DEPO-TESTADIOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEPO-TESTADIOL (DEPO-TESTADIOL).
Testosterone cypionate binds to androgen receptors, modulating gene transcription and promoting male secondary sexual characteristics. Estradiol cypionate binds to estrogen receptors, regulating female reproductive function and bone metabolism.
| Metabolism | Testosterone cypionate undergoes hydrolysis to testosterone, which is metabolized in the liver via 5α-reductase to DHT and via aromatase to estradiol, then conjugated and excreted renally. Estradiol cypionate is hydrolyzed to estradiol, metabolized in the liver via CYP3A4 and other CYP enzymes, and undergoes glucuronidation and sulfation. |
| Excretion | Renal: 90% (metabolites, primarily glucuronide and sulfate conjugates of testosterone and estradiol); Fecal: <10% (biliary excretion of conjugates, minimal enterohepatic recirculation); Unchanged drug: negligible. |
| Half-life | Testosterone cypionate: approximately 8 days after intramuscular injection due to slow release from oil depot; estradiol cypionate: approximately 5-7 days. Clinically, steady-state concentrations require 4-6 weeks of every-4-week dosing. |
| Protein binding | Testosterone: 97-99% bound, primarily to sex hormone-binding globulin (SHBG) and albumin; estradiol: 98-99% bound, primarily to SHBG and albumin. |
| Volume of Distribution | Testosterone: approximately 0.5-1.0 L/kg (distributes widely into tissues, including prostate, seminal vesicles, and fat); estradiol: approximately 1.0-1.5 L/kg (extensive distribution into estrogen-responsive tissues). |
| Bioavailability | Intramuscular: 100% (by design, complete release over weeks). Oral: not applicable (cypionate salts are not orally bioavailable due to first-pass metabolism). |
| Onset of Action | Intramuscular injection: clinical effects (e.g., withdrawal bleeding, menopausal symptom relief) typically begin within 1-2 weeks, with peak hormonal effects by 2-4 weeks. |
| Duration of Action | Intramuscular injection: approximately 3-4 weeks due to sustained release from oil depot; individual variability exists. Dosing interval typically 4 weeks. |
1 mL (50 mg testosterone enanthate / 2 mg estradiol valerate) intramuscularly every 4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No dosage adjustment recommended; monitor fluid balance. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh Class C). In mild to moderate disease, use caution. |
| Pediatric use | Not recommended for use in pediatric patients. |
| Geriatric use | Use lowest effective dose; monitor for prostatic hypertrophy and cardiovascular effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DEPO-TESTADIOL (DEPO-TESTADIOL).
| Breastfeeding | Contraindicated during breastfeeding. Testosterone is excreted into breast milk with M/P ratio unknown; may cause virilization in infant. Estradiol is excreted into breast milk with M/P ratio approximately 0.14 (Cmax infant ~10% maternal). Both may suppress lactation via hormonal feedback. |
| Teratogenic Risk | Contraindicated in pregnancy. Testosterone cypionate and estradiol cypionate are masculinizing to female fetus. First trimester: androgens cause pseudohermaphroditism (labial fusion, clitoromegaly). Second and third trimesters: potential for virilization of female genitalia; possible long-term behavioral effects. Estrogens carry risk of urogenital tract anomalies, cardiovascular defects, and potential transgenerational effects. |
■ FDA Black Box Warning
Estrogens plus progestin therapy: increased risk of endometrial cancer, cardiovascular disorders, breast cancer, and probable dementia. Testosterone: not approved for hypogonadism treatment in men with age-related low testosterone.
| Serious Effects |
Known or suspected pregnancy; undiagnosed abnormal genital bleeding; known or suspected breast cancer (except for palliative treatment); known or suspected estrogen-dependent neoplasia; active thromboembolic disorders; severe hepatic impairment; hypersensitivity to any component.
| Precautions | Cardiovascular risks including stroke and MI; endometrial cancer; breast cancer; venous thromboembolism; hepatic adenoma; hypercalcemia; fluid retention; use lowest effective dose; stop if pregnancy occurs. |
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| Fetal Monitoring | If inadvertent exposure: ultrasound for fetal genitalia and urogenital development; consider fetal karyotyping if ambiguous genitalia. Maternal monitoring: liver function tests, lipid panel, blood pressure, and serum concentrations of testosterone and estradiol if continued use (not recommended). |
| Fertility Effects | Reversible suppression of spermatogenesis in males and ovulation in females due to exogenous androgens/estrogens inhibiting gonadotropin release. In females, possible endometrial atrophy. Recovery may take months after discontinuation. No permanent infertility expected at standard doses. |