis, a market research and business management technique
* Affinity Credit Union, a Saskatchewan-based credit union
* Affinity Equity Pa ...
of K
D = 1 nM) the resulting effects on ribosomal transcription plays a major role in regulation of female reproduction.
In addition, progesterone is an agonist of the more recently discovered
membrane progesterone receptor
Membrane progesterone receptors (mPRs) are a group of cell surface receptors and membrane steroid receptors belonging to the progestin and adipoQ receptor (PAQR) family which bind the endogenous progestogen and neurosteroid progesterone, as well as ...
s (mPRs),
of which the expression has regulation effects in reproduction function (
oocyte maturation, labor, and
sperm motility
Sperm motility describes the ability of sperm to move properly through the female reproductive tract (internal fertilization) or through water ( external fertilization) to reach the egg. Sperm motility can also be thought of as the ''quality'', wh ...
) and cancer although additional research is required to further define the roles.
It also functions as a ligand of the
PGRMC1 (progesterone receptor membrane component 1) which impacts
tumor progression
Tumor progression is the third and last phase in tumor development. This phase is characterised by increased growth speed and invasiveness of the tumor cells. As a result of the progression, phenotypical changes occur and the tumor becomes more agg ...
, metabolic regulation, and viability control of
nerve cells
A neuron (American English), neurone (British English), or nerve cell, is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. They are located in the nervous system and help to ...
.
Moreover, progesterone is also known to be an antagonist of the
sigma
Sigma ( ; uppercase Σ, lowercase σ, lowercase in word-final position ς; ) is the eighteenth letter of the Greek alphabet. In the system of Greek numerals, it has a value of 200. In general mathematics, uppercase Σ is used as an operator ...
σ1 receptor,
a
negative allosteric modulator
In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that a ...
of
nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are Receptor (biochemistry), receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the c ...
s,
and a potent antagonist of the
mineralocorticoid receptor
The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the ''NR3C2'' gene that is located on chromosome 4q31 ...
(MR).
Progesterone prevents MR activation by binding to this receptor with an affinity exceeding even those of
aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...
and
glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...
s such as
cortisol
Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone.
Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...
and
corticosterone
Corticosterone, also known as 17-deoxycortisol and 11β,21-dihydroxyprogesterone, is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands. In the very rare case of congenital adrenal hyperplasia due ...
,
and produces
antimineralocorticoid effects, such as
natriuresis
Natriuresis is the process of sodium excretion in the urine through the action of the kidneys. It is promoted by Brain natriuretic peptide, ventricular and atrial natriuretic peptides as well as calcitonin, and inhibited by chemicals such as aldost ...
, at physiological concentrations.
In addition, progesterone binds to and behaves as a
partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...
of the
glucocorticoid receptor
The glucocorticoid receptor (GR or GCR) also known by its gene name ''NR3C1'' ( nuclear receptor subfamily 3, group C, member 1) is the steroid receptor for glucocorticoids such as cortisol.
The GR is expressed in almost every cell in the bod ...
(GR), albeit with very low potency (
EC50 >100-fold less relative to
cortisol
Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone.
Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...
).
Progesterone, through its
neurosteroid active metabolites such as
5α-dihydroprogesterone and
allopregnanolone
Allopregnanolone is a natural product, naturally occurring neurosteroid which is made in the body from the hormone progesterone. As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso, and used to t ...
, acts indirectly as a
positive allosteric modulator of the
GABAA receptor.
Progesterone and some of its metabolites, such as
5β-dihydroprogesterone, are agonists of the
pregnane X receptor (PXR),
albeit weakly so (
EC50 >10 μM).
In accordance, progesterone
induce
Induce may refer to:
* Induced consumption
* Induced innovation
* Induced character
* Induced coma
* Induced menopause
* Induced metric
* Induced path
* Induced topology
* Induce (musician), American musician
* Labor induction
Labor indu ...
s several
hepatic
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
cytochrome P450
Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s,
such as
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...
,
especially during
pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
when concentrations are much higher than usual.
Perimenopausal women have been found to have greater CYP3A4 activity relative to men and postmenopausal women, and it has been inferred that this may be due to the higher progesterone levels present in perimenopausal women.
Progesterone modulates the activity of
CatSper (cation channels of sperm)
voltage-gated Ca
2+ channels. Since eggs release progesterone, sperm may use progesterone as a homing signal to swim toward eggs (
chemotaxis
Chemotaxis (from ''chemical substance, chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell organism, single-cell or multicellular organisms direct thei ...
). As a result, it has been suggested that substances that block the progesterone binding site on CatSper channels could potentially be used in
male contraception.
Biological function
Hormonal interactions
Progesterone has a number of physiological effects that are amplified in the presence of
estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
s. Estrogens through
estrogen receptor
Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...
s (ERs) induce or
upregulate the
expression of the PR.
One example of this is in
breast
The breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...
tissue, where estrogens allow progesterone to mediate
lobuloalveolar development.
Elevated levels of progesterone potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a reduction in extracellular fluid volume. Progesterone withdrawal, on the other hand, is associated with a temporary increase in sodium retention (reduced natriuresis, with an increase in extracellular fluid volume) due to the compensatory increase in aldosterone production, which combats the blockade of the mineralocorticoid receptor by the previously elevated level of progesterone.
Early sexual differentiation
Placenta
The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...
l progesterone can be converted into
5α-dihydrotestosterone (DHT), a potent
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
that is responsible for the development of male genitalia.
This can be done both by conversion into testosterone, which is then converted to DHT, and via the
androgen backdoor pathway, which is particularly important for
fetal development
Prenatal development () involves the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal deve ...
.
As progesterone is the precursor for both pathways, it plays a key role in sexual differentiation.
Reproductive system

Progesterone has key effects via non-genomic signalling on human sperm as they migrate through the female reproductive tract before
fertilization
Fertilisation or fertilization (see American and British English spelling differences#-ise, -ize (-isation, -ization), spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give ...
occurs, though the receptor(s) as yet remain unidentified.
