Estrogen or oestrogen is a category of
sex hormone responsible for the development and regulation of the female
reproductive system and
secondary sex characteristic
Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a s ...
s.
There are three major
endogenous estrogens that have estrogenic hormonal activity:
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 ...
(E1),
estradiol
Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...
(E2), and
estriol
Estriol (E3), also spelled oestriol, 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 estrone. Levels of estriol in women who are not pregnant are almost ...
(E3).
Estradiol, an
estrane, is the most potent and prevalent.
Another estrogen called
estetrol (E4) is produced only during pregnancy.
Estrogens are synthesized in all vertebrates
and some insects.
Their presence in both vertebrates and insects suggests that estrogenic sex hormones have an ancient evolutionary history. Quantitatively, estrogens circulate at lower levels than
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
s in both men and women.
While estrogen levels are significantly lower in males than in females, estrogens nevertheless have important physiological roles in males.
Like all
steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Withi ...
s, estrogens readily
diffuse
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
across the
cell membrane. Once inside the cell, they bind to and activate
estrogen receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...
s (ERs) which in turn
modulate the
expression
Expression may refer to:
Linguistics
* Expression (linguistics), a word, phrase, or sentence
* Fixed expression, a form of words with a specific meaning
* Idiom, a type of fixed expression
* Metaphorical expression, a particular word, phrase, o ...
of many
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s.
Additionally, estrogens bind to and activate rapid-signaling
membrane estrogen receptor Membrane estrogen receptors (mERs) are a group of receptors which bind estrogen. Unlike the estrogen receptor (ER), a nuclear receptor which mediates its effects via genomic mechanisms, mERs are cell surface receptors which rapidly alter cell signal ...
s (mERs),
such as
GPER
G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans is encoded by the ''GPER'' gene. GPER binds to and is activated by the female sex hormone estradiol and is responsible ...
(GPR30).
In addition to their role as natural hormones, estrogens are used as
medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
s, for instance in
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. These symptoms can include hot flashes, vaginal ...
,
hormonal birth control
Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The origina ...
and
feminizing hormone therapy
Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a co ...
for
transgender women
A trans woman or a transgender woman is a woman who was assigned male at birth. Trans women have a female gender identity, may experience gender dysphoria, and may transition; this process commonly includes hormone replacement therapy and ...
and
nonbinary people.
Synthetic and natural estrogens have been found in the environment and are referred to as
xenoestrogens
Xenoestrogens are a type of xenohormone that imitates estrogen. They can be either synthetic or natural chemical compounds. Synthetic xenoestrogens include some widely used industrial compounds, such as PCBs, BPA, and phthalates, which have estro ...
. Estrogens are among the wide range of endocrine-disrupting compounds (EDCs) and can cause health issues and reproductive disfunction in both wildlife and humans.
Types and examples
The four major naturally occurring estrogens in women are
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 ...
(E1),
estradiol
Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...
(E2),
estriol
Estriol (E3), also spelled oestriol, 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 estrone. Levels of estriol in women who are not pregnant are almost ...
(E3), and
estetrol (E4). Estradiol(E2) is the predominant estrogen during reproductive years both in terms of absolute serum levels as well as in terms of estrogenic activity. During
menopause, estrone is the predominant circulating estrogen and during pregnancy estriol is the predominant circulating estrogen in terms of serum levels. Given by
subcutaneous injection in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol.
Thus, estradiol is the most important estrogen in non-pregnant females who are between the
menarche and menopause stages of life. However, during
pregnancy
Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occur ...
this role shifts to estriol, and in postmenopausal women estrone becomes the primary form of estrogen in the body. Another type of estrogen called
estetrol (E4) is produced only during pregnancy. All of the different forms of estrogen are synthesized from
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
s, specifically
testosterone and
androstenedione, by the
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
aromatase
Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many ...
.
Minor endogenous estrogens, the biosyntheses of which do not involve
aromatase
Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many ...
, include
27-hydroxycholesterol,
dehydroepiandrosterone (DHEA),
7-oxo-DHEA
7-Ketodehydroepiandrosterone (7-keto-DHEA,7-oxo-DHEA), also known as 7-oxoprasterone, is a prohormone produced by metabolism of the prohormone dehydroepiandrosterone (DHEA).
