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There are numerous commonly noted adverse effects associated with Androgen Deprivation Therapy which can be quite debilitating and bothersome. Many of these side effects lessen the overall quality of life for the patient and may impact their desire to continue with therapy. Common side effects and some potential remedies are listed below.

Hot flashes manifest as sudden sensations of discomfort and warmth in the face, neck and upper torso, and may by accompanied by redness, sweating, anxiety and nausea.   

  • Hot flashes become most frequent about 3 months after beginning treatment.
  • They may occur often or infrequently during the day.   
  • Hot flashes can affect 50-80% of patients on ADT.  
  • Many men continue to have hot flashes after therapy has been discontinued
  • 25 % of men undergoing ADT consider hot flashes to be the most significant quality of life effect from treatment.  
  • Any therapy which reduces testosterone levels may result in hot flashes and may vary in severity from patient to patient.

Tolerance of hot flashes vary and most patients have mild to moderate symptoms which are amenable to conservative measures with lifestyle modifications.   Prescription drugs were used for many men in the past, but currently only about 25% of men utilize prescription medications.

Prevention and Treatment of Hot Flashes

Lifestyle and dietary changes offer a first line approach to the patient with hot flashes associated with ADT.  

Lifestyle Changes

  • Avoid hot beverages, spicy food, caffeine or alcohol.
  • Controlled, deep, slow breathing.  
    • At least 15 minutes twice a day or at the beginning of a hot flash.  
    • Controlled, deep breathing lowers blood pressure andmis thought to decrease the length and severity of a hot flash.  
  • Keep a log of frequency and severity of the hot flashes.
    • Identify triggers
    • Identify coping mechanisms
  • Avoid smoking as it makes hot flashes worse.
  • Low impact daily exercise can lower stress, improve mood and lessen hot flashes.
  • Stress reduction.  Relaxation exercises with yoga or meditation may help hot flashes.
  • Use cooling methods with ice, fans, cool rooms, open windows, cool drinks or chilling bedding or pillows will help symptomatically.  
  • Wear loose fitting clothing and layer clothes to keep temperature lower.  
  • Avoid weight gain as there is an increase in hot flashes.

Dietary Supplements and OTC Options

If lifestyle changes do not adequately control hot flashes an additional 25-50% Improvement can be expected with with the use of non prescription supplements and over the counter options.

  • Acupuncture.  Studies have suggested benefit in 1-2 sessions per week with minimal side effects.

A number of remedies have been studied with results not much different to placebo. These include the following.

  • Black Cohash Pills.  Most studies in woman with moderate cost and most studies suggest similar to placebo.
  • Fish Oil Pills.  Minimal effect on hot flashes.
  • Flaxseed Powder.  Minimal effect on hot flashes. Heart healthy and inexpensive.  
  • Magnesium Supplements. Likely no better than placebo.  Inexpensive. May cause diarrhea or loose stools and is to be avoided in kidney disease.
  • Red Clover Pills.  Similar to placebo.  Moderate cost.
  • Soy products. Inexpensive, natural and heart healthy.  Minimal improvement in symptoms.

Prescription Medications

  • Clonidine.  
    • Available in pills and patches. Least effective, inexpensive.
  • Cyproterone Acetate.
    • 100mg/day.  Steroid antiandrogen.  Not available in the US. May increase cardiac risks.
  • Estrogen.
    • Available in numerous forms including pills, patches and injections. Very effective with greater than 50% reduction in hot flashes. Inexpensive, And reduces bone loss.  May have severe cardiovascular side effects with clotting and gynecomastia.
  • Gabapentin.  
    • Pills.  300 mg tid.  Pregabalin 75 mg twice daily.  Very effective. Can titrate dose.  May cause dizziness and drowsiness.
  • Progesterone. Available in Oral or injectable forms.
    • Megestrol Acetate 20-40 mg a day
    • Medroxyprogesterone acetate 20 mg a day
    • Medroxyprogesterone acetate 150-400 mg IM prn.  
    • Most effective.  Adverse effects include increasing weigh, reduction in HDL and decreased sex drive along with salt retention. May decrease hot flashes by 85%.  

There is good evidence that the use of selective serotonin reuptake inhibitors (SSRI’s) and serotonin-norepinephrine reuptake inhibitors (SNRI’s) can be useful.