Detailed characterisation of the events occurring in sperm in response to progesterone has elucidated certain events including intracellular calcium transients and maintained changes,
slow calcium oscillations,
now thought to possibly regulate motility.
It is produced by the ovaries.
Progesterone has also been shown to demonstrate effects on octopus spermatozoa.
Progesterone is sometimes called the "
hormone of pregnancy",
and it has many roles relating to the development of the fetus:
* Progesterone converts the
endometrium
The endometrium is the inner epithelium, epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The funct ...
to its secretory stage to prepare the uterus for implantation. At the same time progesterone affects the
vaginal epithelium
The vaginal epithelium is the inner lining of the vagina consisting of multiple layers of (Epithelium, squamous) cells. The basal membrane provides the support for the first layer of the epithelium-the basal layer. The intermediate layers lie u ...
and
cervical mucus
The cervix (: cervices) or cervix uteri is a dynamic fibromuscular sexual organ of the female reproductive system that connects the vagina with the uterine cavity. The human female cervix has been documented anatomically since at least the tim ...
, making it thick and impenetrable to
sperm
Sperm (: sperm or sperms) is the male reproductive Cell (biology), cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm ...
. Progesterone is anti-
mitogenic in endometrial epithelial cells, and as such, mitigates the tropic effects of
estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
.
If
pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
does not occur, progesterone levels will decrease, leading to
menstruation
Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycle is characterized ...
. Normal menstrual bleeding is progesterone-withdrawal bleeding. If ovulation does not occur and the
corpus luteum
The corpus luteum (Latin for "yellow body"; : corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is the ...
does not develop, levels of progesterone may be low, leading to
anovulatory dysfunctional uterine bleeding.
* During implantation and
gestation
Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregn ...
, progesterone appears to decrease the maternal
immune response to allow for the acceptance of the pregnancy.
* Progesterone decreases contractility of the uterine
smooth muscle
Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...
.
This effect contributes to prevention of
preterm labor.
Studies have shown that in individuals who are pregnant with a single fetus, asymptomatic in the prenatal stage, and at a high risk of giving pre-term birth spontaneously, vaginal progesterone medication has been found to be effective in preventing spontaneous pre-term birth. Individuals who are at a high risk of giving pre-term birth spontaneously are those who have a short cervix of less than 25 mm or have previously given pre-term birth spontaneously. Although pre-term births are generally considered to be less than 37 weeks, these studies found that vaginal progesterone is associated with fewer pre-term births of less than 34 weeks.
* A drop in progesterone levels is possibly one step that facilitates the onset of
labor
Labour or labor may refer to:
* Childbirth, the delivery of a baby
* Labour (human activity), or work
** Manual labour, physical work
** Wage labour, a socioeconomic relationship between a worker and an employer
** Organized labour and the labour ...
.
* In addition, progesterone inhibits
lactation
Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The process ...
during pregnancy. The fall in progesterone levels following delivery is one of the triggers for milk production.
The
fetus
A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic development, embryonic stage, the fetal stage of development takes place. Pren ...
metabolizes placental progesterone in the production of
adrenal steroids.
Breasts
Lobuloalveolar development
Progesterone plays an important role in
breast development
Breast development, also known as mammogenesis, is a complex biological process in primates that takes place throughout a female's life.
It occurs across several phases, including prenatal development, puberty, and pregnancy. At menopause, breas ...
. In conjunction with
prolactin
Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secr ...
, it mediates
lobuloalveolar maturation of the
mammary gland
A mammary gland is an exocrine gland that produces milk in humans and other mammals. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in primates (for example, human ...
s during pregnancy to allow for milk production and thus
lactation
Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The process ...
and
breastfeeding
Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...
of
offspring
In biology, offspring are the young creation of living organisms, produced either by sexual reproduction, sexual or asexual reproduction. Collective offspring may be known as a brood or progeny. This can refer to a set of simultaneous offspring ...
following
parturition
Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiated by hormones which cause the muscular walls of the uterus to contract, expelling the f ...
(childbirth).
Estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
induces expression of the PR in breast tissue and hence progesterone is dependent on estrogen to mediate lobuloalveolar development.
It has been found that is a critical downstream mediator of progesterone-induced lobuloalveolar maturation.
RANKL
knockout mice
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
show an almost identical mammary phenotype to PR knockout mice, including normal mammary ductal development but complete failure of the development of lobuloalveolar structures.
Ductal development
Though to a far lesser extent than estrogen, which is the major mediator of mammary ductal development (via the
ERα
Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein)
that is activated by the se ...
),
progesterone may be involved in ductal development of the mammary glands to some extent as well.
PR knockout mice or mice treated with the
PR antagonist mifepristone
Mifepristone, and also known by its developmental code name RU-486, is a drug typically used in combination with misoprostol to bring about a medical abortion during pregnancy. This combination is 97% effective during the first 63 days (9 wee ...
show delayed although otherwise normal mammary ductal development at puberty.
In addition, mice modified to have
overexpression of
PRA display ductal hyperplasia,
and progesterone induces ductal growth in the mouse mammary gland.
Progesterone mediates ductal development mainly via induction of the
expression of
amphiregulin, the same
growth factor
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for ...
that estrogen primarily induces the expression of to mediate ductal development.
These animal findings suggest that, while not essential for full mammary ductal development, progesterone seems to play a potentiating or accelerating role in estrogen-mediated mammary ductal development.
Breast cancer risk
Progesterone also appears to be involved in the
pathophysiology
Pathophysiology (or physiopathology) is a branch of study, at the intersection of pathology and physiology, concerning disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is ...
of
breast cancer
Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
, though its role, and whether it is a promoter or inhibitor of breast cancer risk, has not been fully elucidated.
Most
progestin
A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a '' synthetic'' progestogen. ...
s, or
synthetic
Synthetic may refer to:
Science
* Synthetic biology
* Synthetic chemical or compound, produced by the process of chemical synthesis
* Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...
progestogens, like
medroxyprogesterone acetate
Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of ...
, have been found to increase the risk of breast cancer in postmenopausal people in combination with estrogen as a component of
menopausal hormone therapy
Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such ...
.
