Estradiol dipropionate

Source: Wikipedia, the free encyclopedia.
Estradiol dipropionate
Clinical data
Trade namesAgofollin, Di-Ovocylin, Progynon DP, others
Other namesEDP; Estradiol dipropionate; Estradiol 3,17β-dipropionate; Estra-1,3,5(10)-triene-3,17β-diol 3,17β-dipropanoate
Routes of
administration		Intramuscular injection
Drug classEstrogen; Estrogen ester
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityIM: High[1]
Protein bindingEstradiol: ~98% (to albumin and SHBGTooltip sex hormone-binding globulin)[2][3]
MetabolismCleavage via esterases in the liver, blood, and tissues[4][5]
MetabolitesEstradiol, benzoic acid, and metabolites of estradiol[4][5]
Elimination half-lifeUnknown
Duration of actionIM (5 mg): 5–8 days[6][7]
ExcretionUrine
Identifiers
  • [(8R,9S,13S,14S,17S)-13-methyl-3-propanoyloxy-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] propanoate
JSmol)
  • O=C(Oc1cc3c(cc1)[C@H]2CC[C@@]4([C@@H](OC(=O)CC)CC[C@H]4[C@@H]2CC3)C)CC
  • InChI=1S/C24H32O4/c1-4-22(25)27-16-7-9-17-15(14-16)6-8-19-18(17)12-13-24(3)20(19)10-11-21(24)28-23(26)5-2/h7,9,14,18-21H,4-6,8,10-13H2,1-3H3/t18-,19-,20+,21+,24+/m1/s1
  • Key:JQIYNMYZKRGDFK-RUFWAXPRSA-N

Estradiol dipropionate (EDP), sold under the brand names Agofollin, Di-Ovocylin, and Progynon DP among others, is an

transgender women and in the treatment of prostate cancer in men.[14][8] Although widely used in the past, estradiol dipropionate has largely been discontinued and is mostly no longer available today.[15][13][11] It appears to remain in use only in Japan, Macedonia, and Australia.[13] Estradiol dipropionate is given by injection into muscle at intervals ranging from once or twice a week to once every week and a half to two weeks.[8][16][14]

fluid retention.[17] Estradiol dipropionate is an estrogen and hence is an agonist of the estrogen receptor, the biological target of estrogens like estradiol.[5][4] It is an estrogen ester and a prodrug of estradiol in the body.[4][5] Because of this, it is considered to be a natural and bioidentical form of estrogen.[4]

Estradiol dipropionate was patented in 1937[18] and was introduced for medical use by 1940.[19][20] It was one of the earliest estradiol esters to be used.[8] Along with estradiol benzoate, estradiol dipropionate was among the most widely used esters of estradiol for many years following its introduction.[15]

Medical uses

The

palliative treatment of prostate cancer in men.[8]

Estradiol dipropionate has typically been used at a dosage of 1 to 5 mg once or twice per week by

transgender women, estradiol dipropionate has been used at dosages of 2 to 10 mg once per week or 5 to 20 mg once every 2 weeks.[14] In the treatment of prostate cancer, estradiol dipropionate has been used at a dosage of 5 mg once per week.[8]

Available forms

See also: Estradiol dipropionate/hydroxyprogesterone caproate

Estradiol dipropionate was previously available by itself as an

oil solution for intramuscular injection provided as vials and ampoules at concentrations of 0.1, 0.2, 0.5, 1, 2.5, and 5 mg/mL.[8][22][23][24][25] The medication has largely been discontinued, with most of these formulations no longer being available.[11][13] Estradiol dipropionate remains available at a concentration of 1 mg/mL in combination with 50 mg/mL hydroxyprogesterone caproate under the brand name EP Hormone Depot (Teikoku Zoki Pharmaceutical Company) in Japan.[26][27][28][29][30][31][32]

Contraindications

See also: Estradiol (medication) § Contraindications

Contraindications of estrogens include coagulation problems, cardiovascular diseases, liver disease, and certain hormone-sensitive cancers such as breast cancer and endometrial cancer, among others.[33][34][35][36]

Side effects

Main article: Estradiol (medication) § Side effects

The

breast tenderness and enlargement, nausea, bloating, edema, headache, and melasma.[17]

Overdose

See also: Estradiol (medication) § Overdose

leg cramps.[33] These side effects can be diminished by reducing the estrogen dosage.[33]

Interactions

See also: Estradiol (medication) § Interactions

Inhibitors and inducers of cytochrome P450 may influence the metabolism of estradiol and by extension circulating estradiol levels.[37]

Pharmacology

Estradiol, the active form of estradiol dipropionate.