The following are a list of previously used medications.

  • Citalopram
  • Desvenlafaxine
  • Fluoxetine
  • Paroxetine
  • Sertraline
  • Venlafaxine

Venlafaxine has the best evidence of improvement with a 50-68% reduction in hot flashes.

Hot flashes are initially managed with education and lifestyle. When medication is required the first line therapy is typically 20 mg of megesterol acetate which can be increased to 40 mg daily. The majority of men then respond very well but if the side effects are intolerable a course of 75 mg venlafaxine daily can be used.

Bone Loss

Osteoporosis with its associated risk of bone fracture for man’s one of the most morbid complications of long-term androgen deprivation therapy. Estrogen modulates bone turnover through estrogen receptors located on osteoblast and osteoclasts. Estrogen is mostly produced by conversion of testosterone by aromatase enzyme. Therefore men on ADT have decreased level to circulate testosterone and estrogen resulting in increased rate of bone resorts in and subsequently a decrease in bone mineral density.

It is estimate the bone loss will reach the maximum decline within the first 12 months of treatment. Most men are asymptomatic, however the use of androgen deprivation therapy increases the risk of fracture by 65%. Overall nearly 20% of men receiving
androgen deprivation therapy will experience a fracture at some point.

Additional risk factor for osteoporosis include age, lower body mass index, smoking, steroid use, alcohol intake and fracture history.

DEXA scans can and should be utilized to determine your overall risk of an adverse skeletal event with advanced prostate cancer and androgen deprivation therapy. Any patient with a FRAX score greater than or equal to 3% and osteopenia or osteoporosis should be started on drug therapy. Although there is no consensus on follow up a one-year follow-up DEXA scan would be advisable.

Prevention and Treatment Options

Lifestyle and diet

  • Weight lifting or resistance exercise and regular aerobic exercise are the best way to decrease the risk of bone loss.
  • Diet rich in calcium foods is also beneficial.
  • Insert table of calcium rich foods

Dietary Supplements

  • Calcium intake should be 1000-1200 mg per day
  • Vitamin D supplementation 800-1000 IU per day

Medical treatment

  • Bisphosphonates
    • Oral medications Fosamax, Boniva, Actonel are available, but rarely used.
    • Infusions with Zometa can be given for patients with osteopenia.
  • Denosumab injections
    • Prolia given every 6 months for osteoporosis prevention and treatment.
    • Xgeva given monthly for patients with bony metastases.

Changes in Lipid Profile

Some prostate cancer treatments can alter serum lipid patterns.  There can be an increase in LDL (bad cholesterol) and lower HDL (good cholesterol).  ADT may also increase triglycerides in some patients especially if they gain weight. This is a consistent finding in clinical trials.

The relationship of hormone deprivation and cardiac disease is less clear, but the impact on cholesterol is consistent making lipid monitoring important.

Prevention and treatment options

Lifestyle and diet

  • Lose weight
  • Exercise
  • Avoid “bad fats”
  • Fiber
  • Read food labels

Supplements

  • Niacin
  • Fish oil

Medical treatment

  • Cholesterol lowering medications are available.  These include the “statin” drugs and there is emerging evidence that they may have an antitumor effect and have been shown to lower cardiac disease risk.

Some studies suggest that there is a relationship between cognitive impairment and the use of ADT, while other studies do not confirm this.  Regardless, one of the known adverse effects of hypogonadism (low testosterone) is decreased mental acuity and advancing age is associated with increasing cognitive impairment. If there is any concern regarding cognitive impairment then the following suggestions may be of help.

Behavioral suggestions

  • Mental exercises to keep the brain “sharp”
    • Reading
    • Puzzles
    • Card games
  • Aerobic exercise

Supplements

  • Minimal data is available to suggest any consistent benefit of any supplement

Medical treatment

  • In cases of true decreased cognitive impairment an evaluation by a neurologist would be suggested.  If related to Alzheimer’s dementia could consider the following:
    • Namenda
    • Aricept

Depression and anxiety are common among patients diagnosed with and being treated for cancer.  It is important to identify “normal” mood changes associated with the stress of having cancer and being treated from “abnormal” mood changes which are much more severe and may need medications.

