Synthetic Conjugated Estrogens, B

Identification

Name
Synthetic Conjugated Estrogens, B
Accession Number
DB09318
Type
Small Molecule
Groups
Approved
Description

Synthetic conjugated estrogens, B tablets contain a blend of ten synthetic estrogenic substances. The estrogenic substances are: sodium estrone sulfate, sodium equilin sulfate, sodium 17α-dihydroequilin sulfate, sodium 17α-estradiol sulfate, sodium 17β­ dihydroequilin sulfate, sodium 17α-dihydroequilenin sulfate, sodium 17β-dihydroequilenin sulfate, sodium equilenin sulfate, sodium 17β-estradiol sulfate, and sodium Δ8,9-dehydroestrone sulfate. This blend of ten estrogen derivatives are plant-derived forms of endogenous estrogens and contain many of the same compounds as the Conjugated Equine Estrogens (CEEs), although they are not considered to be equivalent. Available as the product Cenestin (FDA), this combination of plant-derived estrogenic compounds is indicated for the treatment of moderate to severe vasomotor symptoms, vulvovaginal atrophy, vaginal dryness, and paint with intercourse associated with menopause.

All estrogen products mimic the effects of endogenous estrogens in the body which are responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Estrogens act by binding to estrogen receptors on a wide variety of tissues in the body and modulating the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) through a negative feedback mechanism. Prior to menopause, the primary source of estrogen is the ovarian follicle, which secretes 70-500 micrograms of estradiol daily, depending on the phase of the menstrual cycle. However, once a woman stops ovulating there is a sharp decline in the production of progesterone and estradiol by the ovaries and a consequent fluctuation in LH and FSH due to a lack of feedback control. This shift in hormone production is largely responsible for many of the symptoms experienced during and after menopause and includes hot flashes and other vasomotor symptoms, painful intercourse, vaginal dryness, and vulvovaginal atrophy. These symptoms are able to be reduced by replacing many of the hormones lost during and following menopause with synthetic or naturally occurring forms, in a therapy known as Hormone Replacement Therapy (HRT).

Pharmacologic estrogen products are available in a variety of formats. Although many of them contain several compounds in common (such as the estrogen derivatives sodium estrone sulfate and sodium equilin sulfate), they vary by their original source (such as horse-, human-, or plant-derived), and the remaining mixture of estrogenic derivatives. Conjugated Equine Estrogens (CEEs) are derived from the urine of pregnant mares and contain a blend of at least 10 estrogen derivatives. Marketed under the brand name Premarin, CEEs are the most frequently used form of conjugated estrogens. There is currently no generic form of CEEs available as a detailed analytical characterization of the active ingredients or of their estrogenic activity is not available at this time. Conjugated estrogens are also available in a plant-derived synthetic form that replicates the naturally occurring, horse-derived forms. Available as either "Synthetic Conjugated Estrogens, A" containing 9 estrogen derivatives (available as Cenestin) or as "Synthetic Conjugated Estrogens, B" containing 10 estrogen derivatives (available as Enjuvia), these products are isolated as precursors from yam or soy plants and then chemically modified to mimic the products available in their naturally occurring form.

Synonyms
  • Estrogens, Conjugated Synthetic B
External IDs
CE 10 / CE-10 / CE10
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EnjuviaTablet, film coated0.3 mg/1OralTeva Women's Health2006-04-242017-04-30Us51285 0406 02 nlmimage10 e91ff4af
EnjuviaTablet0.9 mg/1OralPhysicians Total Care, Inc.2010-09-03Not applicableUs54868 616520180906 25352 f65bg
EnjuviaTablet, film coated0.625 mg/1OralTeva Women's Health2006-04-242014-05-31Us
EnjuviaTablet0.3 mg/1OralPhysicians Total Care, Inc.2010-09-03Not applicableUs54868 616420180906 25352 v1luuo
EnjuviaTablet, film coated1.25 mg/1OralTeva Women's Health2006-04-242016-09-30Us51285 0410 02 nlmimage10 0435826c
EnjuviaTablet, film coated0.45 mg/1OralTeva Women's Health2006-04-242017-04-30Us51285 0407 02 nlmimage10 0e35871c
EnjuviaTablet0.625 mg/1OralPhysicians Total Care, Inc.2010-09-03Not applicableUs
EnjuviaTablet, film coated0.9 mg/1OralTeva Women's Health2007-09-282017-01-31Us51285 0409 02 nlmimage10 093584ac
Categories
UNII
8L6LAK9BTR
CAS number
Not Available
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

