Hot Flashes

Non-pharmacologic (non -medicinal)

Since core body temperature has been shown to rise before a hot flash, it is reasonable to try to keep body temperature from rising. Things you can do:

• Wearing open weave cotton clothing that allows the skin to breath.
• Keep air moving with a fan or open window.
• Avoid foods and beverages that increase a sense of warmth such as alcohol, spicy foods, and hot beverages.
• It may help to keep a diary in order to identify your specific triggers.
• Stress has been shown to be a trigger, so managing your stress is also important. Researchers have found that deep abdominal breathing (often done in yoga) can decrease hot flashes. Participants who practiced deep breathing twice a day reduced hot flashes as much as 40%.^{20 63}
• Vitamin E, 800 IU per day, has also been shown in a placebo-controlled study to reduce hot flashes by about 40%.¹¹ Be aware that a new study looking at whether vitamin E 400IU per day protected people with diabetes and vessel disease from heart disease found that people taking vitamin E had more heart failure than those who did not take vitamin E. Be sure to talk to your health care provider about any product you take, either medicine or vitamins or herbs.³⁰
• For milder hot flashes that don't interfere with sleep or other activities, a combination of avoiding triggers, abdominal breathing and vitamin E may provide enough control.^{20 63 11 31}

Pharmacologic

Older medications used to treat hot flashes included clonidine and bellergal. Bellergal has very little research to back up its use in hot flashes. Clonidine has been shown in studies to reduce hot flashes about 40%, but does have some significant side effects such as mouth dryness, constipation, drowsiness, and if used as a patch, itchy skin.

Antidepressants

Newer more effective nonhormonal treatments for hot flashes have been discovered in a group of antidepressant medications that target specific neurotransmitters. There are antidepressants that target mainly serotonin (SSRI, selective serotonin reuptake inhibitor). These medications are:

• paroxetine 25 mg extended release daily
• fluoxetine 20 mg daily
• citalopram 20 mg daily
• antidepressants that have dual activity against both serotonin and norepinephrine Selective Norepinephrine Receptor Inhibitor (SNRI) venlafaxine 75 mg extended release daily.
• All of these medications have been studied in either small or large studies in both men and women.⁵

Venlafaxine has been used in women with hot flashes for up to 2 years.⁵ All of these agents seem to provide similar relief, reducing hot flashes in severity and frequency by about 60%. Since they target neurotransmitters, they work fairly quickly (in 2 weeks) and for hot flashes, the doses used are lower than those used for treating depression. Side effects with these low doses of medications seem to be very few in the short term. Some nausea when starting, a little dry mouth, and appetite loss were seen with venlafaxine. Studies with fluoxetine and citalopram revealed no obvious side effects at the doses used.⁷ Clinical experience has suggested that if an SNRI (venlafaxine) does not work for someone, it may be worthwhile to try another antidepressant, namely an SSRI.

One word of caution about the use of the antidepressant paroxetine in managing hot flashes. One study looked at the metabolites (products that the medication breaks down into) of tamoxifen and found that paroxetine interferes with the metabolism (how the medicine is processed) of one of the metabolites of tamoxifen.⁵⁹ Before this study, no one knew this particular metabolite of tamoxifen existed and therefore it is not known how important this metabolite is to the efficacy of tamoxifen. Nonetheless, it is wise to not use paroxetine for hot flashes if you are taking tamoxifen.

Gabapentin

Mood/Irritability

Non-pharmacologic - (stress management)

The best treatment for irritability is to get proper rest, exercise, eat right and manage stress levels. Therefore, resolving problems that interrupt sleep is an important first step. Planning your days to include time for exercise, even 30 minutes per day, will provide needed help. Exercise is discussed later.

Food can be an important contributor to neuroendocrine balance. Foods that cause wide swings in blood sugar levels such as simple carbohydrates should be avoided. Proteins and complex carbohydrates help to provide a stable chemical environment in your body.²²

Counseling may be a great compliment to an exercise program, to help gain insight into things that are causing stress.

Pharmacologic

Women and men who have participated in hot flash studies with low dose antidepressants report significantly also having less anxiety and irritability. In one research study using citalopram 20 mg daily for hot flashes, participants reported less anger, less tension and an overall improved mood since before they started the medication.^{1 10} If non medicinal changes do not help, you may wish to ask your healthcare provider about trying a low dose antidepressant to see if it may work for you.

Osteoporosis

Non-pharmacologic

For men and women
The use of calcium, vitamin D and weight bearing exercise are the mainstay of usual treatment for bone health. These interventions are associated with as much as a 25% decrease in the risk of having a bone fracture among older women. How much calcium and vitamin D does a menopausal woman or androgen depleted man need? Most sources recommend 1500 mg of elemental calcium daily and from 400 to 800 IU of vitamin D.²⁷ Walking is a great weight bearing exercise that most people are able to perform.

