Polyestriol phosphate

Not to be confused with Polyestradiol phosphate.

Polyestriol phosphate (PE3P, SEP), sold under the brand names Gynäsan, Klimadurin, and Triodurin, is an estrogen medication which was previously used in menopausal hormone therapy (i.e., to treat menopausal symptoms in postmenopausal women) and is no longer available.^{[1][2][3][4][5][6][7][8][9][10][11][12]}

Polyestriol phosphate

Skeletal structure of polyestriol phosphate (top) and ball-and-stick model of estriol phosphate (one monomer of polyestriol phosphate) (bottom)
Clinical data
Trade names	Gynäsan, Klimadurin, Triodurin
Other names	PE3P; SEP; Poly(estriol phosphate); Estriol phosphate polymer; Estriol polymer with phosphoric acid
Routes of administration	Intramuscular injection
Drug class	Estrogen; Estrogen ester
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	IM: High
Metabolites	Estriol, phosphoric acid, and metabolites of estriol
Excretion	Urine (as conjugates)
Identifiers
IUPAC name Estra-1,3,5(10)-triene-3,16α,17β-triol, polymer with phosphoric acid
CAS Number	37452-43-0
UNII	H4BF1S56XC
Chemical and physical data
Formula	(C18H23O5P)n (n = variable)
Molar mass	Polymer: Variable Repeat unit: 350.346 g/mol

Medical uses

PE3P has been used at a dosage of 40 to 80 mg by intramuscular injection once every 4 to 8 weeks in menopausal hormone therapy.^[13][10]

Available forms

PE3P has been available in the form of ampoules containing 50 to 80 mg in 1 or 2 mL aqueous solution.^[13][14][15]

Pharmacology

PE3P is similar to polyestradiol phosphate (PEP), and is, likewise, an estrogen ester – specifically, an ester and prodrug of estriol – in the form of a polymer with phosphate linkers.^[2][4][5][9] When adjusted for differences in molecular weight, PE3P contains the equivalent of about 80% of the amount of estriol.^[16] As such, 40 mg PE3P corresponds to about 32 mg estriol.^[16] Doses of PE3P of 10 mg or more have an extended duration of action.^[17] A single intramuscular injection of 80 mg PE3P has a duration of about 1 month and of 80 mg about 2 months.^[5][14]

The effects of PE3P on the vagina, uterus, pregnancy, prostate gland, coagulation, and fibrinolysis, as well as on mammary and endometrial cancer risk, have been studied.^{[18][19][20][21][22][23][24][25][16]} The endometrial proliferation dose of PE3P over 14 days in women is 40 to 60 mg by intramuscular injection.^[14]

• v
• t
• e

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 aqueous suspensions are of microcrystalline particle size. Estradiol production during the menstrual cycle is 30–640 µg/d (6.4–8.6 mg total per month or cycle). The vaginal epithelium maturation dosage of estradiol benzoate or estradiol valerate has been reported as 5 to 7 mg/week. An effective ovulation-inhibiting dose of estradiol undecylate is 20–30 mg/month. Sources: See template.

Chemistry

See also: List of estrogen esters § Estriol esters

PE3P is a water-soluble polymer of estriol with phosphoric acid.^[17]

History

PE3P was developed by the Swedish pharmaceutical company Leo Läkemedel AB in the 1960s.^[2][9][17] It was introduced for medical use by 1968.^[26][27]

Society and culture

Brand names

PE3P was marketed under brand names including Gynäsan, Klimadurin, and Triodurin.^{[6][13][14][15][28]}

Availability

PE3P was marketed in Germany and Spain.^[14][29]

See also

• Estriol phosphate
• Polytestosterone phloretin phosphate
• Polydiethylstilbestrol phosphate