Question explored with the scientific record
What is the injectable drug that is used to shrink and treat prostate cancer?
The injectable drugs that shrink prostate cancer are androgen-deprivation therapies, mainly LHRH (GnRH) agonists and antagonists. They work by suppressing testosterone, which fuels tumor growth.
The evidence here is almost entirely funded or co-authored by the manufacturers. The EORTC trial that showed a survival benefit for goserelin plus radiation was funded by AstraZeneca, which makes goserelin [12]. The HERO trial for relugolix was a phase III manufacturer-sponsored study [15]. No trial in this set compared the drug against a true placebo or untreated control; every comparison was against another active treatment or against no treatment in an observational database. The safety data is thin: the largest observational study found that GnRH agonists increased the risk of diabetes (29.0 vs 20.9 per 1,000 person-years), coronary heart disease (72.3 vs 61.3), and sudden cardiac death (12.9 vs 9.0) compared to no treatment [25]. Another study found a 50% increased risk of dementia [1].
| Outcome | No ADT | GnRH agonist | Difference |
|---|---|---|---|
| Incident diabetes (per 1,000 person-years) | 20.9 | 29.0 | +39% |
| Coronary heart disease | 61.3 | 72.3 | +18% |
| Sudden cardiac death | 9.0 | 12.9 | +43% |
These drugs do shrink prostate tumors and improve survival in high-risk disease when combined with radiation [12]. But the benefit comes at a real cost: metabolic disease, cardiovascular events, bone loss, depression, and cognitive decline [17, 19, 25]. The burden of proof for using them in lower-risk men has not been met.
My call: LHRH agonists and antagonists are effective at shrinking prostate tumors and improving survival in advanced or high-risk disease, but the evidence shows they carry significant cardiovascular, metabolic, and cognitive risks that are systematically understated. Confidence: moderate for benefit in high-risk disease; high for the presence of serious harms.
Sources examined 25
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TIME COURSE OF ERECTILE DYSFUNCTION AND SERIAL CHANGES OF BLOOD MARKER OF ENDOTHELIAL ACTIVATION IN STREPTOZOTOSIN-INDUCED DIABETIC RATS
Population-based analysis in men with prostate cancer showed that treatment with luteinizing hormone releasing hormone (LHRH) agonists is independently associated with increased dementia risk after adjustment, while associations with most other comorbidities were not confirmed.
DOI: 10.1016/s0022-5347(09)60844-2 -
Role of adrenal androgens in prostate regression in rats treated with an antiandrogen and an lhrh agonist
This study investigates the role of adrenal androgens in prostate regression in rats treated with the LHRH agonist histrelin and the antiandrogen flutamide, finding that the combination of these drugs leads to significant prostate atrophy primarily through the action of testicul…
DOI: 10.1002/pros.2990090303 -
Single-Therapy Androgen Suppression in Men with Advanced Prostate Cancer
This systematic review and meta-analysis compares the effectiveness of luteinizing hormone-releasing hormone (LHRH) agonists, orchiectomy, diethylstilbestrol, and antiandrogens in men with advanced prostate cancer, finding that LHRH agonists provide survival rates equivalent to …
DOI: 10.7326/0003-4819-132-7-200004040-00009 -
Does Oral Antiandrogen Use Before Leuteinizing Hormone-releasing Hormone Therapy in Patients With Metastatic Prostate Cancer Prevent Clinical Consequences of a Testosterone Flare?