Pharmacologic

Bisphosphonates is one class of medications that has been shown to have a good effect in keeping bones healthy. Currently, if osteopenia or osteoporosis is diagnosed, bisphosphonates are being used to prevent further bone loss. Bisphosphonates work by decreasing bone turnover. This is the one medical intervention that appears to be as effective as hormones. There are now many bisphosphonates on the market in many forms, pills as well as liquid that is infused into the veins (an intravenous or "IV"). Studies in men and women are currently in progress looking at taking bisphosphonates early, before bone loss occurs, along with treatments that are already known to decrease bone mass such as various chemotherapy drugs, to see if bone loss can be prevented. Women and men who have had chemotherapy or androgen deprivation treatment should be assessed for bone loss and, if identified, a regimen to prevent further loss should be initiated.^{13 29 47}

For women, another option for bone health may be raloxifene hydrochloride (Evista^®), which is a selective estrogen receptor modifier (SERM) and has been studied for breast cancer prevention in women with a higher risk of getting breast cancer. It has been shown to be helpful in postmenopausal women to reduce the risk of fractures from osteoporosis. It has not been studied in this regard in premenopausal women. Also, there is some concern that raloxifene should not be used in a woman who has been on tamoxifen for five years. One of the main side effects of raloxifene, however, is hot flashes. Raloxifene should not be thought of as a medication for "menopausal symptoms" but rather a medication used for preserving bone health.^{1 18 27}

Sleep

Non-pharmacologic

Good sleep habits are important considerations for getting adequate rest.⁴⁵ These include:

• Going to bed and getting up at the same time daily
• Avoid exercise, drinking or eating anything with caffeine within 4 hours of bedtime,
• Enjoy some type of relaxation routine before going to sleep; (deep breathing, relaxing music, gentle stretching),
• Don't stay in bed if you are not sleeping - get up and read or watch television or listen to relaxing music.
• Keep a pad of paper and pen in reach and if thoughts wake you up or keep you from sleeping, write them down with the perspective that they are there, transcribed, for you to deal with in the morning so you can let them go and go to sleep now.
• A study is in progress now to look at the use of the herb, valerian, to see if it can assist in improving sleep in cancer survivors.

Pharmacologic

There are many medication preparations that can help with sleep. Diphenhydramine (Benadryl^®) is an over the counter medication that produces drowsiness. Acetominophen and buffered aspirin products labeled "PM" or "nighttime" often have diphenhydramine as an additive. If you have minor achiness or a headache as well as sleep issues, these products may be useful. If you do not have pain, plain diphenhydramine is available that you can take to help you fall asleep. Sedatives or hypnotic medications such as zolpidem tartrate (Ambien^®) may also be helpful.

Other medications that can help you stay asleep are benzodiazapenes such as flurazepam hydrochloride (Dalmane^®).³⁴ Amitriptyline hydrochloride (Elavil^®) is an antidepressant that has a long half-life that can cause sleepiness. This medication is sometimes used to help with sleep problems. However, long term use of medications for sleep is not recommended. It is better for your health that the causes of sleep interruption are managed instead.

Heart Disease

Non-pharmacologic

For men and women
There are several things that can be done as far as lifestyle is concerned that can help keep the heart healthy. The most important things are:

• Refuse to use tobacco products.
• Limit your intake of saturated fats
• Control your body weight
• Exercise
• Recognize when- stress is high and take measures to manage that stress.⁸

Pharmacologic

Despite exercise and proper eating, there are familial (family-related) and genetic factors that can affect our bodies and increase our risk for heart related illness. Getting regular physical exams and using medications when necessary to control blood pressure and cholesterol/lipids are important things to do to stay heart healthy.

Skin (for men and women)

Non-pharmacologic

The most valuable thing a person can do to protect their skin from the negative effects of aging is to protect it from the sun and tobacco damage. Therefore, not smoking and using at least an SPF 15 sunscreen on exposed skin is important. The use of clothing including hats with brims, light long sleeve shirts and longer shorts or pants are also effective.

Another intervention is to keep the skin moist. Using daily moisturizers, avoiding drying soaps and patting dry instead of rubbing with a towel will help spare skin cells from excessive drying. Protecting skin, again, from temperature extremes and wind is also important. Drinking lots of water will also help keep needed moisture in the skin. In the winter or in dry climates, use of a humidifier may be helpful.⁵⁵

Some dermatologists recommend the use of oral antioxidants to keep skin healthy. Vitamin E and vitamin C have been touted as important. But to date, there is no clear evidence to support this practice.

