Estradiol valerate/gestonorone caproate

Last updated
Estradiol valerate /
gestonorone caproate
Estradiol valerate.svg
Gestronol caproate.svg
Estradiol valerate (top) and
gestonorone caproate (bottom)
Combination of
Estradiol valerate Estrogen
Gestonorone caproate Progestogen
Clinical data
Other namesEV/GC; EV/NOHPC; EV/OHNPC; SH-834; SH-8.0834
Routes of
administration 		Intramuscular injection

Estradiol valerate/gestonorone caproate (EV/GC), known by the developmental code names SH-834 and SH-8.0834, is a high-dose combination medication of estradiol valerate (EV), an estrogen, and gestonorone caproate (GC; norhydroxyprogesterone caproate), a progestin, which was developed and studied by Schering in the 1960s and 1970s for potential use in the treatment of breast cancer in women but was ultimately never marketed. [1] [2] [3] [4] [5] [6] [7] It contained 90 mg EV and 300 mg GC in each 3 mL of oil solution and was intended for use by intramuscular injection once a week. [3] [6] The combination has also been studied incidentally in the treatment of ovarian cancer. [8]

Both high-dose estrogens and high-dose progestogens have been found to be independently effective in the treatment of breast cancer in women. [6] [9] [10] High-dose estrogens show greater and more consistent effectiveness than high-dose progestogens for this indication. [6] [9] [11] The combination of an estrogen and progestogen, specifically estradiol benzoate and progesterone, was first studied in breast cancer in rodents and women by Charles Huggins and colleagues in 1962. [9] [6] [12] [11] Initially progesterone and hydroxyprogesterone caproate were used as the progestogen component in such studies; [6] [12] [13] the need for a more potent progestogen in such combinations led to the development of EV/GC, which was first reported in the treatment of breast cancer in women in 1966. [6] [1] GC is a relatively pure progestogen that has about 5- to 10-fold the progestogenic potency of hydroxyprogesterone caproate in humans. [14] [15] [16] New reports on EV/GC in breast cancer continued until 1976. [7]

Both progesterone and hydroxyprogesterone caproate, which are relatively pure progestogens, have been found to have modest or negligible effectiveness when employed by themselves in the treatment of breast cancer in women. [9] [11] [17] [18] [19] Conversely, progestins with off-target glucocorticoid and/or androgenic activity, such as medroxyprogesterone acetate, megestrol acetate, and 19-nortestosterone derivatives, have been found to have greater and more clinically useful effectiveness in comparison. [9] [10] This has raised the possibility that the beneficial therapeutic effects of progestogens in breast cancer may be more related to their off-target activity than their progestogenic activity. [9] In accordance, a study found that the effectiveness of an estrogen alone and the combination of EV/GC in the treatment of breast cancer in women was not significantly different. [7] This was the last study of EV/GC to be published. [7]

See also

Related Research Articles

<span class="mw-page-title-main">Progestogen</span> Steroid hormone that activates the progesterone receptor

Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. The progestogens are named for their function in maintaining pregnancy, although they are also present at other phases of the estrous and menstrual cycles.

<span class="mw-page-title-main">Progestogen (medication)</span> Medication producing effects similar to progesterone

A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone.

<span class="mw-page-title-main">Estradiol valerate</span> Chemical compound

Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. It is used in hormone therapy for menopausal symptoms and low estrogen levels, hormone therapy for transgender people, and in hormonal birth control. It is also used in the treatment of prostate cancer. The medication is taken by mouth or by injection into muscle or fat once every 1 to 4 weeks.

<span class="mw-page-title-main">Drospirenone</span> Medication drug

Drospirenone is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy and in menopausal hormone therapy, among other uses. It is available both alone under the brand name Slynd and in combination with an estrogen under the brand name Yasmin among others. The medication is an analog of the drug spironolactone. Drospirenone is taken by mouth.

<span class="mw-page-title-main">Gestonorone caproate</span> Chemical compound

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. It is given by injection into muscle typically once a week.

<span class="mw-page-title-main">Dydrogesterone</span> Chemical compound

Dydrogesterone, sold under the brand name Duphaston among others, is a progestin medication which is used for a variety of indications, including threatened or recurrent miscarriage during pregnancy, dysfunctional bleeding, infertility due to luteal insufficiency, dysmenorrhea, endometriosis, secondary amenorrhea, irregular cycles, premenstrual syndrome, and as a component of menopausal hormone therapy. It is taken by mouth.

