979-32-8

Basic information

• Product Name: Estradiol valerate
• Synonyms: delestrogen;delestrogen4x;dura-estradiol;estradiol17-beta-valerate;estradiolvalerianate;estraval;femogex;neofollin
• CAS NO: 979-32-8
• Molecular Formula: C₂₃H₃₂O₃
• Molecular Weight: 356.5
• EINECS: 213-559-2
• Product Categories: Steroids;Intermediates & Fine Chemicals;Pharmaceuticals;progestogen estrogen;DELESTRGEN;Hormone Drugs
• Mol File: 979-32-8.mol
• Article Data: 4

Chemical Properties

• Melting Point: 144°C
• Boiling Point: 438.83°C (rough estimate)
• Flash Point: 191.1 °C
• Appearance: Na
• Density: 1.1024 (rough estimate)
• Vapor Pressure: 4.47E-10mmHg at 25°C
• Refractive Index: 1.4700 (estimate)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Practically insoluble in water, soluble in alcohol.
• PKA: 10.25±0.60(Predicted)
• Merck: 13,3738
• BRN: 2480357
• CAS DataBase Reference: Estradiol valerate(CAS DataBase Reference)
• NIST Chemistry Reference: Estradiol valerate(979-32-8)
• EPA Substance Registry System: Estradiol valerate(979-32-8)

Safety Data

• Hazard Codes: T
• Statements: 60-61
• Safety Statements: 53-45
• WGK Germany: 3
• RTECS: KG5793000
• Hazardous Substances Data: 979-32-8(Hazardous Substances Data)

Usage

Description

Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. In women, it is used in hormone therapy for menopausal symptoms and low estrogen levels, hormone therapy for transgender women, and in hormonal birth control. It is also used in the treatment of prostate cancer in men. The medication is taken by mouth or by injection into muscle or fat once every 1 to 4 weeks.

Chemical Properties

White to off-white crystalline powder, odorless. Insoluble in water, easily soluble in ethanol, acetone, chloroform, slightly soluble in vegetable oil.

Originator

Delestrogen,Squibb,US,1954

Uses

Estradiol valerate is a female hormone (estrogen). It is used to reduce symptoms of menopause which are vaginal dryness, hot flashes, and others. The symptoms of menopause manifest because the body is making less estrogen; with estradiol valerate, these symptoms are brought to the lowest minimum. This medication therapy can also produce enough estrogen in women with ovarian failure, hypogonadism and can be used by men to treat prostate cancer (palliation only).

Indications

Estradiol valerate is commercially available as an intramuscular injection as the product Delestrogen and is indicated for the treatment of moderate to severe vasomotor symptoms and vulvovaginal atrophy due to menopause, for the treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure, and for the treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only). Estradiol valerate is also available in combination with Dienogest as the commercially available product Natazia used for the prevention of pregnancy and for the treatment of heavy menstrual bleeding.

Definition

ChEBI: Estradiol valerate is a steroid ester. It is the parenterally-administered synthetic valerate ester of estradiol, a steroid sex hormone vital to the maintenance of fertility and secondary sexual characteristics in females.

Manufacturing Process

2.3 parts of estradiol are mixed with 12 parts of pyridine and 10 parts of nvaleric anhydride and the mixture is heated for some time at 115°C in the oil bath. The cooled solution is mixed with 250 parts of water, whereupon an oil separates; this is extracted with ether. The separated ethereal solution is washed successively with N sulfuric acid, water, N sodium carbonate solution and water and then dried. The ether is then removed and the residue purified by distillation in a high vacuum. The estradiol di-n-valerate forms a yellowish oil according to US Patent 2,205,627.1 part of estradiol-3,17-n-divalerianate (boiling point at 0.01 mm = 220° to 230°C bath temperature; made, e.g., by the action of n-valeric anhydride on a solution of estradiol in pyridine) is mixed with 50 parts of a solution of 0.5% strength of potassium carbonate in methyl alcohol of 95% strength, and the whole is stirred for some time at 20°C. The oily n-di-valerianate passes gradually into solution. The solution is neutralized and the precipitate is produced by the addition of about 200 parts of water. This finely crystalline product is filtered and washed successively with water, dilute sodium carbonate solution and again with water. It may be further purified by crystallization from a mixture of methyl alcohol and water. The estradiol-17- mono-n-valerianate melts at 144° to 145°C according to US Patent 2,233,025.

Brand name

Delestrogen (King).

General Description

Estradiol valerate is a synthetic hormone that is extensively metabolized to estradiol and valeric acid before reaching the systemic circulation. It is well suited for treatment of the characteristic symptoms accompanying menopause in women.

Side effects

As with all pharmaceutical medicines, some unwanted effects can occur from the use of estradiol valerate tablets.Always consult a physician for medical advice before use.Common side effects may include: bloating, vomiting, nausea, breast tenderness, headache, weight changes, and mood changes.More severe side effects may include mental changes, breast lumps, vaginal bleeding, liver damage, increased thirst, and sudden vision loss.

Safety Profile

Suspected carcinogen with carcinogenic and teratogenic data. Experimental reproductive effects. When heated to decomposition it emits acrid smoke and irritating fumes. See also ESTRADIOL.

InChI:InChI=1/C23H32O3/c1-3-4-5-22(25)26-21-11-10-20-19-8-6-15-14-16(24)7-9-17(15)18(19)12-13-23(20,21)2/h7,9,14,18-21,24H,3-6,8,10-13H2,1-2H3/t18?,19?,20?,21-,23-/m0/s1

Upstream product

• 50-28-2 estradiol 
• 638-29-9 n-valeryl chloride 
• 63042-21-7 3-benzoyloxy-17β-valeryloxy-estra-1,3,5(10)-triene 
• 109-52-4 valeric acid 
• 63042-28-4 estradiol divalerate 

Downstream Products

• 31299-96-4 estradiol-17β 3-β-D-glucopyranoside 

Relevant articles and documents

PROCESS FOR PREPARATION OF ESTRADIOL VALERATE AND A NOVEL CRYSTALLINE FORM A OF ESTRADIOL DIVALERATE

The present invention relates to the process for the preparation of estradiol valerate (I) which involves isolation of crystalline estradiol divalerate (III) by crystallization from an alcoholic solvent.

Pharmaceutical combined preparation, kit and method for hormonal contraception

PCT No. PCT/DE96/01192 Sec. 371 Date Jun. 3, 1998 Sec. 102(e) Date Jun. 3, 1998 PCT Filed Jun. 27, 1996 PCT Pub. No. WO97/01342 PCT Pub. Date Jan. 16, 1997The present invention describes a two-stage pharmaceutical combined preparation for hormonal contraception containing at least 30 daily unit doses, which preparation, in its first stage, comprises as hormonal active ingredient a combination of an oestrogen preparation and, in a dose that is at least sufficient to inhibit ovulation, a gestagen preparation, in single stage form and, in the second stage comprises as hormonal active ingredient an oestrogen preparation only, wherein the first stage comprises a minimum of 25 and a maximum of 77 daily discrete or continuous unit doses and the second stage comprises 5, 6 or 7 daily discrete or continuous unit doses, and wherein the total number of daily units is equal to the total number of days of the desired cycle of a minimum of 30 and a maximum of 84 days. This combined preparation, in the form of a monthly pack, which is used for female fertility control, permits as low as possible an oestrogen content in each individual unit dose and also has a low total hormone content per cycle of administration, with high contraceptive reliability, low incidence of follicle development, and satisfactory cycle control with reliable avoidance of intermediate bleeding as well as undesired side effects.