Description

Technical Parameters

Introduction

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Products Description

### **1. Overview**

Fluoxymesterone (trade name Halotestin) is a potent synthetic androgen and anabolic steroid (AAS), developed by Pfizer in 1957 and approved by the FDA. As a derivative of testosterone, its unique chemical structure gives it high oral activity and potent androgenic effects, but it is accompanied by significant liver toxicity risks. This article systematically describes its chemical properties, pharmacological mechanisms, synthesis processes, application areas, safety and market status.

### **2. Chemical properties**

#### **2.1 Basic parameters**

- **CAS number**: 76-43-7

- **Chemical name**: 9α-fluoro-11β,17β-dihydroxy-17α-methylandrost-4-ene-3-one

- **Molecular formula**: C₂₀H₂₉FO₃

- **Molecular weight**: 336.45 g/mol

#### **2.2 Chemical structure**

Fluoxymesterone is based on the androstane skeleton, and the key modifications include:

- **9α-position fluorine atom**: Enhance androgen receptor affinity and delay metabolism.

- **17α-methyl**: Improve oral bioavailability, but increase liver toxicity.

- **11β-hydroxy**: Affect metabolic stability and activity.

#### **2.3 Physical and chemical properties**

- **Appearance**: White to off-white crystalline powder.

- **Melting point**: 240-245℃ (decomposition).

- **Solubility**: easily soluble in chloroform and acetone, slightly soluble in ethanol, almost insoluble in water.

- **Stability**: sensitive to light, need to be stored away from light; easy to oxidize, need to be protected by inert gas.

### **3. Pharmacological properties**

#### **3.1 Mechanism of action**

- **Androgen receptor agonist**: binds to intracellular androgen receptors to promote muscle synthesis, erythropoiesis and sexual characteristics maintenance.

- **Antiestrogen effect**: inhibits estrogen receptor activity and is used for breast cancer treatment.

#### **3.2 Indications**

- **Male hypogonadism**: replacement therapy, dose is usually 5-20 mg/day.

- **Palliative treatment of breast cancer**: inhibits estrogen-sensitive tumors, dose is 30-100 mg/day.

- **Aplastic anemia**: stimulates bone marrow hematopoiesis (now mostly replaced by recombinant erythropoietin).

#### **3.3 Pharmacokinetics**

- **Absorption**: Oral bioavailability is >90%, reaching the peak blood drug in 1-2 hours.

- **Metabolism**: Hydroxylation and glucuronidation by liver CYP3A4 enzyme to generate inactive metabolites.

- **Half-life**: About 9-10 hours, requiring daily divided doses.

- **Excretion**: Mainly through urine (60%) and feces (40%).

### **4. Synthesis process**

#### **4.1 Key steps**

1. **Starting material**: Dehydroepiandrosterone (DHEA) is used as the raw material.

2. **Fluorination reaction**: Introducing fluorine atoms at the 9α position requires the use of HF or Selectfluor® at low temperature (-70°C).

3. **Methylation**: Methylation at the 17α position using iodomethane/sodium hydroxide conditions.

4. **Oxidation and hydroxylation**: The 11β-hydroxyl group is oxidized by microorganisms (such as Aspergillus niger).

#### **4.2 Process Challenges**

- **Stereoselectivity control**: Ensure the stereoconfiguration of 9α-F and 11β-OH.

- **Purification**: Multiple recrystallization or chromatographic separation is required to improve the purity (＞99%).

### **5. Application fields**

#### **5.1 Medical applications**

- **Oncology**: Used for advanced breast cancer to relieve bone pain and tumor progression.

- **Endocrinology**: Treat male low testosterone, improve sexual function and bone density.

#### **5.2 Non-medical abuse**

- **Competitive sports**: Because it enhances aggressiveness and strength, it has been abused by weightlifters and boxers and is now a WADA banned drug.

- **Detection method**: Detect metabolites 9α-fluoro-17-ketone compounds in urine by GC-MS.

### **6. Safety and side effects**

#### **6.1 Common side effects**

- **Hepatotoxicity**: cholestatic jaundice, elevated liver enzymes (ALT/AST).

- **Cardiovascular risks**: increased LDL, decreased HDL, increased risk of atherosclerosis.

- **Endocrine effects**: male breast development (estrogen conversion), testicular atrophy.

#### **6.2 Serious risks**

- **Liver tumors**: long-term use can cause hepatic adenoma or liver cancer (rare but fatal).

- **Psychiatric symptoms**: increased aggression, mood swings ("steroid rage").

#### **6.3 Contraindications**

- Pregnant women (causing fetal masculinization), prostate cancer, severe liver and kidney dysfunction.

### **7. Market and regulations**

#### **7.1 Production and supply**

- **Major manufacturers**: Pfizer (original research), India's Sun Pharma, and some Chinese API companies.

- **API standards**: Meet USP/EP purity standards (HPLC purity ≥ 99.5%).

#### **7.2 Regulatory status**

- **USA**: Schedule III controlled drug, prescription required.

- **Global**: Included in WADA banned list, many countries strictly monitor circulation.

### **8. Summary and Outlook**

Fluoxymesterone is still valuable in specific medical fields due to its potent androgenic activity, but its hepatotoxicity and abuse risks limit its widespread application. Future research directions include developing less toxic structural analogs and optimizing detection technology to curb non-medical abuse. With the development of precision medicine, it may be reborn in targeted hormone therapy.