Estriol (E3), sold under the brand name Ovestin among others, is an
estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
medication and
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 sy ...
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). Wi ...
which is used 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, vagina ...
. It is also used in
veterinary medicine
Veterinary medicine is the branch of medicine that deals with the prevention, management, diagnosis, and treatment of disease, disorder, and injury in animals. Along with this, it deals with animal rearing, husbandry, breeding, research on nutri ...
as Incurin to treat
urinary incontinence
Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life. It has been identified as an important issue in geria ...
due to
estrogen deficiency
Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiov ...
in dogs. The medication is taken
by mouth
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...
cream
Cream is a dairy product composed of the higher-fat layer skimmed from the top of milk before homogenization. In un-homogenized milk, the fat, which is less dense, eventually rises to the top. In the industrial production of cream, this process ...
pessary
A pessary is a prosthetic device inserted into the vagina for structural and pharmaceutical purposes. It is most commonly used to treat stress urinary incontinence to stop urinary leakage and to treat pelvic organ prolapse to maintain the locati ...
adverse effect
An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...
s. Side effects may include
breast tenderness
Breast pain is the symptom of discomfort in either one or both breasts. Pain in both breasts is often described as ''breast tenderness'', is usually associated with the menstrual period and is not serious. Pain that involves only one part of a br ...
endometrial hyperplasia
Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus.
Most cases of endometrial hyperplasia result from high levels of estrogens, combined with insufficient levels of t ...
. Estriol 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 sy ...
and
bioidentical
Bioidentical hormone replacement therapy (BHRT), also known as bioidentical hormone therapy (BHT) or natural hormone therapy, is the use of hormones that are identical on a molecular level with endogenous hormones in hormone replacement therapy. ...
estrogen, or an
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
of 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 ...
, the
biological target
A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...
of
estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
s like
endogenous
Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell.
In contrast, exogenous substances and processes are those that originate from outside of an organism.
For example, es ...
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 of f ...
. It is an atypical and relatively weak estrogen, with much lower
potency
Potency may refer to:
* Potency (pharmacology), a measure of the activity of a drug in a biological system
* Virility
* Cell potency, a measure of the differentiation potential of stem cells
* In homeopathic dilutions, potency is a measure of how ...
than
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 of f ...
. When present continuously at adequate concentrations however, estriol produces full estrogenic effects similarly to estradiol.
Estriol was first discovered in 1930, and was introduced for medical use shortly thereafter.Estriol esters such as
estriol succinate
Estriol succinate, sold under the brand name Synapause among others, is an estrogen medication which is used in the treatment of menopausal symptoms. It is taken by mouth, in through the vagina, and by injection.
Medical uses
Estriol succinate ...
are also used. Although it is less commonly employed than other estrogens like estradiol and
conjugated estrogens
Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen (medication), estrogen medication which is used in menopausal hormone therapy and for various other indications. ...
, estriol is widely available for medical use in
Europe
Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...
and elsewhere throughout the world.
Medical uses
Estriol is used 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, vagina ...
to treat
menopausal symptoms
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
, such as
hot flash
Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...
es,
vulvovaginal atrophy
Atrophic vaginitis is inflammation of the vagina as a result of tissue thinning due to not enough estrogen. Symptoms may include pain with sex, vaginal itchiness or dryness, and an urge to urinate or burning with urination. It generally does n ...
, and
dyspareunia
Dyspareunia ( ) is painful sexual intercourse due to medical or psychological causes. The term ''dyspareunia'' covers both female dyspareunia and male dyspareunia, but many discussions that use the term without further specification concern the f ...
(difficult or painful
sexual intercourse
Sexual intercourse (or coitus or copulation) is a sexual activity typically involving the insertion and thrusting of the penis into the vagina for sexual pleasure or reproduction.Sexual intercourse most commonly means penile–vaginal penetrat ...
). The benefits of estriol on
bone mineral 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 optica ...
and
osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
prevention have been inconsistent and are less clear. Estriol has been found to reduce the risk of
urinary tract infection
A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...
lactobacilli
The ''Lactobacillaceae'' are a family of lactic acid bacteria. It is the only family in the lactic acid bacteria which includes homofermentative and heterofermentative organisms; in the ''Lactobacillaceae,'' the pathway used for hexose fermentati ...
as a dual estrogen and
probiotic
Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut microbiota. Probiotics are considered generally safe to consume, but may cause bacteria-host i ...
has been marketed for the treatment of vaginal atrophy and urinary tract infections.
Available forms (except USA)
Estriol is available in
oral
The word oral may refer to:
Relating to the mouth
* Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid
**Oral administration of medicines
** Oral examination (also known as an oral exam or or ...
vaginal
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 hyme ...
cream
Cream is a dairy product composed of the higher-fat layer skimmed from the top of milk before homogenization. In un-homogenized milk, the fat, which is less dense, eventually rises to the top. In the industrial production of cream, this process ...
, and vaginal
suppository
A suppository is a dosage form used to deliver medications by insertion into a body orifice where it dissolves or melts to exert local or systemic effects. There are three types of suppositories, each to insert into a different sections: rectal su ...
forms. It is also available
over-the-counter
Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...
or from
compounding pharmacies
In the field of pharmacy, compounding (performed in compounding pharmacies) is preparation of a custom formulation of a medication to fit a unique need of a patient that cannot be met with commercially available products. This may be done for me ...
in the form of
topical
A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
cream
Cream is a dairy product composed of the higher-fat layer skimmed from the top of milk before homogenization. In un-homogenized milk, the fat, which is less dense, eventually rises to the top. In the industrial production of cream, this process ...
s. The medication is available both as estriol and in the form of estriol ester
prodrug
A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...
s such as
estriol succinate
Estriol succinate, sold under the brand name Synapause among others, is an estrogen medication which is used in the treatment of menopausal symptoms. It is taken by mouth, in through the vagina, and by injection.
