Estriol (E3), also spelled oestriol, is a

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

, a weak

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

, and a minor female

sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects a ...

. It is one of three major

endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...

estrogens, the others being

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

and

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 ...

. Levels of estriol in women who are not

pregnant Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

are almost undetectable. However, during pregnancy, estriol is synthesized in very high quantities by the

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

and is the most produced estrogen in the body by far, although circulating levels of estriol are similar to those of other estrogens due to a relatively high rate of

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

and

excretion Excretion is elimination of metabolic waste, which is an essential process in all organisms. In vertebrates, this is primarily carried out by the lungs, Kidney (vertebrates), kidneys, and skin. This is in contrast with secretion, where the substa ...

. Relative to estradiol, both estriol and estrone have far weaker activity as estrogens. In addition to its role as a natural hormone, estriol is used as a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

, 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. Effects of menopause can include symptoms such ...

; for information on estriol as a medication, see the

estriol (medication) Estriol (E3), sold under the brand name Ovestin among others, is an estrogen (medication), estrogen medication and natural product, naturally occurring steroid hormone which is used in menopausal hormone therapy. It is also used in veterinary m ...

article.

Biological activity

Estriol is an estrogen, specifically an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the

estrogen receptor Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...

ERα Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the se ...

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 t ...

. It is a far less potent estrogen than is estradiol, and as such is a relatively weak estrogen. According to one ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' study, the

relative binding affinity 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 Latin ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a ...

(RBA) of estriol for the human ERα and ERβ was 11.3% and 17.6% of that estradiol, respectively, and the relative transactivational capacity of estriol at the ERα and ERβ was 10.6% and 16.6% of that of estradiol, respectively. According to another ''in vitro'' study however, the RBA of estriol for the ERα and ERβ were 14% and 21% of those of estradiol, respectively, suggesting that unlike estradiol and estrone, estriol may have preferential

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for ERβ. Although estriol is an

efficacious Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made between ...

agonist of the ERs, it is 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 ...

(

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

) activity at the ER; on its own, it is weakly estrogenic, but in the presence of estradiol, it is

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 inh ...

ic. 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 (medicine), bolus into the subcutis, the layer of skin directly below the dermis and ...

in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol. It is notable that unlike estriol, estrone can be

metabolized Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

into estradiol, and most of its potency ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...

'' is in fact actually due to conversion into estradiol. In addition to acting as an agonist of the

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 at high concentrations (~1,000–10,000 nM) also acts as an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.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 ...

, a

membrane estrogen receptor Membrane estrogen receptors (mERs) are a group of receptor (biochemistry), receptors which bind estrogen. Unlike nuclear estrogen receptors, which mediate their effects via slower Genome, genomic mechanisms, mERs are cell surface receptors that rapi ...

where, conversely, estradiol acts as an agonist. Estradiol increases

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

cell growth via activation of the GPER (in addition to the ER), and estriol has been found to inhibit estradiol-induced proliferation of

triple-negative breast cancer Triple-negative breast cancer (TNBC) is any breast cancer that either lacks or shows low levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification (i.e ...

cells through blockade of the GPER.

Biochemistry

Biosynthesis

In non-pregnant women

In women who are not pregnant estriol is produced in only very small quantities, and circulating levels are barely detectable. Unlike estradiol and estrone, estriol is not synthesized in or secreted from the ovaries, and is instead derived mainly if not exclusively from 16α-

hydroxylation In chemistry, hydroxylation refers to the installation of a hydroxyl group () into an organic compound. Hydroxylations generate alcohols and phenols, which are very common functional groups. Hydroxylation confers some degree of water-solubility ...

of estradiol and estrone by

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s (e.g.,

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

) mainly in the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

. Estriol is cleared from the circulation rapidly in non-pregnant women, and so circulating levels are very low, but concentrations of estriol in the

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

are relatively high. Although circulating levels of estriol are very low outside of pregnancy, parous women have been found to have levels of estriol that are to some degree higher than those of

nulliparous In biology and medicine, gravidity and parity are the number of times a female has been pregnant (gravidity) and carried the pregnancies to a viable gestational age (parity). These two terms are usually coupled, sometimes with additional terms, t ...

women.