The combination of natural oral progesterone or the atypical progestin
dydrogesterone with estrogen has been associated with less risk of breast cancer than progestins plus estrogen.
However, this may simply be an artifact of the low progesterone levels produced with oral progesterone.
More research is needed on the role of progesterone in breast cancer.
Skin health
The
estrogen receptor
Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...
, as well as the
progesterone receptor
The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone.
In humans, PR is encoded by a single ''PGR'' gene resi ...
, have been detected in the
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different ...
, including in
keratinocyte
Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...
s and
fibroblast
A fibroblast is a type of cell (biology), biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and ...
s.
At
menopause
Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...
and thereafter, decreased levels of female
sex hormone
Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects a ...
s result in
atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), malnutrition, poor nourishment, poor circulatory system, circulation, loss of hormone, ...
, thinning, and increased
wrinkling of the skin and a reduction in skin
elasticity, firmness, and strength.
These skin changes constitute an acceleration in
skin aging and are the result of decreased
collagen
Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
content, irregularities in the
morphology
Morphology, from the Greek and meaning "study of shape", may refer to:
Disciplines
*Morphology (archaeology), study of the shapes or forms of artifacts
*Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies, ...
of
epidermal skin cells, decreased
ground substance
Ground substance is an amorphous gel-like substance in the extracellular space of animals that contains all components of the extracellular matrix (ECM) except for fibrous materials such as collagen and elastin. Ground substance is active in the d ...
between
skin fibers, and reduced
capillaries
A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the in ...
and
blood flow
Hemodynamics American and British English spelling differences#ae and oe, or haemodynamics are the Fluid dynamics, dynamics of blood flow. The circulatory system is controlled by homeostasis, homeostatic mechanisms of autoregulation, just as hydrau ...
.
The skin also becomes more
dry during menopause, which is due to reduced skin
hydration and
surface lipids (sebum production).
Along with chronological aging and photoaging, estrogen deficiency in menopause is one of the three main factors that predominantly influences skin aging.
Hormone replacement therapy, consisting of systemic treatment with estrogen alone or in combination with a progestogen, has well-documented and considerable beneficial effects on the skin of postmenopausal people.
These benefits include increased skin collagen content, skin thickness and elasticity, and skin hydration and surface lipids.
Topical estrogen has been found to have similar beneficial effects on the skin.
In addition, a study has found that topical 2% progesterone cream significantly increases skin elasticity and firmness and observably decreases wrinkles in peri- and postmenopausal people.
Skin hydration and surface lipids, on the other hand, did not significantly change with topical progesterone.
These findings suggest that progesterone, like estrogen, also has beneficial effects on the skin, and may be independently protective against skin aging.
Sexuality
Libido
Progesterone and its
neurosteroid active metabolite allopregnanolone
Allopregnanolone is a natural product, naturally occurring neurosteroid which is made in the body from the hormone progesterone. As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso, and used to t ...
appear to be importantly involved in
libido
In psychology, libido (; ) is psychic drive or energy, usually conceived of as sexual in nature, but sometimes conceived of as including other forms of desire. The term ''libido'' was originally developed by Sigmund Freud, the pioneering origin ...
in females.
Homosexuality
Dr.
Diana Fleischman, of the
University of Portsmouth
The University of Portsmouth (UoP) is a public university in Portsmouth, England. Comprising five Faculty (division), faculties, the university offers a wide range of academic disciplines. in 2022, with around 28,280 students enrolled in Unde ...
, and colleagues looked for a relationship between progesterone and sexual attitudes in 92 women. Their research, published in the
Archives of Sexual Behavior
The ''Archives of Sexual Behavior'' is a bimonthly peer-reviewed medical journal in sexology. It is the official publication of the International Academy of Sex Research.
History
The journal was established in 1971 by Richard Green, who served a ...
found that women who had higher levels of progesterone scored higher on a questionnaire measuring homoerotic motivation. They also found that men who had high levels of progesterone were more likely to have higher homoerotic motivation scores after affiliative priming compared to men with low levels of progesterone.
Nervous system
Progesterone, like
pregnenolone
Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineraloc ...
and
dehydroepiandrosterone
Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It funct ...
(DHEA), belongs to an important group of endogenous steroids called
neurosteroids. It can be metabolized within all parts of the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
.
Neurosteroids are
neuromodulators, and are
neuroprotective,
neurogenic, and regulate
neurotransmission
Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron ...
and
myelin
Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...
ation.
The effects of progesterone as a neurosteroid are mediated predominantly through its interactions with non-nuclear PRs, namely the mPRs and
PGRMC1, as well as certain other receptors, such as the σ
1 and nACh receptors.
Brain damage
Previous studies have shown that progesterone supports the normal development of neurons in the brain, and that the hormone has a protective effect on damaged brain tissue. It has been observed in animal models that females have reduced susceptibility to
traumatic brain injury
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity ranging from mild traumatic brain injury (mTBI/concussion) to severe traumati ...
and this protective effect has been hypothesized to be caused by increased circulating levels of
estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
and progesterone in females.
Proposed mechanism
The mechanism of progesterone protective effects may be the reduction of inflammation that follows brain trauma and hemorrhage.
Damage incurred by traumatic brain injury is believed to be caused in part by mass
depolarization
In biology, depolarization or hypopolarization is a change within a cell (biology), cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolar ...
leading to
excitotoxicity
In excitotoxicity, neuron, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamic acid, glutamate become pathologically high, resulting in excessive stimulation of cell surface recept ...
. One way in which progesterone helps to alleviate some of this excitotoxicity is by blocking the
voltage-dependent calcium channel
Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'' muscle, glial cells, neurons) with a permeability t ...
s that trigger
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.
Neurotra ...
release.
It does so by manipulating the signaling pathways of
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
s involved in this release. Another method for reducing the excitotoxicity is by up-regulating the
GABAA, a widespread inhibitory neurotransmitter receptor.
Progesterone has also been shown to prevent
apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
in neurons, a common consequence of brain injury. It does so by inhibiting enzymes involved in the apoptosis pathway specifically concerning the mitochondria, such as activated
caspase 3 and
cytochrome c.
