Wikipedia

Gestonorone caproate

Gestonorone caproate, also known as gestronol hexanoate or norhydroxyprogesterone caproate and sold under the brand names Depostat and Primostat, is a progestin medication which is used in the treatment of enlarged prostate and cancer of the endometrium.[5][3][7][1][8] It is given by injection into muscle typically once a week.[4]

Gestonorone caproate
Clinical data
Trade namesDepostat, Primostat
Other namesGestronol hexanoate; Norhydroxy­progesterone caproate; SH-582; SH-80582; NSC-84054; 17α-Hydroxy-19-norpregn-4-ene-3,20-dione hexanoate; 17α-Hydroxy-19-norprogesterone hexanoate
Routes of
administration		Intramuscular injection[1][2][3]
Drug classProgestogen; Progestin; Progestogen ester; Antigonadotropin
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityOral: Low[4]
IM: High[5]
MetabolismReduction (at the C5, C3, and C20 positions)[6]
Metabolites• 19-Norpregnanetriol[6]
• 19-Norpregnanediol-20-one[6]
Elimination half-lifeIM: 7.5 ± 3.1 days[5]
Duration of actionIM: ≥21 days[5]
ExcretionUrine: 28%[5]
Feces: 72%[5]
Identifiers
  • [(8R,9S,10R,13S,14S,17R)-17-acetyl-13-methyl-3-oxo-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl] hexanoate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.013.646 Edit this at Wikidata
Chemical and physical data
FormulaC26H38O4
Molar mass414.586 g·mol−1
3D model (JSmol)
  • CCCCCC(=O)OC1(CCC2C1(CCC3C2CCC4=CC(=O)CCC34)C)C(=O)C
  • InChI=1S/C26H38O4/c1-4-5-6-7-24(29)30-26(17(2)27)15-13-23-22-10-8-18-16-19(28)9-11-20(18)21(22)12-14-25(23,26)3/h16,20-23H,4-15H2,1-3H3/t20-,21+,22+,23-,25-,26-/m0/s1
  • Key:XURCMZMFZXXQDJ-UKNJCJGYSA-N

Side effects of gestonorone caproate include worsened glucose tolerance, decreased libido in men, and injection site reactions.[5] Gestonorone caproate is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological _target of progestogens like progesterone.[9][10] It has no other important hormonal activity.[5][11][12][13]

Gestonorone caproate was discovered in 1960 and was introduced for medical use by 1973.[14][15] It has been used widely throughout Europe, including in the United Kingdom, and has also been marketed in certain other countries such as Japan, China, and Mexico.[1][16][17][18] However, it has since mostly been discontinued, and it remains available today only in a handful of countries, including the Czech Republic, Japan, Mexico, and Russia.[18][19]

Medical uses

edit

Gestonorone caproate is used in the palliative treatment of benign prostatic hyperplasia and endometrial cancer.[5][3][20] It is used at a dose of 100 to 200 mg once a week by intramuscular injection.[5]

Side effects

edit
See also: Progestin § Side effects

Side effects of gestonorone caproate have been reported to include worsened glucose tolerance, decreased libido in men, and local injection site reactions such as irritation.[5]

Pharmacology

edit

Pharmacodynamics

edit

Gestonorone caproate is a potent, long-acting, and pure progestogen,[9][10][13] possessing no androgenic, anabolic, antiandrogenic, estrogenic, antiestrogenic, glucocorticoid, mineralocorticoid, or teratogenic effects.[5][11][12][13][21] It is approximately 20 to 25 times more potent than progesterone or hydroxyprogesterone caproate in animal bioassays when all are given by subcutaneous injection.[5][13][22] In humans, 100 or 200 mg intramuscular gestonorone caproate has been said to be equivalent to 1,000 mg intramuscular hydroxyprogesterone caproate.[23][24] Hence, gestonorone caproate is approximately 5- to 10-fold more potent than hydroxyprogesterone caproate in humans.[11][23][24] The biological effects of gestonorone caproate in women have been studied.[25][26]

Like other potent progestins, gestonorone caproate possesses potent antigonadotropic activity and is capable of markedly suppressing the gonadal production and circulating levels of sex hormones such as testosterone and estradiol.[13][27][28] A clinical study found that 400 mg/week intramuscular gestonorone caproate suppressed testosterone levels by 75% in men, while orchiectomy as a comparator reduced testosterone levels by 91%.[29][30] Levels of luteinizing hormone, conversely, remained unchanged.[29] In general, progestogens can maximally suppress testosterone levels by about 70 to 80%.[31][32][33][29][30] In accordance with its lack of glucocorticoid activity, gestonorone caproate has no anticorticotropic effects, and does not influence the secretion of adrenocorticotropic hormone.[5]