Medical uses
Estriol succinate ...
,
estriol acetate benzoate
Estriol acetate benzoate () (brand name Holin-Depot), or oestriol diacetate benzoate (), is an estrogen medication. It is an estrogen ester
An estrogen ester is an ester of an estrogen, most typically of estradiol but also of other estrogens ...
, and
estriol tripropionate
Estriol tripropionate (brand name Estriel), or estriol tripropanoate, is an estrogen medication. It is an estrogen ester, specifically, an ester of estriol
Estriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female ...
, as well as the
polymer
A polymer (; Greek '' poly-'', "many" + ''-mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
ic ester prodrug polyestriol phosphate.
Estriol was originally marketed in the 1930s in the form of oral capsules containing 0.06, 0.12, or 0.24 mg estriol under the brand names Theelol (
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 ...
) and Estriol ( Lilly, Abbott). Subsequently, many decades later, oral tablets containing 0.35, 1, or 2 mg estriol were introduced under brand names such as Gynäsan, Hormomed, Ovestin, and Ovo-Vinces.
Contraindications
General
contraindication
In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...
s of estrogens include
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 re ...
,
endometrial cancer
Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...
, and others. In animals, estriol is contraindicated during
pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
and in
ferret
The ferret (''Mustela furo'') is a small, Domestication, domesticated species belonging to the family Mustelidae. The ferret is most likely a domesticated form of the wild European polecat (''Mustela putorius''), evidenced by their Hybrid (biol ...
s.
Side effects
Estriol is well- tolerated and produces relatively few
adverse effect
An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...
s.
Breast tenderness
Breast pain is the symptom of discomfort in either one or both breasts. Pain in both breasts is often described as ''breast tenderness'', is usually associated with the menstrual period and is not serious. Pain that involves only one part of a br ...
may sometimes occur as a side effect of estriol. Local reactions with vaginal estriol such as
discomfort
Comfort (or being comfortable'')'' is a sense of physical or psychological ease, often characterized as a lack of hardship. Persons who are lacking in comfort are uncomfortable, or experiencing discomfort. A degree of psychological comfort c ...
(
irritation
Irritation, in biology and physiology, is a state of inflammation or painful reaction to allergy or cell-lining damage. A stimulus or agent which induces the state of irritation is an irritant. Irritants are typically thought of as chemical age ...
,
burning
Combustion, or burning, is a high-temperature exothermic redox chemical reaction between a fuel (the reductant) and an oxidant, usually atmospheric oxygen, that produces oxidized, often gaseous products, in a mixture termed as smoke. Combusti ...
,
itching
Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasan ...
endometrial hyperplasia
Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus.
Most cases of endometrial hyperplasia result from high levels of estrogens, combined with insufficient levels of t ...
similarly to estradiol and other estrogens, and hence should be combined with a
progestogen
Progestogens, also sometimes written 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 progestogen in the body. ...
in women with intact
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 uter ...
es to prevent this risk. However, it appears that typical clinical dosages of vaginal estriol are not associated with an important risk of endometrial proliferation or hyperplasia. As such, combination with a progestogen may not be needed in the case of vaginal estriol. Some studies suggest that this may also be true for oral estriol. However, dosage and frequency of administration, as well as meal consumption, may be determining factors as to whether or not estriol produces endometrial proliferation.
Overdose
Estrogens and other
steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
s are relatively safe in acute
overdose
A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.
. Estriol has been assessed in single oral doses of up to 75 mg. General symptoms of estrogen overdose in humans may include
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
,
vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose.
Vomiting can be the result of ailments like Food-poisoning, foo ...
,
vaginal bleeding
Vaginal bleeding is any expulsion of blood from the vagina. This bleeding may originate from the uterus, vaginal wall, or cervix. Generally, it is either part of a normal menstrual cycle or is caused by hormonal or other problems of the reproductiv ...
, and reversible
feminization
Feminization most commonly refers to:
* Feminization (biology), the hormonally induced development of female sexual characteristics
* Feminization (activity), a sexual or lifestyle practice where a person assumes a female role
* Feminization (soci ...
. While there are no known studies describing the acute
toxicity
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...
of estrogen overdose in dogs, this species is known to be more sensitive to the toxic effects of estrogens than humans and other animals. The most serious short-term adverse effect of estrogens in dogs is
bone marrow suppression
Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity ( leukocytes), carrying oxygen ( erythrocytes), and/or those responsible for normal blood clotting ...
and consequent
pancytopenia
Pancytopenia is a medical condition in which there is significant reduction in the number of almost all blood cells (red blood cells, white blood cells, platelets, monocytes, lymphocytes, etc.).
If only two parameters from the complete blood coun ...
, which can be life-threatening.
Interactions
Interaction
Interaction is action that occurs between two or more objects, with broad use in philosophy and the sciences. It may refer to:
Science
* Interaction hypothesis, a theory of second language acquisition
* Interaction (statistics)
* Interactions o ...
s with estriol might be expected to be similar to those of
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 of f ...
. No interactions with estriol have been reported in animals. However, it should not be used in combination with other drugs that suppress bone marrow production in dogs.
Pharmacology
Pharmacodynamics
Estriol is an estrogen, or an
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
of 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 ...
s (ERs),
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 sex ...
and
ERβ
Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by ...