7-oxo-DHEA is even more effective than DHEA for inducing heat producti ...
,
7α-hydroxy-DHEA
7α-Hydroxydehydroepiandrosterone (7α-hydroxy-DHEA; 7α-OH-DHEA), also known as 3β,7α-dihydroxyandrost-5-ene-17-one, is an endogenous, naturally occurring steroid and a major metabolite of dehydroepiandrosterone (DHEA) that is formed by CYP7B1 ...
,
16α-hydroxy-DHEA,
7β-hydroxyepiandrosterone
7β-Hydroxyepiandrosterone (7β-OH-EPIA), also known as 5α-androstan-3β,7β-diol-17-one, is an endogenous androgen, estrogen, and neurosteroid that is produced from dehydroepiandrosterone and epiandrosterone. It has neuroprotective effects and, ...
,
androstenedione (A4),
androstenediol (A5),
3α-androstanediol, and
3β-androstanediol
3β-Androstanediol, also known as 5α-androstane-3β,17β-diol, and sometimes shortened in the literature to 3β-diol, is an endogenous steroid hormone and a metabolite of androgens like dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT) ...
.
Some estrogen metabolites, such as the
catechol estrogens
2-hydroxyestradiol,
2-hydroxyestrone,
4-hydroxyestradiol, and
4-hydroxyestrone, as well as
16α-hydroxyestrone, are also estrogens with varying degrees of activity.
The biological importance of these minor estrogens is not entirely clear.
Biological function
The actions of estrogen are mediated by the
estrogen receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...
(ER), a dimeric nuclear protein that binds to DNA and controls
gene expression. Like other steroid hormones, estrogen enters passively into the cell where it binds to and activates the estrogen receptor. The estrogen:ER complex binds to specific DNA sequences called a
hormone response element to activate the transcription of target genes (in a study using an estrogen-dependent breast cancer cell line as model, 89 such genes were identified).
Since estrogen enters all cells, its actions are dependent on the presence of the ER in the cell. The ER is expressed in specific tissues including the ovary, uterus and breast. The metabolic effects of estrogen in postmenopausal women have been linked to the genetic polymorphism of the ER.
While estrogens are present in both
men
A man is an adult male human. Prior to adulthood, a male human is referred to as a boy (a male child or adolescent). Like most other male mammals, a man's genome usually inherits an X chromosome from the mother and a Y chro ...
and
women, they are usually present at significantly higher levels in women of reproductive age. They promote the development of female
secondary sexual characteristic
Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a s ...
s, such as
breasts, and are also involved in the thickening of the
endometrium and other aspects of regulating the menstrual cycle. In males, estrogen regulates certain functions of the
reproductive system important to the maturation of
sperm and may be necessary for a healthy
libido
Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act u ...
.
Overview of actions
* Structural
**
Anabolic: Increases
muscle mass and strength, speed of muscle regeneration, and
bone density
Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to optic ...
, increased sensitivity to exercise, protection against muscle damage, stronger
collagen synthesis, increases the collagen content of
connective tissues
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tissue is ...
,
tendons, and
ligaments, but also decreases stiffness of
tendons and
ligaments (especially during
menstruation). Decreased stiffness of tendons gives women much lower predisposition to muscle strains but soft ligaments are much more prone to injuries (
ACL tears are 2-8x more common among women than men).
** Anti-inflammatory properties
** Mediate formation of female
secondary sex characteristics
Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a s ...
** Accelerate
metabolism
** Increased
fat storage in some body parts such as breasts, buttocks, and legs but decreased abdominal and
visceral fat
Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular e ...
(androgenic obesity).
Estradiol
Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...
also regulates energy expenditure, body weight
homeostasis
In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
, and seems to have much stronger anti-obesity effects than testosterone in general.
* Women tend to have lower base strength but on average have about the same increases of muscle mass in responses to resistance training as men and far faster relative increases in strength.