For the treatment of moderate to severe vasomotor symptoms due to menopause and for the treatment of moderate to severe vaginal dryness, pain with intercourse, and symptoms of vulvar and vaginal atrophy due to menopause.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

All estrogen products mimic the effects of endogenous estrogens in the body which are responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Estrogens act by binding to estrogen receptors on a wide variety of tissues in the body and modulating the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) through a negative feedback mechanism. Prior to menopause, the primary source of estrogen is the ovarian follicle, which secretes 70-500 micrograms of estradiol daily, depending on the phase of the menstrual cycle. However, once a woman stops ovulating there is a sharp decline in the production of progesterone and estradiol by the ovaries and a consequent fluctuation in LH and FSH due to a lack of feedback control. This shift in hormone production is largely responsible for many of the symptoms experienced during and after menopause and includes hot flashes and other vasomotor symptoms, painful intercourse, vaginal dryness, and vulvovaginal atrophy. These symptoms are able to be reduced by replacing many of the hormones lost during and following menopause with synthetic or naturally occurring forms, in a therapy known as Hormone Replacement Therapy (HRT).

TargetActionsOrganism
AEstrogen receptor alpha
ligand
Human
Absorption

Synthetic conjugated estrogens, B are soluble in water and are well absorbed from the gastrointestinal tract after release from the drug formulation. The tablets release synthetic conjugated estrogens, B slowly over a period of several hours.

Volume of distribution

The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs.

Protein binding

Estrogens circulate in the blood largely bound to sex hormone binding globulin (SHBG) and albumin.

Metabolism

Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the intestine followed by reabsorption. In postmenopausal women, a significant portion of the circulating estrogens exists as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4).

Route of elimination

Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates.

Half life

The half life of baseline-corrected estrone and equilin was found to be 23.46 hr and 15.09 hr, respectively.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinSynthetic Conjugated Estrogens, B may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinSynthetic Conjugated Estrogens, B may decrease the anticoagulant activities of (S)-Warfarin.
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Synthetic Conjugated Estrogens, B.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Synthetic Conjugated Estrogens, B.
5-androstenedioneThe metabolism of Synthetic Conjugated Estrogens, B can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Synthetic Conjugated Estrogens, B can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Synthetic Conjugated Estrogens, B.
AbacavirAbacavir may decrease the excretion rate of Synthetic Conjugated Estrogens, B which could result in a higher serum level.
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Synthetic Conjugated Estrogens, B.
AbciximabSynthetic Conjugated Estrogens, B may decrease the anticoagulant activities of Abciximab.
Food Interactions
Not Available

References

General References
  1. Bhamra R, Kaercher U, Oleary CM: Pharmacokinetics of a modified-release estrogen tablet. J Reprod Med. 2010 Sep-Oct;55(9-10):404-10. [PubMed:21043366]
  2. 14. (2015). In Pharmacology for Women’s Health. Jones & Bartlett Publishers.
External Links
KEGG Drug
D05987
PubChem Substance
347910438
ChEMBL
CHEMBL1201467
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Conjugated_estrogen
FDA label
Download (7.08 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentMenopause1
4CompletedTreatmentNocturnal Vasomotor Symptoms1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral0.3 mg/1
TabletOral0.625 mg/1
TabletOral0.9 mg/1
Tablet, film coatedOral0.3 mg/1
Tablet, film coatedOral0.45 mg/1
Tablet, film coatedOral0.625 mg/1
Tablet, film coatedOral0.9 mg/1
Tablet, film coatedOral1.25 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6660726No2001-03-082021-03-08Us
US6855703No2001-02-122021-02-12Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Ligand
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da

Drug created on November 17, 2015 10:11 / Updated on November 02, 2018 07:01