If you or a loved one is about to undergo or is undergoing endocrine therapy to fight prostate cancer and are very concerned about the physical effects of endocrine therapy, I believe this article will help you.
Key points of this article:
- Endocrine therapy is important in the treatment of prostate cancer, but endocrine therapy can cause a significant decrease in androgen levels, which can lead to adverse effects such as hot flashes, erectile dysfunction, and osteoporosis.
- LHRH agonists can cause a transient rise in serum testosterone that exacerbates the disease and can be pretreated with nonsteroidal antiandrogenic drugs prior to treatment.
- Endocrine therapy can lead to osteoporosis, and administration of bisphosphonates can help prevent fractures.
- Many prostate cancer patients die not from cancer but from cardiovascular disease, so special vigilance is needed for the effects of endocrine drugs on cardiovascular disease.
- Endocrine therapy can lead to sexual dysfunction, which can affect couples’ lives, so partner support is important. However, there are ways to treat erectile dysfunction.
Endocrine therapy currently has an important place in the treatment of prostate cancer, not only in combination with surgery for limited prostate cancer, but has been the standard treatment option for advanced and metastatic prostate cancer. Classical endocrine therapy options include:
- LHRH (i.e., luteinizing hormone-releasing hormone) agonist analogs: e.g., goserelin, treprostinil, leuprolide;
- Testicular denervation surgery;
- Non-steroidal anti-androgenic drugs: e.g. bicalutamide, flutamide, nilumet;
- Steroidal antiandrogenic drugs: e.g. estrogen, progesterone, etc.
Androgens have physiological functions such as maintaining cognition, stimulating the mind, promoting musculoskeletal development, maintaining male libido, and stimulating hematopoiesis. Patients receiving endocrine therapy may have a range of corresponding complications due to significantly lower androgen levels, including: hot flashes, decreased libido, erectile dysfunction, gynecomastia, and loss of bone mineral density.
Particularly important is the fact that lower blood testosterone levels can cause insulin resistance, atherosclerosis, diabetes mellitus, and metabolic syndrome, and the development of these comorbidities has become the leading cause of non-tumor-specific death in patients with prostate cancer.
Therefore, it has become a concern for patients and physicians to prevent and manage complications due to lowered hormone levels to ensure the safety of endocrine therapy while ensuring good tumor control in prostate cancer patients.
This article summarizes the safety issues and recommendations for endocrine therapy from the recently published “Consensus on Safety of Classical Endocrine Therapy for Prostate Cancer” (2018).
Acute adverse events
Why do acute adverse events occur?
Acute adverse events in endocrine therapy for prostate cancer are primarily associated with pharmacologic debulking and surgical debulking therapy. Although pharmacologic debulking has become the mainstay of debulking therapy, patients with prostate cancer are still treated clinically with surgical debulking.
Orchiectomy is a basic surgical procedure in urology, but still carries some specific risks for patients who develop prostate cancer. The most common complication of surgery is a scrotal hematoma.
In addition, special attention needs to be paid to the fact that prostate cancer patients undergoing surgical debulking are more likely to have concomitant bone metastases, which are predominantly in the mid-column bones, and the patient needs to be taken with extreme caution as transport, movement, and even anesthesia may result in paraplegia. These patients are at higher risk for surgery and require adequate communication with their physicians prior to treatment.
The use of LHRH agonists (goserelin, treprostinil, leuprolide) is associated with a transient increase in serum testosterone, which can lead to PSA flare and worsening of the condition.
How to prevent acute adverse events?
How to prevent acute adverse events?
Most acute adverse events with endocrine therapy for prostate cancer can be prevented.
- For patients of advanced age and poor general condition of chronic anemia with high surgical risk, pharmacologic debulking is recommended as the first choice.
- Patients with preexisting bone metastases spinal cord compression or tumor-associated obstructive nephropathy, as well as those who are elderly and have severe comorbidities, are routinely pretreated with nonsteroidal antiandrogenic drugs for 2 to 3 weeks before receiving pharmacologic debulking therapy in order to avoid possible exacerbation by a transient increase in serum testosterone levels when pharmacologic debulking is chosen.
Osteoporosis and bone dysplasia-related events
Why does endocrine therapy cause osteoporosis?
Patients with prostate cancer are mostly older men who have a high incidence of osteoporosis. Endocrine therapy then accelerates bone loss and increases bone resorption in patients, causing decreased bone mineral density, osteoporosis, and increased risk of osteoporosis-related fractures.
What is an adverse bone-related event?
Bone malnutrition-related events that may result from endocrine therapy include:
- Radiotherapy to relieve skeletal pain or to treat or prevent pathologic fractures or spinal cord compression;
- Pathologic fractures;
- spinal cord compression;
- Skeletal surgery;
- Change in anticancer therapy due to bone disease;
- hypercalcemia due to malignancy, etc.
How to prevent osteoporosis and reduce the incidence of events related to bone dysplasia?