** Stimulate
endometrial growth
** Increase
uterine
The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...
growth
** Increase
vaginal lubrication
** Thicken the
vagina
In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...
l wall
** Maintenance of vessel and skin
** Reduce
bone resorption
Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood.
The osteoclasts are multi-nuclea ...
, increase bone formation
*
Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
synthesis
** Increase
hepatic production of
binding protein A binding protein is any protein that acts as an agent to bind two or more molecules together.
Examples include:
* DNA-binding protein
** Single-strand binding protein
** Telomere-binding protein
*RNA-binding protein
** Poly(A)-binding protein
** ...
s
*
Coagulation
** Increase circulating level of
factors 2,
7,
9,
10,
plasminogen
** Decrease
antithrombin
Antithrombin (AT) is a small glycoprotein that inactivates several enzymes of the coagulation system. It is a 432-amino-acid protein produced by the liver. It contains three disulfide bonds and a total of four possible glycosylation sites. α-A ...
III
** Increase
platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
adhesiveness
** Increase
vWF (estrogen ->
Angiotensin II ->
Vasopressin
Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then trave ...
)
** Increase
PAI-1
Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor or serpin E1 is a protein that in humans is encoded by the ''SERPINE1'' gene. Elevated PAI-1 is a risk factor for thrombosis and atherosclerosis
P ...
and
PAI-2 also through Angiotensin II
*
Lipid
** Increase
HDL,
triglyceride
** Decrease
LDL
Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...
, fat deposition
* Fluid balance
** Salt (
sodium) and water retention
** Increase
cortisol,
SHBG
Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it has also been called androgen ...
*
Gastrointestinal tract
** Reduce bowel motility
** Increase
cholesterol in
bile
*
Melanin
** Increase
pheomelanin
Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the a ...
, reduce
eumelanin
* Cancer
** Support hormone-sensitive breast cancers (see section below)
*
Lung function
The lungs are the primary Organ (anatomy), organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the vertebral co ...
** Promotes lung function by supporting
alveoli (in rodents but probably in humans).
*
Uterus
The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...
lining
** Estrogen together with
progesterone promotes and maintains the uterus lining in preparation for implantation of fertilized egg and maintenance of uterus function during gestation period, also upregulates
oxytocin receptor in myometrium
*
Ovulation
Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilize ...
** Surge in estrogen level induces the release of
luteinizing hormone
Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
, which then triggers ovulation by releasing the egg from the
Graafian follicle in the
ovary.
*
Sexual behavior
Human sexual activity, human sexual practice or human sexual behaviour is the manner in which humans experience and express their sexuality. People engage in a variety of sexual acts, ranging from activities done alone (e.g., masturbation) t ...
** Estrogen is required for female mammals to engage in
lordosis behavior
Lordosis behavior (), also known as mammalian lordosis (Greek lordōsis, from ''lordos'' "bent backward") or presenting, is the naturally occurring body posture for sexual receptivity to copulation present in females of most mammals including rod ...
during
estrus
The estrous cycle (, originally ) is the set of recurring physiological changes that are induced by reproductive hormones in most mammalian therian females. Estrous cycles start after sexual maturity in females and are interrupted by anestrous ...
(when animals are "in heat").
This behavior is required for sexual receptivity in these mammals and is regulated by the
ventromedial nucleus of the
hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
.
**
Sex drive
Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act up ...
is dependent on
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
levels
only in the presence of estrogen, but without estrogen, free testosterone level actually decreases sexual desire (instead of increases sex drive), as demonstrated for those women who have
hypoactive sexual desire disorder, and the sexual desire in these women can be restored by administration of estrogen (using oral contraceptive).
Female pubertal development
Estrogens are responsible for the development of female
secondary sexual characteristic
Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a s ...
s during
puberty, including
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, bre ...
, widening of the
hips, and female
fat distribution
Human body shape is a complex phenomenon with sophisticated detail and function. The general shape or figure of a person is defined mainly by the molding of skeletal structures, as well as the distribution of muscles and fat. Skeletal structure ...
. Conversely,
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
s are responsible for
pubic and
body hair growth, as well as
acne and
axillary odor.
