 | |
| Clinical data | |
|---|---|
| Other names | Buterol; 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-δ-progesterone 3β-butanoate 17α-acetate |
| Drug class | Progestogen; Progestogen ester |
| Identifiers | |
IUPAC name
| |
| PubChem CID | |
| ChemSpider | |
| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C28H40O5 |
| Molar mass | 456.623 g·mol |
| 3D model (JSmol) | |
SMILES
| |
InChI
| |
Butagest, also known as buterol is a modification of megestrol acetate in which the C-3 ketone has been replaced by a C3β butanoyloxy moeity. 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-δ-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.
Pharmacology
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
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
- 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
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
- **Gastrointestinal**:
* Nausea * Vomiting * Constipation or diarrhea
- **Neurological**:
* Headache * Dizziness * Fatigue
- **Breasts**:
* Tenderness * Swelling
- **Mood and Behavioral**:
* Mood swings * Irritability * Depression or anxiety
- **Skin**:
* Acne * Rash or itching (rare)
- **Reproductive**:
* Irregular menstrual bleeding * Spotting
Serious Adverse Effects
These effects require immediate medical attention:
- **Cardiovascular**:
* Blood clots (thromboembolism) * Stroke * Hypertension
- **Hepatic**:
* Jaundice * Elevated liver enzymes
- **Endocrine and Metabolic**:
* Weight gain * Fluid retention
- **Neurological**:
* Severe headaches * Visual disturbances (potential sign of thrombosis)
- **Allergic Reactions**:
* Anaphylaxis (rare) * Angioedema
- **Cancer Risks**:
* Increased risk of hormone-sensitive cancers, such as breast and ovarian cancers, especially with combined hormone therapy.
Precautions
- 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
The toxicology of progesterone, the active ingredient in Butagest, has been studied extensively. Below are key findings:
Acute Toxicity
Progesterone exhibits low acute toxicity. Overdose typically results in mild symptoms such as nausea and dizziness, without life-threatening effects.
Chronic Toxicity
Long-term high-dose use may increase the risk of thromboembolic disorders, cardiovascular diseases, and hormone-sensitive cancers such as breast cancer.
Carcinogenicity
Progesterone is classified by the International Agency for Research on Cancer (IARC) as possibly carcinogenic to humans (Group 2B).
Environmental Toxicity
Improper disposal of progesterone can disrupt aquatic ecosystems, as it is an endocrine-disrupting compound.
See also
References
- Fedotcheva TA, Kruglov AG, Teplova VV, Fedotcheva NI, Rzheznikov VM, Shimanovskiĭ NL (2012). "". Biofizika. 57 (6): 1014–9. PMID 23272582.
- Sergeev PV, Semeĭkin AV, Smirnova ZS, et al. (2004). "". Eksp Klin Farmakol. 67 (4): 54–6. PMID 15500049.
- Tapil'skaia NI, Petrosian MA, Lesik EA (2002). "". Eksp Klin Farmakol. 65 (1): 44–5. PMID 12025785.
- 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.
- Korkhov VV, Lesik EA, Petrosian MA (2005). "". Eksp Klin Farmakol. 68 (1): 39–41. PMID 15786963.
- Kareva EN, Grinenko GS, Gasparian ND, Ovchinnikova EV, Gorenkova OS (2006). "". Eksp Klin Farmakol. 69 (4): 36–8. PMID 16995436.
- ^ "Progesterone and Cancer Risk". IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 72: 563–590. 1999. Retrieved 2024-11-30.
- "Progesterone: Hazardous Substances Data Bank (HSDB)". National Center for Biotechnology Information (NCBI). Retrieved 2024-11-30.
- 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.
- "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: (https://www.who.int)
- National Institutes of Health. (2023). "Butagest: Drug Information." (https://www.nih.gov).