17α-Hydroxyprogesterone has weak progestogenic activity, but C17α esterification results in higher progestogenic activity.[6] Of a variety of different esters, the caproate (hexanoate) ester was found to have the strongest progestogenic activity, and this formed the basis for the development of gestonorone caproate, as well as other caproate progestogen esters such as hydroxyprogesterone caproate.[6]

Gestonorone caproate has been found to decrease the weights of the prostate gland and seminal vesicles by 40 to 70% in adult male rats.[5] It has been shown in canines to mediate these effects both via its antigonadotropic effects and by direct actions in these tissues.[5] Gestonorone caproate decreases the uptake of testosterone into the prostate gland.[5] It has also been found to have direct antiproliferative effects on human ovarian cancer cells in vitro.[5]

Gestonorone caproate has been reported to act to some extent as a 5α-reductase inhibitor, similarly to progesterone.[34][35]

Parenteral potencies and durations of progestogens[a][b]
Compound Form Dose for specific uses (mg)[c] DOA[d]
TFD[e] POICD[f] CICD[g]
Algestone acetophenide Oil soln. – – 75–150 14–32 d
Gestonorone caproate Oil soln. 25–50 – – 8–13 d
Hydroxyprogest. acetate[h] Aq. susp. 350 – – 9–16 d
Hydroxyprogest. caproate Oil soln. 250–500[i] – 250–500 5–21 d
Medroxyprog. acetate Aq. susp. 50–100 150 25 14–50+ d
Megestrol acetate Aq. susp. – – 25 >14 d
Norethisterone enanthate Oil soln. 100–200 200 50 11–52 d
Progesterone Oil soln. 200[i] – – 2–6 d
Aq. soln. ? – – 1–2 d
Aq. susp. 50–200 – – 7–14 d
Notes and sources:
  1. ^ Sources: [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]
  2. ^ All given by intramuscular or subcutaneous injection.
  3. ^ Progesterone production during the luteal phase is ~25 (15–50) mg/day. The OIDTooltip ovulation-inhibiting dose of OHPC is 250 to 500 mg/month.
  4. ^ Duration of action in days.
  5. ^ Usually given for 14 days.
  6. ^ Usually dosed every two to three months.
  7. ^ Usually dosed once monthly.
  8. ^ Never marketed or approved by this route.
  9. ^ a b In divided doses (2 × 125 or 250 mg for OHPC, 10 × 20 mg for P4).

Pharmacokinetics

edit

Like the closely related progestins hydroxyprogesterone caproate and 19-norprogesterone, gestonorone caproate shows poor activity orally and must be administered parenterally; specifically, via intramuscular injection.[4] Gestonorone caproate is administered by intramuscular injection, and acts as a long-lasting depot by this route.[5][55][56][57] After an intramuscular injection, gestonorone caproate is completely released from the local depot and is highly bioavailable.[5] A single intramuscular injection of 25 to 50 mg gestonorone caproate in oil solution has been found to have a duration of action of 8 to 13 days in terms of clinical biological effect in the uterus in women.[26][58][59] At high doses, the duration of action of gestonorone caproate by intramuscular injection has been found to be at least 21 days.[5] Clinical studies have found gestonorone caproate to be satisfactorily effective as a progestogen when injected once a month, whereas it was poorly effective as an injectable contraceptive when it was injected once every two months.[60][61]

Following a single intramuscular injection of 200 mg radiolabeled gestonorone caproate in 1 mL of solution in men with prostate cancer, maximal levels of gestonorone caproate occurred after 3 ± 1 days and were 420 ± 160 ng/mL.[5] The elimination half-life of gestonorone caproate and its metabolites was 7.5 ± 3.1 days.[5] Approximately 5% of the radioactive steroid content in the blood was unchanged gestonorone caproate.[5] No free gestonorone was observed in circulation or in urine.[5] Gestonorone caproate and its metabolites were eliminated 72% in feces and 28% in urine.[5][62] Approximately 48 ± 18% of the injected dose had been eliminated after 14 days and approximately 85 ± 12% of the injected dose had been excreted after 30 days.[5]