In pregnant women

Estriol is produced in quantities that are notable only during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

. Levels of estriol increase 1,000-fold during pregnancy, whereas levels of estradiol and estrone increase 100-fold, and estriol accounts for 90% of the estrogens in the urine of pregnant women. At term, the daily production of estriol by the placenta is 35 to 45 mg, and levels in the maternal circulation are 8 to 13 ng/dL. The

produces

pregnenolone Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineraloc ...

and

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 ma ...

from circulating

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

. Pregnenolone is taken up by the fetal

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...

s and converted into

dehydroepiandrosterone Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It funct ...

(DHEA), which is then

sulfated Sulfation (sometimes spelled sulphation in British English) is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected ...

steroid sulfotransferase In enzymology, a steroid sulfotransferase () is an enzyme that catalyzes the chemical reaction :3'-phosphoadenylyl sulfate + a phenolic steroid \rightleftharpoons adenosine 3',5'-bisphosphate + steroid O-sulfate Thus, the two substrates of this ...

into

dehydroepiandrosterone sulfate Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroepia ...

(DHEA-S). DHEA-S is

hydroxylated In chemistry, hydroxylation refers to the installation of a hydroxyl group () into an organic compound. Hydroxylations generate alcohols and phenols, which are very common functional groups. Hydroxylation confers some degree of water-solubility ...

by high

CYP3A7 CYP3A7 is an enzyme belonging to the cytochrome P450 family. It is 503 amino acids in size and shares 87% of its sequence with CYP3A4. It carries out a similar role in fetuses that CYP3A4 serves in adults. The gene location is 7q22.1. The CYP3A ...

expression and activity into 16α-hydroxy-DHEA-S (16α-OH-DHEA-S) in the fetal

and to a limited extent in the fetal adrenal glands. 16α-OH-DHEA-S is then taken up by the placenta. Due to high expression of

steroid sulfatase Steroid sulfatase (STS), or steryl-sulfatase (EC 3.1.6.2), formerly known as arylsulfatase C, is a sulfatase enzyme involved in the metabolism of steroids. It is encoded by the ''STS'' gene. Reactions This enzyme catalysis, catalyses the follow ...

in the placenta, 16α-OH-DHEA-S is rapidly cleaved into 16α-OH-DHEA. Then, 16α-OH-DHEA is converted by 3β-hydroxysteroid dehydrogenase

type I Type 1 or Type I or ''variant'', may refer to: Health *Diabetes mellitus type 1 (also known as "Type 1 Diabetes"), insulin-dependent diabetes * Type I female genital mutilation * Type 1 personality *Type I hypersensitivity (or immediate hypersensit ...

(3β-HSD1) into 16α-hydroxyandrostenedione (16α-OH-A4) and 16α-OH-A4 is converted by

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 man ...

into 16α-hydroxyestrone (16α-OH-E1), which is subsequently converted into estriol 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 ...

and then secreted predominantly into the maternal circulation. Approximately 90% of precursors in estriol formation originate from the fetus. During pregnancy, 90 to 95% of estriol in the maternal circulation is conjugated in the form of

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 ...

and

estriol sulfate Estriol sulfate, or estriol 3-sulfate, is a conjugated metabolite of estriol that is present in high quantities during pregnancy. It is formed from estriol in the liver and is eventually excreted in the urine by the kidneys. It has much higher wa ...

, and levels of unconjugated estriol are slightly less than those of unconjugated estradiol and similar to those of unconjugated estrone. As such, target tissues are likely to be exposed to similar amounts of free estriol, estradiol, and estrone during pregnancy.

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

are also produced in the placenta during pregnancy. However, in the case of estrone and estradiol, DHEA-S is taken up by the placenta and cleaved by steroid sulfatase into

(DHEA), DHEA is converted by 3β-hydroxysteroid dehydrogenase

into

androstenedione Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroe ...