Not only does progesterone help prevent further damage, it has also been shown to aid in
neuroregeneration
Neuroregeneration is the regrowth or repair of nervous tissues, cells or cell products. Neuroregenerative mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous ...
.
One of the serious effects of traumatic brain injury includes edema. Animal studies show that progesterone treatment leads to a decrease in
edema
Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...
levels by increasing the concentration of
macrophage
Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s and
microglia
Microglia are a type of glia, glial cell located throughout the brain and spinal cord of the central nervous system (CNS). Microglia account for about around 5–10% of cells found within the brain. As the resident macrophage cells, they act as t ...
sent to the injured tissue.
This was observed in the form of reduced leakage from the
blood brain barrier in secondary recovery in progesterone treated rats. In addition, progesterone was observed to have
antioxidant
Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...
properties, reducing the concentration of
oxygen free radicals faster than without.
There is also evidence that the addition of progesterone can also help re
myelin
Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...
ate damaged
axons
An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see spelling differences) is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action pot ...
due to trauma, restoring some lost neural signal conduction.
Another way progesterone aids in regeneration includes increasing the circulation of endothelial progenitor cells in the brain. This helps new
vasculature
In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart an ...
to grow around scar tissue which helps repair the area of insult.
Addiction
Progesterone enhances the function of
serotonin receptor
5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...
s in the brain, so an excess or deficit of progesterone has the potential to result in significant neurochemical issues. This provides an explanation for why some people resort to substances that enhance
serotonin
Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...
activity such as
nicotine
Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...
,
alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
, and
cannabis
''Cannabis'' () is a genus of flowering plants in the family Cannabaceae that is widely accepted as being indigenous to and originating from the continent of Asia. However, the number of species is disputed, with as many as three species be ...
when their progesterone levels fall below optimal levels.
* Sex differences in hormone levels may induce women to respond differently than men to nicotine. When women undergo cyclic changes or different hormonal transition phases (menopause, pregnancy, adolescence), there are changes in their progesterone levels.
Therefore, females have an increased biological vulnerability to nicotine's reinforcing effects compared to males and progesterone may be used to counter this enhanced vulnerability. This information supports the idea that progesterone can affect behavior.
* Similar to nicotine, cocaine also increases the release of dopamine in the brain. The neurotransmitter is involved in the reward center and is one of the main neurotransmitters involved with substance abuse and reliance. In a study of cocaine users, it was reported that progesterone reduced craving and the feeling of being stimulated by cocaine. Thus, progesterone was suggested as an agent that decreases cocaine craving by reducing the dopaminergic properties of the drug.
Societal
In a 2012 University of Amsterdam study of 120 women, women's luteal phase (higher levels of progesterone, and increasing levels of estrogen) was correlated with a lower level of competitive behavior in gambling and math contest scenarios, while their premenstrual phase (sharply-decreasing levels of progesterone, and decreasing levels of estrogen) was correlated with a higher level of competitive behavior.
Other effects
* Progesterone also has a role in skin elasticity and bone strength, in
respiration, in nerve tissue and in
female sexuality, and the presence of progesterone receptors in certain muscle and fat tissue may hint at a role in
sexually dimorphic
Sexual dimorphism is the condition where sexes of the same species exhibit different Morphology (biology), morphological characteristics, including characteristics not directly involved in reproduction. The condition occurs in most dioecy, di ...
proportions of those.
* During pregnancy, progesterone is said to decrease uterine irritability.
* During pregnancy, progesterone helps to suppress immune responses of the mother to fetal antigens, which prevents rejection of the fetus.
* Progesterone raises
epidermal growth factor-1 (EGF-1) levels, a factor often used to induce proliferation, and used to sustain cultures, of
stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...
s.
* Progesterone increases core temperature (thermogenic function) during ovulation.
* Progesterone reduces
spasm
A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ, such as the bladder.
A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a musc ...
and relaxes
smooth muscle
Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...
.
Bronchi
A bronchus ( ; : bronchi, ) is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi to branch from the trachea at the carina are the right main bronchus and the left main bronchus. Thes ...
are widened and
mucus
Mucus (, ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both Serous fluid, serous and muc ...
regulated. (PRs are widely present in
submucosal tissue.)
* Progesterone acts as an
antiinflammatory agent and regulates the
immune response
An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellula ...
.
* Progesterone reduces
gall-bladder
In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow Organ (anatomy), organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath t ...
activity.
* Progesterone normalizes
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells.
Blood is com ...
clotting and vascular tone,
zinc
Zinc is a chemical element; it has symbol Zn and atomic number 30. It is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic tabl ...
and
copper
Copper is a chemical element; it has symbol Cu (from Latin ) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkish-orang ...
levels,
cell oxygen
Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
levels, and use of fat stores for energy.
* Progesterone may affect gum health, increasing risk of gingivitis (gum inflammation).
* Progesterone appears to prevent
endometrial cancer
Endometrial cancer is a cancer that arises from the endometrium (the epithelium, lining of the uterus or womb). It is the result of the abnormal growth of cells (biology), cells that can invade or spread to other parts of the body. The first s ...
(involving the uterine lining) by regulating the effects of estrogen.
* Progesterone plays an important role in the signaling of insulin release and pancreatic function, and may affect the susceptibility to diabetes or gestational diabetes.
* Progesterone levels in the blood were found to be lower in those who had higher weight and higher BMI among those who became pregnant through in vitro fertilization.
* Current data shows that micronized progesterone, which is chemically identical to the progesterone produced in people's bodies, in combination with estrogen in menopausal hormone therapy does not seem to have significant effects on venous thromboembolism (blood clots in veins) and ischemic stroke (lack of blood flow to the brain due to blockage of a blood vessel that supplies the brain). However, more studies need to be conducted to see whether or not micronized progesterone alone or in combined menopausal hormone therapy changes the risk of myocardial infarctions (heart attacks).
* There have not been any studies done yet on the effects of micronized progesterone on hair loss due to menopause.
* Despite suggestions for using hormone therapy to prevent loss of muscle mass in post-menopausal individuals (50 and older), menopausal hormone therapy involving either estrogen alone or estrogen and progesterone has not been found to preserve muscle mass.