Depression in men is manifest by loss of interest in activities, fatigue, apathy, sleep disturbance and low self esteem.  These symptoms are also commonly seen in many of the other adverse effects associated with ADT such as hypogonadism with its side effect profile.

Behavioral suggestions

  • Diet.  A good diet helps decrease weight changes and generally helps people feel better
  • Exercise.  Activity boosts energy and improves mood.
  • Sleep.  Adequate sleep is necessary to have a normal mood.
  • Avoid alcohol.  Alcohol affects sleep quality and weight.  Drink minimally.
  • Sunlight.  Getting outdoors can help improve your mood.
  • Stress reduction.  Exercise, meditate, take some time for yourself.
  • Express yourself.  Write in a journal, talk to someone, get counseling.

Supplements

  • DO NOT TAKE ST. JOHN’S WORT.  Decreases efficacy of many drugs.
  • Some new supplements look interesting but no data suggests utility at this time.

Medical treatment

  • There are many available antidepressant medications available on the market.
  • The choice of medication will be determined by your doctor, but several antidepressant medications have efficacy for hot flushes as well and might be beneficial for both.

A loss of libido means that the individual has a decreased or absent interest in sexual activity.  Erectile dysfunction is an inability to obtain or maintain an erection adequate for sexual activity.  Both of these are affected by prostate cancer therapy and any treatment which affects hormonal function will affect libido and erectile function.  

Behavioral

Controlling risk factors for erectile dysfunction is similar to controlling risk factors for heart disease.  Heart friendly is also “penis friendly” and may improve vascular and neurogenic factors associated with erectile dysfunction.  Additionally libido and lack of interest in activities can be associated with depression and activities useful for depression may also be useful.

  • Diet
  • Exercise
  • Control blood pressure
  • Control blood sugar
  • Weight loss

Sleep disturbance is quite common with cancer treatments and is exacerbated by the anxiety, stress and depression associated with daily life in the cancer patient.  Lack of quality sleep increases the risks of anxiety, depression, stress and fatigue.

It is imperative to get adequate amounts of quality sleep in order to improve physical and mental health.  When a patient does not get adequate sleep many daily functions suffer such as memory and concentration, irritability, fatigue and immune system impairment.

Prevention and treatment of Insomnia

Lifestyle Changes

  • Regular exercise. Exercise in the evening can reduce stress and relax your body.
  • Avoid tobacco products. Chemicals in tobacco products have a stimulating effect on the body.
  • Avoid alcohol. Alcohol may help people fall asleep, but the quality of sleep is oftentimes poor.
  • Avoid caffeine. Caffeine is a stimulant and with a half life of 5 hours caffeine in the after 5 pm increases the liklihood of insomnia.
  • Cool surroundings.  Cold showers and a cooler temperature along with shielding from sunlight aid in sleep.
  • Avoid stimulation in the bedroom.  Limit bright lights, television, electronics and noise in the bedroom.
  • Sleep to get rest.  Oversleeping and long naps may make it more difficult to fall asleep at night.  Set an alarm clock to wake up at a reasonable time and avoid naps longer than 20-30 minutes.
  • Go to bed when you are sleepy.

Dietary supplements and OTC options

  • Decongestants and some OTC medications can have stimulant so read the labels.
  • Antihistamines.  Benedryl and other antihistamines can be found in cold and allergy medications.  They are useful as OTC sleep aids as they make you feel sleepy. They may also cause changes in balance, cognition and dry eyes, mouth and urinary hesitancy.  They make people drowsy, but do not help deep sleep or overall quality of sleep. Avoid using for long term.
  • Melatonin.  Sleep inducer and helps people fall asleep, but not necessarily stay asleep.  Take 0.5-1.0 mg 15-30 minutes before sleeping.
  • Valerian.  Valerian is the supplement that can be effective at helping someone fall asleep, stay in deeper sleep and stay in more refreshing states of sleep.  DO NOT take with other sleep aids or pain medications. Should be purchased as root extract with at least 0.8% valerenic acid May need to take for several weeks.  Dosages of 200-600 mg daily 60 minutes prior to bedtime.

