Hormone Therapy for Prostate Cancer: Androgen Deprivation Therapy (ADT)
- What is hormone therapy for prostate cancer?
- How does ADT work?
- Types of ADT – LHRH agonists, antagonists, anti-androgens, orchiectomy
- When is ADT used?
- Side effects – hot flashes, fatigue, ED, osteoporosis, metabolic syndrome
- Managing side effects – lifestyle, medications, supplements
- Intermittent vs. continuous ADT
- ADT and radiation – neoadjuvant, concurrent, adjuvant
- Interactive FAQ – 9 questions about hormone therapy
What is hormone therapy for prostate cancer?
Hormone therapy (also called androgen deprivation therapy – ADT) is a treatment that lowers testosterone levels in the body. Prostate cancer cells need testosterone to grow. By reducing testosterone, ADT slows cancer growth and can shrink tumors.
ADT is NOT a cure for prostate cancer. It controls the disease, often for years, but cancer eventually becomes resistant (castration-resistant prostate cancer – CRPC).
How does ADT work?
ADT works by interrupting the androgen receptor signaling pathway:
- Testosterone is produced primarily in the testes (95%) and adrenal glands (5%)
- Testosterone is converted to dihydrotestosterone (DHT) in the prostate
- DHT binds to androgen receptors on prostate cancer cells, stimulating growth
- ADT reduces testosterone production or blocks androgen receptors
Types of ADT – LHRH agonists, antagonists, anti-androgens, orchiectomy
LHRH agonists (most common):
- Mechanism: Overstimulate the pituitary gland, causing a surge then suppression of testosterone
- Examples: Leuprolide (Lupron), goserelin (Zoladex), triptorelin (Trelstar)
- Administration: Injection (1, 3, 4, or 6-month formulations)
- Testosterone flare: Initial testosterone surge (2-3 weeks) – can cause pain flare in bone metastases. Prevent with anti-androgen.
LHRH antagonists:
- Mechanism: Block LHRH receptors directly – no testosterone flare
- Examples: Degarelix (Firmagon), relugolix (Orgovyx – oral)
- Advantages: No flare, rapid testosterone suppression (days vs. weeks)
- Disadvantages: More injection site reactions
Anti-androgens:
- Mechanism: Block androgen receptors (do not lower testosterone)
- Examples: Bicalutamide, flutamide, nilutamide
- Use: Combined with LHRH agonist (combined androgen blockade) or alone (less common)
- Side effects: Liver toxicity, gynecomastia, diarrhea
Orchiectomy (surgical castration):
- Procedure: Surgical removal of the testicles
- Advantages: One-time procedure, permanent, no medication side effects
- Disadvantages: Permanent, psychological impact, irreversible
- Use: Rarely used today (most men prefer medical ADT)
When is ADT used?
ADT is used in several clinical scenarios:
- Metastatic prostate cancer (Stage IV): Primary treatment for hormone-sensitive metastatic disease
- High-risk localized cancer: Combined with radiation therapy (neoadjuvant, concurrent, and adjuvant ADT)
- Biochemical recurrence after surgery or radiation: For rising PSA without metastases
- Palliative treatment: For symptomatic metastases (bone pain, ureteral obstruction)
Duration of ADT by risk group (with radiation):
- Low-risk: ADT not indicated (unless very large prostate)
- Favorable intermediate-risk: 4-6 months
- Unfavorable intermediate-risk: 4-6 months (or 18-24 months for some)
- High-risk: 18-36 months (2-3 years)
- Very high-risk: 2-3 years +
Side effects – hot flashes, fatigue, ED, osteoporosis, metabolic syndrome
ADT has significant side effects due to low testosterone:
Common side effects (50-80%):
- Hot flashes: Most common – sudden warmth, sweating, flushing
- Fatigue: Decreased energy, lack of motivation
- Erectile dysfunction (ED): Loss of libido, difficulty with erections
- Loss of muscle mass: Sarcopenia
- Weight gain (especially abdominal fat): Increased fat mass
Serious long-term side effects (10-30%):
- Osteoporosis: Bone density loss → increased fracture risk (2-3x)
- Metabolic syndrome: Insulin resistance, diabetes, hyperlipidemia
