Five drugs. Five hit points. One axis: hypothalamus to pituitary to testes to prostate. Knock testosterone out, the tumor stops growing.
Clinical scenario: A 68-year-old man with new prostate cancer and lumbar vertebral metastases is started on leuprolide. Two weeks in, his back pain spikes and he develops new lower-extremity weakness. What did the leuprolide do to him?
Leuprolide is a GnRH agonist. It mimics the hypothalamic hormone, but given as a steady drip instead of a pulse. For the first two weeks it stimulates the pituitary the way GnRH normally does, so LH and FSH rise, testes pump out testosterone, and the tumor gets fed before downregulation kicks in. With vertebral mets, that flare can push cord compression. Always cover leuprolide with an antiandrogen (flutamide or bicalutamide) for the first 2 weeks, or switch to a GnRH antagonist like degarelix when flare is dangerous.
📷 Prostate cancer bone mets · bone scan · tap to expand
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The Axis & Five Hit Points
Tap each numbered marker to see which drug class hits there.
📷 HPG axis pharmacology diagram · tap to expand
Tap a number
Five drug classes, five places to break the axis
Each marker shows where a drug class hits. The closer to the brain, the more downstream signaling shuts off. The closer to the prostate, the more selective the kill.
Pattern: stop testosterone reaching the prostate. Pick the hit point that fits the stem.
The Lineup
Five villains. Tap a card to flip it for mechanism and the board move.
📷 Bone mets · tap to expand
Leuprolide / Goserelin
GnRH agonist · The Paradox
HitPituitary GnRH receptor
UsePCa, endometriosis, fibroids
Flare 2 weeks. Then castration.
tap to flip →
Why It Works
Trace It
Continuous, non-pulsatile GnRH stimulation first agonizes the pituitary, then desensitizes it. Initial 2-week testosterone flare, then chemical castration as receptors are pulled off the cell surface.
Long-Term ADT Effects
Osteoporosis, hot flashes, metabolic syndrome, increased cardiovascular risk. Screen and manage proactively.
Lock It
Cover leuprolide with an antiandrogen (flutamide or bicalutamide) for the first 2 weeks to block the flare at the prostate.
📷 HPG axis diagram · tap to expand
Degarelix / Relugolix
GnRH antagonist · The Silencer
HitPituitary GnRH receptor (block)
UsePCa when flare is dangerous
No flare. Castrate in days.
tap to flip →
Why It Works
Trace It
Competitive antagonist at the pituitary GnRH receptor. No agonist phase, so LH and FSH drop immediately and testosterone follows within days. Unlike leuprolide, no initial surge.
When to pick this
Vertebral mets, impending cord compression, severe bone pain, anywhere a flare would be catastrophic.
Lock It
When the stem hints at flare danger, pick the GnRH antagonist (degarelix), not the agonist.
📷 AR antagonist action · tap to expand
Flutamide / Bicalutamide / Enzalutamide
Antiandrogen · The Receptor Plug
HitAndrogen receptor in prostate cells
UseFlare cover, monotherapy, CRPC
Testosterone made. Prostate deaf.
tap to flip →
Why It Works
Trace It
Competitive block of the androgen receptor in prostate tissue. Testosterone and DHT cannot signal growth. Enzalutamide is 2nd-gen: no agonist activity (unlike flutamide), crosses the BBB.
Key Distinction
Enzalutamide crosses the blood-brain barrier and lowers the seizure threshold. Avoid in seizure history. Flutamide does NOT cross the BBB and has partial agonist activity.
Lock It
Bicalutamide covers the leuprolide flare. Enzalutamide is for CRPC, with a seizure caution. Seizure hx = do NOT use enzalutamide.
📷 CYP17A1 block site · tap to expand
Abiraterone
CYP17A1 inhibitor · The Synthesis Killer
Hit17α-hydroxylase / 17,20-lyase
UseCastration-resistant PCa (CRPC)
Always pair with prednisone.
tap to flip →
Why It Works
Trace It
Blocks CYP17A1 in testes, adrenals, and tumor itself. Cuts testosterone synthesis at the source, including the adrenal pool that GnRH agonists miss (why CRPC still has some T).
Why Prednisone
Blocking CYP17A1 diverts precursors into mineralocorticoid pathway (DOCA surge). Without prednisone: HTN, hypokalemia, fluid retention. Prednisone suppresses ACTH and cuts off the upstream signal.
Lock It
Abiraterone always with prednisone. HTN + hypokalemia on abiraterone = forgot the prednisone, or the dose slipped.
📷 mCRPC bone mets · tap to expand
Docetaxel / Cabazitaxel
Taxane · The Spindle Freeze
Hitβ-tubulin / mitotic spindle
UsemCRPC after hormonal therapy fails
Stabilizes microtubules. Cell stuck.
tap to flip →
Why It Works
Trace It
Binds β-tubulin and prevents depolymerization. The mitotic spindle freezes, the cell cannot finish division, and apoptosis follows. Same family as paclitaxel. First-line chemo for mCRPC.
Taxane stabilizes the spindle. Vinca alkaloid prevents assembly. Opposite mechanics, same G2/M arrest.
Order of attack in metastatic PCa: hormonal first (GnRH agonist or antagonist ± AR blocker) → abiraterone or enzalutamide when castration resistant → docetaxel when hormones fail.
Break the Axis
Drag each drug to its correct target on the HPG axis. Get them all right to win.
⚡ Break the Axis
Drag drugs to where they hit. Tap a placed chip to remove it.
Leuprolide
Degarelix
Bicalutamide
Enzalutamide
Abiraterone
Finasteride
Docetaxel
Hypothalamus / Pit. (agonize)
GnRH agonist here
Hypothalamus / Pit. (block)
GnRH antagonist here
Androgen Receptor
AR blockers here (2 max)
Testes + Adrenal (CYP17)
CYP17A1 inhibitor here
5-Alpha Reductase
5-AR inhibitor here
Tumor Cell Spindle
Taxane here
All correct! You broke the axis.
5-AR inhibitors (finasteride, dutasteride) lower PSA by ~50%. Adjust your interpretation: multiply the measured PSA by 2 to get the true value.
