Dimethisterone

Last updated
Dimethisterone
Dimethisterone.svg
Dimethisterone 3D ball.png
Clinical data
Trade names Lutagan, Secrosteron, others
Other namesDimethindrone; 6α,21-Dimethylethisterone; 6α,21-Dimethyl-17α-ethynyltestosterone; 17α-Ethynyl-6α,21-dimethylandrost-4-en-17β-ol-3-one; 6α,21-Dimethyl-17β-hydroxy-17α-pregn-4-en-20-yn-3-one
Routes of
administration 		By mouth
Drug class Progestogen; Progestin
Identifiers
  • (6S,8R,9S,10R,13S,14S,17S)-17-hydroxy-6,10,13-trimethyl-17-prop-1-ynyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard 100.001.106 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C23H32O2
Molar mass 340.507 g·mol−1
3D model (JSmol)
  • CC#C[C@@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2C[C@@H](C4=CC(=O)CC[C@]34C)C)C)O
  • InChI=1S/C23H32O2/c1-5-9-23(25)12-8-19-17-13-15(2)20-14-16(24)6-10-21(20,3)18(17)7-11-22(19,23)4/h14-15,17-19,25H,6-8,10-13H2,1-4H3/t15-,17+,18-,19-,21+,22-,23-/m0/s1
  • Key:LVHOURKCKUYIGK-RGUJTQARSA-N

Dimethisterone, formerly sold under the brand names Lutagan and Secrosteron among others, is a progestin medication which was used in birth control pills and in the treatment of gynecological disorders but is now no longer available. [1] [2] [3] [4] It was used both alone and in combination with an estrogen. [1] [5] It is taken by mouth. [6]

Contents

Side effects of dimethisterone are similar to those of other progestins. When used in combination with high doses of an estrogen, an increased risk of endometrial cancer can occur. [7] Dimethisterone is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. [8] [9] [10] It has some antimineralocorticoid activity and no other important hormonal activity. [8] [9] [10]

Dimethisterone was first described and was introduced for medical use in 1959. [1] [8] It started being used in birth control pills in 1965. [5] However, due to its low potency and consequent inability to prevent the increased risk of endometrial cancer with estrogens, dimethisterone was soon discontinued for such purposes. [7]

Medical uses

Dimethisterone was used alone in the treatment of gynecological disorders and in combination with ethinylestradiol in birth control pills. [7] [11]

Side effects

Side effects of dimethisterone are similar to those of other progestins.[ citation needed ]

Pharmacology

Pharmacodynamics

Dimethisterone was derived from modification of ethisterone via introduction of methyl groups at the C6α and C21 positions. [12] [13] Relative to ethisterone, it is 12 times as potent orally as a progestogen in animals (Clauberg test), [8] [13] and, unlike ethisterone, [14] is a pure progestogen with no androgenic (or estrogenic) activity in animals even at very high doses (although some weak antimineralocorticoid activity was observed at high doses in animals). [8] [9] [10] However, in spite of its improved potency over ethisterone, it is a weak progestogen relative to most other progestins, [3] in fact one of the weakest known. [2]

Chemistry

Dimethisterone, also known as 6α,21-dimethylethisterone or as 6α,21-dimethyl-17α-ethynyltestosterone, as well as 17α-ethynyl-6α,21-dimethylandrost-4-en-17β-ol-3-one or as 6α,21-dimethyl-17β-hydroxy-17α-pregn-4-en-20-yn-3-one, is a synthetic androstane steroid and a derivative of testosterone. [1]

Synthesis

Chemical syntheses of dimethisterone have been published. [15]

History

Dimethisterone was developed by the British pharmaceutical company British Drug Houses (which subsequently merged with Merck KGaA) and was first reported in the medical literature in 1959, [1] [8] with introduction for medical use under the brand name Secrosteron following in the same year. [13] [16] It was introduced in the United States as an oral contraceptive in combination with high doses of ethinylestradiol under the brand name Oracon (25 mg dimethisterone, 100 μg ethinylestradiol) in 1965. [5] Due to the fact that it contains a weak progestogen in combination with a large dose of a potent estrogen, this preparation was eventually found to be associated with a substantially increased risk of endometrial cancer in women, and is now no longer marketed. [7]

The improved potency of dimethisterone due to 6α-methylation reportedly served as the basis for the synthesis of medroxyprogesterone acetate. [13] Whereas hydroxyprogesterone acetate (the 6α-demethylated analogue of medroxyprogesterone acetate) is around twice as potent as ethisterone orally, [17] medroxyprogesterone acetate shows 10 to 25 times the potency of ethisterone. [13]

Society and culture

Generic names

Dimethisterone is the generic name of the drug and its INN, USAN, and BAN. [1]

Brand names

Dimethisterone was marketed alone under the brand names Lutagan and Secrosteron and in combination with ethinylestradiol under the brand names Oracon, Ovin, Secrodyl, Secrovin, and Tova. [1] [5] [18]

Related Research Articles

<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">Norethisterone acetate</span> Chemical compound

Norethisterone acetate (NETA), also known as norethindrone acetate and sold under the brand name Primolut-Nor among others, is a progestin medication which is used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication available in low-dose and high-dose formulations and is used alone or in combination with an estrogen. It is ingested orally.