. In terms of
relative binding affinities
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a mol ...
(RBA) for the ERs compared to
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 of f ...
, it was found in one study to possess 11 to 14% of the RBA for the human ERα and 18 to 21% of the RBA for the human ERβ. Its
relative transactivational capacities
Intrinsic activity (IA) and efficacy refer to the relative ability of a drug-receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its mol ...
at the ERs compared to estradiol were 11% at ERα and 17% at ERβ. In addition to being a
ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
of the classical
nuclear
Nuclear may refer to:
Physics
Relating to the nucleus of the atom:
* Nuclear engineering
*Nuclear physics
*Nuclear power
*Nuclear reactor
*Nuclear weapon
*Nuclear medicine
*Radiation therapy
*Nuclear warfare
Mathematics
*Nuclear space
*Nuclear ...
ERs, estriol is an
antagonist
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...
of the
G protein-coupled estrogen receptor
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 ...
(GPER), a
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 ...
(mER), at high concentrations (~1,000–10,000 μM). This is in contrast to estradiol, which is an agonist of this receptor. Like other estrogens, estriol does not importantly interact with other
steroid hormone receptor
Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors (typically cytoplasmic or nuclear) and initiate signal transduction for steroid hormones which ...
s.
Estriol is a much less potent estrogen than is estradiol, and is somewhat weak and atypical in its properties. Given by
subcutaneous injection
Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion.
A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, ...
in mice, estradiol is about 10-fold more potent than
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 about 100-fold more potent than estriol. With clinical use, estriol is said to be weakly estrogenic in certain tissues, such as the
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
and
endometrium
The endometrium is the inner 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 functional laye ...
, but produces pronounced and full estrogenic responses in the
vaginal
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 hyme ...
epithelium
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...
. The medication has been found to reduce
hot flash
Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...
postmenopausal
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
content, suppress
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 ...
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 secret ...
epithelium. Conversely, estriol does not consistently affect
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-nucleated ...
or
fracture
Fracture is the separation of an object or material into two or more pieces under the action of stress. The fracture of a solid usually occurs due to the development of certain displacement discontinuity surfaces within the solid. If a displa ...
risk, does not seem to increase
breast density
Breast cancer screening is the medical screening of asymptomatic, apparently healthy women for breast cancer in an attempt to achieve an earlier diagnosis. The assumption is that early detection will improve outcomes. A number of screening test ...
, and, at oral doses of 2 to 4 mg/day, does not affect liver proteins,
lipid metabolism
Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown or storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In anim ...
, or
hemostatic
An antihemorrhagic (antihæmorrhagic) agent is a substance that promotes hemostasis (stops bleeding). It may also be known as a hemostatic (also spelled haemostatic) agent.
Antihemorrhagic agents used in medicine have various mechanisms of action: ...
parameters. Additionally, vaginal estriol does not appear to produce endometrial proliferation or increase the risk of
endometrial hyperplasia
Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus.
Most cases of endometrial hyperplasia result from high levels of estrogens, combined with insufficient levels of t ...
, and some studies have found this to be the case for oral estriol as well. On the other hand, it appears that estriol may be able to stimulate the growth of active
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 re ...
. In rodents, estriol induces mammary gland development similar to that with estrone. By the oral route in women, estriol has approximately 30% of the potency of estradiol in terms of
hot flash
Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...
es relief and suppression of
follicle-stimulating hormone
Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...
secretion 440px
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
, and about 20% of the potency of estradiol on stimulation of
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
production
Production may refer to:
Economics and business
* Production (economics)
* Production, the act of manufacturing goods
* Production, in the outline of industrial organization, the act of making products (goods and services)
* Production as a stati ...
of
high-density lipoprotein
High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are ty ...
(HDL)
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
. A study of
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 fertilized ...
inhibition by estrogens in women found that prevention of ovulation occurred with 5 mg/day oral estriol in only 1 of 7 cycles. Due to its differing effects from those of estradiol, estriol may be considered a safer estrogen in certain regards.
The weak and atypical estrogenicity of estriol is thought to be related to its short
duration
Duration may refer to:
* The amount of time elapsed between two events
* Duration (music) – an amount of time or a particular time interval, often cited as one of the fundamental aspects of music
* Duration (philosophy) – a theory of time and ...
in the body and hence the fact that it stays bound to the ER for a relatively short amount of time. Whereas estradiol remains bound to the ER for 6 to 24 hours with a single short-acting
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 ...
, estriol dissociates from the receptor much more rapidly and stays bound for only 1 to 6 hours. As a result, estriol can only induce estrogenic effects which require short-term interaction with the ERs. Induction of
endometrial
The endometrium is the inner 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 functional layer ...
mitoses
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintai ...
requires the ligand to remain bound for at least 9 to 12 hours, and this is thought to be responsible for the lack of endometrial proliferation with estriol in many studies. If estriol is delivered more continuously than a single administration per day however, for instance if it is given as a subcutaneous pellet, as a
depot injection
A depot injection is a term for an injection formulation of a medication which releases slowly over time to permit less frequent administration of a medication. They are designed to increase medication adherence and consistency, especially in pa ...
, or in multiple doses two or three times per day, this results in more sustained exposure to estriol and full estrogenic responses equivalent to those of estradiol occur. For these reasons, estriol has been described as a "short-acting" estrogen and it has been said that descriptors like "weak" and "impeded" are inaccurate. Consumption of food after oral administration of estriol also results in more prolonged exposure to estriol, due to
enterohepatic recycling
Enterohepatic circulation refers to the circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver. ...
and resurgences in estriol levels. As such, if avoidance of endometrial hyperplasia or other full estrogenic effects is intended, it may be preferable to take estriol in a single dose, as low as possible, once per day at night before bedtime.