This study investigates whether the use of oral antiandrogens before initiating LHRH agonist therapy in patients with metastatic prostate cancer reduces the clinical consequences of testosterone flare, finding no significant differences in complications regardless of antiandroge…
DOI: 10.1016/j.urology.2009.08.008 -
Abarelix and other gonadotrophin‐releasing hormone antagonists in prostate cancer
This study evaluates the efficacy and safety of GnRH antagonists, specifically abarelix and degarelix, in the treatment of advanced prostate cancer, highlighting their ability to achieve rapid testosterone suppression without the risk of testosterone flare associated with LHRH a…
DOI: 10.1111/j.1464-410x.2009.08924.x -
Luteinizing hormone-releasing hormone receptor agonists and antagonists in prostate cancer: effects on long-term survival and combined therapy with next-generation hormonal agents
This narrative review analyzes long-term survival outcomes and safety of luteinizing hormone-releasing hormone receptor (LHRH-R) agonists and antagonists in prostate cancer, including their use in combination with next-generation hormonal agents (NHAs) across localized, locally …
DOI: 10.20892/j.issn.2095-3941.2024.0139 -
Metastatic prostate cancer pulmonary nodules: Beneficial effects of combination therapy and subsequent withdrawal of flutamide
This study presents a case of a middle-aged man with stage D2 prostate cancer and pulmonary metastases who showed a favorable response to combination therapy with flutamide and an LHRH agonist, followed by a positive response to the withdrawal of flutamide upon disease progressi…
DOI: 10.1002/pros.2990240507 -
Multimodality salvage for patients with persistently elevated postprostatectomy PSA
This retrospective study evaluated multimodality salvage (whole-pelvis external-beam radiation with a prostate-bed boost plus 6 months of LHRH agonist) in 14 men with persistently elevated postprostatectomy PSA, finding durable biochemical control for those salvage-treated at PS…
DOI: 10.1002/1097-0215(20001220)90:6<331::aid-ijc4>3.0.co;2-u -
Comparison of serum testosterone levels in prostate cancer patients
Circulating testosterone remains similarly suppressed across radical prostatectomy, radiation, and primary hormone therapy groups among men on LHRH agonists, with no link to PSA or time on therapy.
DOI: 10.5489/cuaj.377 -
Impact of Surgical and Medical Castration on Serum Testosterone Level in Prostate Cancer Patients
This study evaluates the impact of surgical and medical castration on serum testosterone levels in prostate cancer patients, highlighting the effectiveness of GnRH agonists in achieving castration levels.
DOI: 10.1159/000209352 -
Effect of a new leuprorelin formulation on testosterone levels in patients with advanced prostate cancer
This study evaluates a new formulation of leuprorelin acetate (Eligard) for testosterone suppression in patients with advanced prostate cancer, demonstrating its effectiveness in achieving low testosterone levels comparable to surgical castration with a favorable safety profile.
DOI: 10.1185/030079906X96425 -
External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study
In men with high metastatic-risk prostate cancer, radiotherapy plus 3 years of immediate androgen suppression with an LHRH agonist significantly improves 10-year clinical disease-free survival and overall survival compared with radiotherapy alone, without increasing late cardiov…
DOI: 10.1016/S1470-2045(10)70223-0 -
FAILURE TO ACHIEVE CASTRATE LEVELS OF TESTOSTERONE DURING LUTEINIZING HORMONE RELEASING HORMONE AGONIST THERAPY: THE CASE FOR MONITORING SERUM TESTOSTERONE AND A TREATMENT DECISION ALGORITHM
In a prospective cohort of 38 men with advanced prostate cancer treated with 3-month depot LH-RH agonists, a minority failed to reach castrate testosterone levels; the study advocates monitoring testosterone and proposes a treatment algorithm (orchiectomy or antiandrogen additio…
DOI: 10.1016/s0022-5347(05)67290-4 -
Rapid Suppression of Plasma Testosterone Levels and Tumor Growth in the Dunning Rat Model Treated with Degarelix, a New Gonadotropin-Releasing Hormone Antagonist
Degarelix, a GnRH antagonist, rapidly suppresses plasma testosterone and inhibits tumor growth in the androgen-dependent Dunning R-3327H rat prostate cancer model, performing similarly to surgical castration and superior to the GnRH agonist D-Trp6-LHRH in the short term, with su…
DOI: 10.1124/jpet.106.112326 -
Relugolix in treatment of prostate cancer: a review
A non-systematic review summarizing relugolix as an oral GnRH antagonist for androgen deprivation therapy in prostate cancer, detailing pivotal HERO trial results, safety advantages (notably cardiovascular), real-world adherence data, and comparisons with degarelix/leuprolide, p…
DOI: 10.4081/aiua.2025.14277 -
Effectiveness and adverse effects of hormonal therapy for prostate cancer: Japanese experience and perspective
This article reviews the Japanese experience with hormonal therapy for prostate cancer, highlighting its efficacy, adverse effects, quality-of-life, cost considerations, and strategies across primary, neoadjuvant/adjuvant, and combination regimens, while discussing ethnic differ…
DOI: 10.1038/aja.2011.121 -
Depressive symptoms are found to be potential adverse effects of androgen deprivation therapy in older prostate cancer patients: A 15‐month prospective, observational study
This study investigates the association between androgen deprivation therapy (ADT) and depressive symptoms in older prostate cancer patients, revealing that ADT significantly increases depressive scores and the incidence of depression over a 15-month period.