Breast development
Estrogen, in conjunction with
growth hormone (GH) and its secretory product
insulin-like growth factor 1 (IGF-1), is critical in mediating breast development during
puberty, as well as breast maturation during
pregnancy
Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occur ...
in preparation of
lactation and
breastfeeding
Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
.
Estrogen is primarily and directly responsible for inducing the ductal component of breast development,
as well as for causing
fat deposition and
connective tissue growth.
It is also indirectly involved in the lobuloalveolar component, by increasing
progesterone receptor expression in the breasts
and by inducing the secretion of
prolactin
Prolactin (PRL), also known as lactotropin, 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 secreted from the pit ...
.
Allowed for by estrogen,
progesterone and prolactin work together to complete lobuloalveolar development during pregnancy.
Androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
s such as testosterone powerfully oppose estrogen action in the breasts, such as by reducing
estrogen receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...
expression in them.
Female reproductive system
Estrogens are responsible for maturation and maintenance of the
vagina
In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...
and
uterus
The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...
, and are also involved in
ovarian function, such as maturation of
ovarian follicles. In addition, estrogens play an important role in regulation of
gonadotropin
Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/ chorioni ...
secretion. For these reasons, estrogens are required for female
fertility.
Neuroprotection and DNA repair
Estrogen regulated
DNA repair mechanisms in the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
have neuroprotective effects. Estrogen regulates the
transcription of DNA
base excision repair genes as well as the translocation of the base excision repair enzymes between different subcellular compartments.
Brain and behavior
Sex drive
Estrogens are involved in
libido
Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act u ...
(sex drive) in both women and men.
Cognition
Verbal memory
Verbal memory is a term used in cognitive psychology which refers to memory of words and other abstractions involving language.
Verbal encoding
Verbal encoding refers to the interpretation of verbal stimuli. Verbal encoding appears to be strongly ...
scores are frequently used as one measure of higher level
cognition. These scores vary in direct proportion to estrogen levels throughout the menstrual cycle, pregnancy, and menopause. Furthermore, estrogens when administered shortly after natural or surgical menopause prevents decreases in verbal memory. In contrast, estrogens have little effect on verbal memory if first administered years after menopause.
Estrogens also have positive influences on other measures of cognitive function.
However the effect of estrogens on cognition is not uniformly favorable and is dependent on the timing of the dose and the type of cognitive skill being measured.
The protective effects of estrogens on cognition may be mediated by estrogen's anti-inflammatory effects in the brain.
Studies have also shown that the Met allele gene and level of estrogen mediates the efficiency of
prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46 ...
dependent working memory tasks. Researchers have urged for further research to illuminate the role of estrogen and its potential for improvement on cognitive function.
Mental health
Estrogen is considered to play a significant role in women's
mental health
Mental health encompasses emotional, psychological, and social well-being, influencing cognition, perception, and behavior. It likewise determines how an individual handles stress, interpersonal relationships, and decision-making. Mental hea ...
. Sudden estrogen withdrawal, fluctuating estrogen, and
periods of sustained low estrogen levels correlate with a significant lowering of mood. Clinical recovery from
postpartum
The postpartum (or postnatal) period begins after childbirth and is typically considered to end within 6 weeks as the mother's body, including hormone levels and uterus size, returns to a non-pregnant state. The terms puerperium, puerperal pe ...
,
perimenopause, and
postmenopause depression has been shown to be effective after levels of estrogen were stabilized and/or restored.
Menstrual exacerbation (including menstrual psychosis) is typically triggered by low estrogen levels, and is often mistaken for
premenstrual dysphoric disorder.
Compulsions in male lab mice, such as those in obsessive-compulsive disorder (OCD), may be caused by low estrogen levels. When estrogen levels were raised through the increased activity of the enzyme
aromatase
Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many ...
in male lab mice, OCD rituals were dramatically decreased.
Hypothalamic protein levels in the gene
COMT
Catechol-''O''-methyltransferase (COMT; ) is one of several enzymes that degrade catecholamines (neurotransmitters such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol struct ...
are enhanced by increasing estrogen levels which are believed to return mice that displayed OCD rituals to normal activity. Aromatase deficiency is ultimately suspected which is involved in the synthesis of estrogen in humans and has therapeutic implications in humans having obsessive-compulsive disorder.