The metabolism of unesterified gestonorone (17α-hydroxy-19-norprogesterone) is analogous to that of 17α-hydroxyprogesterone, with the corresponding 19-norpregnane metabolites produced.[6] Gestonorone caproate has been found to undergo 5α-reduction similarly to progesterone, 17α-hydroxyprogesterone, and gestonorone, and at a similar rate as these steroids.[6] Conversely however, due to its caproate ester, 5β-reduction of gestonorone caproate is decreased relative to these steroids.[6] As progesterone is metabolized mainly into 5β-pregnanes, decreased 5β-reduction of gestonorone caproate may be involved in its greater potency compared to progesterone.[6] The major metabolites of gestonorone caproate have been reported to be isomers of 19-norpregnanetriol and 19-norpregnanediol-20-one.[6][21] These metabolites indicate that gestonorone caproate is metabolized mainly by reduction at the C3, C5, and C20 positions.[6] Following an intramuscular injection of 300 mg gestonorone caproate, only a slight increase in urinary pregnanetriol excretion has been observed.[6] Cleavage of the caproate ester of gestonorone caproate is minimal, which indicates that it is not a prodrug of the unesterified steroid.[6]

Chemistry

edit
See also: List of progestogens, Progestogen ester, and List of progestogen esters

Gestonorone caproate, also known as norhydroxyprogesterone caproate, 17α-hydroxy-19-norprogesterone 17α-hexanoate, or 17α-hydroxy-19-norpregn-4-ene-3,20-dione 17α-hexanoate, is a synthetic norpregnane steroid and a derivative of progesterone.[63][16] It is specifically a combined derivative of 17α-hydroxyprogesterone and 19-norprogesterone, or of gestronol (17α-hydroxy-19-norprogesterone), with a hexanoate (caproate) ester at the C17α position.[63][16] Analogues and derivatives of gestonorone caproate include algestone acetophenide (dihydroxyprogesterone acetophenide), demegestone, nomegestrol acetate, norgestomet, and segesterone acetate, as well as 18-methylsegesterone acetate and the caproate esters chlormadinone caproate, hydroxyprogesterone caproate, medroxyprogesterone caproate, megestrol caproate, and methenmadinone caproate.[63][16]

Synthesis

edit

Chemical syntheses of gestonorone caproate have been published.[5][7][64]

History

edit

Gestonorone caproate was first described in 1960.[14] It was developed by Schering and has been marketed since at least 1968.[12][15]

Society and culture

edit

Generic names

edit

Gestonorone caproate is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, and JANTooltip Japanese Accepted Name, while gestronol hexanoate is its BANMTooltip British Approved Name.[63][16] It has also been referred to as norhydroxyprogesterone caproate, and is also known by its former developmental code names SH-582 and SH-80582.[63][16][17]

Brand names

edit

Gestonorone caproate has been marketed exclusively under the brand names Depostat and Primostat.[63][16][17][18][19]

Availability

edit
 
Availability of gestonorone caproate in countries throughout the world as of March 2018. Blue is currently marketed, green is formerly marketed.

Gestonorone caproate has been available widely in Europe, including in the United Kingdom, and has also been marketed in Japan, China, Mexico, and certain other countries.[1][16][17][18] However, it has been discontinued in most countries and its availability is more limited today; it appears to remain marketed only in the Czech Republic, Japan, Mexico, and Russia.[18][19][65] It has not been marketed in the United States, Canada, and many other countries.[16][17][18][19]

Research

edit

Gestonorone caproate was studied in the treatment of prostate cancer in men at a dosage of 400 mg per week by intramuscular injection but, in contrast to the case of benign prostatic hyperplasia, was found to be ineffective.[66][67]

SH-834 was a combination of 90 mg estradiol valerate and 300 mg gestonorone caproate for weekly intramuscular injection that was developed by Schering in the 1960s and 1970s.[68][22][69] It was investigated clinically as a treatment for breast cancer and was found to be effective.[68][70][69] However, its effectiveness was found to be no better than that of an estrogen alone, and the combination was ultimately never marketed.[71]

Gestonorone caproate was studied by Schering for use as a progestogen-only injectable contraceptive across a dose range of 2.5 to 200 mg once every one or two months but was never marketed.[61][72][73][74][75][76][77][78] There is very little clinical experience of gestonorone caproate for this indication.[61]

Gestonorone caproate has been studied in the treatment of ovarian cancer (in combination with cyclophosphamide),[5][22][79][80] menstrual cycle-related mouth ulcers,[21] and as a component of menopausal hormone therapy.[60]