Menopausal hormone therapy also does not result in body weight reduction, BMI reduction, or change in glucose metabolism.
Biochemistry
Biosynthesis

In mammals, progesterone, like all other
steroid
A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration.
Steroids have two principal biological functions: as important components of cell membranes t ...
hormone
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
s, is synthesized from
pregnenolone
Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineraloc ...
, which itself is derived from
cholesterol
Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils.
Cholesterol is biosynthesis, biosynthesized by all anima ...
.
Cholesterol undergoes double oxidation to produce
22''R''-hydroxycholesterol and then
20α,22''R''-dihydroxycholesterol. This vicinal
diol
A diol is a chemical compound containing two hydroxyl groups ( groups). An aliphatic diol may also be called a glycol. This pairing of functional groups is pervasive, and many subcategories have been identified. They are used as protecting gro ...
is then further oxidized with loss of the side chain starting at position C22 to produce pregnenolone. This reaction is catalyzed by
cytochrome
Cytochromes are redox-active proteins containing a heme, with a central iron (Fe) atom at its core, as a cofactor. They are involved in the electron transport chain and redox catalysis. They are classified according to the type of heme and its ...
P450scc.
The conversion of pregnenolone to progesterone takes place in two steps. First, the 3β-
hydroxyl
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
group is oxidized to a
keto group and second, the
double bond
In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...
is moved to C4, from C5 through a keto/
enol
In organic chemistry, enols are a type of functional group or intermediate in organic chemistry containing a group with the formula (R = many substituents). The term ''enol'' is an abbreviation of ''alkenol'', a portmanteau deriving from "-ene ...
tautomer
In chemistry, tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert.
The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the reloca ...
ization reaction.
This reaction is catalyzed by
3β-hydroxysteroid dehydrogenase/δ5-4-isomerase.
Progesterone in turn is the precursor of the mineralocorticoid
aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...
, and after conversion to
17α-hydroxyprogesterone, of
cortisol
Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone.
Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...
and
androstenedione
Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroe ...
. Androstenedione can be converted to
testosterone
Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
,
estrone
Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estriol. Estrone, as well as the other estrogens, are synthesized ...
, and
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
, highlighting the critical role of progesterone in testosterone synthesis.
Pregnenolone and progesterone can also be synthesized by
yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...
.
Approximately 30 mg of progesterone is secreted from the ovaries per day in reproductive-age women, while the adrenal glands produce about 1 mg of progesterone per day.
Distribution
Progesterone binds extensively to
plasma protein
Plasma proteins, sometimes referred to as blood proteins, are proteins present in blood plasma. They perform many different functions, including transport of hormones, vitamins and minerals in activity and functioning of the immune system. Other b ...
s, including
albumin
Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...
(50–54%) and
transcortin (43–48%).
It has similar affinity for albumin relative to the PR.
Metabolism
The
metabolism
Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...
of progesterone is rapid and extensive and occurs mainly in the
liver
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
,
though
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s that metabolize progesterone are also expressed widely in the
brain
The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
,
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different ...
, and various other
extrahepatic tissues.
Progesterone has an
elimination half-life
Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...
of only approximately 5 minutes in
circulation.
The metabolism of progesterone is complex, and it may form as many as 35 different
unconjugated metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
s when it is ingested orally.
Progesterone is highly susceptible to enzymatic
reduction via
reductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually uti ...
s and
hydroxysteroid dehydrogenases due to its
double bond
In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...
(between the C4 and C5 positions) and its two
ketone
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
s (at the C3 and C20 positions).
The major
metabolic pathway
In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), cell. The reactants, products, and Metabolic intermediate, intermediates of an enzymatic reaction are known as metabolites, which are ...
of progesterone is reduction by
5α-reductase and
5β-reductase into the dihydrogenated
5α-dihydroprogesterone and
5β-dihydroprogesterone, respectively.
This is followed by the further reduction of these metabolites via
3α-hydroxysteroid dehydrogenase and
3β-hydroxysteroid dehydrogenase into the tetrahydrogenated
allopregnanolone
Allopregnanolone is a natural product, naturally occurring neurosteroid which is made in the body from the hormone progesterone. As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso, and used to t ...
,
pregnanolone,
isopregnanolone, and
epipregnanolone.
Subsequently,
20α-hydroxysteroid dehydrogenase
In enzymology, a 20-α-hydroxysteroid dehydrogenase () is an enzyme that catalysis, catalyzes the chemical reaction
:17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(P)+ \rightleftharpoons 17alpha-hydroxyprogesterone + NAD(P)H + H+
The 3 substra ...
and
20β-hydroxysteroid dehydrogenase reduce these metabolites to form the corresponding hexahydrogenated
pregnanediols (eight different
isomer
In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...
s in total),
which are then conjugated via
glucuronidation
Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gly ...
and/or
sulfation
Sulfation (sometimes spelled sulphation in British English) is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected ...
, released from the liver into circulation, and
excreted by the
kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
s into the
urine
Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
.
The major metabolite of progesterone in the urine is the 3α,5β,20α isomer of
pregnanediol glucuronide, which has been found to constitute 15 to 30% of an injection of progesterone.
Other metabolites of progesterone formed by the enzymes in this pathway include
3α-dihydroprogesterone,
3β-dihydroprogesterone,
20α-dihydroprogesterone, and
20β-dihydroprogesterone, as well as various combination products of the enzymes aside from those already mentioned.
Progesterone can also first be
hydroxylated (see below) and then reduced.
Endogenous progesterone is metabolized approximately 50% into 5α-dihydroprogesterone in the
corpus luteum
The corpus luteum (Latin for "yellow body"; : corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is the ...
, 35% into 3β-dihydroprogesterone in the liver, and 10% into 20α-dihydroprogesterone.
Relatively small portions of progesterone are
hydroxylated via
17α-hydroxylase (CYP17A1) and
21-hydroxylase (CYP21A2) into
17α-hydroxyprogesterone and
11-deoxycorticosterone (21-hydroxyprogesterone), respectively,
and
pregnanetriols are formed secondarily to 17α-hydroxylation.