- Patients are advised to undergo bone densitometry (DEXA) to assess bone mass levels before endocrine therapy and to be monitored for bone mass changes every 1 to 2 years after treatment;
- Appropriate physical activity, smoking and alcohol cessation, and calcium and vitamin D supplementation;
- For patients at high risk of fracture, zoledronic acid or denosumab can be administered in parallel with endocrine therapy to reduce the incidence of osteoporotic fractures.
Metabolism-related adverse events
Hot flashes
Hot flashes are a common side effect of surgical or pharmacologic debulking therapy. Typical symptoms are episodes of hot flashes on the face, face, and upper body with sweating. Common triggers include heat, stress, change in body position, or eating. Hot flashes can recur throughout the course of endocrine therapy and resolve on their own in only a small percentage of patients.
Despite the high incidence of hot flashes, the vast majority of patients do not require pharmacologic treatment. Patients with severe hot flashes can be treated with hormones (megestrol, methacholine), 5-hydroxytryptamine reuptake inhibitors (sertraline, paroxetine), gabapentin, and other medications.
Glucose/lipid metabolism abnormalities and metabolic syndrome
Abnormal lipid metabolism, as evidenced by elevated glucose, total cholesterol, LDL, and triglycerides, may increase the risk of cardiovascular disease in patients.
How to prevent and treat metabolic abnormalities caused by endocrine therapy?
- Many prostate cancer patients have a combination of metabolic syndrome, and these patients are likely to have increased metabolic abnormalities after receiving endocrine therapy. Therefore, it is important to inform your doctor of your medical history before receiving endocrine therapy.
- During endocrine therapy, patients should pay attention to adjust their diet and exercise appropriately to maintain their weight; after endocrine therapy, patients should monitor their blood glucose to detect and treat diabetes as early as possible; if necessary, doctors will give lipid-lowering drugs to correct the abnormalities of lipid metabolism.
- For patients with combined metabolic syndrome or diabetes, fasting blood glucose, glycosylated hemoglobin and lipids should be actively monitored during endocrine therapy, and endocrinologists should be consulted to develop a personalized treatment plan if necessary.
Anemia
After endocrine therapy, most patients with prostate cancer will have varying degrees of anemia, but it usually does not need to be managed. For those with severe anemia but normal bone marrow hematopoiesis, erythropoietin may be considered.
Lack of energy
Long-term endocrine therapy can lead to malaise, which may be associated with a decrease in body muscle mass and an increase in fat, along with a combination of pain and depression. Patients can increase their intake of high-quality protein and engage in appropriate physical exercise, including resistance training and aerobic training. For depressed patients, they can seek psychological counseling from a psychiatrist, and family members should also pay more attention to the patient’s mental health.
Adverse cardiovascular events
Cardiovascular events are now the #2 cause of death in prostate cancer patients. The main cardiovascular adverse events include myocardial infarction, arrhythmias, ischemic heart disease, heart failure, and stroke.
Endocrine therapy may induce cardiovascular disease either directly by affecting cardiomyocyte calcium exchange and myocardial contractility, or indirectly by lowering androgen levels leading to hyperinsulinemia, insulin resistance, hypertension, abnormal lipid metabolism, and other mechanisms.
The US Food and Drug Administration, the American Urological Association, and the American Cardiovascular Society all recommend that the cardiovascular effects of endocrine drugs be specifically noted in the instructions for depot drugs.
How to prevent cardiovascular events?
- For patients without comorbid underlying cardiovascular disease, while receiving endocrine therapy.
- Moderate diet and exercise to control weight and stop smoking;
- Concurrent blood pressure control in patients with hypertension;
- Regular monitoring of blood glucose and lipid changes for early detection of diabetes and appropriate treatment.
- For patients with comorbid underlying cardiovascular disease, comprehensive prevention and treatment measures such as diet modification, reduction of saturated fat and cholesterol intake, weight control, smoking cessation, and aggressive control of hypertension with low-dose aspirin are recommended.
- For those patients with more severe comorbidities, a joint urology, oncology, and cardiovascular medicine consultation may need to be requested if necessary.
Sexual dysfunction
After endocrine therapy, it is common for patients to have decreased libido, erectile dysfunction, and breast development due to decreased serum testosterone levels.
Patients should therefore be fully informed about the effects of treatment on sexual function before receiving endocrine therapy, and family members should provide encouragement and comfort. For patients with sexual needs, intermittent endocrine therapy may be an option if the condition permits. For treatment of erectile dysfunction, treatment modalities such as phosphodiesterase-5 inhibitors (e.g., sildenafil), intracavernous penile injections, negative compression devices, and penile prosthesis implants may be considered.
In addition, patients can experience depression, stress, anxiety, fatigue, irritability, and other emotional states after endocrine therapy, but the vast majority can return to normal after discontinuation of the drug. As family members, they should recognize that these emotional changes may be due to treatment and try to understand and encourage the patient as much as possible to increase their confidence in overcoming the disease.
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