See also

edit

References

edit
  1. ^ a b c d Muller (19 June 1998). European Drug Index: European Drug Registrations (Fourth ed.). CRC Press. pp. 338–. ISBN 978-3-7692-2114-5.
  2. ^ Aronson JK (21 February 2009). Meyler's Side Effects of Endocrine and Metabolic Drugs. Elsevier. pp. 289–. ISBN 978-0-08-093292-7.
  3. ^ a b c Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 132–. ISBN 978-94-011-4439-1.
  4. ^ a b c Breuer H, Lisboa BP (January 1966). "[Studies on the metabolism of 17-alpha-hydroxy-19-norprogesterone caproate by humans in vivo and of 17-alpha-hydroxy-19-norprogesterone by rats in vitro]" [Studies on the metabolism of 17-alpha-hydroxy-19-norprogesterone caproate by humans in vivo and of 17-alpha-hydroxy-19-norprogesterone by rats in vitro]. Acta Endocrinologica (in German). 51 (1): 114–130. doi:10.1530/acta.0.0510114. PMID 4285463.
  5. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac von Bruchhausen F, Dannhardt G, Ebel S, Frahm AW, Hackenthal E, Holzgrabe U (2 July 2013). Hagers Handbuch der Pharmazeutischen Praxis: Band 8: Stoffe E-O. Springer-Verlag. pp. 343–. ISBN 978-3-642-57994-3.
  6. ^ a b c d e f g h i j k l m Die Gestagene. Springer-Verlag. 27 November 2013. pp. 6, 278–279. ISBN 978-3-642-99941-3.
  7. ^ a b William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1761–1762. ISBN 978-0-8155-1856-3.
  8. ^ Thurston DE (22 November 2006). Chemistry and Pharmacology of Anticancer Drugs. CRC Press. pp. 154–155. ISBN 978-1-4200-0890-6.
  9. ^ a b Raspé G (22 October 2013). Hormones and Embryonic Development: Advances in The Biosciences. Elsevier Science. p. 79. ISBN 978-1-4831-5171-7.
  10. ^ a b Schoonees R, de Klerk JN, Murphy GP (1969). "The effect of depostat (SH 582) on the baboon prostate". Journal of Surgical Oncology. 1 (4): 317–324. doi:10.1002/jso.2930010404. PMID 5000209. S2CID 33568137.
  11. ^ a b c Horský J, Presl J (1981). "Genital Cycle". In Horsky J, Presl J (eds.). Ovarian Function and its Disorders: Diagnosis and Therapy. Developments in Obstetrics and Gynecology. Springer Science & Business Media. pp. 70–129. doi:10.1007/978-94-009-8195-9_11. ISBN 978-94-009-8195-9. Gestonorone caproate is a depot gestagen, five times more potent than 17α-hydroxyprogesterone caproate.
  12. ^ a b c Schering, A. G. (1968). Depostat (SH 582): A New Treatment for Prostatic Hypertrophy. https://scholar.google.com/scholar?cluster=13658296147916476056
  13. ^ a b c d e Aubrey DA, Khosla T (September 1971). "The effect of 17-alpha-hydroxy-19-norprogesterone caproate (SH582) on benign prostatic hypertrophy". The British Journal of Surgery. 58 (9): 648–652. doi:10.1002/bjs.1800580904. PMID 4105896. S2CID 40905771.
  14. ^ a b Kaiser R (1960). "Klinische Erfahrungen mit Norprogesteronderivaten". ZBL. Gynäk. 82: 2009.
  15. ^ a b Subbiah N, Mortensen J (February 1973). "The treatment of benign enlargement of the prostate with nor progesterone caproate (primostat)". The Australian and New Zealand Journal of Surgery. 42 (3): 304–307. doi:10.1111/j.1445-2197.1973.tb06805.x. PMID 4129814.
  16. ^ a b c d e f g h i Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. p. 278. ISBN 978-3-88763-075-1.
  17. ^ a b c d e "List of Progestins".
  18. ^ a b c d e f "Micromedex Products: Please Login".
  19. ^ a b c d Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2105. ISBN 978-0-85369-840-1.
  20. ^ Smith HJ, Williams H (10 October 2005). Smith and Williams' Introduction to the Principles of Drug Design and Action, Fourth Edition. CRC Press. pp. 493–. ISBN 978-0-203-30415-0.
  21. ^ a b c Ferguson MM, McKay Hart D, Lindsay R, Stephen KW (October 1978). "Progeston therapy for menstrually related aphthae". International Journal of Oral Surgery. 7 (5): 463–470. doi:10.1016/S0300-9785(78)80038-6. PMID 102602.
  22. ^ a b c Ward HW (June 1972). "Progestogen therapy for ovarian carcinoma". The Journal of Obstetrics and Gynaecology of the British Commonwealth. 79 (6): 555–559. doi:10.1111/j.1471-0528.1972.tb14200.x. PMID 4555897. S2CID 2586346.