<span class="mw-page-title-main">Hydroxyprogesterone caproate</span> Medication

Hydroxyprogesterone caproate, sold under the brand names Proluton and Makena among others, is a medication used to reduce the risk of preterm birth in women pregnant with one baby who have a history of spontaneous preterm birth. In March 2023, the manufacturer, Covis Pharma, agreed to withdraw the drug from the US market. The approvals of Makena and its generics were withdrawn by the US Food and Drug Administration (FDA) in April 2023.

<span class="mw-page-title-main">Dienogest</span> Chemical compound

Dienogest, sold under the brand name Visanne among others, is a progestin medication which is used in birth control pills and in the treatment of endometriosis. It is also used in menopausal hormone therapy and to treat heavy periods. Dienogest is available both alone and in combination with estrogens. It is taken by mouth.

Combined injectable contraceptives (CICs) are a form of hormonal birth control for women. They consist of monthly injections of combined formulations containing an estrogen and a progestin to prevent pregnancy.

<span class="mw-page-title-main">Chlormadinone acetate</span> Chemical compound

Chlormadinone acetate (CMA), sold under the brand names Belara, Gynorelle, Lutéran, and Prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hormone therapy, in the treatment of gynecological disorders, and in the treatment of androgen-dependent conditions like enlarged prostate and prostate cancer in men and acne and hirsutism in women. It is available both at a low dose in combination with an estrogen in birth control pills and, in a few countries like France and Japan, at low, moderate, and high doses alone for various indications. It is taken by mouth.

<span class="mw-page-title-main">Algestone acetophenide</span> Chemical compound

Algestone acetophenide, also known more commonly as dihydroxyprogesterone acetophenide (DHPA) and sold under the brand names Perlutal and Topasel among others, is a progestin medication which is used in combination with an estrogen as a form of long-lasting injectable birth control. It has also been used alone, but is no longer available as a standalone medication. DHPA is not active by mouth and is given once a month by injection into muscle.

<span class="mw-page-title-main">Nomegestrol acetate</span> Chemical compound

Nomegestrol acetate (NOMAC), sold under the brand names Lutenyl and Zoely among others, is a progestin medication which is used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. It is available both alone and in combination with an estrogen. NOMAC is taken by mouth. A birth control implant for placement under the skin was also developed but ultimately was not marketed.

<span class="mw-page-title-main">Segesterone acetate</span> Progestin medication

Segesterone acetate (SGA), sold under the brand names Nestorone, Elcometrine, and Annovera, is a progestin medication which is used in birth control and in the treatment of endometriosis in the United States, Brazil, and other South American countries. It is available both alone and in combination with an estrogen. It is not effective by mouth and must be given by other routes, most typically as a vaginal ring or implant that is placed into fat.

<span class="mw-page-title-main">Hydroxyprogesterone heptanoate</span> Chemical compound

Hydroxyprogesterone heptanoate (OHPH), also known as hydroxyprogesterone enanthate (OHPE) and sold under the brand names H.O.P., Lutogil A.P., and Lutogyl A.P. among others, is a progestin medication used for progestogenic indications. It has been formulated both alone and in together with estrogens, androgens/anabolic steroids, and other progestogens in several combination preparations. OHPH is given by injection into muscle at regular intervals.

<span class="mw-page-title-main">Progestogen ester</span> Drug class

A progestogen ester is an ester of a progestogen or progestin. The prototypical progestogen is progesterone, an endogenous sex hormone. Esterification is frequently employed to improve the pharmacokinetics of steroids, including oral bioavailability, lipophilicity, and elimination half-life. In addition, with intramuscular injection, steroid esters are often absorbed more slowly into the body, allowing for less frequent administration. Many steroid esters function as prodrugs.

<span class="mw-page-title-main">Bromoketoprogesterone</span> Chemical compound

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<span class="mw-page-title-main">High-dose estrogen therapy</span> Type of hormone therapy

High-dose estrogen therapy (HDE) is a type of hormone therapy in which high doses of estrogens are given. When given in combination with a high dose of progestogen, it has been referred to as pseudopregnancy. It is called this because the estrogen and progestogen levels achieved are in the range of the very high levels of these hormones that occur during pregnancy. HDE and pseudopregnancy have been used in medicine for a number of hormone-dependent indications, such as breast cancer, prostate cancer, and endometriosis, among others. Both natural or bioidentical estrogens and synthetic estrogens have been used and both oral and parenteral routes may be used.

