Metabolic complications of prostate cancer

The treatment of metabolic complications of patients with advanced prostate cancer it is very important and improves the quality of life and its survival. Advanced disease occurs when the patient has metastatic disease, that is, the patient has lesions of prostate cancer spread through the skeleton, ganglia and / or in the most advanced stage in viscera (lung, liver and brain). Metabolic complications are caused by testosterone deficiency extreme to which these patients are submitted. The testosterone level is frequently less than 20 ng / mL in patients treated with antiandrogenic therapy. Its level considered normal in our body must be greater than 300 ng / dL.

As metabolic complications testosterone suppression are mainly linked to musculoskeletal events, cardiovascular diseases, diabetes mellitus and neurovegetative diseases. In addition, they cause significant changes in quality of life such as: worsening of the quality of erection, loss of libido, fatigue, hot flashes (hot flushes) among others.

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Protective role of testosterone in the cardiovascular system

The normal testosterone level throughout life is critical to the vitality of many organs, including the heart. In this way, testosterone promotes coronary vasodilation and scientific evidence proves its effects:
Injection of intracoronary testosterone causes vasodilation of coronary arteries
In men with cardiocirculatory disease, the normal testosterone level prolongs the ischemia time in the stress test
Causes stability of coronary atheromatous plaque
Testosterone has antiarrhythmic effect and reduced QT interval on the electrocardiogram
Has a favorable effect on the body composition of several organs
The drop in testosterone in men with cardiocirculatory disease is a marker of increased mortality from all causes, including cardiovascular.

The drop in testosterone in the treatment of advanced prostate cancer causes obesity

A direct relationship between weight gain and drop in testosterone, caused by important metabolic changes that occur in body fat. These patients have their clinical effects proven by:

• Weight gain after one year of treatment with a drop in testosterone is about 1,5 to 4 kg and is greater in younger, non-obese patients,
• Increase in total body fat of up to 9-11% and decrease in lean body mass of 3-4%, and
• Sarcopenic obesity - abdominal obesity is associated with reduced muscle mass and significantly increases mortality from all causes. Sarcopenia refers to the loss of muscle mass in these patients.

Antiandrogenic therapy and dyslipidemia

Dyslipidemia is commonly seen during antiandrogen therapy (caused by extreme testosterone deficiency). Therefore, this treatment increases:

• total cholesterol around 10%,
• LDL around 7%,
• HDL around 8% to 10% and
• triglyceride levels by approximately 26%.

Thus, treatment with antiandrogenic drugs increases HDL, but the presence of testosterone is necessary for the reverse transport of cholesterol from the arterial wall to the liver. Therefore, this therapy causes a liquid and is pro-atherogenic.

Metabolic syndrome and antiandrogen therapy

The metabolic aberrations of antiandrogenic therapy in patients with advanced prostate cancer are similar, but not identical, to those of the classic metabolic syndrome. Its prevalence is 20% to 25% in the adult population. Male hypogonadism is an independent risk factor for metabolic syndrome, while low testosterone and SHBG levels can predict metabolic syndrome in men.
In patients treated with antiandrogen therapy for more than 1 year, its prevalence is higher, around 36% to 55%, regardless of age, race and stage of prostate cancer.

One of the most dangerous metabolic complications: The metabolic syndrome and its definition

The International Diabetes Federation defines the metabolic syndrome in the presence of 3 of the 5 criteria:

• triglycerides higher than 150 mg / dL,
• reduced HDL-cholesterol less than 40 mg / dL,
• systolic high blood pressure greater than 130 mmHg and diastolic blood pressure greater than 85 mmHg,
• an increase in fasting plasma glucose greater than 100 mg / dL (diabetes type 2)
• obesity center is defined by waist circumference greater than 94 cm in men and greater than 80 cm in women.

Metabolic complications - Common comorbidities in men with non-metastatic prostate cancer

In a study that evaluated 3.183 men with non-metastatic prostate cancer, the most common common comorbidities were cardiovascular disease, rheumatic diseases, diabetes mellitus, depression, gastrointestinal ulcer, chronic obstructive pulmonary disease, inflammatory bowel disease and liver disease (cirrhosis) . Cardiovascular diseases include angina, congestive heart failure, hypertension, myocardial infarction and stroke.

The most frequent was cardiovascular with 51%, followed by rheumatics with 20% and the third was diabetes with 9% and the others with less than 5%. However, several patients had more than 1 or 2 comorbidities. Patients' survival declines progressively from patients without comorbidities to those who have one or more. Sometimes, these diseases are more important than the presence of cancer.

Therefore, understanding the comorbidities of patients with prostate cancer is essential to start a treatment that may also cause more comorbidities or even aggravate existing ones. Therefore, sometimes treating with less aggressive and less radical drugs, such as peripheral testosterone blockers or even not starting a treatment, may be better than treating as recommended by urological societies. Therefore, the great is the enemy of the good.

The most frequent of the metabolic complications. Risk and timing of cardiovascular disease before antiandrogen therapy begins in men with prostate cancer.

