Butagest, also known as buterol is a modification of megestrol acetate in which the C-3 ketone has been replaced by a C3β butanoyloxy moeity.[1] It is chemically known as 3β-hydroxy-6-methyl-17α-hydroxypregna-4,6-dien-20-one 3β-butanoate 17α-acetate or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 steroidalprogestin 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]
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.[7]
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.[8]
Chronic Toxicity
Long-term high-dose use may increase the risk of thromboembolic disorders, cardiovascular diseases, and hormone-sensitive cancers such as breast cancer.[7]
Carcinogenicity
Progesterone is classified by the International Agency for Research on Cancer (IARC) as possibly carcinogenic to humans (Group 2B).[9]
Environmental Toxicity
Improper disposal of progesterone can disrupt aquatic ecosystems, as it is an endocrine-disrupting compound.[10]
^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. PMID23272582.
^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. PMID15500049.
^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. PMID12025785.
^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). "[Gestagenic and contraceptive activity of new synthetic progesterone analogs in experimental animals]". Eksp Klin Farmakol. 68 (1): 39–41. PMID15786963.
^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. PMID16995436.
^ ab"Progesterone and Cancer Risk". IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 72: 563–590. 1999. Retrieved 2024-11-30.
^"Environmental Impact of Hormonal Pharmaceuticals". Journal of Environmental Toxicology. 45 (3): 275–282. 2020. doi:10.1016/j.envtox.2020.01.015 (inactive 11 July 2025).{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (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).
