Andrew Siegel MD 9/25/2021
Androgen Deprivation Therapy (ADT) for Prostate Cancer
“Androgen” refers to testosterone, the main male sex hormone. Androgen deprivation therapy (ADT), a.k.a. hormonal therapy, is a means of managing prostate cancer by reducing levels of testosterone. Testosterone — 90-95% produced in the testicles — stimulates both benign and malignant prostate growth and its suppression with ADT restrains this growth. For years, ADT has been the standard of care for advanced prostate cancer. Although it does not cure prostate cancer, lowering testosterone levels often makes prostate cancers shrink and grow more slowly and many patients will experience long-term remissions. Although it delays disease progression, the effects on survival are less clear. It is important to know that given enough time, prostate cancer cells are capable of mutating and ultimately becoming able to thrive in a low testosterone environment, a condition referred to as castrate-resistant prostate cancer. Because of side effects, ADT should only be used when clearly indicated and avoided when possible.
ADT is useful in the following circumstances:
- When definitive treatment needs to be deferred
- When poor health or advanced age contraindicates more aggressive treatments
- In conjunction with radiation therapy because of synergistic effect of radiation with ADT
- Prior to surgery, radiation, or ablative therapies to shrink the prostate
- To manage surgery or radiation failures
- As primary treatment for metastatic disease
ADT for prostate cancer can be achieved either surgically or medically:
Orchiectomy (surgical castration) is an operation in which the urologist removes the testicles. This is a simple outpatient procedure and is the least expensive and most uncomplicated way to reduce testosterone levels in the body. Unlike other methods of lowering testosterone levels, it is permanent and irreversible, and many men — understandably so — do not relish the concept of having their testicles removed. However, it is a choice for someone who favors an inexpensive and one-and-done approach to ADT.
Luteinizing hormone-releasing hormone (LHRH) analogs (also called LHRH agonists) lower testosterone levels as effectively as surgical castration, only chemically as opposed to surgically. They are the most commonly used means of ADT in the United States. LHRH analogs are given by needle injection either monthly or every 3, 4, or 6 months. The LHRH analogs available in the United States include leuprolide (Lupron, Viadur, Eligard), goserelin (Zoladex), and triptorelin (Trelstar).
Luteinizing hormone-releasing hormone (LHRH) antagonists reduce testosterone rapidly without the short-term increase in testosterone levels seen with the LHRH analogs. Degarelix (Firmagon) is an LHRH antagonist that induces “castrate” levels of testosterone within 3 days of the injection. This medication requires monthly injections.
Anti-androgens block the body’s ability to use testosterone, thus “starving” prostate cancer cells from being stimulated by testosterone. Anti-androgen treatment may be combined with LHRH analogs, antagonists or surgical castration as first-line hormone therapy. The newer-generation anti-androgens include enzalutamide (Xtandi), abirataron (Zytiga), and apalutamide (Erleada).
Possible side effects of all forms of ADT include the following:
- hot flashes
- diminished sex drive; erectile dysfunction
- breast tenderness and growth
- anemia (low red blood cell count)
- decreased mental acuity
- loss of muscle and bone mass; increase in body fat and weight gain
- fatigue and weakness
- altered lipid profiles: increase in cholesterol, triglycerides, and decrease in HDL (“good”) cholesterol; increased insulin resistance, type 2 diabetes and coronary disease
- depression
What’s New in ADT?
In December 2020, the FDA approved Myovant Science’s Orgovyx (Relugolix-pronounced “rel-you-go-lix”) — an oral LHRH receptor antagonist– the first once-a-day pill for the treatment of adult patients with advanced prostate cancer.
Orgovyx is dosed at three 120 mg tablets the first day and 120 mg daily thereafter. Castrate levels of testosterone are achieved within one week and are thereafter sustained.
Benefits of this new product are the following:
- Once daily oral dosing (versus conventional injections)
- Rapid testosterone suppression within days (versus much slower with the injectable LHRH analogs)
- Avoidance of the testosterone surge (flare) seen with the injectable LHRH analogs
- Rapid testosterone recovery: Within 3 months of discontinuing the medication, more than 50% of patients will have testosterone levels that are above the lower limit of the normal range (versus much slower recovery with the injectable LHRH analogs)
- Decreased potential risks of major cardiac events (heart attack and stroke) as compared to the injectable LHRH analogs
The most common side effects of Orgovyx are hot flashes, elevated serum glucose, elevated serum triglycerides, musculoskeletal pain, anemia, abnormal liver function tests, constipation and diarrhea.
In a large clinical trial, serious adverse reactions occurred in 12% of patients, including myocardial infarction (0.8%), acute kidney injury (0.6%), arrhythmia (0.6%), hemorrhage (0.6%), and urinary tract infection (0.5%). Fatal and non-fatal myocardial infarction and stroke were reported in 2.7% of patients.
As with many new drugs, cost is a major concern with the pricing set at $2300/monthly with insurance coverage remaining to be seen, but typically quite variable from carrier to carrier.
Wishing you the best of health,
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Dr. Andrew Siegel is a physician and urological surgeon who is board-certified in urology as well as in female pelvic medicine and reconstructive surgery. He is an Assistant Clinical Professor of Surgery at the Rutgers-New Jersey Medical School and is a Castle Connolly Top Doctor New York Metro Area, Inside Jersey Top Doctor and Inside Jersey Top Doctor for Women’s Health. His mission is to “bridge the gap” between the public and the medical community. He is a urologist at New Jersey Urology, the largest urology practice in the United States. He is the co-founder of PelvicRx and Private Gym. His latest book is Prostate Cancer 20/20: A Practical Guide to Understanding Management Options for Patients and Their Families.
Video trailer for Prostate Cancer 20/20
Preview of Prostate Cancer 20/20
Andrew Siegel MD Amazon author page
PROSTATE CANCER 20/20 is now available at Audible, iTunes and Amazon as an audiobook read by the author (just over 6 hours).
Dr. Siegel’s other books:
PROMISCUOUS EATING— Understanding and Ending Our Self-Destructive Relationship with Food
MALE PELVIC FITNESS: Optimizing Sexual and Urinary Health
THE KEGEL FIX: Recharging Female Pelvic, Sexual, and Urinary Health
Tags: ADT, Andrew Siegel MD, androgen deprivation therapy, Orgovyx, prostate cancer, Relugolix
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