  23. ^ a b Karlstedt K (April 1971). "Progesterone treatment for local recurrence and metastases in carcinoma corporis uteri". Acta Radiologica. 10 (2): 187–192. doi:10.3109/02841867109129755. PMID 5556820. The preparations used were Proluton Depot (17a-hydroxy-progesterone caproate) and in 3 patients SH 5132 (17a-hydroxy-19-norprogesterone caproate); 100 mg of the latter corresponds to 1000 mg of Proluton Depot.
  24. ^ a b Moe N (1972). "Short-term progestogen treatment of endometrial carcinoma. Histological, histochemical and hormonal studies". Acta Obstetricia et Gynecologica Scandinavica. 51 (1): 55–62. doi:10.3109/00016347209154968. PMID 4261828. S2CID 7181971. Thirteen patients with primary adenocarcinoma of the uterine corpus were treated for 21 days with 17alpha-hydroxy-progesterone-caproate (Primolut Depot®, Schering), 1000 mg daily, or 17alpha-hydroxy-19-nor-progesterone-caproate (Depostat®, Schering), 200 mg daily. These doses can be considered as equivalent.
  25. ^ Jürgensen O, Taubert HD (February 1969). "[Clinical observations on the effect of depot gestagen 17 alpha-hydroxy-19-nor-progesterone caproate in women with eumenorrhea]" [Clinical observations on the effect of the depot gestagen 17α-hydroxy-19-nor-progesterone capronate in women with eumenorrhea]. Klinische Wochenschrift. 47 (3): 162–165. doi:10.1007/BF01746052. PMID 5369019. S2CID 41105630.
  26. ^ a b Ferin J (September 1972). "Effects, Duration of Action and Metabolism in Man". In Tausk M (ed.). Pharmacology of the Endocrine System and Related Drugs: Progesterone, Progestational Drugs and Antifertility Agents. Vol. II. Pergamon Press. pp. 13–24. ISBN 978-0080168128. OCLC 278011135.
  27. ^ Raspé G, Brosig W (22 October 2013). International Symposium on the Treatment of Carcinoma of the Prostate, Berlin, November 13 to 15, 1969: Life Science Monographs. Elsevier. p. 169. ISBN 978-1-4831-8711-2.
  28. ^ Makrigiannis D, Gaca A (1971). "Evaluation of Depostat in prostatic adenoma on the ground of clinical and sphincterotonometric studies". International Urology and Nephrology. 3 (1): 21–29. doi:10.1007/BF02081794. PMID 4117491. S2CID 7679705.
  29. ^ a b c Sander S, Nissen-Meyer R, Aakvaag A (1978). "On gestagen treatment of advanced prostatic carcinoma". Scandinavian Journal of Urology and Nephrology. 12 (2): 119–121. doi:10.3109/00365597809179977. PMID 694436.
  30. ^ a b Kjeld JM, Puah CM, Kaufman B, Loizou S, Vlotides J, Gwee HM, et al. (November 1979). "Effects of norgestrel and ethinyloestradiol ingestion on serum levels of sex hormones and gonadotrophins in men". Clinical Endocrinology. 11 (5): 497–504. doi:10.1111/j.1365-2265.1979.tb03102.x. PMID 519881. S2CID 5836155. Another synthetic gestogen, 17-hydroxy-19-norprogesterone caproate (Depostat-Schering), 400 mg by i.m. weekly injections suppressed T levels to 25% of pretreatment values (Sander er al., 1978).
  31. ^ Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA (25 August 2011). Campbell-Walsh Urology: Expert Consult Premium Edition: Enhanced Online Features and Print, 4-Volume Set. Elsevier Health Sciences. pp. 2938–. ISBN 978-1-4160-6911-9.
  32. ^ Knuth UA, Hano R, Nieschlag E (November 1984). "Effect of flutamide or cyproterone acetate on pituitary and testicular hormones in normal men". The Journal of Clinical Endocrinology and Metabolism. 59 (5): 963–969. doi:10.1210/jcem-59-5-963. PMID 6237116.
  33. ^ Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R (June 1980). "Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial". British Journal of Urology. 52 (3): 208–215. doi:10.1111/j.1464-410x.1980.tb02961.x. PMID 7000222.
  34. ^ Orestano F, Altwein JE (December 1976). "Testosterone metabolism in benign prostatic hypertrophy: in vivo studies of gestonorone caproate and cyproterone acetate". British Journal of Urology. 48 (6): 485–491. doi:10.1111/j.1464-410X.1976.tb06687.x. PMID 64267.