Local application of estrogen in the rat hippocampus has been shown to inhibit the re-uptake of
serotonin. Contrarily, local application of estrogen has been shown to block the ability of
fluvoxamine
Fluvoxamine, sold under the brand name Luvox and Faverin among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is primarily used to treat major depressive disorder and obsessive–compulsive disorder ...
to slow serotonin clearance, suggesting that the same pathways which are involved in SSRI efficacy may also be affected by components of local estrogen signaling pathways.
Parenthood
Studies have also found that fathers had lower levels of cortisol and testosterone but higher levels of estrogen (estradiol) than did non-fathers.
Binge eating
Estrogen may play a role in suppressing
binge eating. Hormone replacement therapy using estrogen may be a possible treatment for binge eating behaviors in females. Estrogen replacement has been shown to suppress binge eating behaviors in female mice.
The mechanism by which estrogen replacement inhibits binge-like eating involves the replacement of
serotonin (5-HT) neurons. Women exhibiting binge eating behaviors are found to have increased brain uptake of neuron 5-HT, and therefore less of the neurotransmitter serotonin in the cerebrospinal fluid.
Estrogen works to activate 5-HT neurons, leading to suppression of binge like eating behaviors.
It is also suggested that there is an interaction between hormone levels and eating at different points in the female
menstrual cycle. Research has predicted increased emotional eating during hormonal flux, which is characterized by high
progesterone and
estradiol
Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...
levels that occur during the mid-
luteal phase
The corpus luteum (Latin for "yellow body"; plural 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 th ...
. It is hypothesized that these changes occur due to brain changes across the menstrual cycle that are likely a genomic effect of hormones. These effects produce menstrual cycle changes, which result in hormone release leading to behavioral changes, notably binge and emotional eating. These occur especially prominently among women who are genetically vulnerable to binge eating phenotypes.
Binge eating is associated with decreased estradiol and increased progesterone.
Klump et al.
Progesterone may moderate the effects of low estradiol (such as during dysregulated eating behavior), but that this may only be true in women who have had clinically diagnosed binge episodes (BEs). Dysregulated eating is more strongly associated with such ovarian hormones in women with BEs than in women without BEs.
The implantation of 17β-estradiol pellets in ovariectomized mice significantly reduced binge eating behaviors and injections of GLP-1 in ovariectomized mice decreased binge-eating behaviors.
The associations between binge eating, menstrual-cycle phase and ovarian hormones correlated.
Masculinization in rodents
In rodents, estrogens (which are locally aromatized from androgens in the brain) play an important role in psychosexual differentiation, for example, by masculinizing territorial behavior;
the same is not true in humans.
In humans, the masculinizing effects of prenatal androgens on behavior (and other tissues, with the possible exception of effects on bone) appear to act exclusively through the androgen receptor.
Consequently, the utility of rodent models for studying human psychosexual differentiation has been questioned.
Skeletal system
Estrogens are responsible for both the pubertal growth spurt, which causes an acceleration in linear growth, and
epiphyseal closure, which limits
height
Height is measure of vertical distance, either vertical extent (how "tall" something or someone is) or vertical position (how "high" a point is).
For example, "The height of that building is 50 m" or "The height of an airplane in-flight is ab ...
and
limb length, in both females and males. In addition, estrogens are responsible for bone maturation and maintenance of
bone mineral density throughout life. Due to hypoestrogenism, the risk of
osteoporosis increases during
menopause.
Cardiovascular system
Women are less impacted by heart disease due to vasculo-protective action of estrogen which helps in preventing atherosclerosis.
It also helps in maintaining the delicate balance between fighting infections and protecting arteries from damage thus lowering the risk of cardiovascular disease.
During
pregnancy
Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occur ...
, high levels of estrogens increase
coagulation and the risk of
venous thromboembolism. Estrogen has been shown to upregulate the
peptide hormone
Peptide hormones or protein hormones are hormones whose molecules are peptide, or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including h ...
adropin
Adropin is a peptide encoded by the energy homeostasis-associated gene ENHO, which is highly conserved across mammals. Adropin's biological role was first described in mice by a group led by Andrew Butler, as a protein hormone, secreted from the ...
