Mechanism of Action
- Directly and competitively bind to gonadotropin-releasing hormone (GnRH/LHRH) receptors in the pituitary.
- This immediately suppresses LH and FSH release, leading to a rapid decline in testosterone (medical castration).
- Unlike LHRH agonists, antagonists do not cause an initial testosterone “flare”, which is clinically important in patients with symptomatic or advanced prostate cancer (e.g., spinal cord compression, urinary obstruction).
Key Agents
| Drug | Route | Notes / Monitoring |
|---|---|---|
| Degarelix (Firmagon®) | Subcutaneous injection (monthly) | Rapid testosterone suppression; injection site reactions common; monitor liver function, testosterone, and PSA |
| Relugolix (Orgovyx®) | Oral, once daily | First oral LHRH antagonist; faster recovery of testosterone after discontinuation compared to agonists; fewer CV events reported in some studies; monitor adherence, electrolytes, ECG (QT prolongation risk) |
Indications
- Advanced/metastatic prostate cancer (as part of androgen deprivation therapy, ADT).
- Often used when rapid testosterone suppression is required or to avoid tumor flare.
- May be combined with androgen receptor signaling inhibitors (ARSIs) or chemotherapy in mCSPC or mCRPC.
Adverse Effects (Class Effects)
- Hot flashes, fatigue, decreased libido, erectile dysfunction.
- Metabolic: weight gain, hyperglycemia, dyslipidemia.
- Long-term: osteoporosis, cardiovascular risk.
- Degarelix → higher rates of injection site reactions.
- Relugolix → possible drug–drug interactions (CYP3A, P-gp substrate).
Pharmacist’s Role
- Ensure correct administration and adherence (oral vs injection).
- Monitor for testosterone and PSA response to confirm castration (< 50 ng/dL).
- Manage long-term toxicities: bone health (denosumab/zoledronic acid, calcium/vitamin D), CV risk, metabolic effects.
- Screen for drug–drug interactions with relugolix (avoid strong P-gp and CYP3A modulators).
- Educate patients about hot flashes, sexual dysfunction, bone health strategies.
LHRH antagonists are often preferred over agonists when immediate testosterone suppression is needed or in patients with high cardiovascular risk (relugolix showed lower major CV events vs leuprolide in trials).