  35. ^ Orestano F, Altwein JE, Knapstein P, Bandhauer K (June 1975). "Mode of action of progesterone, gestonorone capronate (Depostat) and cyproterone acetate (Androcur) on the metabolism of testosterone in human prostatic adenoma: in vitro and in vivo investigations". Journal of Steroid Biochemistry. 6 (6): 845–851. doi:10.1016/0022-4731(75)90313-1. PMID 1177428.
  36. ^ Knörr K, Beller FK, Lauritzen C (17 April 2013). Lehrbuch der Gynäkologie. Springer-Verlag. pp. 214–. ISBN 978-3-662-00942-0.
  37. ^ Knörr K, Knörr-Gärtner H, Beller FK, Lauritzen C (8 March 2013). Geburtshilfe und Gynäkologie: Physiologie und Pathologie der Reproduktion. Springer-Verlag. pp. 583–. ISBN 978-3-642-95583-9.
  38. ^ Labhart A (6 December 2012). Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. pp. 554–. ISBN 978-3-642-96158-8.
  39. ^ Horský J, Presl J (1981). "Hormonal Treatment of Disorders of the Menstrual Cycle". In Horsky J, Presl K (eds.). Ovarian Function and its Disorders: Diagnosis and Therapy. Springer Science & Business Media. pp. 309–332. doi:10.1007/978-94-009-8195-9_11. ISBN 978-94-009-8195-9.
  40. ^ Ufer J (1969). The Principles and Practice of Hormone Therapy in Gynaecology and Obstetrics. de Gruyter. p. 49. ISBN 9783110006148. 17α-Hydroxyprogesterone caproate is a depot progestogen which is entirely free of side actions. The dose required to induce secretory changes in primed endometrium is about 250 mg. per menstrual cycle.
  41. ^ Pschyrembel W (1968). Praktische Gynäkologie: für Studierende und Ärzte. Walter de Gruyter. pp. 598, 601. ISBN 978-3-11-150424-7.
  42. ^ Ferin J (September 1972). "Effects, Duration of Action and Metabolism in Man". In Tausk M (ed.). Pharmacology of the Endocrine System and Related Drugs: Progesterone, Progestational Drugs and Antifertility Agents. Vol. II. Pergamon Press. pp. 13–24. ISBN 978-0080168128. OCLC 278011135.
  43. ^ Henzl MR, Edwards JA (10 November 1999). "Pharmacology of Progestins: 17α-Hydroxyprogesterone Derivatives and Progestins of the First and Second Generation". In Sitruk-Ware R, Mishell DR (eds.). Progestins and Antiprogestins in Clinical Practice. Taylor & Francis. pp. 101–132. ISBN 978-0-8247-8291-7.
  44. ^ Brotherton J (1976). Sex Hormone Pharmacology. Academic Press. p. 114. ISBN 978-0-12-137250-7.
  45. ^ Sang GW (April 1994). "Pharmacodynamic effects of once-a-month combined injectable contraceptives". Contraception. 49 (4): 361–385. doi:10.1016/0010-7824(94)90033-7. PMID 8013220.
  46. ^ Toppozada MK (April 1994). "Existing once-a-month combined injectable contraceptives". Contraception. 49 (4): 293–301. doi:10.1016/0010-7824(94)90029-9. PMID 8013216.
  47. ^ Goebelsmann U (1986). "Pharmacokinetics of Contraceptive Steroids in Humans". In Gregoire AT, Blye RP (eds.). Contraceptive Steroids: Pharmacology and Safety. Springer Science & Business Media. pp. 67–111. doi:10.1007/978-1-4613-2241-2_4. ISBN 978-1-4613-2241-2.
  48. ^ Becker H, Düsterberg B, Klosterhalfen H (1980). "[Bioavailability of cyproterone acetate after oral and intramuscular application in men (author's transl)]" [Bioavailability of Cyproterone Acetate after Oral and Intramuscular Application in Men]. Urologia Internationalis. 35 (6): 381–385. doi:10.1159/000280353. PMID 6452729.
  49. ^ Moltz L, Haase F, Schwartz U, Hammerstein J (May 1983). "[Treatment of virilized women with intramuscular administration of cyproterone acetate]" [Efficacy of Intra muscularly Applied Cyproterone Acetate in Hyperandrogenism]. Geburtshilfe und Frauenheilkunde. 43 (5): 281–287. doi:10.1055/s-2008-1036893. PMID 6223851.
  50. ^ Wright JC, Burgess DJ (29 January 2012). Long Acting Injections and Implants. Springer Science & Business Media. pp. 114–. ISBN 978-1-4614-0554-2.
