Prasterone enanthate

Prasterone enanthate, also known as dehydroepiandrosterone enanthate (DHEA-E) and sold in combination with estradiol valerate under the brand name Gynodian Depot among others, is a weak androgen, estrogen, and neurosteroid medication which is used as a component of menopausal hormone therapy to treat menopausal symptoms in women.^{[3][1][4][5][6][7][8][9][10]} It is available only as an injectable preparation in combination with estradiol valerate.^{[3][11][12][13]} The medication is given by injection into muscle typically once every 4 weeks.^[3][1][4]

Prasterone enanthate

Clinical data
Trade names	With estradiol valerate: Gynodian Depot, others
Other names	DHEA enanthate; Prasterone heptanoate; DHEA heptanoate; DHEA-E; EDHEA; SH-90300-D; SH-70833-D (with EVTooltip estradiol valerate); Androst-5-en-3β-ol-17-one 3β-heptanoate
Routes of administration	Intramuscular injection
Drug class	Androgen; Anabolic steroid; Androgen ester; Estrogen; Neurosteroid
ATC code	G03EA03 (WHO) A14AA07 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	IM: 100%[1]
Metabolites	• Prasterone (DHEA)[1] • Others[1]
Elimination half-life	IM: 9 days[1] IV: 44 minutes[1]
Duration of action	18 days[2]
Excretion	Urine, feces[1]
Identifiers
IUPAC name [(3S,8R,9S,10R,13S,14S)-10,13-Dimethyl-17-oxo-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-yl] heptanoate
CAS Number	23983-43-9
PubChem CID	163331
DrugBank	DB16625
ChemSpider	143333
UNII	2W8I1S6T5L
CompTox Dashboard (EPA)	DTXSID00946833
ECHA InfoCard	100.041.777
Chemical and physical data
Formula	C26H40O3
Molar mass	400.603 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCCCCCC(=O)O[C@H]1CC[C@@]2([C@H]3CC[C@]4([C@H]([C@@H]3CC=C2C1)CCC4=O)C)C
InChI InChI=1S/C26H40O3/c1-4-5-6-7-8-24(28)29-19-13-15-25(2)18(17-19)9-10-20-21-11-12-23(27)26(21,3)16-14-22(20)25/h9,19-22H,4-8,10-17H2,1-3H3/t19-,20-,21-,22-,25-,26-/m0/s1 Key:HHENOUDBWKNPAB-BNCSLUSBSA-N

Prasterone enanthate is a synthetic androgen, estrogen, and neurosteroid.^[3][1][4] It is a steroid ester and a long-lasting prodrug of prasterone (dehydroepiandrosterone; DHEA) in the body.^[3][1][4] Prasterone is a naturally occurring prohormone of androgens and estrogens and hence is an agonist of the androgen and estrogen receptors, the respective biological targets of androgens like testosterone and estrogens like estradiol.^[14][15] Prasterone also has a variety of activities of its own, including neurosteroid and other activities.^[15] An injection of prasterone enanthate has a duration of action in terms of elevated prasterone levels of about 18 days.^[3][1][4]

The combination of estradiol valerate and prasterone enanthate was developed as early as 1966 and was introduced for medical use in 1975.^[16][17] The formulation is marketed widely throughout Europe, and is also available in several Latin American countries and in Egypt.^{[11][12][18][13][19]} It is not available in any predominantly English-speaking countries.^[11][19]

Medical uses

The combination of estradiol valerate and prasterone enanthate is used in menopausal hormone therapy to treat menopausal symptoms in peri- and postmenopausal women.^[3][16] Estradiol valerate serves as an estrogen in the preparation, while prasterone enanthate is intended to serve as a weak androgen.^[3][16] It is thought that the inclusion of prasterone enanthate in the formulation may provide additional psychotropic benefits.^{[16][20][21][22]}

• v
• t
• e

Androgen replacement therapy formulations and dosages used in women

Route	Medication	Major brand names	Form	Dosage
Oral	Testosterone undecanoate	Andriol, Jatenzo	Capsule	40–80 mg 1x/1–2 days
	Methyltestosterone	Metandren, Estratest	Tablet	0.5–10 mg/day
	Fluoxymesterone	Halotestin	Tablet	1–2.5 mg 1x/1–2 days
	Normethandronea	Ginecoside	Tablet	5 mg/day
	Tibolone	Livial	Tablet	1.25–2.5 mg/day
	Prasterone (DHEA)b	–	Tablet	10–100 mg/day
Sublingual	Methyltestosterone	Metandren	Tablet	0.25 mg/day
Transdermal	Testosterone	Intrinsa	Patch	150–300 μg/day
		AndroGel	Gel, cream	1–10 mg/day
Vaginal	Prasterone (DHEA)	Intrarosa	Insert	6.5 mg/day
Injection	Testosterone propionatea	Testoviron	Oil solution	25 mg 1x/1–2 weeks
	Testosterone enanthate	Delatestryl, Primodian Depot	Oil solution	25–100 mg 1x/4–6 weeks
	Testosterone cypionate	Depo-Testosterone, Depo-Testadiol	Oil solution	25–100 mg 1x/4–6 weeks
	Testosterone isobutyratea	Femandren M, Folivirin	Aqueous suspension	25–50 mg 1x/4–6 weeks
	Mixed testosterone esters	Climacterona	Oil solution	150 mg 1x/4–8 weeks
		Omnadren, Sustanon	Oil solution	50–100 mg 1x/4–6 weeks
	Nandrolone decanoate	Deca-Durabolin	Oil solution	25–50 mg 1x/6–12 weeks
	Prasterone enanthatea	Gynodian Depot	Oil solution	200 mg 1x/4–6 weeks
Implant	Testosterone	Testopel	Pellet	50–100 mg 1x/3–6 months
Notes: Premenopausal women produce about 230 ± 70 μg testosterone per day (6.4 ± 2.0 mg testosterone per 4 weeks), with a range of 130 to 330 μg per day (3.6–9.2 mg per 4 weeks). Footnotes: a = Mostly discontinued or unavailable. b = Over-the-counter. Sources: See template.