<span class="mw-page-title-main">Estradiol benzoate/progesterone</span> Drug combination

Estradiol benzoate/progesterone (EB/P4), sold under the brand names Duogynon and Sistocyclin among others, is a combination medication of estradiol benzoate (EB), an estrogen, and progesterone (P4), a progestogen. It has been formulated both as short-acting oil solutions and long-acting microcrystalline aqueous suspensions and is given by injection into muscle either once or continuously at regular intervals.

<span class="mw-page-title-main">Estradiol valerate/hydroxyprogesterone caproate</span> Pharmaceutical combination

Estradiol valerate/hydroxyprogesterone caproate (EV/OHPC), sold under the brand names Gravibinon and Injectable No. 1 among others, is a combined estrogen and progestogen medication which is used in the treatment of threatened miscarriage and other indications and as a form of combined injectable birth control to prevent pregnancy. It contains estradiol valerate (EV), an estrogen, and hydroxyprogesterone caproate (OHPC), a progestin. The medication is given by injection into muscle once a day to once a month depending on the indication.

<span class="mw-page-title-main">Estradiol benzoate/hydroxyprogesterone caproate</span> Combination drug

Estradiol benzoate/hydroxyprogesterone caproate (EB/OHPC), sold under the brand name Primosiston among others, is a combined estrogen and progestogen medication which is used to treat gynecological disorders and habitual abortion. It contains estradiol benzoate (EB), an estrogen, and hydroxyprogesterone caproate (OHPC), a progestin. The medication is given by injection into muscle.

