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Updated: Dec 2, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Endocrine consequences of treatment with the new androgen receptor axis-targeted agents for advanced prostate cancer
Nikolaos Pyrgidis1, Ioannis Vakalopoulos1, Petros Sountoulides2
11st Department of Urology, Aristotle University of Thessaloniki, 15-17 Agiou Evgeniou Street, TK 55133, Thessaloniki, Greece.
Purpose:
Prostate cancer (PCa) is the commonest non-cutaneous malignancy worldwide and the second cause of cancer death among males in the USA. Approval of the new androgen receptor axis-targeted (ARAT) agents (abiraterone acetate, enzalutamide, apalutamide, and darolutamide) has altered the course of advanced PCa. We aimed to assess the endocrine and metabolic adverse events associated with treatment using ARAT compounds.
Methods:
We searched the PubMed, Cochrane Library, and Scopus databases from database inception to August 2020. We included randomized controlled trials reporting the endocrine and metabolic side effects of ARAT agents compared to each other or to placebo.
Results:
Although metastatic PCa remains incurable, ARAT medications combined with androgen deprivation therapy improve overall metastasis-free and progression-free survival in metastatic hormone-sensitive PCa, non-metastatic castration-resistant PCa, and metastatic castration-resistant PCa patients. This benefit comes at the cost of certain endocrine and metabolic consequences. Treatment with abiraterone acetate induces mineralocorticoid excess, hypokalemia, hypertension, elevated liver function tests, insulin resistance, and hyperglycemia. Enzalutamide may induce or worsen hypertension and increase the risk of falls and fractures in elderly patients, while common endocrine adverse events of apalutamide include hypothyroidism, hypertension, and skin rash. On the other hand, darolutamide seems to have a somewhat safer endocrine and metabolic profile.
Conclusion:
Treatment of advanced PCa should be personalized, with administration of a combination of androgen deprivation therapy, ARAT agents, and chemotherapy being based on the patient's safety profile and the risk of side effects.
Insights
Androgen receptor axis-targeted (ARAT) agents improve survival in advanced prostate cancer (PCa) but cause endocrine and metabolic side effects. Darolutamide appears to have a safer profile than other ARAT agents.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Prostate cancer (PCa) is a leading cause of cancer death in men.
- Androgen receptor axis-targeted (ARAT) agents represent a significant advancement in treating advanced PCa.
- Understanding the endocrine and metabolic adverse events of ARAT agents is crucial for patient management.
Purpose of the Study:
- To assess the endocrine and metabolic adverse events associated with ARAT agents used in advanced prostate cancer treatment.
- To compare the side effect profiles of different ARAT agents.
Main Methods:
- Systematic literature search of PubMed, Cochrane Library, and Scopus databases up to August 2020.
- Inclusion of randomized controlled trials comparing ARAT agents to each other or placebo.
- Focus on reporting endocrine and metabolic side effects.
Main Results:
- ARAT agents improve survival outcomes in metastatic hormone-sensitive PCa, non-metastatic castration-resistant PCa, and metastatic castration-resistant PCa.
- Abiraterone acetate is associated with mineralocorticoid excess, hypokalemia, hypertension, elevated LFTs, insulin resistance, and hyperglycemia.
- Enzalutamide may cause or worsen hypertension and increase fall/fracture risk; apalutamide is linked to hypothyroidism, hypertension, and rash.
- Darolutamide demonstrates a comparatively favorable endocrine and metabolic safety profile.
Conclusions:
- Personalized treatment of advanced PCa is essential, considering patient safety profiles and side effect risks.
- Combination therapy (androgen deprivation therapy, ARAT agents, chemotherapy) should be tailored to individual patients.
- Careful monitoring for endocrine and metabolic adverse events is necessary during ARAT agent treatment.
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