In a study of 41.362 men with prostate cancer treated with antiandrogenic therapy versus comparison with the time the patient received some treatment for cardiovascular disease. The control group was patients without prostate cancer, showed:
The risk of cardiovascular disease increased by 21% in men receiving GnRH agonists (these drugs lower testosterone to values ​​close to 20 ng / mL). In addition, the risk of cardiovascular disease is highest in the first 6 months of antiandrogenic treatment in men who have experienced two or more cardiovascular events in the 6 months prior to therapy. The risk in these patients is almost doubled. Those who had 1 event that happened more than 1 year ago, the risk was equal to patients without cardiovascular disease.

Therefore, normal testosterone has beneficial positive effects on cardiac perfusion, ischemic threshold, exercise threshold, cardiac output. On the other hand, its deficiency impairs cardiovascular function.

Recommendations for patients on antiandrogen treatment

• Daily use of preventive aspirin

In a study of 10.422 men with non-metastatic prostate cancer, patients considered to be at high risk who received daily aspirin had lower specific cancer mortality. There was a 40% reduction compared to those who were not treated with aspirin (HR = 0,60; 95% CI, 0,37 to 0,97). Therefore, it appears that aspirin by causing platelet inhibition has antitumor activity. Thus, it appears that normal activated platelets promote cancer metastasis through multiple mechanisms.

Obesity and insulin resistance

To an intimate correlation between obesity and the development of diabetes. Abdominal obesity is associated with metabolic complications, a chronic state of inflammation, with a significant increase in adipocytokines such as TNF-α, IL-6 and resistin. Antiandrogenic therapy decreases insulin sensitivity in diabetic men at 12 weeks. There is a 26% increase in plasma fasting insulin and a 13% decrease in insulin sensitivity.
In the SEER data, with 73.196 prostate cancer patients treated with GnRH agonists, they had a higher incidence of diabetes mellitus (HR 1,42), which means a 42% increase in relation to non-diabetic people.
Thus, the antiandrogenic therapy may worsen glycemic control and increase HbA1c (glycated Hb) in diabetics.

• Metformin to prevent metabolic syndrome associated with antiandrogen therapy

One study showed a slight improvement in survival in patients with prostate cancer who had received metformin. However, a recent study in patients with advanced cancer who received antiandrogenic therapy was carried out, with one group of non-diabetic patients receiving metformin and another group not. However, this study showed no benefit from its use.

Meat consumption and prostate cancer

Heart disease remains a greater threat to many prostate cancer patients than cancer itself. Some knowledge about it:
Healthier heart diet: less meat and more vegetables
Some evidence that the diet can influence the prostate cancer
Low-fat, vegan diet in patients undergoing active surveillance decreased PSA by 4% compared to the average 6% increase in the control group
MEAL study: the vegetable-based diet did not notice an improvement in PSA (7 servings of vegetables per day vs 1 serving vegetables)
The Massa study showed an improvement in the PSA doubling time, increasing the consumption of whole grains, legumes, green and yellow vegetables and decreasing the consumption of animal protein and processed foods.

Exercises to overcome the metabolic complications of antiandrogen therapy

A meta-analysis article of 15 studies with 1.135 prostate cancer patients on antiandrogenic therapy reached the following conclusions:
Exercise can significantly improve the strength of the upper and lower limb muscles, increase exercise tolerance, help control your body fat mass, body mass index (BMI), lower cholesterol and help maintain sexual function.

However, there was no systematic difference between resistance training and aerobic exercise.

Concluding about metabolic complications

Therefore, doctors who treat cancer should encourage physical activity, regular exercise, a healthy diet with reduced consumption of animal protein, weight control and smoking cessation in all patients undergoing antiandrogen therapy during the course of your treatment. Use Aspirin prevent.

In addition, the NCCN recommends the use of Calcium (1000-1200 mg) daily, in the diet and with supplementation and also supply of vitamin D3 (400-1000 IU) daily. These measures must be performed due to the risk of osteopenia and osteoporosis in these patients with testosterone deficiency severe. In addition, there may be a need to use medications to increase bone density. Furthermore, many foods can interfere with the metabolism of the neoplastic cell, reducing its growth. Find out more at: https://www.drfranciscofonseca.com.br/alimentacao-e-prevencao-do-cancer/

Metabolic complications: The good news to minimize them, drink 2 glasses of wine a day

Cancer-free men who drink alcohol have a lower risk of lethal prostate cancer. Even more:
• Men with prostate cancer who drink red wine have a lower risk of progression to lethal disease.
• Thus, if confirmed, 15 to 30 grams of alcohol after the diagnosis of prostate cancer is associated with lower risk of death.

However, if you would like to know more about this and other diseases of the genitourinary tract, access our content area for patients to understand and gain knowledge. There are more than 140 articles on various urological subjects available for your reading. Culture always makes a difference. You will be surprised!

Taking up references

https://uroweb.org/guideline/prostate-cancer/

https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf

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