References

  1. 1 2 Notter G, Kaigas M (September 1966). "Behandlung des inoperablen und metastasierenden Mammakarzinoms mit gestagenen und östrogenen Hormonen" [The treatment of inoperable and metastasizing breast carcinoma with gestational and estrogenic hormones]. Munchener medizinische Wochenschrift (in German). 108 (39): 1920–1923. ISSN   0027-2973. PMID   6014870.
  2. ↑ British Empire Cancer Campaign for Research (1966). Annual Report. Vol. 44. The Campaign. pp. 394–395. Progesterone in the Treatment of Advanced Tumours of the Breast. The clinical trial with a progestogen/oestrogen compound, Trial No. SH 834 has been continued. An assessment of its effectiveness in 25 patients with advanced cancer of the breast, of whom 8 were in a terminal stage of the disease and in almost all of whom other types of treatment had failed or become ineffective, has been made. In the group of 8 terminal cases only 2 showed a temporary improvement. Of the remaining 17 cases with treatment periods up to 10 months 16 are still alive; in 9 cases the results were good and in 7 of these, after other measures had failed, SH 834 brought about a temporary arrest of the disease with considerable, though incomplete, regression of the skin infiltrations and amelioration of the general condition and well-being of the patients.
  3. 1 2 Berndt G, Stender HS (November 1970). "Die Östrogen-Gestagen-Kombinationsbehandlung des metastasierenden Mammakarzinoms mit SH 834" [The combined estrogen-gestagen treatment of metastasizing mammary carcinoma using with SH 834]. Dtsch. Med. Wochenschr. (in German). 95 (48): 2399–2404. doi:10.1055/s-0028-1108843. ISSN   0012-0472. PMID   5529652. S2CID   70908169.
  4. ↑ Hildebrandt L (1971). Die Hormonbehandlung des progredienten Mamma-Carcinoms unter besonderer Berücksichtigung der Therapie mit der Gestagen-Oestrogen-Kombination SH 834 [The hormone treatment of progressive breast carcinoma with special consideration of the therapy with the gestagen-estrogen combination SH 834] (Dissertation) (in German). Medizinische Hochschule Hannover. pp. 1–39. OCLC   634592499.
  5. ↑ Berndt G, Eckel H, Notter G, Stender HS. "Die Wirkung einer Ostrogen-Gestagen-Kombinationstherapie beim fortgeschrittenen Mammakarzinom mit besonderer Berucksichtigung der Lungenmetastasen" [Effect of combined estrogen-gestagen therapy on advanced breast carcinoma with special consideration of lung metastases]. Strahlentherapie (in German). 141 (5): 540–548. ISSN   0039-2073. Archived from the original on 2017-07-29. Retrieved 2019-06-09.
  6. 1 2 3 4 5 6 7 Notter G, Berndt G (October 1975). "Hormonal treatment of mammary carcinoma with Progynon-Depot and Depostat". Acta Radiol Ther Phys Biol. 14 (5): 433–42. doi:10.3109/02841867509132684. PMID   1202923.
  7. 1 2 3 4 Firusian N, Schietzel M (September 1976). "Zur additiven Therapie des metastasierenden Mamma-Karzinoms unter Berücksichtigung des Postmenopausalaltes (Ergebnisse einer randomisierten Studie)" [Additive treatment of metastasizing breast cancer with special reference to postmenopausal age (results of a randomized study)]. Strahlentherapie (in German). 152 (3): 235–47. ISSN   0039-2073. PMID   968923.
  8. ↑ Ward HW (June 1972). "Progestogen therapy for ovarian carcinoma". J Obstet Gynaecol Br Commonw. 79 (6): 555–9. doi:10.1111/j.1471-0528.1972.tb14200.x. PMID   4555897. S2CID   2586346.
  9. 1 2 3 4 5 6 Dao TL (1975). "Pharmacology and Clinical Utility of Hormones in Hormone Related Neoplasms". In Sartorelli AC, Johns DG (eds.). Antineoplastic and Immunosuppressive Agents. pp. 170–192. doi:10.1007/978-3-642-65806-8_11. ISBN   978-3-642-65806-8.
  10. 1 2 Muss HB, Cruz JM (August 1992). "High-dose progestin therapy for metastatic breast cancer". Annals of Oncology. 3 (suppl 3): 15–20. doi: 10.1093/annonc/3.suppl_3.S15 . PMID   1390312.
  11. 1 2 3 Ufer J (1968). "Die therapeutische Anwendung der Gestagene beim Menschen" [Therapeutic Use of Progestogens in Humans]. Die Gestagene [Progestogens]. Springer-Verlag. pp. 1026–1124. doi:10.1007/978-3-642-99941-3_7. ISBN   978-3-642-99941-3.
  12. 1 2 Landau RL (1962). "Estradiol Benzoate and Progesterone in Advanced Human-Breast Cancer". JAMA. 182 (6): 632–6. doi:10.1001/jama.1962.03050450032008. ISSN   0098-7484. PMID   12305404.
  13. ↑ Crowley LG, MacDonald I (April 1965). "Delalutin and estrogens for the treatment of advanced mammary carcinoma in the postmenopausal woman". Cancer. 18 (4): 436–446. doi:10.1002/1097-0142(196504)18:4<436::AID-CNCR2820180407>3.0.CO;2-D. ISSN   0008-543X. PMID   14278040. S2CID   31370289.
  14. ↑ Horský J, Presl J (1981). "Genital Cycle". In Horsky J, Presl J (eds.). Ovarian Function and its Disorders: Diagnosis and Therapy. 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.
  15. ↑ Karlstedt K (1971). "Progesterone treatment for local recurrence and metastases in carcinoma corporis uteri". Acta Radiologica: Therapy, Physics, Biology. 10 (2): 187–92. 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.
  16. ↑ Moe N (1972). "Short-term progestogen treatment of endometrial carcinoma. Histological, histochemical and hormonal studies". Acta Obstet Gynecol Scand. 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.
  17. ↑ Lundgren S (1992). "Progestins in breast cancer treatment. A review". Acta Oncol. 31 (7): 709–22. doi:10.3109/02841869209083859. PMID   1476750.
  18. ↑ Taylor SG, Morris RS (January 1951). "Hormones in breast metastasis therapy". Med. Clin. North Am. 35 (1): 51–61. doi:10.1016/S0025-7125(16)35321-4. PMID   14796108.
  19. ↑ Gordon D, Horwitt BN, Segaloff A, Murison PJ, Schlosser JV (March 1952). "Hormonal therapy in cancer of the breast. III. Effect of progesterone on clinical course and hormonal excretion". Cancer. 5 (2): 275–7. doi: 10.1002/1097-0142(195203)5:2<275::aid-cncr2820050213>3.0.co;2-h . PMID   14905411.



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