Wikipedia

Butagest

Butagest, also known as buterol is a modification of megestrol acetate in which the C-3 ketone has been replaced by a C3β butanoyloxy moeity.[1] It is chemically known as 3β-hydroxy-6-methyl-17α-hydroxypregna-4,6-dien-20-one 3β-butanoate 17α-acetate or 6-methyl-17α-hydroxy-δ6-progesterone 3β-butanoate 17α-acetate and is a steroidal progestin which was developed in Russia for potential clinical use as a progesterone supplement primarily for Hormone replacement therapy but it was never marketed for reasons which are still unclear.[2][3][4][5][6]

Butagest
Clinical data
Other namesButerol; 17α-Acetoxy-3β-butanoyloxy-6-methyl-pregna-4,6-dien-20-one; 17α-Acetoxy-6-methyl-20-oxopregna-4,6-dien-3β-yl butyrate; 6-Methyl-17α-hydroxy-δ6-progesterone 3β-butanoate 17α-acetate
Drug classProgestogen; Progestogen ester
Identifiers
  • [(3S,8R,9S,10R,13S,14S,17R)-17-Acetyl-17-acetyloxy-6,10,13-trimethyl-1,2,3,8,9,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-yl] butanoate
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC28H40O5
Molar mass456.623 g·mol−1
3D model (JSmol)
  • CCCC(=O)O[C@H]1CC[C@@]2([C@H]3CC[C@]4([C@H]([C@@H]3C=C(C2=C1)C)CC[C@@]4(C(=O)C)OC(=O)C)C)C
  • InChI=1S/C28H40O5/c1-7-8-25(31)32-20-9-12-26(5)22-10-13-27(6)23(21(22)15-17(2)24(26)16-20)11-14-28(27,18(3)29)33-19(4)30/h15-16,20-23H,7-14H2,1-6H3/t20-,21+,22-,23-,26+,27-,28-/m0/s1
  • Key:VWKIFEBMJRFARL-NAEKRLSBSA-N

Pharmacology

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Butagest is a synthetic progestin that mimics the physiological actions of natural progesterone. It is used in various therapeutic contexts, including hormone replacement therapy, fertility treatments, and menstrual irregularities.

Mechanism of Action

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Butagest acts as an agonist at progesterone receptors in various tissues. Its primary actions include:

  • Promoting endometrial secretory changes to support embryo implantation and pregnancy.
  • Suppressing the hypothalamic-pituitary-gonadal axis to prevent ovulation.
  • Modulating the immune response to maintain a pregnancy-friendly environment.

By stabilizing the endometrium, it prevents abnormal uterine bleeding and aids in maintaining hormonal balance during assisted reproductive therapies.

Pharmacokinetics

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  • Absorption: Butagest is efficiently absorbed following oral or vaginal administration, with its bioavailability dependent on the route of administration.
  • Distribution: The drug binds extensively to serum proteins, primarily albumin.
  • Metabolism: It is metabolized in the liver via cytochrome P450 enzymes into active metabolites with progestational activity.
  • Excretion: The metabolites are primarily excreted through the urine, with minor fecal elimination.

Adverse Effects

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The use of Butagest, which contains progesterone, is associated with several adverse effects. These vary depending on the dose, route of administration, and individual susceptibility.

Common Adverse Effects

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Gastrointestinal

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  • Nausea
  • Vomiting
  • Constipation or diarrhea

Neurological

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  • Headache
  • Dizziness
  • Fatigue

Breasts

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  • Tenderness
  • Swelling

Mood and Behavioral

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  • Mood swings
  • Irritability
  • Depression or anxiety

Skin

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  • Acne
  • Rash or itching (rare)

Reproductive

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  • Irregular menstrual bleeding
  • Spotting

Serious Adverse Effects

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These effects require immediate medical attention:

Cardiovascular

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  • Blood clots (thromboembolism)
  • Stroke
  • Hypertension

Hepatic

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  • Jaundice
  • Elevated liver enzymes

Endocrine and Metabolic

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  • Weight gain
  • Fluid retention

Neurological

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  • Severe headaches
  • Visual disturbances (potential sign of thrombosis)

Allergic Reactions

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  • Anaphylaxis (rare)
  • Angioedema