.
Immune system
Estrogen has
anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...
properties and helps in mobilization of polymorphonuclear white blood cells or
neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...
s.
Associated conditions
Researchers have implicated estrogens in various
estrogen-dependent conditions, such as ER-positive
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...
, as well as a number of
genetic conditions involving estrogen signaling or metabolism, such as
estrogen insensitivity syndrome
Estrogen insensitivity syndrome (EIS), or estrogen resistance, is a form of congenital estrogen deficiency or hypoestrogenism which is caused by a defective estrogen receptor (ER) – specifically, the estrogen receptor alpha (ERα) – that res ...
,
aromatase deficiency, and
aromatase excess syndrome
Aromatase excess syndrome (AES or AEXS) is a rare genetic and endocrine syndrome which is characterized by an overexpression of aromatase, the enzyme responsible for the biosynthesis of the estrogen sex hormones from the androgens, in turn resu ...
.
High estrogen can amplify
stress-hormone responses in
stress
Stress may refer to:
Science and medicine
* Stress (biology), an organism's response to a stressor such as an environmental condition
* Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
ful situations.
Biochemistry
Biosynthesis
Estrogens, in females, are produced primarily by the
ovaries
The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
, and during pregnancy, the
placenta.
Follicle-stimulating hormone (FSH) stimulates the ovarian production of estrogens by the
granulosa cell
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete (called an oocyte or egg) in the ovary of mammals.
Structure and function
In the primordial ovarian follicle, and la ...
s of the
ovarian follicles and
corpora lutea
The corpus luteum (Latin for "yellow body"; plural 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 th ...
. Some estrogens are also produced in smaller amounts by other tissues such as the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
,
pancreas,
bone
A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
,
adrenal glands,
skin,
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
,
adipose tissue
Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular ...
,
and the
breast
The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues.
In females, it serves as the mammary gland, which produces and sec ...
s. These secondary sources of estrogens are especially important in postmenopausal women.
The pathway of estrogen biosynthesis in extragonadal tissues is different. These tissues are not able to synthesize C19 steroids, and therefore depend on C19 supplies from other tissues
and the level of aromatase.
In females, synthesis of estrogens starts in
theca interna
Theca interna cells express receptors for luteinizing hormone (LH) to produce androstenedione, which via a few steps, gives the granulosa the precursor for estrogen manufacturing.
After rupture of the mature ovarian follicle, the theca interna c ...
cells in the ovary, by the synthesis of
androstenedione from
cholesterol. Androstenedione is a substance of weak androgenic activity which serves predominantly as a
precursor for more potent androgens such as testosterone as well as estrogen. This compound crosses the
basal membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (th ...
into the surrounding granulosa cells, where it is converted either immediately into estrone, or into testosterone and then estradiol in an additional step. The conversion of androstenedione to testosterone is catalyzed by
17β-hydroxysteroid dehydrogenase
A hydroxysteroid is a molecule derived from a steroid with a hydrogen replaced with a hydroxy group. When the hydroxy group is specifically at the C3 position, hydroxysteroids are referred to as sterols, with an example being cholesterol.
See ...
(17β-HSD), whereas the conversion of androstenedione and testosterone into estrone and estradiol, respectively is catalyzed by aromatase, enzymes which are both expressed in granulosa cells. In contrast, granulosa cells lack
17α-hydroxylase
Cytochrome P450 17A1 (steroid 17α-monooxygenase, 17α-hydroxylase, 17-alpha-hydroxylase, 17,20-lyase, 17,20-desmolase) is an enzyme of the hydroxylase type that in humans is encoded by the ''CYP17A1'' gene on chromosome 10. It is ubiquitously exp ...
and
17,20-lyase
Cytochrome P450 17A1 (steroid 17α-monooxygenase, 17α-hydroxylase, 17-alpha-hydroxylase, 17,20-lyase, 17,20-desmolase) is an enzyme of the hydroxylase type that in humans is encoded by the ''CYP17A1'' gene on chromosome 10. It is ubiquitously exp ...