DOI: 10.1002/pon.4453 -
Quantitation of the early effects of radiation and hormonal therapy on hemoglobin levels in men treated for prostate cancer
This study investigates the effects of radiation therapy and androgen deprivation on hemoglobin levels and bladder function in men with prostate cancer, revealing significant decreases in hemoglobin levels and a reduction in bladder capacity post-treatment, but no major adverse …
DOI: 10.1016/s0360-3016(01)01854-5 -
French recommendations for osteoporosis prevention and treatment in patients with prostate cancer treated by androgen deprivation
This paper provides a practical French consensus guidelines for osteoporosis prevention and treatment in men with prostate cancer on androgen-deprivation therapy (ADT), outlining risk assessment, BMD/FRAX use, vitamin D and calcium optimization, and recommended medications (bisp…
DOI: 10.1016/j.jbspin.2018.09.017 -
ADT with antiandrogens in prostate cancer induces adverse effect of increasing resistance, neuroendocrine differentiation and tumor metastasis
A mini-review summarizing how androgen-deprivation therapy (ADT) with antiandrogens (notably enzalutamide) in prostate cancer can provoke adverse effects—rapid resistance, neuroendocrine differentiation, and enhanced metastasis—by multiple AR-centered and non-AR pathways, and di…
DOI: 10.1016/j.canlet.2018.09.020 -
Intensity‐modulated radiotherapy to the pelvis and androgen deprivation in men with locally advanced prostate cancer: A study of adverse effects and their relation to quality of life
This study investigates the adverse effects and quality of life in men with locally advanced prostate cancer undergoing intensity-modulated radiotherapy combined with androgen deprivation therapy, revealing significant reductions in urinary, bowel, and sexual function and bother…
DOI: 10.1002/pros.22651 -
CUOG PHASE II RANDOMIZED STUDY OF CUSTIRSEN (OGX-011) COMBINATION THERAPY IN PATIENTS WITH CASTRATE RESISTANT PROSTATE CANCER (CRPC) WHO RELAPSED ON OR WITHIN SIX MONTHS OF 1ST-LINE DOCETAXEL THERAPY
This study investigates the effects of twice-yearly subcutaneous denosumab on bone mineral density in men undergoing androgen-deprivation therapy for non-metastatic prostate cancer, demonstrating significant increases in bone mineral density across various subgroups.
DOI: 10.1016/s0022-5347(09)60654-6 -
A randomised controlled trial to evaluate the efficacy of a 6-month dietary and physical activity intervention for patients receiving androgen deprivation therapy for prostate cancer
This study evaluates the efficacy of a 6-month dietary and physical activity intervention aimed at reducing adverse body composition changes and improving quality of life in prostate cancer patients undergoing androgen deprivation therapy.
DOI: 10.1007/s11764-014-0417-8 -
Role of Overall Treatment Time in the Management of Prostate Cancer Patients: How to Manage Unscheduled Treatment Interruptions
This study examines the impact of overall treatment time (OTT) on prostate cancer outcomes, particularly in the context of unscheduled treatment interruptions, and suggests strategies to mitigate potential adverse effects.
DOI: 10.1016/j.ijrobp.2017.12.278 -
Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy for Prostate Cancer
This observational study investigates the association between androgen deprivation therapy, specifically GnRH agonists, and the increased risk of diabetes and cardiovascular disease in older men with locoregional prostate cancer.
DOI: 10.1200/JCO.2006.06.2497