Estropipate

Estropipate
Clinical data
Trade namesHarmogen, Improvera, Ogen, Ortho-Est, Sulestrex, others
Other namesPiperazine estrone sulfate; Estrone sulfate piperazine salt; Pipestrone
AHFS/Drugs.comMonograph
Routes of
administration		By mouth
Drug classEstrogen; Estrogen ester
ATC code
  • None
Identifiers
  • [(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
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.027.906 Edit this at Wikidata
Chemical and physical data
FormulaC22H32N2O5S
Molar mass436.57 g·mol−1
3D model (JSmol)
  • O=S(=O)(O)Oc1cc4c(cc1)[C@@H]3[C@H]([C@@H]2CCC(=O)[C@@]2(C)CC3)CC4.N1CCNCC1
  • 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 checkY
  • Key:HZEQBCVBILBTEP-ZFINNJDLSA-N checkY
  (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. It is a salt of estrone sulfate and piperazine, and is transformed into estrone and estradiol in the body. It is taken by mouth.

Medical uses

Estropipate is used to:[additional citation(s) needed]

Estrogen dosages for menopausal hormone therapy
Route/formEstrogenLowStandardHigh
OralEstradiol0.5–1 mg/day1–2 mg/day2–4 mg/day
Estradiol valerate0.5–1 mg/day1–2 mg/day2–4 mg/day
Estradiol acetate0.45–0.9 mg/day0.9–1.8 mg/day1.8–3.6 mg/day
Conjugated estrogens0.3–0.45 mg/day0.625 mg/day0.9–1.25 mg/day
Esterified estrogens0.3–0.45 mg/day0.625 mg/day0.9–1.25 mg/day
Estropipate0.75 mg/day1.5 mg/day3 mg/day
Estriol1–2 mg/day2–4 mg/day4–8 mg/day
Ethinylestradiola2.5–10 μg/day5–20 μg/day–
Nasal sprayEstradiol150 μg/day300 μg/day600 μg/day
Transdermal patchEstradiol25 μg/dayb50 μg/dayb100 μg/dayb
Transdermal gelEstradiol0.5 mg/day1–1.5 mg/day2–3 mg/day
VaginalEstradiol25 μg/day––
Estriol30 μg/day0.5 mg 2x/week0.5 mg/day
IMTooltip Intramuscular or SC injectionEstradiol valerate––4 mg 1x/4 weeks
Estradiol cypionate1 mg 1x/3–4 weeks3 mg 1x/3–4 weeks5 mg 1x/3–4 weeks
Estradiol benzoate0.5 mg 1x/week1 mg 1x/week1.5 mg 1x/week
SC implantEstradiol25 mg 1x/6 months50 mg 1x/6 months100 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.

Relative oral potencies of estrogens
EstrogenHFTooltip Hot flashesVETooltip Vaginal epitheliumUCaTooltip Urinary calciumFSHTooltip Follicle-stimulating hormoneLHTooltip Luteinizing hormoneHDLTooltip High-density lipoprotein-CTooltip CholesterolSHBGTooltip Sex hormone-binding globulinCBGTooltip TranscortinAGTTooltip AngiotensinogenLiver
Estradiol1.01.01.01.01.01.01.01.01.01.0
Estrone???0.30.3?????
Estriol0.30.30.10.30.30.2???0.67
Estrone sulfate?0.90.90.8–0.90.90.50.90.5–0.71.4–1.50.56–1.7
Conjugated estrogens1.21.52.01.1–1.31.01.53.0–3.21.3–1.55.01.3–4.5
Equilin sulfate??1.0??6.07.56.07.5?
Ethinylestradiol12015040060–150100400500–600500–6003502.9–5.0
Diethylstilbestrol???2.9–3.4??26–2825–37205.7–7.5
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. Estrone can then be transformed into estradiol by 17β-hydroxysteroid dehydrogenase.

Chemistry

History

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

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.

Brand names

Estropipate was marketed under the brand names Genoral, Harmogen, Improvera, Ogen, Ortho-Est, and Sulestrex among others.

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.

References

  1. 1 2 3 "Ogen, estropipate tablets, USP" (PDF). Pharmacia & Upjohn Co. U.S. Food and Drug Administration. December 2004. Archived from the original (PDF) on February 16, 2017.
  2. 1 2 3 4 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.
  3. 1 2 3 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.
  4. ↑ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia (3rd ed.). Elsevier. pp. 1484–. ISBN 978-0-8155-1856-3.
  5. 1 2 3 4 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.
  6. ↑ Budoff PW (1 August 1983). No more hot flashes, and other good news. Putnam. p. 28. ISBN 978-0-399-12793-9.
  7. ↑ P & T. CORE Medical Journals. July 1993.
  8. 1 2 3 Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 408–. ISBN 978-3-88763-075-1.
  9. 1 2 3 "Estropipate". Drugs.com.