Pharmacodynamics

See also: Pharmacodynamics of estradiol

Estradiol dipropionate is an

molecular weight than estradiol due to the presence of its C3 and C17β propionate esters.[10][11] Because estradiol dipropionate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.[4]

Potencies and durations of natural estrogens by intramuscular injection
Estrogen Form Dose (mg) Duration by dose (mg)
EPD CICD
Estradiol Aq. soln. ? – <1 d
Oil soln. 40–60 – 1–2 ≈ 1–2 d
Aq. susp. ? 3.5 0.5–2 ≈ 2–7 d; 3.5 ≈ >5 d
Microsph. ? – 1 ≈ 30 d
Estradiol benzoate Oil soln. 25–35 – 1.66 ≈ 2–3 d; 5 ≈ 3–6 d
Aq. susp. 20 – 10 ≈ 16–21 d
Emulsion ? – 10 ≈ 14–21 d
Estradiol dipropionate Oil soln. 25–30 – 5 ≈ 5–8 d
Estradiol valerate Oil soln. 20–30 5 5 ≈ 7–8 d; 10 ≈ 10–14 d;
40 ≈ 14–21 d; 100 ≈ 21–28 d
Estradiol benz. butyrate Oil soln. ? 10 10 ≈ 21 d
Estradiol cypionate Oil soln. 20–30 – 5 ≈ 11–14 d
Aq. susp. ? 5 5 ≈ 14–24 d
Estradiol enanthate
 Oil soln. ? 5–10 10 ≈ 20–30 d
Estradiol dienanthate
 Oil soln. ? – 7.5 ≈ >40 d
Estradiol undecylate Oil soln. ? – 10–20 ≈ 40–60 d;
25–50 ≈ 60–120 d
Polyestradiol phosphate Aq. soln. 40–60 – 40 ≈ 30 d; 80 ≈ 60 d;
160 ≈ 120 d
Estrone Oil soln. ? – 1–2 ≈ 2–3 d
Aq. susp. ? – 0.1–2 ≈ 2–7 d
Estriol Oil soln. ? – 1–2 ≈ 1–4 d
Polyestriol phosphate Aq. soln. ? – 50 ≈ 30 d; 80 ≈ 60 d
Notes and sources
Notes: All
ovulation-inhibiting dose of estradiol undecylate
is 20–30 mg/month. Sources: See template.

Pharmacokinetics

See also: Pharmacokinetics of estradiol

Compared to

duration of action of estradiol benzoate is said to be 2 to 3 days, the duration of estradiol dipropionate has been said to be 1 to 2 weeks.[39] However, newer estradiol esters have longer durations than either estradiol benzoate or estradiol dipropionate; the duration of estradiol valerate has been said to be 1 to 3 weeks, and the duration of estradiol cypionate has been said to be 3 to 4 weeks.[39][16] A single intramuscular injection of 5 mg estradiol dipropionate has a duration of about 5 to 8 days.[6][7]

A single intramuscular injection of 50 μg/kg estradiol dipropionate in oil in 15 pubertal girls (about 1 mg for a 50-kg (110-lb) girl) was found to produce peak estradiol levels of about 215 pg/mL after 1.5 days.[40] Estradiol levels declined to about 90 pg/mL after 4 days.[40]

Hormone levels with estradiol dipropionate by intramuscular injection
  • Estradiol levels after a single intramuscular injection of 50 μg/kg estradiol dipropionate in oil in pubertal girls.[40] This dose would be 1 mg in a 50-kg (110-lb) girl.[40] Source was Presl et al. (1976).[40]
    Estradiol levels after a single intramuscular injection of 50 μg/kg estradiol dipropionate in oil in pubertal girls.[40] This dose would be 1 mg in a 50-kg (110-lb) girl.[40] Source was Presl et al. (1976).[40]
  • Vaginal cornification with a single intramuscular injection of different estradiol esters in oil solution in women.[41] Source was Schwartz & Soule (1955).[41]
    cornification with a single intramuscular injection of different estradiol esters in oil solution in women.[41] Source was Schwartz & Soule (1955).[41]