Available forms

See also: Estradiol valerate/prasterone enanthate

Prasterone enanthate is available only as a combination formulation of 4 mg estradiol valerate and 200 mg prasterone enanthate in oil for depot intramuscular injection.^[12][13][11]

Side effects

See also: Prasterone § Side effects

Prasterone enanthate, in combination with estradiol valerate at the dosages used clinically, has no masculinizing side effects.^[16] This is in contrast to combinations of estrogens with other androgens, such as testosterone esters.^[16]

The following is a list of possible side-effects that may occur in medicines that contain Estradiol Valerate / Prasterone Enanthate. This is not a comprehensive list. These side-effects are possible, but do not always occur. Some of the side-effects may be rare but serious. Consult your doctor if you observe any of the following side-effects, especially if they do not go away.

Dysmenorrhea Vaginitis Ovarian cancer Endometrial hyperplasia Endometrial cancer Breast cancer Stroke Increase in blood pressure Pulmonary embolism Nausea Vomiting Abdominal cramps Bloating Cholestatic jaundice Pruritus Rash Dizziness

Estradiol Valerate / Prasterone Enanthate may also cause side-effects not listed here.^[23]

Pharmacology

See also: Prasterone § Pharmacology

Pharmacodynamics

See also: Dehydroepiandrosterone § Biological activity

Pharmacokinetics

See also: Dehydroepiandrosterone § Biochemistry

Estradiol and DHEA levels after a single intramuscular injection of Gynodian Depot (4 mg estradiol valerate, 200 mg prasterone enanthate in oil) in women.^[3][2][24]

The pharmacokinetics of prasterone enanthate have been assessed in a number of studies.^[2][25]

Prasterone enanthate is a prodrug of prasterone in the body.^[3][1][2] It is completely hydrolyzed into prasterone and heptanoic acid (enanthic acid) following absorption from the tissue depot after intramuscular injection.^[1]

Levels of DHEA peak at about 9 ng/mL within 1 to 4 days of an injection of prasterone enanthate.^[1] Subsequently, DHEA levels return to baseline by about 18 days following the injection.^[1] Prasterone enanthate has an elimination half-life of about 9 days.^[1] The plasma half-life of DHEA/prasterone enanthate following an intravenous injection is about 44 minutes.^[1] The half-lives of DHEA metabolites range up to 3.6 days.^[1]

Within 30 days, 91% of a dose of prasterone enanthate is eliminated.^[1] Approximately 94% is excreted in urine and 6% in feces.^[1] Prasterone enanthate is eliminated mainly in the form of metabolites and conjugates.^[1]

Chemistry

See also: Androgen ester and List of androgen esters § Esters of other natural AAS

Prasterone enanthate, also known as 5-dehydroepiandrosterone 3β-enanthate or as androst-5-en-3β-ol-17-one 3β-heptanoate, is a synthetic androstane steroid and the C3β heptanoate (enanthate) ester of prasterone (5-dehydroepiandrosterone).^[26][27][18]

History

See also: Prasterone § History

Prasterone enanthate was patented by Schering in 1968 and 1971.^[13][18] The combination of estradiol valerate and prasterone enanthate was developed and marketed by Schering, was first tested clinically as early as 1966, was first described in the scientific literature in 1972, and was first introduced for medical use in April 1975.^{[16][17][28][13]}

Society and culture

Brand names

The major brand name of the combination of estradiol valerate and prasterone enanthate is Gynodian Depot.^{[11][12][13][19]} Other brand names of this formulation include Binodian Depot, Cidodian Depot, Klimax, and Supligol NF.^{[11][12][13][19]}

Availability

The combination of estradiol valerate and prasterone enanthate is marketed widely throughout Europe, and is also available in several Latin American countries and in Egypt.^{[11][12][18][13][19]} In Europe, it is available in Austria, the Czech Republic, Germany, Italy, Poland, Russia, Spain, and Switzerland.^{[11][12][18][13][19]} In Latin America, it is available in Argentina, Chile, Mexico, and Venezuela.^[11][19] The medication is not available in any predominantly English-speaking countries, including the United States, Canada, the United Kingdom, Ireland, Australia, New Zealand, or South Africa.^[11][19]

See also

• Estradiol valerate/prasterone enanthate