Estradiol benzoate

BRAND NAMES

• Progynon-B: Early brand of estradiol benzoate for estrogen therapy and menopausal symptoms.

• Agofollin: Injectable estradiol benzoate for hormone deficiency and reproductive disorders.

• Oestradiol Benzoate Injection: Generic injectable form for controlled estrogen release.

• Oestroform: Estradiol benzoate injection for menopause and delayed puberty.

• Delestrec: Long-acting estrogen preparation containing estradiol benzoate, now less common.

MECHANISM OF ACTION

Estradiol freely enters target cells, such as those in female reproductive organs, breasts, the hypothalamus, and the pituitary gland, where it binds to estrogen receptors. Once bound, the receptor-ligand complex translocates to the cell nucleus and modulates gene transcription, leading to the production of messenger RNA. This mRNA directs ribosomes to synthesize specific proteins that mediate estradiol’s effects in the target cell. Additionally, estrogens enhance hepatic production of proteins like sex hormone-binding globulin (SHBG) and thyroid-binding globulin (TBG), while suppressing follicle-stimulating hormone (FSH) secretion from the anterior pituitary.

PHARMACOKINETICS

• Absorption: Estradiol benzoate is slowly absorbed from intramuscular injections, providing sustained plasma levels.

• Distribution: It binds to plasma proteins and distributes to estrogen-sensitive tissues, with temporary storage in fat.

• Metabolism: Hydrolyzed to estradiol, it is metabolized in the liver to active and inactive conjugates.

• Excretion: Metabolites are primarily excreted in urine, with a smaller amount eliminated in feces.

PHARMACODYNAMICS

Estradiol benzoate acts as a prodrug of estradiol, binding to and activating estrogen receptors (ERα and ERβ) in target tissues such as the uterus, breasts, and brain. Through this receptor interaction, it regulates gene expression and cellular activity, affecting the female reproductive system while also producing mild metabolic and anabolic effects and enhancing blood coagulability. Therapeutically, it is used to prevent ovulation in contraceptive regimens and to suppress lactation.

ADMINISTRATION

Estradiol benzoate is typically administered via intramuscular injection into the gluteal or deltoid muscle. It is formulated as an oil solution to allow slow release over days. Injection sites should be rotated to minimize irritation. The drug is usually given in clinical settings under supervision. Proper aseptic technique is essential to avoid infections.

DOSAGE AND STRENGTH

Dosage varies depending on the indication, age, and patient’s hormone levels. Common strengths range from 1 mg/mL to 10 mg/mL in oil solution. In adults, doses for estrogen replacement or menstrual regulation are usually 1–5 mg every 2–3 days or as prescribed. Veterinary doses may differ. Titration is often required to achieve optimal hormonal balance.

DRUG INTERACTIONS

Estradiol benzoate may interact with drugs that induce or inhibit liver enzymes (e.g., CYP3A4), altering its metabolism. Anticoagulants, corticosteroids, and antiepileptics may have reduced or enhanced effects when co-administered. Herbal supplements like St. John’s Wort can decrease estrogen levels. Concomitant use with other estrogens can increase side effect risk. Monitoring hormone levels and adjusting doses may be necessary.

FOOD INTERACTIONS

There are no significant food interactions reported because estradiol benzoate is given intramuscularly. Oral bioavailability is not a concern with IM administration. Fat-rich meals do not affect its absorption. Patients do not need dietary restrictions specifically for this medication. Alcohol does not significantly affect its pharmacokinetics but may exacerbate liver-related risks.

CONTRAINDICATIONS

Estradiol benzoate is contraindicated in individuals with known hypersensitivity to estrogens or the benzoate component. It should not be used in patients with active or past estrogen-dependent cancers, unexplained vaginal bleeding, liver disease, or thromboembolic disorders. Pregnancy and lactation are relative contraindications, depending on the clinical context. Careful evaluation of cardiovascular risk is essential before use.

SIDE EFFECTS

• Pain, tenderness, or swelling in the breasts

• Headaches or migraines

• Nausea, vomiting, or abdominal discomfort

• Mood swings, irritability, or depression

• Weight gain or water retention

• Leg cramps or muscle spasms

• Joint pain or stiffness

• Skin changes, including darkening or rashes

• Menstrual irregularities, such as spotting or abnormal bleeding

• Vaginal irritation, itching, or unusual discharge

OVER DOSE

Acute overdose may cause nausea, vomiting, dizziness, and breast tenderness. Extremely high doses can lead to fluid retention, hypertension, or thromboembolic events. Management is generally supportive, including discontinuation of the drug and symptomatic treatment. Monitoring vital signs and liver function may be necessary. No specific antidote exists for estradiol overdose.

TOXICITY

Chronic excessive exposure can increase the risk of thromboembolic disorders, liver tumors, or estrogen-dependent cancers. Toxic effects may manifest as severe fluid retention, hypertension, or gynecomastia in males. Toxicity is usually dose- and duration-dependent. Monitoring hormone levels, liver function, and cardiovascular health helps mitigate risks. Adhering to prescribed dosages minimizes toxicity potential.