Although estriol is an estrogen, it has also been reported to have mixed
agonist–antagonist
In pharmacology the term agonist-antagonist or mixed agonist/antagonist is used to refer to a drug which under some conditions behaves as an agonist (a substance that fully activates the receptor that it binds to) while under other conditions, beh ...
or
partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic e ...
activity at the ERs. On its own, it is said to be weakly estrogenic, but in the presence of estradiol, it has been found to be
antiestrogen
Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or ...
ic. However, this is again due to the fact that estriol is a "short-acting" estrogen. If estriol is present continuously with estradiol, it shows no antagonism of estradiol. The co-administration of estriol with estradiol has been found not to influence the effects of the latter in women, including neither enhancing nor antagonizing the effects of estradiol.
Pharmacokinetics
Absorption
Estriol has significant
bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
, but its
potency
Potency may refer to:
* Potency (pharmacology), a measure of the activity of a drug in a biological system
* Virility
* Cell potency, a measure of the differentiation potential of stem cells
* In homeopathic dilutions, potency is a measure of how ...
is limited by rapid
metabolism
Metabolism (, from el, μεταβολή ''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 cell ...
and
excretion
Excretion is a process in which metabolic waste
is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...
and its relatively weak estrogenic activity. With
oral administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are in ...
, during
first-pass metabolism
The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemi ...
, a considerable portion of estriol is conjugated via
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 ...
into
estriol sulfate
Estriol sulfate, or estriol 3-sulfate, is a conjugation (biochemistry), conjugated metabolite of estriol that is present in high quantities during pregnancy. It is formed from estriol in the liver and is eventually excretion, excreted in the urine ...
and rapidly excreted. Only about 10 to 20% of a dose of estriol remains in the circulation, and of this, only about 1 to 2% is present in its active, unconjugated form.
Peak Peak or The Peak may refer to:
Basic meanings Geology
* Mountain peak
** Pyramidal peak, a mountaintop that has been sculpted by erosion to form a point Mathematics
* Peak hour or rush hour, in traffic congestion
* Peak (geometry), an (''n''-3)-di ...
levels of estriol occur about 1 to 3 hours after an oral dose. Similarly to the case of
progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
, taking oral estriol with food greatly enhances its
absorption
Absorption may refer to:
Chemistry and biology
* Absorption (biology), digestion
**Absorption (small intestine)
*Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials
*Absorption (skin), a route by which ...
. In addition, due to
enterohepatic recycling
Enterohepatic circulation refers to the circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver. ...
, consuming a meal 4 hours after taking oral estriol can produce a second peak in estriol levels. Dosages of oral estriol of 4 to 10 mg have been found to result in a fairly large range of maximal estriol levels of 80 to 340 pg/mL. After a single oral dose of 8 mg estriol in
postmenopausal
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
women, maximal levels of 65 pg/mL estriol and 60 ng/mL estriol conjugates were produced within an hour. With continued daily administration, this increased to peak levels of 130 pg/mL estriol, whereas maximal levels of estriol conjugates remained at 60 ng/mL. Levels of estriol rapidly decreased to low levels following occurrence of peak levels. Consumption of a meal 4 hours after taking an oral dose of 8 mg estriol during continuous daily administration resulted in a second estriol peak 2 hours later of 120 pg/mL, with estriol levels declining slowly thereafter to about 25 pg/mL after 24 hours.
The bioavailability of estriol is markedly increased with
vaginal administration
Intravaginal administration is a route of administration where the substance is applied inside the vagina. Pharmacologically, it has the potential advantage to result in effects primarily in the vagina or nearby structures (such as the vaginal p ...
compared to oral administration. The relative bioavailability of oral estriol was found to be about 10% of that of vaginal estriol. In accordance, a single dose of 8 mg oral estriol and of 0.5 mg vaginal estriol have been found to produce similar circulating concentrations of estriol. It has been said that 0.5 to 1 mg vaginal estriol may be equivalent in clinical effect to 8 to 12 mg oral estriol. The high bioavailability of vaginal estriol is due to rapid absorption and low metabolism in atrophic vaginal mucosa. Vaginal estriol at typical clinical dosages results both in high local concentrations of estriol in 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 in systemic action. Vaginal administration of low doses of 30 µg estriol and of higher doses of 0.5 and 1 mg estriol have been found to produce equivalent local effects in the vagina and improvement of vaginal symptoms, suggesting that a saturation of estrogenic effect of vaginal estriol has been reached in the vagina by a dose of only 30 µg estriol. In contrast to higher doses of vaginal estriol however, 30 µg/day estriol is not associated with systemic effects. Similarly, the use of 0.5 mg vaginal estriol twice a week instead of daily has been said to largely attenuate the systemic effects of estriol. Whereas oral estriol results in high levels of estriol conjugates which greatly exceed those of unconjugated estriol, vaginal estriol has been found to produce levels of unconjugated estriol and estriol conjugates that are similar.
The absorption of estrogens by the skin is described as low for estriol, moderate for estradiol, and high for estrone. This is related to the number of
hydroxyl group
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 g ...
s in the molecules; the more hydroxyl groups, the lower the skin permeability. This may account for the relative lack of use of
transdermal
Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery.
The drug is administered in the form of a patch or ointme ...
or
topical
A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
estriol.