, whereas theca cells express these enzymes and 17β-HSD but lack aromatase. Hence, both granulosa and theca cells are essential for the production of estrogen in the ovaries.
Estrogen levels vary through the
menstrual cycle, with levels highest near the end of the
follicular phase just before
ovulation
Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilize ...
.
Note that in males, estrogen is also produced by the
Sertoli cell
Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis (the production of sperm) as a structural component of the seminiferous tubules. They are activated by follicle-stimu ...
s when FSH binds to their FSH receptors.
Distribution
Estrogens are
plasma protein bound to
albumin and/or
sex hormone-binding globulin
Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it has also been called androgen ...
in the circulation.
Metabolism
Estrogens are
metabolized via
hydroxylation by
cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s such as
CYP1A1 and
CYP3A4 and via
conjugation by
estrogen sulfotransferases (
sulfation
Sulfation 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 less directly. Regardless of the mechanism, the ...
) and
UDP-glucuronyltransferases (
glucuronidation). In addition, estradiol is
dehydrogenated by
17β-hydroxysteroid dehydrogenase
A hydroxysteroid is a molecule derived from a steroid with a hydrogen replaced with a hydroxy group. When the hydroxy group is specifically at the C3 position, hydroxysteroids are referred to as sterols, with an example being cholesterol.
See ...
into the much less potent estrogen estrone. These reactions occur primarily in the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
, but also in other
tissues.
Excretion
Estrogens are
excreted primarily by the
kidneys as
conjugates via the
urine.
Medical use
Estrogens are used as
medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
s, mainly in
hormonal contraception,
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. These symptoms can include hot flashes, vaginal ...
,
and to treat gender dysphoria in
transgender women
A trans woman or a transgender woman is a woman who was assigned male at birth. Trans women have a female gender identity, may experience gender dysphoria, and may transition; this process commonly includes hormone replacement therapy and ...
and other
transfeminine individuals as part of feminizing hormone therapy.
Chemistry
The estrogen steroid hormones are
estrane steroids.
History
In 1929,
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 po ...
and
Edward Adelbert Doisy
Edward Adelbert Doisy (November 13, 1893 – October 23, 1986) was an American biochemist. He received the Nobel Prize in Physiology or Medicine in 1943 with Henrik Dam for their discovery of vitamin K (K from "Koagulations-Vitamin" in German) an ...
independently isolated and purified estrone, the first estrogen to be discovered.
Then, estriol and estradiol were discovered in 1930 and 1933, respectively. Shortly following their discovery, estrogens, both natural and synthetic, were introduced for medical use. Examples include
estriol glucuronide
Estriol glucuronide (E3G), or oestriol glucuronide, also known as estriol monoglucuronide, as well as estriol 16α-β-D-glucosiduronic acid, is a natural, steroidal estrogen and the glucuronic acid (β-D-glucopyranuronic acid) conjugate of estri ...
(
Emmenin
Conjugated estriol, sold under the brand names Progynon and Emmenin, is an estrogen medication which was previously used for estrogen-type indications such as the treatment of menopausal symptoms in women. The term specifically refers to formul ...
,
Progynon),
estradiol benzoate,
conjugated estrogens
Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of the ...
(
Premarin),
diethylstilbestrol, and
ethinylestradiol
Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disord ...
.
The word estrogen derives from
Ancient Greek
Ancient Greek includes the forms of the Greek language used in ancient Greece and the ancient world from around 1500 BC to 300 BC. It is often roughly divided into the following periods: Mycenaean Greek (), Dark Ages (), the Archaic p ...
. It is derived from "oestros"
(a periodic state of sexual activity in female mammals), and genos (generating).
It was first published in the early 1920s and referenced as "oestrin". With the years, American English adapted the spelling of estrogen to fit with its phonetic pronunciation. Nevertheless, both estrogen and oestrogen are used nowadays, yet some still wish to maintain its original spelling as it reflects the origin of the word.