Even smaller amounts of progesterone may be also hydroxylated via
11β-hydroxylase (CYP11B1) and to a lesser extent via
aldosterone synthase
Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzym ...
(CYP11B2) into
11β-hydroxyprogesterone
11β-Hydroxyprogesterone (11β-OHP), also known as 21-deoxycorticosterone, as well as 11β-hydroxypregn-4-ene-3,20-dione, is a naturally occurring, endogenous steroid and derivative of progesterone. It is a potent mineralocorticoid. Syntheses ...
.
[ In addition, progesterone can be hydroxylated in the liver by other ]cytochrome P450
Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...
enzymes which are not steroid-specific. 6β-Hydroxylation, which is catalyzed mainly by CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...
, is the major transformation, and is responsible for approximately 70% of cytochrome P450-mediated progesterone metabolism. Other routes include 6α-, 16α-, and 16β-hydroxylation. However, treatment of women with ketoconazole
Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin inf ...
, a strong CYP3A4 inhibitor, had minimal effects on progesterone levels, producing only a slight and non-significant increase, and this suggests that cytochrome P450 enzymes play only a small role in progesterone metabolism.
Levels
Progesterone levels are relatively low during the preovulatory phase of the menstrual cycle
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eg ...
, rise after ovulation
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
, and are elevated during the luteal phase
The menstrual cycle is on average 28 days in length. It begins with Menstruation, menses (day 1–7) during the follicular phase (day 1–14), followed by ovulation (day 14) and ending with the luteal phase (day 14–28). While historically, medi ...
, as shown in the diagram above. Progesterone levels tend to be less than 2 ng/mL prior to ovulation and greater than 5 ng/mL after ovulation. If pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
occurs, human chorionic gonadotropin
Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantat ...
is released, maintaining the corpus luteum and allowing it to maintain levels of progesterone. Between 7 and 9 weeks, the placenta begins to produce progesterone in place of the corpus luteum in a process called the luteal-placental shift.
After the luteal-placental shift, progesterone levels start to rise further and may reach 100 to 200 ng/mL at term. Whether a decrease in progesterone levels is critical for the initiation of labor
Labour or labor may refer to:
* Childbirth, the delivery of a baby
* Labour (human activity), or work
** Manual labour, physical work
** Wage labour, a socioeconomic relationship between a worker and an employer
** Organized labour and the labour ...
has been argued and may be species-specific. After delivery of the placenta and during lactation, progesterone levels are very low.
Progesterone levels are low in children and postmenopausal people. Adult males have levels similar to those in women during the follicular phase of the menstrual cycle.
Ranges
Blood test results should always be interpreted using the reference ranges provided by the laboratory that performed the results. Example reference ranges are listed below.
Sources
Animal
Progesterone is produced in high amounts in the ovaries
The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocr ...
(by the corpus luteum
The corpus luteum (Latin for "yellow body"; : corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is the ...
) from the onset of puberty
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a female, the testicles i ...
to menopause
Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...
, and is also produced in smaller amounts by the adrenal gland
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...
s after the onset of adrenarche
Adrenarche is an early stage in sexual maturation that happens in some higher primates (including humans), typically peaks at around 20 years of age, and is involved in the development of pubic hair, body odor, skin oiliness#Oily skin, skin oiline ...
in both males and females. To a lesser extent, progesterone is produced in nervous tissue
Nervous tissue, also called neural tissue, is the main tissue component of the nervous system. The nervous system regulates and controls body functions and activity. It consists of two parts: the central nervous system (CNS) comprising the brain ...
, especially in the brain, and in adipose (fat) tissue, as well.
During human pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
, progesterone is produced in increasingly high amounts by the ovaries and placenta
The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...
. At first, the source is the corpus luteum that has been "rescued" by the presence of human chorionic gonadotropin
Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantat ...
(hCG) from the conceptus. However, after the 8th week, production of progesterone shifts to the placenta. The placenta utilizes maternal cholesterol as the initial substrate, and most of the produced progesterone enters the maternal circulation, but some is picked up by the fetal circulation and used as substrate for fetal corticosteroids. At term the placenta produces about 250 mg progesterone per day.
An additional animal source of progesterone is milk products. After consumption of milk products the level of bioavailable progesterone goes up.
Plants
In at least one plant, ''Juglans regia
''Juglans regia'', known by various common names including the common walnut, English walnut, or Persian walnut amongst other names, is a species of walnut. It is native to Eurasia in at least southwest and central Asia and southeast Europe, ...
'', progesterone has been detected. In addition, progesterone-like steroid
A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration.
Steroids have two principal biological functions: as important components of cell membranes t ...
s are found in ''Dioscorea mexicana
''Dioscorea mexicana'', Mexican yam or ''cabeza de negro'' is a species of Yam (vegetable), yam in the genus ''Dioscorea''.
''Dioscorea mexicana'' is a caudiciform dioscorea having either a partly to completely above-ground dome-shaped caudex ...
''. ''Dioscorea mexicana'' is a plant that is part of the yam family native to Mexico
Mexico, officially the United Mexican States, is a country in North America. It is the northernmost country in Latin America, and borders the United States to the north, and Guatemala and Belize to the southeast; while having maritime boundar ...
. It contains a steroid called diosgenin that is taken from the plant and is converted into progesterone. Diosgenin and progesterone are also found in other '' Dioscorea'' species, as well as in other plants that are not closely related, such as fenugreek
Fenugreek (; ''Trigonella foenum-graecum'') is an annual plant in the family Fabaceae, with leaves consisting of three small Glossary_of_leaf_morphology#Leaf_and_leaflet_shapes, obovate to oblong leaflets. It is cultivated worldwide as a semiar ...
.
Another plant that contains substances readily convertible to progesterone is '' Dioscorea pseudojaponica'' native to Taiwan
Taiwan, officially the Republic of China (ROC), is a country in East Asia. The main geography of Taiwan, island of Taiwan, also known as ''Formosa'', lies between the East China Sea, East and South China Seas in the northwestern Pacific Ocea ...
