Estradiol dienanthate (EDE), sold under the brand names Climacteron among others, is a long-acting

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 ...

medication which was previously 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. Effects of menopause can include symptoms such ...

for women and to suppress

lactation Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The process ...

in women. It was formulated in

combination In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are ...

with

estradiol benzoate Estradiol benzoate (EB), sold under the brand name Progynon-B among others, is an estrogen medication which is used in hormone therapy for menopausal symptoms and low estrogen levels in women, in hormone therapy for transgender women, and in the ...

(EB), a short-acting estrogen, and testosterone enanthate benzilic acid hydrazone (TEBH), a long-acting

androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...

anabolic steroid Anabolic steroids, also known as anabolic-androgenic steroids (AAS), are a class of drugs that are structurally related to testosterone, the main male sex hormone, and produce effects by binding to the androgen receptor (AR). Anabolism, Anaboli ...

. EDE has not been made available for medical use alone. The medication, in combination with EB and TEBH, was given by injection into muscle once or at regular intervals, for instance once every 6 weeks.

Side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of EDE 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 ...

, breast enlargement,

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

, and fluid retention. EDE is an

and hence is 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 ...

, 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 ...

s like

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 ...

. It is an

estrogen ester An estrogen ester is an ester of an estrogen, most typically of estradiol but also of other estrogens such as estrone, estriol, and even nonsteroidal estrogens like diethylstilbestrol. Esterification renders estradiol into a prodrug of estradiol ...

and a

prodrug A prodrug is a pharmacologically inactive 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 ...

in the body. Because of this, it is considered to be a

natural Nature is an inherent character or constitution, particularly of the ecosphere or the universe as a whole. In this general sense nature refers to the laws, elements and phenomena of the physical world, including life. Although humans are part ...

and bioidentical form of estrogen. EDE was first described by 1959. It was previously available in

Canada Canada is a country in North America. Its Provinces and territories of Canada, ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, making it the world's List of coun ...

and

Germany Germany, officially the Federal Republic of Germany, is a country in Central Europe. It lies between the Baltic Sea and the North Sea to the north and the Alps to the south. Its sixteen States of Germany, constituent states have a total popu ...

but was discontinued by 2005. The medication is no longer available in any form.

Medical uses

EDE, a long-acting estrogen, was used in combination with EB, a short-acting estrogen, and TEBH, a long-acting androgen/anabolic steroid, in

in perimenopausal,

postmenopausal 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 ...

, hypogonadal, and oophorectomized women, as well as for suppression of

postpartum The postpartum (or postnatal) period begins after childbirth and is typically considered to last for six to eight weeks. There are three distinct phases of the postnatal period; the acute phase, lasting for six to twelve hours after birth; the ...

women.

Available forms

EDE was available only in combination EB and TEBH. The combination was available in two different dose forms, one for menopausal hormone therapy (brand names Climacteron, Amenose) and the other for lactation suppression (brand names Lactimex, Lactostat). Climacteron and Amenose contained 1.0 mg EB, 7.5 mg EDE, and 150 mg TEBH (69 mg free

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

) and was given by repeated intramuscular injection at regular intervals. Lactimex and Lactostat contained 6 mg EB, 15 mg EDE, and 300 mg TEBH in 2 mL of

corn oil Corn oil (North American) or maize oil (British) is oil extracted from the germ of corn (maize). Its main use is in cooking, where its high smoke point makes refined corn oil a valuable frying oil. It is also a key ingredient in some margarin ...

and was administered as a single intramuscular injection after

childbirth Childbirth, also known as labour, parturition and delivery, is the completion of pregnancy, where one or more Fetus, fetuses exits the Womb, internal environment of the mother via vaginal delivery or caesarean section and becomes a newborn to ...

or during

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

Pharmacology

Pharmacodynamics

EDE is an

estradiol ester This is a list of estrogen esters, or ester prodrugs of estrogens. It includes esters, as well as ethers, of steroidal estrogens like estradiol, estrone, and estriol and of nonsteroidal estrogens like the stilbestrols diethylstilbestrol an ...

, or a

. As such, it is an

, or an

of the

s. EDE is of about 82% higher

molecular weight A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

than estradiol due to the presence of its C3 and C17β heptanoate (enanthate) esters. Because EDE is a prodrug of estradiol, it is considered to be a

and bioidentical form of estrogen.

Pharmacokinetics

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

levels following a single

intramuscular injection Intramuscular injection, often abbreviated IM, is the medical injection, injection of a substance into a muscle. In medicine, it is one of several methods for parenteral, parenteral administration of medications. Intramuscular injection may be ...

of Climacteron (including 1 mg EB, 7.5 mg EDE, and 150 mg TEBH equivalent to 69 mg free

) versus 10 mg

estradiol valerate Estradiol valerate (EV), sold for use oral administration, by mouth under the brand name Progynova and for use by injection (medicine), injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen (medication), es ...

have been studied over 28 days.

Chemistry

EDE is a

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

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 ...

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 ...

and the C3 and C17β heptanoate (enanthate)

diester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distinc ...

. It is also known as estradiol 3,17β-heptanoate or as estra-1,3,5(10)-triene-3,17β-diol 3,17β-diheptanoate. EDE is structurally related to estradiol enanthate (estradiol 17β-heptanoate), which has a single heptanoate ester rather than two.

History

EDE was first described and introduced for medical use by 1959.

Society and culture

Brand names

EDE was marketed in combination with EB and TEBH under the brand names Climacteron, Amenose, Lactimex, and Lactostat.

Availability

EDE is no longer available but was previously used in

and other countries.

References

{{Estrogen receptor modulators Abandoned drugs Enanthate esters Estradiol esters Synthetic estrogens