Rectal administration
Rectal administration uses the rectum as a route of administration for medication and other fluids, which are absorbed by the rectum's blood vessels,The rectum has numerous blood vessels available to absorb drugs. and flow into the body's ci ...
of estriol has been assessed in one study. Administration of a rectal
suppository
A suppository is a dosage form used to deliver medications by insertion into a body orifice where it dissolves or melts to exert local or systemic effects. There are three types of suppositories, each to insert into a different sections: rectal su ...
containing 100 mg estriol resulted in estriol levels in
pregnant
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 ...
women at term increasing by about 53%. Estriol levels at term are normally between 5,000 and 20,000 pg/mL, which suggests that estriol levels may have increased following the suppository by about 5,000 to 10,000 pg/mL (precise levels were not provided).
Estriol succinate
Estriol succinate, sold under the brand name Synapause among others, is an estrogen medication which is used in the treatment of menopausal symptoms. It is taken by mouth, in through the vagina, and by injection.
Medical uses
Estriol succinate ...
is an
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
prodrug
A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...
of estriol which is used medically via oral and vaginal routes similarly. In estriol succinate, two of the
hydroxyl group
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 g ...
s of estriol, those at the C16α and C17β positions, are esterified with
succinic acid
Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin ''succinum'', meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological ro ...
. As such, when adjusted for differences in
molecular weight
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
, a dose of 2 mg estriol succinate is equivalent to 1.18 mg unconjugated estriol. Unlike other estrogen esters, such as
estradiol valerate
Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and Primiwal E4 and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. It is used in hormone therapy fo ...
, estriol succinate is
hydrolyzed
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysis ...
almost not at all in the
intestinal
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...
mucosa
A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
when taken orally, and in relation to this, is absorbed more slowly than is estriol. Consequently, oral estriol succinate is a longer-acting form of estriol than oral estriol. Instead of in the
gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
, oral estriol succinate is cleaved into estriol mainly in the
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
. After a single 8 mg oral dose of estriol succinate, maximum levels of circulating estriol of 40 pg/mL are attained within 12 hours, and this increases up to 80 pg/mL with continued daily administration.
Distribution
Similarly to estradiol, but unlike
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 ...
, estriol is accumulated in target tissues. The
plasma protein binding
Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse th ...
of estriol is approximately 92%, with about 91% bound to
albumin
Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...
, 1% bound to
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 ...
(SHBG), and 8% free or unbound. Estriol has very low
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 Par ...
for SHBG, with only about 0.3% of the affinity of
testosterone
Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
for this protein (or about 0.6% of that of estradiol). Relative to estradiol, which is about 98% plasma protein-bound, a significantly greater fraction of estriol is unbound in the circulation and hence available for biological activity (2% relative to 8%, respectively). This appears to account for the greater than expected biological activity of estriol relative to estradiol when considering its affinities for 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 ...
s.
Metabolism
Estriol is
metabolized
Metabolism (, from el, μεταβολή ''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 cell ...
extensively via
conjugation
Conjugation or conjugate may refer to:
Linguistics
* Grammatical conjugation, the modification of a verb from its basic form
* Emotive conjugation or Russell's conjugation, the use of loaded language
Mathematics
* Complex conjugation, the chang ...
, including
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 glycosid ...
and
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 ...
. Glucuronidation of estriol takes place mainly in the
intestinal
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...
mucosa
A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
, while sulfation occurs in the
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
. More minor amounts of estriol can be
oxidized
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
and
hydroxylated
In chemistry, hydroxylation can refer to:
*(i) most commonly, hydroxylation describes a chemistry, chemical process that introduces a hydroxyl group () into an organic compound.
*(ii) the ''degree of hydroxylation'' refers to the number of OH gr ...
at various positions. One such reaction is transformation into 16α-hydroxyestrone. Estriol is an end-product of phase I estrogen metabolism and cannot be converted into estradiol or estrone. The main
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 of estriol are
estrogen conjugate
An estrogen conjugate is a conjugate of an endogenous estrogen. They occur naturally in the body as metabolites of estrogens and can be reconverted back into estrogens. They serve as a circulating reservoir for estrogen, particularly in the c ...
s, including
estriol sulfate
Estriol sulfate, or estriol 3-sulfate, is a conjugation (biochemistry), conjugated metabolite of estriol that is present in high quantities during pregnancy. It is formed from estriol in the liver and is eventually excretion, excreted in the urine ...
s,
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 product, natural, steroidal estrogen and the glucuronic acid (β-D-glucopyranuronic acid) co ...
biological half-life
Biological half-life (also known as elimination half-life, pharmacologic 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 bl ...
of oral estriol has been reported to be in the range of 5 to 10 hours. The
elimination half-life
Biological half-life (also known as elimination half-life, pharmacologic 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 bl ...
of estriol following an
intramuscular injection
Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...
of 1 mg estriol has been found to be 1.5 to 5.3 hours. The blood half-life of unconjugated estriol has been reported to be 20 minutes. The metabolic clearance rate of estriol is approximately 1,110 L/day/m2, which is about twice that of estradiol. Hence, estriol is eliminated from the body more rapidly than is estradiol.
Enterohepatic recycling
Enterohepatic circulation refers to the circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver. ...
may extend the duration of oral estriol.
A single 1 to 2 mg dose of estriol in oil solution by intramuscular injection has a duration of about 3 or 4 days.Estriol esters such as estriol dipropionate and estriol dihexanoate, when administered via intramuscular injection in an
oil solution
An oil is any nonpolar chemical substance that is composed primarily of hydrocarbons and is hydrophobic (does not mix with water) & lipophilic (mixes with other oils). Oils are usually flammable and surface active. Most oils are unsaturated ...