Maternal use of androgens or high doses of certain weakly androgenic synthetic progestogens (progestins) structurally related to testosterone can masculinize (virilize) the vulva of a female fetus during susceptible times in pregnancy.

<span class="mw-page-title-main">Megestrol acetate</span> Pharmaceutical drug - appetite stimulant

Megestrol acetate (MGA), sold under the brand name Megace among others, is a progestin medication which is used mainly as an appetite stimulant to treat wasting syndromes such as cachexia. It is also used to treat breast cancer and endometrial cancer, and has been used in birth control. MGA is generally formulated alone, although it has been combined with estrogens in birth control formulations. It is usually taken by mouth.

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

Norethisterone, also known as norethindrone and sold under many brand names, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication is available in both low-dose and high-dose formulations and both alone and in combination with an estrogen. It is used by mouth or, as norethisterone enanthate, by injection into muscle.

<span class="mw-page-title-main">Medroxyprogesterone</span> Steroidal progestin drug

Medroxyprogesterone (MP), is a progestin which is not used medically. A derivative, medroxyprogesterone acetate (MPA), is used as a medication in humans, and is far more widely known in comparison. Medroxyprogesterone is sometimes used as a synonym for medroxyprogesterone acetate, and what is almost always being referred to when the term is used is MPA and not medroxyprogesterone.

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

Ethisterone, also known as ethinyltestosterone, pregneninolone, and anhydrohydroxyprogesterone and formerly sold under the brand names Proluton C and Pranone among others, is a progestin medication which was used in the treatment of gynecological disorders but is now no longer available. It was used alone and was not formulated in combination with an estrogen. The medication 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.

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">Medroxyprogesterone acetate</span> Injectible form of birth control

Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of birth control and as a part of menopausal hormone therapy. It is also used to treat endometriosis, abnormal uterine bleeding, paraphilia, and certain types of cancer. The medication is available both alone and in combination with an estrogen. It is taken by mouth, used under the tongue, or by injection into a muscle or fat.

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

Medrogestone, sold under the brand name Colprone among others, is a progestin medication which has been used in menopausal hormone therapy and in the treatment of gynecological disorders. It is available both alone and in combination with an estrogen. It is taken by mouth.

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

Norethisterone enanthate (NETE), also known as norethindrone enanthate, is a form of hormonal birth control which is used to prevent pregnancy in women. It is used both as a form of progestogen-only injectable birth control and in combined injectable birth control formulations. It may be used following childbirth, miscarriage, or abortion. The failure rate per year in preventing pregnancy for the progestogen-only formulation is 2 per 100 women. Each dose of this form lasts two months with only up to two doses typically recommended.

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

Hydroxyprogesterone acetate (OHPA), sold under the brand name Prodox, is an orally active progestin related to hydroxyprogesterone caproate (OHPC) which has been used in clinical and veterinary medicine. It has reportedly also been used in birth control pills.

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

Anagestone acetate, sold under the brand names Anatropin and Neo-Novum, is a progestin medication which was withdrawn from medical use due to carcinogenicity observed in animal studies.

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

Ethynerone, also known as 17α-(2-chloroethynyl)estra-4,9-dien-17β-ol-3-one, is a steroidal progestin of the 19-nortestosterone group that was first reported in 1961 but was never marketed. Under the developmental code name MK-665, it was studied in combination with mestranol as an oral contraceptive. Development of the drug was discontinued due to concerns surrounding toxicity findings in dogs. It is a chloroethynylated derivative of norethisterone.

<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">Quingestrone</span> Progestin medication

Quingestrone, also known as progesterone 3-cyclopentyl enol ether (PCPE) and sold under the brand name Enol-Luteovis, is a progestin medication which was previously used in birth control pills in Italy but is now no longer marketed. It is taken by mouth.

<span class="mw-page-title-main">17α-Methylprogesterone</span> Chemical compound

17α-Methylprogesterone (17α-MP), or 17α-methylpregn-4-ene-3,20-dione, is a steroidal progestin related to progesterone that was synthesized and characterized in 1949 but was never marketed. Along with ethisterone (1938) and 19-norprogesterone (1951), 17α-MP was one of the earliest derivatives of progesterone to be identified as possessing progestogenic activity. Similarly to progesterone and derivatives like 17α-hydroxyprogesterone and 19-norprogesterone, 17α-MP was found to possess poor oral bioavailability, but showed improved progestogenic activity relative to progesterone when administered via other routes. In addition to its activity as a progestogen, 17α-MP has also been found to possess some antiglucocorticoid activity.

