Formestane

What is Formestane?

Formestane, also known by its former brand name Lentaron, is a steroidal, selective aromatase inhibitor. Its primary medical use is in the treatment of estrogen receptor-positive breast cancer in postmenopausal women. The drug is not active when taken orally and was typically administered via intramuscular depot injection. Its other name is 4-hydroxyandrost-4-ene-3,17-dione.

Aromatase is an enzyme that converts androgens (male hormones) into estrogens (female hormones). By inhibiting this enzyme, Formestane significantly reduces the levels of estrogen in the body. This action is beneficial in treating breast cancers that are stimulated by estrogen.

Side Effects and Benefits

Benefits:

• Estrogen Reduction: As a powerful aromatase inhibitor, Formestane effectively lowers circulating estrogen levels. This is its main therapeutic benefit in breast cancer treatment.

• Anti-Tumor Activity: It has shown to be effective in stabilizing or reducing tumor growth in a significant percentage of postmenopausal women with advanced breast cancer.

• Alternative to Other Therapies: In clinical trials, it has shown comparable efficacy to other treatments like tamoxifen and megestrol, especially as a second-line therapy.

Side Effects:

• Local Injection Site Reactions: Since it was administered as an intramuscular injection, the most common side effects were local reactions at the injection site.

• Systemic Hormonal Effects: Side effects are often related to the hormonal changes it induces. These can include hot flashes, increased sweating, fatigue, and other symptoms associated with reduced estrogen levels.

• Other Side Effects: Less common side effects reported in studies include depression, insomnia, anxiety, headache, and nausea.

Pros and Cons

Pros:

• Effective Estrogen Suppression: It is a potent and effective aromatase inhibitor.

• Non-Oral Administration: The intramuscular injection provides a sustained release, which can be convenient for patients.

• Good Tolerability: It is generally well-tolerated, with adverse events rarely leading to discontinuation of therapy.

Cons:

• Not Orally Active: The necessity of intramuscular injection made it less convenient than newer, orally active aromatase inhibitors.

• Limited Availability: Due to the development of more convenient oral alternatives, its use has declined, and it may no longer be widely available as a prescription medication.

• Potential for Illicit Use: Because of its powerful anti-estrogenic effects, Formestane has been used illicitly by some athletes and bodybuilders to mitigate estrogenic side effects from anabolic steroid use, which is a significant health risk and is prohibited in sports.

Dosage and Frequency

In its clinical use for breast cancer, the typical dosage was a 250 mg or 500 mg intramuscular injection administered once every two weeks. The dosage and frequency would be determined by a healthcare professional based on the patient's condition and treatment plan.

Half-Life and Detection Time

Formestane's terminal elimination half-life after a single intravenous injection is very short, approximately 18 minutes. However, when administered as an intramuscular depot injection, it provides a sustained release of the drug, leading to a much longer effective presence in the body.

The detection time for Formestane in anti-doping tests can be complicated. While the parent drug has a short half-life, its metabolites can be detected in urine for a longer period. Furthermore, because Formestane can be produced endogenously in small amounts, anti-doping agencies have specific criteria and testing methods (like Isotope Ratio Mass Spectrometry) to differentiate between endogenous and exogenous (from drug use) sources. This means that a positive test can be a result of the drug being in the system for an extended period, or it could require further analysis to confirm its origin.

Estrogenic, Progestogenic, Prolactin Affects

• Estrogenic: Formestane is a powerful anti-estrogen. It works by inhibiting the aromatase enzyme, which directly prevents the conversion of androgens into estrogens. This results in a significant reduction in estrogen levels in the body.

• Progestogenic: Formestane is a steroidal compound, but it is not known to have significant progestogenic activity.

• Prolactin: Formestane's effect on prolactin is indirect. By reducing estrogen levels, it can help to prevent estrogen-induced increases in prolactin. High estrogen levels can stimulate prolactin production, which can lead to issues like gynecomastia in men or galactorrhea (milky discharge from the nipples) in women. By keeping estrogen in check, Formestane can indirectly help to manage these issues.

Anabolic Androgenic Ratio

Formestane is an aromatase inhibitor, not an anabolic-androgenic steroid. Therefore, it does not have a traditional anabolic-androgenic ratio. Its primary function is to block the conversion of other steroids into estrogen. It is a derivative of androstenedione, but its own androgenic properties are very weak.