From the Guidelines
Patients on testosterone deprivation therapy should be closely monitored for potential long-term complications, including bone density loss, cardiovascular complications, metabolic changes, and cognitive disturbances, as these can significantly impact morbidity, mortality, and quality of life. The most recent and highest quality study, published in 2020 in the Annals of Oncology 1, highlights the importance of monitoring bone health in men with prostate cancer on androgen deprivation therapy (ADT), as the risk of fragility fracture exceeds accepted intervention thresholds.
Key complications to look out for include:
- Bone density loss leading to osteoporosis and increased fracture risk
- Cardiovascular complications such as increased risk of heart attacks and strokes
- Metabolic changes including insulin resistance and diabetes
- Sexual dysfunction, hot flashes, gynecomastia (breast enlargement), cognitive changes, fatigue, and mood disturbances including depression
Regular monitoring should include:
- Bone density scans every 1-2 years
- Lipid panels
- Blood glucose testing
- Blood pressure checks
- Cardiovascular risk assessments
Patients may benefit from calcium (1200-1500 mg daily) and vitamin D (800-1000 IU daily) supplementation to mitigate bone loss, as well as weight-bearing exercise and resistance training to maintain bone density and muscle mass 1. The risk of complications increases with longer duration of therapy, making regular monitoring essential for early intervention. Additionally, a study published in 2019 in the Journal of the National Comprehensive Cancer Network 1 suggests that orchiectomy may be safer than LHRH agonist in terms of fracture, peripheral arterial disease, and cardiac-related complications.
It is essential to prioritize the patient's overall health and well-being, considering the potential long-term effects of testosterone deprivation therapy on morbidity, mortality, and quality of life. By closely monitoring for these complications and implementing preventive measures, healthcare providers can help mitigate the risks associated with ADT and improve patient outcomes.
From the FDA Drug Label
Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH. (5.1) Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), have been reported in patients using testosterone products. Evaluate patients with signs or symptoms consistent with DVT or PE. (5.4) Some postmarketing studies have shown an increased risk of myocardial infarction and stroke associated with use of testosterone replacement therapy. (5. 5) Exogenous administration of androgens may lead to azoospermia. (5.8) Edema, with or without congestive heart failure, may be a complication in patients with preexisting cardiac, renal, or hepatic disease. (5.10) Sleep apnea may occur in those with risk factors. (5.12) Monitor prostate specific antigen (PSA), hematocrit, and lipid concentrations periodically. (5.1,5.3,5. 13)
The potential long-term complications to look for in patients with testosterone deprivation therapy include:
- Cardiovascular events: myocardial infarction, stroke, and venous thromboembolism (VTE) 2
- Prostate issues: worsening of benign prostatic hyperplasia (BPH) and changes in prostate specific antigen (PSA) levels 2
- Hematologic changes: azoospermia and changes in hematocrit levels 2
- Edema and congestive heart failure: especially in patients with preexisting cardiac, renal, or hepatic disease 2
- Sleep apnea: in patients with risk factors 2
- Lipid changes: changes in lipid concentrations 2
From the Research
Potential Long-term Complications of Testosterone Deprivation Therapy
The potential long-term complications to look for in patients with testosterone deprivation therapy include:
- Osteoporosis: decreased bone mineral density and increased fracture risk 3
- Metabolic complications: insulin resistance, diabetes, dyslipidemia, and metabolic syndrome 4, 5
- Cardiovascular disease: increased risk of cardiovascular mortality 4, 5
- Sexual dysfunction: decreased libido and sexual dysfunction 6, 7
- Gynecomastia: breast tenderness and enlargement 6, 7
- Vasomotor complications: hot flushes 6
- Neurocognitive deficits: decreased cognitive function 6
- Thromboembolic disease: increased risk of blood clots 6
- Depression: decreased mental health and well-being 6
- Anemia: decreased red blood cell count 7
- Fatigue: decreased energy levels 7
- Changes in body composition: weight gain, decreased muscle mass, and increased body fat 7
Strategies to Mitigate Adverse Effects
Several strategies can be used to mitigate the adverse effects of testosterone deprivation therapy, including:
- Lifestyle modifications: regular exercise, healthy diet, smoking cessation, and moderate alcohol consumption 3, 7
- Medications: bisphosphonates, denosumab, selective estrogen receptor modulators for bone loss 7
- Medications: metformin for metabolic syndrome 7
- Medications: tamoxifen, prophylactic radiation for gynecomastia 7
- Medications: venlafaxine, medroxyprogesterone, cyproterone acetate, gabapentin for hot flashes 7
- Resistance and aerobic exercise for muscle loss 7