, have been found to maintain elevated levels of estriol for much longer amounts of time than oral or vaginal estriol, in the range of days to months. These two estriol esters have not been marketed, but
estriol acetate benzoate
Estriol acetate benzoate () (brand name Holin-Depot), or oestriol diacetate benzoate (), is an estrogen medication. It is an estrogen ester
An estrogen ester is an ester of an estrogen, most typically of estradiol but also of other estrogens ...
and
estriol tripropionate
Estriol tripropionate (brand name Estriel), or estriol tripropanoate, is an estrogen medication. It is an estrogen ester, specifically, an ester of estriol
Estriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female ...
are medically used estriol esters which are given via
depot
Depot ( or ) may refer to:
Places
* Depot, Poland, a village
* Depot Island, Kemp Land, Antarctica
* Depot Island, Victoria Land, Antarctica
* Depot Island Formation, Greenland
Brands and enterprises
* Maxwell Street Depot, a restaurant in ...
intramuscular injection and are long-acting similarly.Polyestriol phosphate is an ester of estriol in the form of a
polymer
A polymer (; Greek '' poly-'', "many" + ''-mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
, and has a very long duration of action.
Excretion
Estriol is
excreted
Excretion is a process in which metabolic waste
is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...
more than 95% in
urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra.
Cel ...
. This is due to the fact that estriol conjugates in the colon are completely
hydrolyzed
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysis ...
via
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
l
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. A ...
s and in turn estriol in this part of the body is reabsorbed into the body. The main urinary
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 of
exogenous
In a variety of contexts, exogeny or exogeneity () is the fact of an action or object originating externally. It contrasts with endogeneity or endogeny, the fact of being influenced within a system.
Economics
In an economic model, an exogeno ...
estriol administered via
intravenous injection
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutri ...
in
baboon
Baboons are primates comprising the genus ''Papio'', one of the 23 genera of Old World monkeys. There are six species of baboon: the hamadryas baboon, the Guinea baboon, the olive baboon, the yellow baboon, the Kinda baboon and the chacma ba ...
s have been found to be
estriol 16α-glucuronide
Estriol glucuronide (E3G), or oestriol glucuronide, also known as estriol monoglucuronide, as well as estriol 16α-β-D-glucosiduronic acid, is a natural product, natural, steroidal estrogen and the glucuronic acid (β-D-glucopyranuronic acid) co ...
(65.8%),
estriol 3-glucuronide
Estriol 3-glucuronide, or oestriol 3-glucuronide, also known as estriol 3-β-D-glucosiduronic acid, is a natural, steroidal estrogen and a glucuronic acid (β-D-glucopyranuronic acid) conjugate of estriol. It is found in the urine of women as a ...
(14.2%),
estriol 3-sulfate
Estriol sulfate, or estriol 3-sulfate, is a conjugation (biochemistry), conjugated metabolite of estriol that is present in high quantities during pregnancy. It is formed from estriol in the liver and is eventually excretion, excreted in the urine ...
(13.4%), and
estriol 3-sulfate 16α-glucuronide
Estriol sulfate glucuronide, or estriol 3-sulfate 16α-glucuronide, is an endogenous, naturally occurring diconjugated metabolite of estriol. It is generated in the liver from estriol sulfate by UDP-glucuronyltransferase and is eventually excre ...
(5.1%). The
metabolism
Metabolism (, from el, μεταβολή ''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 cell ...
and
excretion
Excretion is a process in which metabolic waste
is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...
of estriol in these animals closely resembled that which has been observed in humans.
Chemistry
Estriol, also known as 16α-hydroxyestradiol or as estra-1,3,5(10)-triene-3,16α,17β-triol, 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 sy ...
estrane
Estrane is a C18 steroid derivative, with a gonane core.
''Estrenes'' are estrane derivatives that contain a double bond, with an example being nandrolone. '' Estratrienes'' (estrins) are estrane derivatives that contain three double bonds, fo ...
steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
with
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 ...
s between the C1 and C2, C3 and C4, and C5 and C10 positions and
hydroxyl group
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 g ...
s at the C3, C16α, and C17β positions. The name ''estriol'' and the abbreviation ''E3'' were derived from the chemical terms '' estrin'' (estra-1,3,5(10)-triene) and ''
triol
In chemistry, a triol is a chemical compound containing three hydroxyl groups ( functional groups),
isomer
In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers.
Iso ...
derivative
In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. F ...
s and
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
s.
16β-Epiestriol
Epiestriol () (brand names Actriol, Arcagynil, Klimadoral), or epioestriol (), also known as 16β-epiestriol or simply 16-epiestriol as well as 16β-hydroxy-17β-estradiol, is a minor and weak endogenous estrogen (medication), estrogen, and the ...
16β,17α-epiestriol
16β,17α-Epiestriol, or 16,17-epiestriol, also known as 16β-hydroxy-17α-estradiol, as well as estra-1,3,5(10)-triene-3,16β,17α-triol, is a minor and weak endogenous steroidal estrogen that is related to 17α-estradiol and estriol. Along wi ...
are isomers of estriol that are endogenous weak estrogens.
Mytatrienediol
Mytatrienediol (developmental code name SC-6924; former tentative brand names Manvene, Anvene), also known as 16α-methyl-16β-epiestriol 3-methyl ether or 16β-hydroxy-16α-methylestradiol 3-methyl ether, is a synthetic steroidal estrogen medic ...