Pharmacologic

Products that put antioxidants directly on the skin such as topical retinoids (vitamin A compounds) have shown promise in keeping skin smooth and tight. One study with 53 people over 80 years of age showed that using a 1% topical retinoid for 7 days showed improved collagen synthesis (the stuff that makes skin look smooth and tight) and some fibroblast growth on skin that was protected from the sun (the buttocks).⁶² There is some evidence that retinoids can help prevent photoaging (aging effects on the skin from the sun) and wrinkles. Unfortunately, 4 to 6 months of continuous use is required before significant results are noted.²⁵

Vaginal Dryness (for women only)

Non-pharmacologic

The goal of therapies to help vaginal dryness is to keep the vaginal tissues as healthy as possible with enough blood supply to allow enough lubrication (wetness) and flexibility. One way to do this is through regular stimulation of these tissues. The more frequent sexual activity is, the more those tissues will get blood flow and the healthier and more responsive they will remain. One study showed that women who engaged in sexual activity as little as 3 times per month had much more lubrication than women who did not engage in any sexual activity.⁶⁴

Other ways to lubricate the tissues include over the counter lubricating jellies such as a polycarbophil-based vaginal moisturizer (Replens^®). Replens^® binds to the tissues, providing more than just a brief surface lubrication. However, research studies have not shown a large difference between preference or satisfaction with any of these products over the others. One study found that Replens^® worked equally well increasing vaginal moisture and decreasing pain with intercourse as a very low dose estrogen vaginal cream.¹⁶ A study done comparing a generic jelly lubricant and Replens^® for vaginal dryness showed that both worked well in relieving vaginal dryness.⁴⁰ Ask your healthcare provider for a recommendation of what to try, if this is a problem for you.

Pharmacologic

Although taking estrogen pills is not recommended for many cancer survivors, there are many products that can be ordered by a health care provider that put estrogen directly on the vaginal tissues. These are in the form of a tablet (17 beta estradiol, Vagifem^®), a ring (estradiol, Estring^® ) and various creams (conjugated equine estrogen, Premarin^®, as an example). Even though some estrogen is still absorbed into the general body, the thought is that by putting estrogen on the vaginal tissues, much less estrogen gets into the system. The tablet and ring give out a very low constant dose of estrogen and are thought to have the lowest systemic absorption of estrogen. The tablet provides 25 micrograms of estrogen in 24 hours and the ring provides 7.5 micrograms of estrogen in 24 hours. The ring is actively delivering estrogen for 90 days, while the tablet is active over a 24 hour period. Estrogen creams were studied using daily doses that are much higher than the tablet or ring.

None of these products have been studied in women with a history of breast cancer and we do not know how much estrogen is too much in a women with a history of breast cancer. Studies in postmenopausal women without breast cancer have shown that there is a clear connection that the more estrogen given to the vaginal cells, the more the body absorbs. Therefore, using very small amounts once or twice per week may help with the symptoms without increasing estrogen levels in the body.^{2 3 26 49 42} However, the research has not been done to help us know how much or how little is helpful. The main goal would be to get rid of the unwanted symptoms without increasing estrogen levels as more estrogen could help breast cancer cells grow.

Incontinence (for women only)

Non-pharmacologic

It is important that you and your health care provider figure out if you are experiencing stress incontinence, urge incontinence or both, as the treatment for each is different. For stress incontinence, making sure that your bladder is empty before doing any moderately vigorous activities and be mindful of contracting (squeezing or holding tight) pelvic muscles during sneezing or coughing is helpful. Doing kegel exercises to increase muscle tone and learning to use biofeedback to learn proper muscle contraction are methods that have been tried and found helpful.¹⁷

For urge incontinence, learning what foods and beverages irritate the bladder is important. Caffeine is a known bladder irritant, for example. Another strategy is to learn bladder re-training, which involves ignoring the signals of the unwanted contractions and learning to empty the bladder only when it is full. This sort of training is done with the help of a health care professional who specializes in these issues.¹⁵ Again, your healthcare professional will help you determine what kind of intervention you will need.

It is important to try to prevent urinary tract and bladder infections as women are at greater risk due to the change in the acid environment (pH) of the cells. Drinking lots of water, including some acidic beverages such as cranberry juice may be helpful. Avoiding hot tubs is helpful as the water can be a source of germs. Careful hygiene is also required, being sure to wipe from front to back.⁶¹

Pharmacologic

There are several medications that may be useful for stress versus urge incontinence. Drugs such as alpha agonists that stimulate smooth muscle and increase outlet resistance such as pseudoephedrine (Sudafed^®) are used for stress incontinence. Surgery may also be an option in stress incontinence.^{37 60}

Drugs that affect other receptors such as tolterodine (Detrol^®) and oxybutinin (Ditropan^®) are useful in urge incontinence. These drugs inhibit the unwanted contractions by stopping the muscarinic action of the substance acetylcholine on smooth muscle.^{1 23 37}