, and androstenedione is aromatized into estrone. Then, placental

interconverts estrone and estradiol and the two hormones are secreted into the maternal circulation. DHEA-S that is taken up by the placenta is mainly produced by the fetal adrenal glands.

Distribution

Estriol is poorly 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 is called androgen-binding prot ...

(SHBG), with much lower

binding affinity 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 Latin ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usuall ...

for this protein, relative to estradiol, and hence a greater fraction available for

biological activity In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...

Metabolism

Estriol is

via

glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gly ...

and

sulfation Sulfation (sometimes spelled sulphation in British English) is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected ...

Excretion

The main

urinary The human urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressu ...

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 is the opposite of endogeneity or endogeny, the fact of being influenced from within a system. Economics In an economic model, an ...

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 nutr ...

baboon Baboons are primates comprising the biology, genus ''Papio'', one of the 23 genera of Old World monkeys, in the family Cercopithecidae. There are six species of baboon: the hamadryas baboon, the Guinea baboon, the olive baboon, the yellow 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, steroidal estrogen and the glucuronic acid (β-D-glucopyranuronic acid) conjugate of estri ...

(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 conjugated metabolite of estriol that is present in high quantities during pregnancy. It is formed from estriol in the liver and is eventually excreted in the urine by the kidneys. It has much higher wa ...

(13.4%), and

estriol 3-sulfate 16α-glucuronide Estriol sulfate glucuronide, or estriol 3-sulfate 16α-glucuronide, is an endogenous, natural product, naturally occurring conjugation (biochemistry), diconjugated metabolite of estriol. It is generated in the liver from estriol sulfate by UDP-glu ...

(5.1%). The

and

of estriol in these animals closely resembled that which has been observed in humans. In non-pregnant women, estriol urinary excretion ranges between 0.02–0.1 mg every 24 hours. In comparison, in near-term pregnant women, estriol urinary excretion ranges from 50–150 mg every 24 hours.

Medical use

Estriol is used as a

, primarily in

hormone therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are hormonal therap ...

for

menopausal Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

symptom Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

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 ...

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, for i ...

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 ...

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 an organic compound containing three hydroxyl groups ( functional groups), It was isolated and purified from the

of pregnant women by Marrian and colleagues.

Use in screening

Estriol can be measured in maternal blood or urine and can be used as a marker of fetal health and well-being. If levels of unconjugated estriol (uE3 or free estriol) are abnormally low in a pregnant woman, this may indicate chromosomal or congenital anomalies like Down syndrome or

Edward's syndrome Trisomy 18, also known as Edwards syndrome, is a genetic disorder caused by the presence of a third copy of all or part of chromosome 18. Many parts of the body are affected. Babies are often born small and have heart defects. Other features inc ...

. It is included as part of the

triple test The triple test, also called triple screen, the Kettering test or the Bart's test, is an investigation performed during pregnancy in the second trimester to classify a patient as either high-risk or low-risk for chromosomal abnormalities (and n ...

and quadruple test for antenatal screening for fetal anomalies. Because many pathological conditions in a pregnant woman can cause deviations in estriol levels, these screenings are often seen as less definitive of fetal-placental health than a

nonstress test A nonstress test (NST) is a screening test used in pregnancy to assess fetal status by means of the fetal heart rate and its responsiveness. A cardiotocograph is used to monitor the fetal heart rate and presence or absence of uterine contraction ...

. Conditions which can create

false positives A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test res ...

and

false negatives A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test resu ...

in estriol testing for fetal distress include

preeclampsia Pre-eclampsia is a multi-system disorder specific to pregnancy, characterized by the new onset of high blood pressure and often a significant amount of protein in the urine or by the new onset of high blood pressure along with significant end- ...

anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...

, and impaired

kidney function Assessment of kidney function occurs in different ways, using the presence of symptoms and medical sign, signs, as well as measurements using urine tests, blood tests, and medical imaging. Renal physiology, Functions of a healthy kidney include ...