Prescription medications to aid in sleep

  • Diuretic drugs can disturb sleep.  Take early in the day.
  • Sleep medications are very effective.  They work quickly and should be taken just before bed.
    • Ambien (Zolpidem)
    • Lunesta (Eszopiclone)
    • Sonata (Zaleplon)
  • Rozerem (Ramelteon) is a prescription drug that stimulates the melatonin receptors in the brain.
  • Benzodiazepines.
    • Ativan (Lorazapem)
    • Clonazepam (Klonopin)
    • Dalmane (Flurazepam)
    • Eurodin/Prosom (Estazolam)
    • Halcion (Triazolam)
    • Restoril (Temazepam)

GERD (Acid reflux)

Increases with weight gain

Prevention and Treatment Options.

Lifestyle and Diet Tips

  • Eliminate tobacco and reduce caffeine and alcohol.
  • Eliminate or reduce chocolate.
  • Weight loss
  • Elevate head to sleep
  • Eat smaller meals
  • Limit fatty or fried foods along with acidic pills and liquids.
  • Fiber is helpful

Dietary Supplements or Over-the Counter

  • Over the counter antacids
    • Rolaids, Tums, Maalox and Mylanta
    • Pepcid, Zantac, Prevacid, Prilosec
  • Enzyme based dietary supplements
    • Beano (alpha-galactosidase

Prescription Medications

  • Aciphex
  • Nexium
  • Prevacid
  • Prilosec
  • Protonix
  • Zantac’

Some of these agents are available either over the counter or prescription.

Long term use of medications for acid reflux can reduce the absorption of calcium and reduce B12  and magnesium levels.

Allergic Reactions

Prevention and Treatment Options

Any new medication can result in an adverse drug reaction known as hypersensitivy or an allergic reaction.  These can be mild, moderate or severe. An allergic reaction can occur to an infusion or oral medication and they may present over time.

Symptoms of an allergic reaction.  They tend to occur within a few minutes of exposure to the medication.  Mild reactions include itching, flushing, rash, difficulty breathing, fever, chills or low blood pressure.  Severe reactions include serious difficulty breathing, severe decrease in blood pressure, systemic rash and itching.

Less severe reactions may permit continued treatment with lower doses or slower infusion rates.  Severe reactions demand that the offending medication be stopped immediately and not reintroduced.

Lifestyle and Diet Tips

  • Report previous allergic reactions and symptoms
  • Pay attention to any strange feelings especially after taking a new medication.
    • Report itching, redness, bumps,breathing changes, flushing or swelling.

Dietary Supplements and Over the Counter Options

Do not start any new supplements or products without talking to your physician.  Proven OTC medications used to reduce or treat reactions:

  • Diphenhydramine(Benedryl)
  • Antihistamine drugs Loratadine or Cetirizine.
  • Hydrocortisone cream can be used to treat some skin reactions.
  • Tylenol or alternative medications are often times given for pain or fevers associated with infusions.

Prescription Medications

Concerns with infusion related allergies may require the use of a steroid pill, intravenous Diphenhydramine or intravenous steroids.  Epi pens may be given to patients at risk for systemic allergic reaction and a bronchodilator may be used for patients with reactive airway disease or respiratory symptoms.

Breast Pain and Enlargement

Some men undergoing prostate cancer therapy develop a condition called gynecomastia which involves increased sensitivity of the nipples of the breast with potentially an increase in the volume of breast tissue.

Treatment with antiandrogen medications is responsible for this side effect.

Prevention and treatment options

Prescription Medications and medical therapy

  • Daily anti-Estrogen medication
    • Tamoxifen or aromatase inhibitor. These medications block the ability of estrogen to stimulate breast growth.
  • Prophylactic breast radiation. A short (single) dose of radiation is preventative.
  • Substotal Mastectomy. For men who have significant pain and enlargement surgical removal of breast tissue is curative.

Joint and Muscle Pain
Penile shrinkage
Sweating
Taste Changes
Tingling and Numbness
Watery Eyes

Chemotherapy adverse effects

  • Anemia
  • Fever
  • Hair Loss
  • Mouth Sores
  • Nail Changes
  • Nausea and Vomiting
  • Neutropenia
  • Peripheral Neuropathy
  • Thrombocytopenia
  • Nosebleeds
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