(16α-methyl-16β-epiestriol 3-methyl ether) is a synthetic derivative of 16β-epiestriol that was never marketed.
Estriol acetate benzoate
Estriol acetate benzoate () (brand name Holin-Depot), or oestriol diacetate benzoate (), is an estrogen medication. It is an estrogen ester
An estrogen ester is an ester of an estrogen, most typically of estradiol but also of other estrogens ...
,
estriol succinate
Estriol succinate, sold under the brand name Synapause among others, is an estrogen medication which is used in the treatment of menopausal symptoms. It is taken by mouth, in through the vagina, and by injection.
Medical uses
Estriol succinate ...
, and
estriol tripropionate
Estriol tripropionate (brand name Estriel), or estriol tripropanoate, is an estrogen medication. It is an estrogen ester, specifically, an ester of estriol
Estriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female ...
ether
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be c ...
of estriol and has also been marketed.Polyestriol phosphate, an ester of estriol in the form of a
polymer
A polymer (; Greek '' poly-'', "many" + ''-mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
, has been marketed previously as well. These esters, ethers, and polymers are
prodrug
A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...
s of estriol.
Ethinylestriol
Ethinylestriol (EE3), or 17α-ethynylestriol, also known as 17α-ethynylestra-1,3,5(10)-triene-3,16α,17β-triol, is a synthetic estrogen which was never marketed. Nilestriol, the 3-cyclopentyl ether of ethinylestriol, is a prodrug of ethiny ...
and
nilestriol
Nilestriol () (brand name Wei Ni An; developmental code name LY-49825), also known as nylestriol (, ), is a synthetic estrogen which was patented in 1971 and is marketed in China. It is the 3-cyclopentyl ether of ethinylestriol, and is also k ...
are synthetic C17α
ethynyl In organic chemistry, the term ethynyl designates a functional group with a double bond with 2 carbon atoms both with
sp hybridisation and a triple bond(1 sigma and 2 pi bond) . It is a species similar to acetylene (or in IUPAC ethyne ) with a less ...
ated derivatives of estriol. Ethinylestriol has not been marketed, but nilestriol, which is the 3-cyclopentyl ether of ethinylestriol and a prodrug of it, has been.
Estetrol
Estetrol (E4), or oestetrol, is one of the four natural estrogenic steroid hormones found in humans, along with estrone (E1), estradiol (E2), and estriol (E3), estetrol is a major estrogen in the body. In contrast to estrone and estradiol, estet ...
(E4), also known as 15α-hydroxyestriol, 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 sy ...
analogue of estriol with an additional
hydroxyl group
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 g ...
, at the C15α position. It is closely related to estriol and has similar but non-identical
pharmacological
Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
properties. Like estriol, estetrol is a relatively weak and atypical estrogen. Estetrol is under development for potential clinical use for a variety of indications, such as menopausal hormone therapy and
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 original ...
.
History
Estriol was discovered in 1930. Subsequently, it was introduced for medical use in
oral
The word oral may refer to:
Relating to the mouth
* Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid
**Oral administration of medicines
** Oral examination (also known as an oral exam or or ...
and
transdermal
Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery.
The drug is administered in the form of a patch or ointme ...
formulations under brand names such as ''Estriol'', ''Oestrosalve'', ''Theelol'', and ''Tridestrin''. In addition,
conjugated estriol
Conjugated estriol, sold under the brand names Progynon and Emmenin, is an estrogen (medication), estrogen medication which was previously used for estrogen-type indications such as the treatment of menopausal symptoms in women. The term specifi ...
, containing mainly
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 product, natural, steroidal estrogen and the glucuronic acid (β-D-glucopyranuronic acid) co ...
, was marketed in the 1930s, under the brand names ''Emmenin'' and ''Progynon''. They were the first orally active estrogen preparations to be introduced in medicine. In contrast to estrone, free estriol was never introduced for use by
intramuscular injection
Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...
. Estriol continues to be used medically today, widely throughout the world and in a variety of different formulations and brand names.
American English
American English, sometimes called United States English or U.S. English, is the set of variety (linguistics), varieties of the English language native to the United States. English is the Languages of the United States, most widely spoken lan ...
and its , , , , and . It is pronounced . ''Estriolo'' is the name of estriol in
Italian
Italian(s) may refer to:
* Anything of, from, or related to the people of Italy over the centuries
** Italians, an ethnic group or simply a citizen of the Italian Republic or Italian Kingdom
** Italian language, a Romance language
*** Regional Ita ...
and ''estriolum'' is its name in
Latin
Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
, whereas its name remains unchanged as ''estriol'' in
Spanish
Spanish might refer to:
* Items from or related to Spain:
**Spaniards are a nation and ethnic group indigenous to Spain
**Spanish language, spoken in Spain and many Latin American countries
**Spanish cuisine
Other places
* Spanish, Ontario, Can ...
,
Portuguese
Portuguese may refer to:
* anything of, from, or related to the country and nation of Portugal
** Portuguese cuisine, traditional foods
** Portuguese language, a Romance language
*** Portuguese dialects, variants of the Portuguese language
** Portu ...
German
German(s) may refer to:
* Germany (of or related to)
** Germania (historical use)
* Germans, citizens of Germany, people of German ancestry, or native speakers of the German language
** For citizens of Germany, see also German nationality law
**Ge ...
. ''Oestriol'', in which the "O" is silent, was the former of estriol and its name in
British English
British English (BrE, en-GB, or BE) is, according to Lexico, Oxford Dictionaries, "English language, English as used in Great Britain, as distinct from that used elsewhere". More narrowly, it can refer specifically to the English language in ...