  51. ^ Chu YH, Li Q, Zhao ZF (April 1986). "Pharmacokinetics of megestrol acetate in women receiving IM injection of estradiol-megestrol long-acting injectable contraceptive". The Chinese Journal of Clinical Pharmacology. The results showed that after injection the concentration of plasma MA increased rapidly. The meantime of peak plasma MA level was 3rd day, there was a linear relationship between log of plasma MA concentration and time (day) after administration in all subjects, elimination phase half-life t1/2β = 14.35 ± 9.1 days.
  52. ^ Runnebaum BC, Rabe T, Kiesel L (6 December 2012). Female Contraception: Update and Trends. Springer Science & Business Media. pp. 429–. ISBN 978-3-642-73790-9.
  53. ^ Artini PG, Genazzani AR, Petraglia F (11 December 2001). Advances in Gynecological Endocrinology. CRC Press. pp. 105–. ISBN 978-1-84214-071-0.
  54. ^ King TL, Brucker MC, Kriebs JM, Fahey JO (21 October 2013). Varney's Midwifery. Jones & Bartlett Publishers. pp. 495–. ISBN 978-1-284-02542-2.
  55. ^ Denis L (6 December 2012). The Medical Management of Prostate Cancer. Springer Science & Business Media. pp. 112–. ISBN 978-3-642-73238-6. Gestonorone caproate, another progestational agent, was investigated at our institution. Eighteen patients with painful metastatic [prostate cancer] with objective relapse after orchiectomy were treated with 400 mg/week i.m.
  56. ^ Runnebaum BC, Rabe T, Kiesel L (6 December 2012). Future Aspects in Contraception: Proceeding of an International Symposium held in Heidelberg, 5–8 September 1984 Part 1 Male Contraception. Springer Science & Business Media. pp. 133–. ISBN 978-94-009-4910-2. Gestonorone [caproate] 100 or 200 mg/week i.m.
  57. ^ Palanca E, Juco W (2008). "Conservative treatment of benign prostatic hyperplasia". Current Medical Research and Opinion. 4 (7): 513–520. doi:10.1185/03007997709109342. PMID 66118. S2CID 31798723. A study was carried out in 30 male patients with benign prostate hyperplasia to assess the effectiveness of treatment with a progestational agent, gestonorone caproate (200 mg), given intramuscularly every 7 days over a period of 2 to 3 months.
  58. ^ Nevinny-Stickel J (1962). "Die gestagene Wirkung von Hydroxy-nor-Progesteronestern bei der Frau". Gewebs- und Neurohormone [The progestational effects of hydroxy-nor-progesterone esters in women]. Symposion der Deutschen Gesellschaft für Endokrinologie. Springer. pp. 248–255. doi:10.1007/978-3-642-86860-3_27. ISBN 978-3-540-02909-0. Das Hydroxy-nor-Progesteron-Capronat stand in öliger Lösung zm intramuskulären Injektion zur Verfügung. Die Wirkungsdauer betrug 10-13 Tage. Nach Verabreichung von 25 mg waren als beginnende Sekretionszeichen (1) an den geschlängelten Drüsen basale Vacuolen der Epithelien zu sehen. Eine volle Umwandlung der Schleimhaut erfolgte erst auf 50 mg des Capronsäureesters (Abb. l und 2).
  59. ^ Horský J, Presl J (1981). "Hormonal Treatment of Disorders of the Menstrual Cycle". In Horsky J, Presl J (eds.). Ovarian Function and its Disorders: Diagnosis and Therapy. Developments in Obstetrics and Gynecology. Springer Science & Business Media. pp. 309–332. doi:10.1007/978-94-009-8195-9_11. ISBN 978-94-009-8195-9.
  60. ^ a b Lindsay R, Hart DM, Purdie D, Ferguson MM, Clark AS, Kraszewski A (February 1978). "Comparative effects of oestrogen and a progestogen on bone loss in postmenopausal women". Clinical Science and Molecular Medicine. 54 (2): 193–195. doi:10.1042/cs0540193. PMID 340117. S2CID 1799407.
  61. ^ a b c Toppozada M (June 1977). "The clinical use of monthly injectable contraceptive preparations". Obstetrical & Gynecological Survey. 32 (6): 335–347. doi:10.1097/00006254-197706000-00001. PMID 865726.
  62. ^ Nagel R, Kolb K, Kroemer C, Maksimović P, Laudahn G (1973). "Verteilungsstudien und pharmakokinetische Parameter nach i.m. Gabe von Gestonoron-capronat (Depostat) und Cyproteron-acetat (Androcur) beim Menschen". 24. Tagung vom 13. Bis 16. September 1972 in Hannover [Distribution studies and pharmacokinetic parameters after i.m. administration of gestonoron-capronate (Depostat) and cyproterone-acetate (Androcur) in man]. Verhandlungsbericht der Deutschen Gesellschaft für Urologie. Vol. 24. pp. 133–138. doi:10.1007/978-3-642-80738-1_36. ISBN 978-3-540-06186-1. ISSN 0070-413X.