Society and culture
Etymology
The name ''estrogen'' is derived from the
Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
(), literally meaning "verve" or "inspiration" but figuratively sexual passion or desire, and the suffix ''
-gen'', meaning "producer of".
Environment
A range of synthetic and natural substances that possess estrogenic activity have been identified in the
environment and are referred to
xenoestrogen
Xenoestrogens are a type of xenohormone that imitates estrogen. They can be either synthetic or natural chemical compounds. Synthetic xenoestrogens include some widely used industrial compounds, such as PCBs, BPA, and phthalates, which have estr ...
s.
* Synthetic substances such as
bisphenol A as well as
metalloestrogens (e.g.,
cadmium).
* Plant products with estrogenic activity are called
phytoestrogens (e.g.,
coumestrol,
daidzein
Daidzein (7-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one) is a naturally occurring compound found exclusively in soybeans and other legumes and structurally belongs to a class of compounds known as isoflavones. Daidzein and other isoflavones ar ...
,
genistein
Genistein (C15H10O5) is a naturally occurring compound that structurally belongs to a class of compounds known as isoflavones. It is described as an angiogenesis inhibitor and a phytoestrogen.
It was first isolated in 1899 from the dyer's bro ...
,
miroestrol).
* Those produced by fungi are known as
mycoestrogens Mycoestrogens are xenoestrogens produced by fungi. They are sometimes referred to as mycotoxins. Among important mycoestrogens are zearalenone, zearalenol and zearalanol. Although all of these can be produced by various ''Fusarium'' species, zea ...
(e.g.,
zearalenone
Zearalenone (ZEN), also known as RAL and F-2 mycotoxin, is a potent estrogenic metabolite produced by some ''Fusarium'' and ''Gibberella'' species. Specifically, the ''Gibberella zeae ,'' the fungal species where zearalenone was initially detected, ...
).
Estrogens are among the wide range of
endocrine-disrupting compounds (EDCs) because they have high estrogenic potency. When an EDC makes its way into the environment, it may cause male reproductive dysfunction to wildlife and humans.
The estrogen excreted from farm animals makes its way into fresh water systems.
During the germination period of reproduction the fish are exposed to low levels of estrogen which may cause reproductive dysfunction to male fish.
Cosmetics
Some hair
shampoos on the market include estrogens and placental extracts; others contain
phytoestrogens. In 1998, there were case reports of four prepubescent African-American girls developing breasts after exposure to these shampoos.
In 1993, the FDA determined that not all
over-the-counter topically applied hormone-containing drug products for human use are
generally recognized as safe and effective
Generally recognized as safe and effective (abbreviated as GRASE, GRAS/E, or GRAS/GRAE) is designation for certain old drugs that do not require prior approval from the U.S. Food and Drug Administration in order to enter the United States marketpl ...
and are misbranded. An accompanying proposed rule deals with cosmetics, concluding that any use of natural estrogens in a cosmetic product makes the product an unapproved new drug and that any cosmetic using the term "hormone" in the text of its labeling or in its ingredient statement makes an implied drug claim, subjecting such a product to regulatory action.
In addition to being considered misbranded drugs, products claiming to contain placental extract may also be deemed to be misbranded cosmetics if the extract has been prepared from placentas from which the hormones and other biologically active substances have been removed and the extracted substance consists principally of protein. The FDA recommends that this substance be identified by a name other than "placental extract" and describing its composition more accurately because consumers associate the name "placental extract" with a therapeutic use of some biological activity.
See also
*
List of steroid abbreviations
*
Breastfeeding and fertility
References
External links
* Nussey and Whitehead:
Endocrinology, an integrated approach', Taylor and Francis 2001. Free online textbook.
{{Authority control
Phenols
Cyclopentanols
Antigonadotropins
Estranes
Fertility
Hepatotoxins
Hormones of the hypothalamus-pituitary-gonad axis
Hormones of the hypothalamic-pituitary-prolactin axis
Hormones of the ovary
Hormones of the pregnant female
Hormones of the testis
Human female endocrine system
Human hormones
Mammal female reproductive system
Prolactin releasers
Sex hormones
1929 in science
1929 in Germany
Sterols
Puberty