. Research has shown that the Taiwanese yam contains saponin
Saponins (Latin ''sapon'', 'soap' + ''-in'', 'one of') are bitter-tasting, usually toxic plant-derived secondary metabolites. They are organic chemicals that become foamy when agitated in water and have high molecular weight. They are present ...
s — steroids that can be converted to diosgenin and thence to progesterone.
Many other ''Dioscorea'' species of the yam family contain steroidal substances from which progesterone can be produced. Among the more notable of these are '' Dioscorea villosa'' and '' Dioscorea polygonoides''. One study showed that the ''Dioscorea villosa'' contains 3.5% diosgenin. '' Dioscorea polygonoides'' has been found to contain 2.64% diosgenin as shown by gas chromatography-mass spectrometry. Many of the ''Dioscorea'' species that originate from the yam family grow in countries that have tropical and subtropical climates.
Medical use
Progesterone is used as a medication
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...
. It is used in combination with estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
s mainly in hormone therapy
Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are hormonal therap ...
for menopausal symptom
Signs and symptoms are diagnostic indications of an illness, injury, or condition.
Signs are objective and externally observable; symptoms are a person's reported subjective experiences.
A sign for example may be a higher or lower temperature ...
s and low sex hormone levels. It may also be used alone to treat menopausal symptoms. Studies have shown that transdermal progesterone (skin patch) and oral micronized progesterone are effective treatments for certain symptoms of menopause such as hot flashes and night sweats, which are otherwise referred to as vasomotor symptoms or VMS.
It is also used to support pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
and fertility
Fertility in colloquial terms refers the ability to have offspring. In demographic contexts, fertility refers to the actual production of offspring, rather than the physical capability to reproduce, which is termed fecundity. The fertility rate ...
and to treat gynecological disorders. Progesterone has been shown to prevent miscarriage in those with 1) vaginal bleeding early in their current pregnancy and 2) a previous history of miscarriage. Progesterone can be taken by mouth
Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications.
Oral administ ...
, through the vagina, and by injection
Injection or injected may refer to:
Science and technology
* Injective function, a mathematical function mapping distinct arguments to distinct values
* Injection (medicine), insertion of liquid into the body with a syringe
* Injection, in broadca ...
into muscle
Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...
or fat
In nutrition science, nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such chemical compound, compounds, most commonly those that occur in living beings or in food.
The term often refers specif ...
, among other routes.
Chemistry
Progesterone is a naturally occurring
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical ...
pregnane
Pregnane, also known as 17β-ethylandrostane or as 10β,13β-dimethyl-17β-ethylgonane, is a C21 steroid and, indirectly, a parent of progesterone. It is a parent hydrocarbon for two series of steroids stemming from 5α-pregnane (originally all ...
steroid
A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration.
Steroids have two principal biological functions: as important components of cell membranes t ...
and is also known as pregn-4-ene-3,20-dione. It has a double bond
In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...
( 4-ene) between the C4 and C5 positions and two ketone
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
group
A group is a number of persons or things that are located, gathered, or classed together.
Groups of people
* Cultural group, a group whose members share the same cultural identity
* Ethnic group, a group whose members share the same ethnic iden ...
s (3,20- dione), one at the C3 position and the other at the C20 position.
Synthesis
Progesterone is commercially produced by semisynthesis. Two main routes are used: one from yam diosgenin first pioneered by Marker in 1940, and one based on soy phytosterol
Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanol ester, stanols. More than 250 sterols and related compounds have been identified ...
s scaled up in the 1970s. Additional (not necessarily economical) semisyntheses of progesterone have also been reported starting from a variety of steroids. For the example, cortisone
Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug. Cortisol is converted by the action of the enzyme corticosteroid 11-beta-dehydrogenase ...
can be simultaneously deoxygenated at the C-17 and C-21 position by treatment with iodotrimethylsilane in chloroform
Chloroform, or trichloromethane (often abbreviated as TCM), is an organochloride with the formula and a common solvent. It is a volatile, colorless, sweet-smelling, dense liquid produced on a large scale as a precursor to refrigerants and po ...
to produce 11-keto-progesterone (ketogestin), which in turn can be reduced at position-11 to yield progesterone.
Marker semisynthesis
An economical semisynthesis
Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbiology, microbial cell cultures or plant material) as the starting materials to produce novel ...
of progesterone from the plant steroid diosgenin isolated from yams was developed by Russell Marker in 1940 for the Parke-Davis
Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although Parke, Davis & Co. is no longer an independent corporation, it was once America's oldest and largest drug maker, and played an important role in medical history. In 1970 ...
pharmaceutical company. This synthesis is known as the Marker degradation.
The 16-DPA
16-Dehydropregnenolone acetate (16-DPA) is a chemical compound used as an intermediate or synthon in the production of many semisynthesis, semisynthetic steroids. As 7-ACA is for cephalosporins and 6-APA is for penicillins, 16-DPA is for steroids ...
intermediate is important to the synthesis of many other medically important steroids. A very similar approach can produce 16-DPA from solanine
Solanine is a glycoalkaloid poison found in species of the Solanaceae, nightshade family within the genus ''Solanum'', such as the potato (''Solanum tuberosum''). It can occur naturally in any part of the plant, including the Leaf, leaves, frui ...
.
Soy semisynthesis
Progesterone can also be made from the stigmasterol
Stigmasterol – a plant sterol (''phytosterol'') – is among the most abundant of plant sterols, having a major function to maintain the structure and physiology of cell membranes. In the European Union, it is a food additive listed with E nu ...
found in soybean oil
Soybean oil (British English: soyabean oil) is a vegetable oil extracted from soybean (''Glycine max'') legumes. It is one of the most widely consumed cooking oils and the second most consumed vegetable oil. As a drying oil, processed soybean oil ...
also. c.f. Percy Julian.
