Estropipate

Estropipate
Clinical data
Trade names	Harmogen, Improvera, Ogen, Ortho-Est, Sulestrex, others
Other names	Piperazine estrone sulfate; Estrone sulfate piperazine salt; Pipestrone
AHFS/Drugs.com	Monograph
Routes of; administration	By mouth
Drug class	Estrogen; Estrogen ester
ATC code	None;
Legal status
Legal status	US: WARNING;
Identifiers
	IUPAC name [(8R,9S,13S,14S)-13-Methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] hydrogen sulfate; piperazine;
CAS Number	7280-37-7 ;
PubChem CID	5284555;
DrugBank	DB04574 ;
ChemSpider	4447610 ;
UNII	SVI38UY019;
KEGG	D00948 ;
ChEBI	CHEBI:4873 ;
ChEMBL	ChEMBL1200980 ;
CompTox Dashboard (EPA)	DTXSID3023005 ;
ECHA InfoCard	100.027.906
Chemical and physical data
Formula	C22H32N2O5S
Molar mass	436.57 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=S(=O)(O)Oc1cc4c(cc1)[C@@H]3[C@H]([C@@H]2CCC(=O)[C@@]2(C)CC3)CC4.N1CCNCC1;
	InChI InChI=1S/C18H22O5S.C4H10N2/c1-18-9-8-14-13-5-3-12(23-24(20,21)22)10-11(13)2-4-15(14)16(18)6-7-17(18)19;1-2-6-4-3-5-1/h3,5,10,14-16H,2,4,6-9H2,1H3,(H,20,21,22);5-6H,1-4H2/t14-,15-,16+,18+;/m1./s1 ; Key:HZEQBCVBILBTEP-ZFINNJDLSA-N ;
	(verify)

Estropipate, also known as piperazine estrone sulfate and sold under the brand names Harmogen, Improvera, Ogen, Ortho-Est, and Sulestrex among others, is an estrogen medication which is used mainly in menopausal hormone therapy in the treatment of menopausal symptoms.^[2]^[3]^[4]^[5] It is a salt of estrone sulfate and piperazine, and is transformed into estrone and estradiol in the body.^[3]^[4] It is taken by mouth.^[2]

Medical uses

Estropipate is used to:^[2]^{[additional citation(s) needed]}

Alleviate symptoms of menopause as menopausal hormone therapy
Treat some types of infertility
Treat some conditions leading to underdevelopment of female sexual characteristics
Treat vaginal atrophy
Treat some types of breast cancer (particularly in men and postmenopausal women)
Treat prostate cancer
Prevent osteoporosis

v
t
e
Estrogen dosages for menopausal hormone therapy
Route/form	Estrogen	Low	Standard	High
Oral	Estradiol	0.5–1 mg/day	1–2 mg/day	2–4 mg/day
	Estradiol valerate	0.5–1 mg/day	1–2 mg/day	2–4 mg/day
	Estradiol acetate	0.45–0.9 mg/day	0.9–1.8 mg/day	1.8–3.6 mg/day
	Conjugated estrogens	0.3–0.45 mg/day	0.625 mg/day	0.9–1.25 mg/day
	Esterified estrogens	0.3–0.45 mg/day	0.625 mg/day	0.9–1.25 mg/day
	Estropipate	0.75 mg/day	1.5 mg/day	3 mg/day
	Estriol	1–2 mg/day	2–4 mg/day	4–8 mg/day
	Ethinylestradiol^a	2.5–10 μg/day	5–20 μg/day	–
Nasal spray	Estradiol	150 μg/day	300 μg/day	600 μg/day
Transdermal patch	Estradiol	25 μg/day^b	50 μg/day^b	100 μg/day^b
Transdermal gel	Estradiol	0.5 mg/day	1–1.5 mg/day	2–3 mg/day
Vaginal	Estradiol	25 μg/day	–	–
Vaginal	Estriol	30 μg/day	0.5 mg 2x/week	0.5 mg/day
IMTooltip Intramuscular or SC injection	Estradiol valerate	–	–	4 mg 1x/4 weeks
	Estradiol cypionate	1 mg 1x/3–4 weeks	3 mg 1x/3–4 weeks	5 mg 1x/3–4 weeks
	Estradiol benzoate	0.5 mg 1x/week	1 mg 1x/week	1.5 mg 1x/week
SC implant	Estradiol	25 mg 1x/6 months	50 mg 1x/6 months	100 mg 1x/6 months
Footnotes: ^a = No longer used or recommended, due to health concerns. ^b = As a single patch applied once or twice per week (worn for 3–4 days or 7 days), depending on the formulation. Note: Dosages are not necessarily equivalent. Sources: See template.

Available forms

Estropipate was available in the form of 0.75, 1.5, 3, and 6 mg oral tablets and 1.5 mg/gram vaginal cream. Estropipate is no longer available in the United States.