, but the spelling was eventually changed to ''estriol''.
Brand names
Estriol is or has been marketed under a variety of brand names throughout the world, including Aacifemine, Colpogyn, Elinol, Estriel, Estriol, Estriosalbe, Estrokad, Evalon, Gydrelle, Gynäsan, Gynest, Gynoflor (in combination with
lactobacilli
The ''Lactobacillaceae'' are a family of lactic acid bacteria. It is the only family in the lactic acid bacteria which includes homofermentative and heterofermentative organisms; in the ''Lactobacillaceae,'' the pathway used for hexose fermentati ...
), Incurin (
veterinary
Veterinary medicine is the branch of medicine that deals with the prevention, management, diagnosis, and treatment of disease, disorder, and injury in animals. Along with this, it deals with animal rearing, husbandry, breeding, research on nutri ...
Estriol succinate
Estriol succinate, sold under the brand name Synapause among others, is an estrogen medication which is used in the treatment of menopausal symptoms. It is taken by mouth, in through the vagina, and by injection.
Medical uses
Estriol succinate ...
has been marketed under the brand names Blissel, Evalon, Gelistrol, Hemostyptanon, Orgastyptin, Ovestin, Pausan, Sinapause, Styptanon, Synapsa, Synapasa, Synapausa, and Synapause.Estriol diacetate benzoate has been marketed under the brand name Holin-Depot and
estriol tripropionate
Estriol tripropionate (brand name Estriel), or estriol tripropanoate, is an estrogen medication. It is an estrogen ester, specifically, an ester of estriol
Estriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female ...
has been marketed under the brand name Estriel.Polyestriol phosphate has been marketed under the brand names Gynäsan, Klimadurin, and Triodurin.
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 ...
and
Progynon
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 ...
were estriol products marketed in the 1930s which were manufactured from the
urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra.
Cel ...
of
pregnant
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 ...
women and contained
estriol conjugate
An estrogen conjugate is a conjugation (biochemistry), conjugate of an endogenous estrogen. They occur natural product, naturally in the body as metabolites of estrogens and can be reconverted back into estrogens. They serve as a circulating re ...
s, primarily
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 product, natural, steroidal estrogen and the glucuronic acid (β-D-glucopyranuronic acid) co ...
.
Estriol for
multiple sclerosis
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
had the tentative brand name Trimesta but did not complete development and was never marketed.
Availability
Estriol is marketed widely throughout the world, including in
Europe
Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...
,
South Africa
South Africa, officially the Republic of South Africa (RSA), is the southernmost country in Africa. It is bounded to the south by of coastline that stretch along the South Atlantic and Indian Oceans; to the north by the neighbouring countri ...
,
Australia
Australia, officially the Commonwealth of Australia, is a Sovereign state, sovereign country comprising the mainland of the Australia (continent), Australian continent, the island of Tasmania, and numerous List of islands of Australia, sma ...
,
New Zealand
New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 smaller islands. It is the sixth-largest island count ...
,
Asia
Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...
,
Latin America
Latin America or
* french: Amérique Latine, link=no
* ht, Amerik Latin, link=no
* pt, América Latina, link=no, name=a, sometimes referred to as LatAm is a large cultural region in the Americas where Romance languages — languages derived f ...
, and elsewhere. The medication is also available in some countries in the form of
estriol succinate
Estriol succinate, sold under the brand name Synapause among others, is an estrogen medication which is used in the treatment of menopausal symptoms. It is taken by mouth, in through the vagina, and by injection.
Medical uses
Estriol succinate ...
, an
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
prodrug
A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...
of estriol. Estriol and its esters are not approved for use in the
United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
or
Canada
Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...
, although estriol has been produced and sold by
compounding pharmacies
In the field of pharmacy, compounding (performed in compounding pharmacies) is preparation of a custom formulation of a medication to fit a unique need of a patient that cannot be met with commercially available products. This may be done for me ...
in
North America
North America is a continent in the Northern Hemisphere and almost entirely within the Western Hemisphere. It is bordered to the north by the Arctic Ocean, to the east by the Atlantic Ocean, to the southeast by South America and the Car ...
for use as a component of bioidentical hormone therapy. In addition, topical creams containing estriol are not regulated in the United States and are available
over-the-counter
Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...
in this country.
Research
Estriol may have
immunomodulatory
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
effects and has been of investigational interest in the treatment of
multiple sclerosis
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
and a number of other conditions.
Estriol succinate
Estriol succinate, sold under the brand name Synapause among others, is an estrogen medication which is used in the treatment of menopausal symptoms. It is taken by mouth, in through the vagina, and by injection.
Medical uses
Estriol succinate ...
was under development for the treatment of multiple sclerosis in the
United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
s for this indication, but development was discontinued due to insufficient effectiveness. It had the tentative brand name Trimesta.
Veterinary use
Estriol is used in
veterinary medicine
Veterinary medicine is the branch of medicine that deals with the prevention, management, diagnosis, and treatment of disease, disorder, and injury in animals. Along with this, it deals with animal rearing, husbandry, breeding, research on nutri ...
, under the brand name Incurin, in the treatment of
urinary incontinence
Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life. It has been identified as an important issue in geria ...
due to
estrogen deficiency
Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiov ...
in dogs. Certain estrogens, like
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 of f ...
, can cause
bone marrow suppression
Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity ( leukocytes), carrying oxygen ( erythrocytes), and/or those responsible for normal blood clotting ...
in dogs, which can be fatal, but estriol appears to pose less or possibly no risk.