Total synthesis
A total synthesis
Total synthesis, a specialized area within organic chemistry, focuses on constructing complex organic compounds, especially those found in nature, using laboratory methods. It often involves synthesizing natural products from basic, commercially ...
of progesterone was reported in 1971 by W.S. Johnson. The synthesis begins with reacting the phosphonium salt 7 with phenyl lithium to produce the phosphonium ylide 8. The ylide 8 is reacted with an aldehyde
In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...
to produce the alkene
In organic chemistry, an alkene, or olefin, is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or at the terminal position. Terminal alkenes are also known as Alpha-olefin, α-olefins.
The Internationa ...
9. The ketal
In organic chemistry, an acetal is a functional group with the connectivity . Here, the R groups can be organic fragments (a carbon atom, with arbitrary other atoms attached to that) or hydrogen, while the R' groups must be organic fragments n ...
protecting group
A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis.
In man ...
s of 9 are hydrolyzed to produce the diketone 10, which in turn is cyclized to form the cyclopentenone 11. The ketone of 11 is reacted with methyl lithium to yield the tertiary alcohol 12, which in turn is treated with acid to produce the tertiary cation 13. The key step of the synthesis is the π-cation cyclization of 13 in which the B-, C-, and D-rings of the steroid are simultaneously formed to produce 14. This step resembles the cationic cyclization reaction used in the biosynthesis of steroids and hence is referred to as ''biomimetic''. In the next step the enol
In organic chemistry, enols are a type of functional group or intermediate in organic chemistry containing a group with the formula (R = many substituents). The term ''enol'' is an abbreviation of ''alkenol'', a portmanteau deriving from "-ene ...
orthoester is hydrolyzed to produce the ketone 15. The cyclopentene A-ring is then opened by oxidizing with ozone to produce 16. Finally, the diketone 17 undergoes an intramolecular aldol condensation by treating with aqueous potassium hydroxide to produce progesterone.
History
George W. Corner and Willard M. Allen discovered the hormonal action of progesterone in 1929. By 1931–1932, nearly pure crystalline material of high progestational activity had been isolated from the corpus luteum
The corpus luteum (Latin for "yellow body"; : corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is the ...
of animals, and by 1934, pure crystalline progesterone had been refined and obtained and the chemical structure
A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...
of progesterone was determined. This was achieved by Adolf Butenandt
Adolf Friedrich Johann Butenandt (; 24 March 1903 – 18 January 1995) was a German biochemist. He was awarded the Nobel Prize in Chemistry in 1939 for his "work on sex hormones." He initially rejected the award in accordance with government pol ...
at the ''Chemisches Institut'' of Technical University
An institute of technology (also referred to as technological university, technical university, university of technology, polytechnic university) is an institution of tertiary education that specializes in engineering, technology, applied science ...
in Danzig, who extracted this new compound from several thousand liters of urine
Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
.
Chemical synthesis
Chemical synthesis (chemical combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In modern laboratory uses ...
of progesterone from stigmasterol
Stigmasterol – a plant sterol (''phytosterol'') – is among the most abundant of plant sterols, having a major function to maintain the structure and physiology of cell membranes. In the European Union, it is a food additive listed with E nu ...
and pregnanediol was accomplished later that year. Up to this point, progesterone, known generically as corpus luteum hormone, had been being referred to by several groups by different names, including corporin, lutein, luteosterone, and progestin. In 1935, at the time of the Second International Conference on the Standardization of Sex Hormones in London, England
London is the Capital city, capital and List of urban areas in the United Kingdom, largest city of both England and the United Kingdom, with a population of in . London metropolitan area, Its wider metropolitan area is the largest in Wester ...
, a compromise was made between the groups and the name progesterone (progestational steroidal ketone) was created.
Veterinary use
The use of progesterone tests in dog breeding to pinpoint ovulation is becoming more widely used. There are several tests available but the most reliable test is a blood test with blood drawn by a veterinarian and sent to a lab for processing. Results can usually be obtained with 24 to 72 hours. The rationale for using progesterone tests is that increased numbers begin in close proximity to preovulatory surge in gonadotrophins and continue through ovulation and estrus. When progesterone levels reach certain levels they can signal the stage of estrus the female is. Prediction of birth date of the pending litter can be very accurate if ovulation date is known. Puppies deliver with a day or two of 9 weeks gestation in most cases. It is not possible to determine pregnancy using progesterone tests once a breeding has taken place, however. This is due to the fact that, in dogs, progesterone levels remain elevated throughout the estrus period.
Pricing
Pricing for progesterone can vary depending location, insurance coverage, discount coupons, quantity, shortages, manufacturers, brand or generic versions, different pharmacies, and so on. As of currently, 30 capsules of 100 mg of the generic version, Progesterone, from CVS Pharmacy is around $40 without any discounts or insurance applied. The brand version, Prometrium, is around $450 for 30 capsules without any discounts or insurance applied. In comparison, Walgreens offers 30 capsules of 100 mg in the generic version for $51 without insurance or coupons applied. The brand name costs around $431 for 30 capsules of 100 mg.
References
*
External links
Progesterone MS Spectrum
*
*
{{Navboxes
, title = Biological activity
In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...
, titlestyle = background:#ccccff
, list1 =
{{GABAA receptor positive modulators
{{Glucocorticoid receptor modulators
{{Mineralocorticoid receptor modulators
{{Nicotinic acetylcholine receptor modulators
{{Progesterone receptor modulators
{{Sigma receptor modulators
{{Xenobiotic-sensing receptor modulators
5α-Reductase inhibitors
11β-Hydroxysteroid dehydrogenase inhibitors
Alkene derivatives
Antimineralocorticoids
Diketones
GABAA receptor positive allosteric modulators
Glucocorticoids
Glycine receptor antagonists
Neurosteroids
Hepatotoxins
Hormones of the hypothalamus-pituitary-adrenal axis
Hormones of the hypothalamus-pituitary-gonad axis
Hormones of the hypothalamic-pituitary-prolactin axis
Hormones of the ovary
Hormones of the placenta
Hormones of the suprarenal cortex
Hormones of the brain
Hormones of the pregnant female
Human female endocrine system
Human hormones
Pregnane X receptor agonists
Pregnanes
Progestogens
Prolactin releasers
Sex hormones
Sigma antagonists
Steroid hormones
Total synthesis