  63. ^ a b c d e f Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 595–. ISBN 978-1-4757-2085-3.
  64. ^ Kleemann A, Engel J (2001). Pharmaceutical substances: syntheses, patents, applications. Thieme. p. 962. ISBN 978-3-13-558404-1.
  65. ^ "Find product information about medicines".
  66. ^ Smith PH (29 June 2013). Cancer of the Prostate and Kidney. Springer Science & Business Media. pp. 309–. ISBN 978-1-4684-4349-3.
  67. ^ Sander S, Nissen-Meyer R, Aakvaag A (1977). "On gestagen treatment of advanced prostatic carcinoma". Scandinavian Journal of Urology and Nephrology. 12 (2): 119–121. doi:10.3109/00365597809179977. PMID 694436.
  68. ^ a b Notter G, Berndt G (October 1975). "Hormonal treatment of mammary carcinoma with Progynon-Depot and Depostat". Acta Radiologica. 14 (5): 433–442. doi:10.3109/02841867509132684. PMID 1202923.
  69. ^ a b Berndt G, Eckel H, Notter G, St Stender H (May 1971). "[Effect of estrogen-gestagen combination therapy in advanced breast carcinoma with special reference to pulmonary metastases]" [Effect of Estrogen-Gestagen Combination Therapy in Advanced Breast Carcinoma with Special Reference to Pulmonary Metastases]. Strahlentherapie (in German). 141 (5): 540–548. PMID 5088730. Archived from the original on 2017-07-29. Retrieved 2019-05-20.
  70. ^ Berndt G, Stender HS (November 1970). "[The combined estrogen-gestagen treatment of metastasizing mammary carcinoma using with SH 834]". Deutsche Medizinische Wochenschrift. 95 (48): 2399+. doi:10.1055/s-0028-1108843. PMID 5529652. S2CID 70908169.
  71. ^ Firusian N, Schietzel M (September 1976). "[Additive treatment of metastasizing breast cancer with special reference to postmenopausal age (results of a randomized study)]" [Additive treatment of metastasizing breast cancer with special reference to postmenopausal age (results of a randomized study)]. Strahlentherapie (in German). 152 (3): 235–247. PMID 968923.
  72. ^ Toppozada MK (1983). "Monthly Injectable Contraceptives". In Goldsmith A, Toppozada MK (eds.). Long-Acting Contraception. pp. 93–103. OCLC 35018604.
  73. ^ Kadam SS (July 2007). Principles of Medicinal Chemistry Volume 2. Pragati Books Pvt. Ltd. pp. 381–. ISBN 978-81-85790-03-9.
  74. ^ Karim M, El-mahgoub S (September 1970). "Injectable steroids as a method of contraception". Ain Shams Medical Journal. 21 (5): 543–550. PMID 12313080.
  75. ^ Carlborg L (July 1973). "Effect of norhydroxyprogesterone caproate on cervical sperm penetration and secretion of ovarian steroids in the human female". Upsala Journal of Medical Sciences. 78 (3): 189–190. doi:10.3109/03009737309178626. PMID 4797435.
  76. ^ Hurtado H, Kesseru E, Larrañaga A (2015). "Empleo del capronato de 17-hidroxi-19-norprogesterona como anticonceptivo inyectable de depósito". Revista Peruana de Ginecología y Obstetricia. 14 (2): 223–233. doi:10.31403/rpgo.v14i1457.
  77. ^ Nazer J, Valenzuela CY (March 1973). "[Possible biological effects of contraceptives]". Revista Médica de Chile (in Spanish). 101 (3): 234–236. PMID 4732140.
  78. ^ Rodriguez-Restrepo R (1969). "17-alpha-hydroxy 19 norprogesterone capronate as a prolonged-action injectable contraceptive agent". Revista Colombiana de Obstetricia y Ginecologia. 20: 247–255. Archived from the original on 2018-09-19.
  79. ^ Guthrie D (July 1979). "The treatment of advanced cystadenocarcinoma of the ovary with gestronol and continuous oral cyclophosphamide". British Journal of Obstetrics and Gynaecology. 86 (7): 497–500. doi:10.1111/j.1471-0528.1979.tb10799.x. PMID 476014. S2CID 31408925.
  80. ^ Darwish DH (August 1978). "The effect of sex steroids on the in vitro synthesis of DNA by malignant ovarian tumours". British Journal of Obstetrics and Gynaecology. 85 (8): 627–633. doi:10.1111/j.1471-0528.1978.tb14933.x. PMID 687544. S2CID 30816473.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Gestonorone_caproate&oldid=1257279409"
  NODES
admin 6
INTERN 7
Note 2