Baseline Hypothalamic-Pituitary-Gonadal Testosterone Control
Placeholder lead — the intact HPG axis maintains steady testosterone output.
- ~500 ng/dL: Baseline serum testosterone (Placeholder short caption text here.)
- ~10 mIU/mL: Baseline LH (Placeholder short caption text here.)
- 100%: GnRH receptor density (Placeholder short caption text here.)
- ~90 min: GnRH pulse frequency (Placeholder short caption text here.)
Hypothalamic GnRH pulse generator
Placeholder body text — pulsatile GnRH release drives the axis.
Pituitary LH secretion
Placeholder body text — gonadotrophs respond with LH pulses.
Testicular Leydig cell output
Placeholder body text — LH stimulates Leydig cell testosterone synthesis.
Leuprolide Injection — Initial GnRH Receptor Agonism
Placeholder lead — leuprolide first behaves as a potent GnRH-receptor agonist.
- GnRH agonist: Drug class (Placeholder short caption text here.)
- Depot injection: Formulation (Placeholder short caption text here.)
- Higher: Receptor affinity vs native GnRH (Placeholder short caption text here.)
- Hours: Onset of stimulation (Placeholder short caption text here.)
Depot pharmacokinetics
Placeholder body text — sustained-release depot maintains drug exposure.
Receptor occupancy surge
Placeholder body text — leuprolide occupies GnRH receptors continuously.
Why agonism precedes suppression
Placeholder body text — continuous stimulation differs from pulsatile signaling.
Testosterone Flare — The First 1-2 Weeks
Placeholder lead — LH and testosterone transiently spike above baseline.
- ~800-900 ng/dL: Flare peak testosterone (Placeholder short caption text here.)
- Day 5-8: Typical flare peak day (Placeholder short caption text here.)
- ~5-6× baseline: Flare LH peak (Placeholder short caption text here.)
- Bone metastases: Clinical concern group (Placeholder short caption text here.)
LH surge kinetics
Placeholder body text — LH rises sharply within the first days.
Testicular response lag
Placeholder body text — testosterone follows LH with a short delay.
Symptom-worsening risk
Placeholder body text — flare can transiently worsen bone-metastasis symptoms.
Continued Exposure — Pituitary Receptor Downregulation
Placeholder lead — sustained stimulation desensitizes and downregulates receptors.
- ~20%: Receptor density by day 21 (Placeholder short caption text here.)
- Internalization: Mechanism (Placeholder short caption text here.)
- Progressive decline: LH trend after peak (Placeholder short caption text here.)
- Falling toward castrate: Testosterone trend (Placeholder short caption text here.)
Receptor internalization
Placeholder body text — GnRH receptors are pulled from the membrane.
Uncoupled signal transduction
Placeholder body text — remaining receptors signal less effectively over time.
Falling gonadotropin output
Placeholder body text — LH secretion progressively declines despite continued drug.
Sustained Castration-Level Testosterone Suppression
Placeholder lead — testosterone reaches and sustains castrate levels.
- <50 ng/dL: Castrate threshold (Placeholder short caption text here.)
- ~4 weeks: Time to castrate levels (Placeholder short caption text here.)
- Continued dosing: Maintenance (Placeholder short caption text here.)
- Anti-androgen co-therapy: Flare mitigation (Placeholder short caption text here.)
Sustained suppression
Placeholder body text — castrate testosterone persists with ongoing therapy.
Anti-androgen co-treatment
Placeholder body text — peripheral receptor blockade blunts flare-related risk.
Clinical monitoring
Placeholder body text — testosterone and symptoms are tracked through week four.