Pharmacology

Pharmacodynamics

Estropipate is a prodrug of estrone and estradiol. Hence, it is an estrogen, or an agonist of the estrogen receptors.

v
t
e
Relative oral potencies of estrogens
Estrogen	HFTooltip Hot flashes	VETooltip Vaginal epithelium	UCaTooltip Urinary calcium	FSHTooltip Follicle-stimulating hormone	LHTooltip Luteinizing hormone	HDLTooltip High-density lipoprotein-CTooltip Cholesterol	SHBGTooltip Sex hormone-binding globulin	CBGTooltip Corticosteroid-binding globulin	AGTTooltip Angiotensinogen	Liver
Estradiol	1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
Estrone	?	?	?	0.3	0.3	?	?	?	?	?
Estriol	0.3	0.3	0.1	0.3	0.3	0.2	?	?	?	0.67
Estrone sulfate	?	0.9	0.9	0.8–0.9	0.9	0.5	0.9	0.5–0.7	1.4–1.5	0.56–1.7
Conjugated estrogens	1.2	1.5	2.0	1.1–1.3	1.0	1.5	3.0–3.2	1.3–1.5	5.0	1.3–4.5
Equilin sulfate	?	?	1.0	?	?	6.0	7.5	6.0	7.5	?
Ethinylestradiol	120	150	400	60–150	100	400	500–600	500–600	350	2.9–5.0
Diethylstilbestrol	?	?	?	2.9–3.4	?	?	26–28	25–37	20	5.7–7.5
Sources and footnotes Notes: Values are ratios, with estradiol as standard (i.e., 1.0). Abbreviations: HF = Clinical relief of hot flashes. VE = Increased proliferation of vaginal epithelium. UCa = Decrease in UCaTooltip urinary calcium. FSH = Suppression of FSHTooltip follicle-stimulating hormone levels. LH = Suppression of LHTooltip luteinizing hormone levels. HDL-C, SHBG, CBG, and AGT = Increase in the serum levels of these liver proteins. Liver = Ratio of liver estrogenic effects to general/systemic estrogenic effects (hot flashes/gonadotropins). Sources: See template.

Pharmacokinetics

Estropipate is hydrolyzed into estrone in the body.^[6] Estrone can then be transformed into estradiol by 17β-hydroxysteroid dehydrogenase.

Chemistry

History

Estropipate was introduced for medical use by Abbott in 1968.^[7] It was approved by the FDATooltip Food and Drug Administration in the United States in 1991.^[8]

Society and culture

Generic names

Estropipate is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, and BANTooltip British Approved Name.^[3]^[4]^[9]^[6]^[10]

Brand names

Estropipate was marketed under the brand names Genoral, Harmogen, Improvera, Ogen, Ortho-Est, and Sulestrex among others.^[10]^[3]^[9]^[6]

Availability

Estropipate has been discontinued in the United States. In the past, estropipate has also been marketed in Canada, the United Kingdom, Ireland, Switzerland, Australia, South Africa, Mexico, and Indonesia.^[10]^[9]^[6]

References

^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
^ ^a ^b ^c "Ogen, estropipate tablets, USP" (PDF). Pharmacia & Upjohn Co. U.S. Food and Drug Administration. December 2004.
^ ^a ^b ^c ^d Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 900–. ISBN 978-1-4757-2085-3.
^ ^a ^b ^c Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 114–. ISBN 978-94-011-4439-1.
^ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia (3rd ed.). Elsevier. pp. 1484–. ISBN 978-0-8155-1856-3.
^ ^a ^b ^c ^d Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2101. ISBN 978-0-85369-840-1.
^ Budoff PW (1 August 1983). No more hot flashes, and other good news. Putnam. p. 28. ISBN 978-0-399-12793-9.
^ P & T. CORE Medical Journals. July 1993.
^ ^a ^b ^c Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 408–. ISBN 978-3-88763-075-1.
^ ^a ^b ^c "Estropipate". Drugs.com.

[FDA-AllBoxedWarnings-1] "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.

[OgenLabel-2] "Ogen, estropipate tablets, USP" (PDF). Pharmacia & Upjohn Co. U.S. Food and Drug Administration. December 2004.

[Elks2014-3] Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 900–. ISBN 978-1-4757-2085-3.

[MortonHall2012-4] Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 114–. ISBN 978-94-011-4439-1.

[Publishing2013-5] William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia (3rd ed.). Elsevier. pp. 1484–. ISBN 978-0-8155-1856-3.

[Martindale-6] Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2101. ISBN 978-0-85369-840-1.

[Budoff1983-7] Budoff PW (1 August 1983). No more hot flashes, and other good news. Putnam. p. 28. ISBN 978-0-399-12793-9.

[CORE1993-8] P & T. CORE Medical Journals. July 1993.

[IndexNominum2000-9] Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 408–. ISBN 978-3-88763-075-1.

[Drugs.com-10] "Estropipate". Drugs.com.

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v t e Estradiol
Topics	Estradiol (as a hormone) Estradiol (as a medication) Pharmacodynamics of estradiol Pharmacokinetics of estradiol Estrogen (as a hormone) Estrogen (as a medication) Menopausal hormone therapy Feminizing hormone therapy Estradiol-containing birth control pill Combined injectable birth control High-dose estrogen Hydroxylation of estradiol
Esters	Estradiol acetate Estradiol acetylsalicylate Estradiol anthranilate Estradiol benzoate butyrate Estradiol benzoate cyclooctenyl ether Estradiol benzoate Estradiol butyrylacetate Estradiol cyclooctyl acetate Estradiol cypionate Estradiol decanoate Estradiol diacetate Estradiol dibutyrate Estradiol dienantate Estradiol dipropionate Estradiol distearate Estradiol disulfate Estradiol diundecylate Estradiol diundecylenate Estradiol enantate Estradiol furoate Estradiol glucuronide Estradiol hemisuccinate Estradiol hexahydrobenzoate Estradiol monopropionate Estradiol mustard Estradiol palmitate Estradiol phenylpropionate Estradiol phosphate Estradiol pivalate Estradiol propoxyphenylpropionate Estradiol salicylate Estradiol stearate Estradiol sulfamate Estradiol sulfate Estradiol undecylate Estradiol undecylenate Estradiol valerate Estramustine phosphate (estradiol normustine phosphate) Estrogen ester Polyestradiol phosphate
Related	Estrone Estriol Estetrol Ethinylestradiol Conjugated estrogens Esterified estrogens Estrone sulfate Estropipate (piperazine estrone sulfate)