Chemistry

See also: Estrogen ester and List of estrogen esters § Estradiol esters

Estradiol dipropionate, also known as estradiol 3,17β-dipropionate, is a

dipropionate ester of estradiol.[10][11]

The experimental

octanol/water partition coefficient (logP) of estradiol dipropionate is 4.9.[42]

Structural properties of selected estradiol esters
Estrogen Structure Ester(s) Relative
mol. weight		 Relative
E2 contentb		 log Pc
Position(s) Moiet(ies) Type Lengtha
Estradiol
– – – – 1.00 1.00 4.0
Estradiol acetate
C3
Ethanoic acid
 Straight-chain fatty acid 2 1.15 0.87 4.2
Estradiol benzoate
C3 Benzoic acid Aromatic fatty acid – (~4–5) 1.38 0.72 4.7
Estradiol dipropionate
C3, C17β
Propanoic acid
(×2)		 Straight-chain fatty acid 3 (×2) 1.41 0.71 4.9
Estradiol valerate
C17β
Pentanoic acid
 Straight-chain fatty acid 5 1.31 0.76 5.6–6.3
Estradiol benzoate butyrate
C3, C17β Benzoic acid, butyric acid Mixed fatty acid – (~6, 2) 1.64 0.61 6.3
Estradiol cypionate
C17β
Cyclopentylpropanoic acid
 Cyclic fatty acid – (~6) 1.46 0.69 6.9
Estradiol enanthate
C17β
Heptanoic acid
 Straight-chain fatty acid 7 1.41 0.71 6.7–7.3
Estradiol dienanthate
C3, C17β
Heptanoic acid
(×2)		 Straight-chain fatty acid 7 (×2) 1.82 0.55 8.1–10.4
Estradiol undecylate
C17β
Undecanoic acid
 Straight-chain fatty acid 11 1.62 0.62 9.2–9.8
Estradiol stearate
C17β
Octadecanoic acid
 Straight-chain fatty acid 18 1.98 0.51 12.2–12.4
Estradiol distearate
C3, C17β
Octadecanoic acid
(×2)		 Straight-chain fatty acid 18 (×2) 2.96 0.34 20.2
Estradiol sulfate
C3 Sulfuric acid Water-soluble conjugate – 1.29 0.77 0.3–3.8
Estradiol glucuronide
C17β Glucuronic acid Water-soluble conjugate – 1.65 0.61 2.1–2.7
Estramustine phosphated
C3, C17β Normustine, phosphoric acid Water-soluble conjugate – 1.91 0.52 2.9–5.0
Polyestradiol phosphatee
C3–C17β Phosphoric acid Water-soluble conjugate – 1.23f 0.81f 2.9g
Footnotes: a = Length of
hydrophobicity). Retrieved from PubChem, ChemSpider, and DrugBank. d = Also known as estradiol normustine phosphate. e = Polymer of estradiol phosphate (~13 repeat units
). f = Relative molecular weight or estradiol content per repeat unit. g = log P of repeat unit (i.e., estradiol phosphate). Sources: See individual articles.

History

Estradiol dipropionate was first

estradiol esters to be introduced for medical use.[48][45] Prior to the development and introduction of longer-acting estradiol esters like estradiol valerate and estradiol cypionate in the 1950s, estradiol dipropionate and estradiol benzoate were the most widely used estradiol esters.[15][49]

Society and culture

Generic names

Estradiol dipropionate is the

JANTooltip Japanese Approved Name.[10][11][12][13]

Brand names

Estradiol dipropionate has been marketed under a variety of brand names, including Agofollin, Akrofolline, Dihidrofolina "Kével", Dimenformon, Dimenformon Dipropionate, Diovocylin, Di-Ovocylin, Diprostron, Diprovex, Endofollicolina D.P., EP Hormone Depot (in combination with

oil solution of estradiol dipropionate that was previously marketed in the Czech Republic and Slovakia.[53]

Availability

Estradiol dipropionate has been discontinued in most countries, but remains available in Japan and Macedonia alone under the brand names Ovahormon and Oestradiol Galenika and/or in combination with hydroxyprogesterone caproate under the brand name EP Hormone Depot.[11][13] It is also marketed for use in veterinary medicine in combination with hydroxyprogesterone caproate and nandrolone decanoate under the brand name Reepair in Australia.[13]

See also

References

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