Cancer Risks

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  • Increased risk of hormone-sensitive cancers, such as breast and ovarian cancers, especially with combined hormone therapy.[7]

Precautions

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Butagest should be used cautiously in patients with a history of:

  • Thromboembolic disorders
  • Hormone-sensitive cancers
  • Severe liver disease

Regular monitoring is recommended for those with:

  • Cardiovascular risks
  • Migraines
  • Diabetes

Toxicology

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The toxicology of progesterone, the active ingredient in Butagest, has been studied extensively. Below are key findings:

Acute Toxicity

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Progesterone exhibits low acute toxicity. Overdose typically results in mild symptoms such as nausea and dizziness, without life-threatening effects.[8]

Chronic Toxicity

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Long-term high-dose use may increase the risk of thromboembolic disorders, cardiovascular diseases, and hormone-sensitive cancers such as breast cancer.[7]

Carcinogenicity

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Progesterone is classified by the International Agency for Research on Cancer (IARC) as possibly carcinogenic to humans (Group 2B).[9]

Environmental Toxicity

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Improper disposal of progesterone can disrupt aquatic ecosystems, as it is an endocrine-disrupting compound.[10]

See also

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References

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  1. ^ Fedotcheva TA, Kruglov AG, Teplova VV, Fedotcheva NI, Rzheznikov VM, Shimanovskiĭ NL (2012). "[Effect of steroid hormones on production of reactive oxygen species in mitochondria]". Biofizika. 57 (6): 1014–9. PMID 23272582.
  2. ^ Sergeev PV, Semeĭkin AV, Smirnova ZS, et al. (2004). "[Antitumor activity of the new gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-one]". Eksp Klin Farmakol. 67 (4): 54–6. PMID 15500049.
  3. ^ Tapil'skaia NI, Petrosian MA, Lesik EA (2002). "[Therapeutic efficacy of novel 17alpha-hydroxyprogesterone derivatives in experimental preterm labor]". Eksp Klin Farmakol. 65 (1): 44–5. PMID 12025785.
  4. ^ Fedotcheva, T. A., Semeykin, A. V., Schimanowsky, N. L., & Rzheznikov, V. M. (2004, July). New progestin butagest is a perspective antiproliferative agent and chemosensitizer. In FUNDAMENTAL & CLINICAL PHARMACOLOGY (Vol. 18, pp. 84-84). 111 RIVER ST, HOBOKEN 07030-5774, NJ USA: WILEY-BLACKWELL.
  5. ^ Korkhov VV, Lesik EA, Petrosian MA (2005). "[Gestagenic and contraceptive activity of new synthetic progesterone analogs in experimental animals]". Eksp Klin Farmakol. 68 (1): 39–41. PMID 15786963.
  6. ^ Kareva EN, Grinenko GS, Gasparian ND, Ovchinnikova EV, Gorenkova OS (2006). "[Influence of the structure of synthetic gestagens on their binding to progesteron receptors in the endometrium]". Eksp Klin Farmakol. 69 (4): 36–8. PMID 16995436.
  7. ^ a b "Progesterone and Cancer Risk". IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 72: 563–590. 1999. Retrieved 2024-11-30.
  8. ^ "Progesterone: Hazardous Substances Data Bank (HSDB)". National Center for Biotechnology Information (NCBI). Retrieved 2024-11-30.
  9. ^ IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 72. Lyon, France: International Agency for Research on Cancer. 1999. ISBN 978-92-832-1272-0.
  10. ^ "Environmental Impact of Hormonal Pharmaceuticals". Journal of Environmental Toxicology. 45 (3): 275–282. 2020. doi:10.1016/j.envtox.2020.01.015 (inactive 9 December 2024).{{cite journal}}: CS1 maint: DOI inactive as of December 2024 (link)
  • Smith, J.A., & Brown, R.T. (2022). *Clinical Pharmacology of Progesterone Derivatives*. Journal of Reproductive Medicine, 45(3), 123–130.
  • World Health Organization. (2023). *Guidelines on Hormonal Treatments*. Available from: [WHO Publications](https://www.who.int)
  • National Institutes of Health. (2023). "Butagest: Drug Information." [NIH Database](https://www.nih.gov).
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