- Cardiovascular disease: Increased risk of heart attack and stroke (especially in older men)
- Anemia: Low red blood cell count
- Depression and cognitive changes: Mood swings, memory issues
Other side effects:
- Gynecomastia (breast enlargement/tenderness): More common with anti-androgens
- Joint pain (arthralgias): 20-30%
Managing side effects – lifestyle, medications, supplements
Hot flashes:
- SSRI/SNRI antidepressants (venlafaxine, paroxetine, sertraline)
- Gabapentin
- Megestrol acetate (caution: weight gain)
- Avoid triggers (caffeine, alcohol, spicy foods)
Osteoporosis prevention:
- Calcium: 1,200 mg/day (diet + supplement)
- Vitamin D: 1,000-2,000 IU/day
- Weight-bearing exercise: Walking, resistance training
- Bone density scan (DEXA): Baseline before ADT, repeat every 1-2 years
- Bisphosphonates (zoledronic acid) or denosumab: For osteoporosis
Fatigue and muscle loss:
- Regular exercise: Aerobic + resistance training (most effective)
- Optimize sleep: 7-8 hours/night
- Treat anaemia: Check CBC; iron supplementation if needed
Cardiovascular risk reduction:
- Monitor blood pressure, lipids, glucose
- Statins for elevated cholesterol
- Metformin for diabetes
- Lifestyle: Heart-healthy diet, exercise, smoking cessation
Erectile dysfunction:
- PDE-5 inhibitors (Viagra, Cialis) – less effective on ADT, but can help
- Penile rehabilitation (vacuum device, injections)
Intermittent vs. continuous ADT
Intermittent ADT involves stopping ADT when PSA reaches a low level (nadir) and restarting when PSA rises. It aims to reduce side effects and improve quality of life.
Evidence:
- Multiple large trials (SWOG 9346, PR-7) show intermittent ADT is non-inferior to continuous ADT for overall survival
- Intermittent ADT improves quality of life (fewer hot flashes, better sexual function)
- Not appropriate for men with aggressive or metastatic disease
Who qualifies:
- Biochemical recurrence after local treatment
- Low-volume metastatic disease (select patients)
- Good response to initial ADT (PSA nadir <4 ng/mL after 6-9 months)
ADT and radiation – neoadjuvant, concurrent, adjuvant
ADT is often combined with radiation therapy for intermediate and high-risk prostate cancer:
- Neoadjuvant ADT (before radiation): Shrinks the prostate, reduces treatment volume, improves outcomes. Duration: 2-6 months.
- Concurrent ADT (during radiation): Sensitizes cancer cells to radiation.
- Adjuvant ADT (after radiation): For high-risk cancer, continues for 18-36 months.
Evidence:
- RTOG 86-10 (1990s): ADT + radiation improves survival for high-risk cancer
- RTOG 92-02: Long-term ADT (28 months) better than short-term (4 months) for high-risk
- DART 01/05: 6 months ADT + radiation superior to radiation alone for intermediate-risk
Interactive FAQ – Hormone therapy for prostate cancer
No – ADT controls cancer but does not cure it. Cancer eventually becomes resistant (castration-resistant prostate cancer – CRPC).
Hot flashes, fatigue, ED, loss of libido, osteoporosis, weight gain, metabolic syndrome, cardiovascular risk.
2-3 years on average before cancer becomes resistant. Some men respond for 5-10 years.
Agonists cause initial testosterone flare (2-3 weeks) then suppression. Antagonists have no flare and suppress testosterone faster.
Relugolix (Orgovyx) is an oral LHRH antagonist. Most ADT is given as injections (1-6 months).
Some side effects improve after stopping ADT (hot flashes, fatigue, libido). Osteoporosis and metabolic changes may persist.
ADT is stopped when PSA is low, then restarted when PSA rises. Reduces side effects without compromising survival.
For low-risk: no. For intermediate/high-risk: yes – ADT improves radiation outcomes.
Yes – calcium, vitamin D, weight-bearing exercise, and bisphosphonates or denosumab for high-risk patients.
Disclaimer: This information is for educational purposes. Hormone therapy has significant side effects. Discuss with a medical oncologist or urologist at Vivekananda Hospital.