References

  1. 1 2 3 4 5 6 7 Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 430–. ISBN   978-1-4757-2085-3.
  2. 1 2 Paoletti R, Pasetto N, Ambrus JL (6 December 2012). The Menopause and Postmenopause: The Proceedings of an International Symposium held in Rome, June 1979. Springer Science & Business Media. pp. 374–. ISBN   978-94-011-7230-1.
  3. 1 2 Voigt LF, Weiss NS (6 December 2012). "Epidemiology of endometrial cancer". In Surwit EA, Alberts D (eds.). Endometrial Cancer. Springer Science & Business Media. pp. 11–. ISBN   978-1-4613-0867-6.
  4. ↑ Patterson R (21 December 2012). Drugs in Litigation: Damage Awards Involving Prescription and Nonprescription Drugs. LexisNexis. pp. 483–484. ISBN   978-0-327-18698-4.
  5. 1 2 3 4 William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1331–. ISBN   978-0-8155-1856-3.
  6. ↑ Gadappa S, Yelikar K, Deshpande S (7 May 2015). "Drugs in Obstetrics and Gynecology". In Yelikar K (ed.). Practical Cases in Obstetrics & Gynecology. JP Medical Ltd. pp. 98–. ISBN   978-93-5090-536-4.
  7. 1 2 3 4 Briton LA, Schifman M (2009). "Epidemiology of Gynecological Cancer". In Barakat RR, Markman M, Randall M (eds.). Principles and Practice of Gynecologic Oncology. Lippincott Williams & Wilkins. pp. 5–. ISBN   978-0-7817-7845-9. Studies have shown that women who used Oracon, a sequential preparation that employed dimethisterone (weak progestogen) with a large dose of a potent estrogen (ethinyl estradiol), had substantially elevated risks of uterine cancer (6,21). The risk associated with the use of other sequential oral contraceptives remains unclear, mainly because these drugs are no longer marketed.
  8. 1 2 3 4 5 6 David A, Fellowes KP, Millson DR (1959). "Some biological properties of dimethisterone "secrosteron" a new orally active progestational agent". The Journal of Pharmacy and Pharmacology. 11: 491–5. doi:10.1111/j.2042-7158.1959.tb12587.x. PMID   13814263. S2CID   34304113.
  9. 1 2 3 Vademecum International. J. Morgan Jones Publications. 1959. p. 90. Secrosteron (dimethisterone) is an orally active purely progestational agent twelve times as potent as ethisterone.
  10. 1 2 3 Jackson H (8 March 2013). "The Development of Antifertility Substances". In Jucker (ed.). Fortschritte der Arzneimittelforschung / Progress in Drug Research / Progrès des recherches pharmaceutiques. Birkhäuser. pp. 166–. ISBN   978-3-0348-7053-5.
  11. ↑ IARC Working Group on the Evaluation of the Carcinogenic Risk of Chemicals to Humans (1978). IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. IARC. p. 379.
  12. ↑ Lemke TL, Williams DA (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1316–. ISBN   978-0-7817-6879-5.
  13. 1 2 3 4 5 Applezweig N (1962). Steroid Drugs . Blakiston Division, McGraw-Hill. pp.  101–102. At The British Drug Houses, Ltd., V. Petrow and his group decided that substitution at the 6 position should help to strengthen the progesterone molecule. They prepared a series of 6α and 6β derivatives and, finding enhancement with 6α-methyl, proceeded to modify ethisterone and finally produced 6α,21-dimethylethisterone, which proved to have twelve times the oral activity of ethisterone. This latter product is marketed by British Drug Houses under the name of Secrosteron.
  14. ↑ Juchau MR (6 December 2012). "Chemical teratogenesis in humans: Biochemical and molecular mechanisms". In Jucker E (ed.). Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrès des recherches pharmaceutiques. Vol. 49. Birkhäuser. pp. 25–92. doi:10.1007/978-3-0348-8863-9_2. ISBN   978-3-0348-8863-9. PMID   9388384.{{cite book}}: |journal= ignored (help)
  15. ↑ Die Gestagene. Springer-Verlag. 27 November 2013. p. 12. ISBN   978-3-642-99941-3.
  16. ↑ Medical Proceedings: A South African Journal for the Advancement of Medical Science. Juta and Company. 1959. p. 269. Secrosteron a new oral progestational substance British Drug Houses (South Africa) (Pty.) Ltd., announce the introduction of Secrosteron, a new fundamental discovery from the Research Laboratories of the British Drug Houses Ltd., London.
  17. ↑ Davis ME, Wied GL (1957). "17-alpha-HYDROXYPROGESTERONE acetate; an effective progestational substance on oral administration". The Journal of Clinical Endocrinology and Metabolism. 17 (10): 1237–44. doi:10.1210/jcem-17-10-1237. PMID   13475464. It is the purpose of this paper to introduce and describe a new steroid for oral administration, 17-a-hydroxyprogesterone acetate*, and to compare it with the most widely used oral substance with progestational properties, 20,21-anhydro-17-/3-hydroxyprogesterone. * Prodox, Upjohn Co., Kalamazoo, Michigan [...] It was found that 17-a-hydroxyprogesterone acetate has a progestational activity which is at least twice that of anhydrohydroxyprogesterone.
  18. ↑ IARC Working Group on the Evaluation of the Carcinogenic Risk of Chemicals to Man (1974). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man: Sex Hormones (PDF). World Health Organization. p. 78,167. ISBN   9789283212065.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.