August 2008: Managing Menopausal Symptoms

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What can be done for hot flashes?

Question from guest1: Why do hot flashes occur and can you take anything for them?

Answers —Charles Loprinzi, M.D.: Hot flashes are common with breast cancer therapy. They come from women going through menopause related to chemotherapy, or they might be related to hormone treatment they are receiving, like tamoxifen or aromatase inhibitors. They can be quite problematic, as they can be for women who get hot flashes unrelated to breast cancer. With breast cancer, the hot flashes are oftentimes more substantial than for other women, because the menopause may come on more abruptly. We generally avoid hormones in patients with breast cancer. Over the last decade, information has become available that non-hormonal drugs can decrease hot flashes moderately. The first class of medications that have been helpful are some of the newer antidepressants in low to moderate doses. The best-studied ones are venlafaxine (brand name: Effexor), and paroxetine (brand name: Paxil). The latter one should not be used with tamoxifen, however. Newer information suggests that Celexa (chemical name: citalopram) may also be helpful. Lastly, two other classes of drugs also seem to decrease hot flashes moderately. Those include an anti-seizure medication, gabapentin (brand name: Neurontin) and an older blood-pressure medication called clonidine (brand name: Catapres).

Mindy Goldman, M.D.: For some breast cancer patients, some of the medicines may be able to help out in many ways. For some women who have had mastectomies, they may have chest wall pain that may be helped by neuropathic pain relievers such as gabapentin. It's important for your physicians to visualize therapy and important for them to know about some of the alternatives that may be helpful for menopausal symptoms like hot flashes. There are also non-prescription meds like black cohosh that may be helpful for some women, but in general, most of these haven't been studied well enough for us to tell women about their effectiveness and safety. Finally, if the hot flashes really are unbearable, it's important to talk to your breast cancer physicians about the treatments you are on to determine whether a change in treatment might be an option.

Does Taxol cause menopause?

Question from JJ: Where does Taxol fall in the most/least likely to induce permanent menopause? I know that different chemotherapy drugs have different degrees of impact on ovaries.

Answer —Charles Loprinzi, M.D.: It's not well-known how Taxol (chemical name: paclitaxel) rates in terms of causing menopause. This is because it is rarely used alone in young women with breast cancer. My guess is that it would not be high on the list of drugs that cause menopausal symptoms, such as Cytoxan (chemical name: cyclophosphamide).

Vaginal dryness goes away after tamoxifen?

Question from Karen: Does the vaginal dryness go away once I am off the tamoxifen?

Answers —Mindy Goldman, M.D.: We think that most of the side effects of tamoxifen do go away when women stop the drug. But it sometimes is difficult to know for sure because after someone completes tamoxifen, they may go on to other medications such as aromatase inhibitors if they are menopausal, and these drugs have significant effects on vaginal dryness. Tamoxifen is used on pre-menopausal women and typically they are given 5 years of therapy depending on how old they are when they finish treatment, meaning if they are perimenopausal or menopausal they will have natural decline in ovarian function and with less estrogen being produced they may still experience vaginal dryness.

Charles Loprinzi, M.D.: Interestingly, tamoxifen is more likely to cause vaginal discharge, i.e. increased vaginal lubrication, than it is to cause vaginal dryness, although it varies from woman to woman.

Mindy Goldman, M.D.: If you are having other symptoms besides dryness, such as irritation or burning, it's important to see your physician to determine if there are other things going on.

How to tell real menopause from side effects?

Question from Glorine: How do you differentiate menopausal side effects from chemotherapy and radiation from real menopause symptoms?

Answers —Charles Loprinzi, M.D.: Menopausal symptoms are caused by a decrease in hormonal production. This happens naturally to a woman between 45-55 years of age. Chemotherapy can cause the same process to happen a bit more quickly. Some of the drugs, like tamoxifen, appear to cause those symptoms because they prevent the estrogen (normally produced by the ovaries) from acting to prevent hot flashes. To more directly answer the question, it's somewhat of a guess by the physicians and patients. If there is a situation where a woman is less than 40 years of age, starts chemotherapy and then gets menopausal symptoms, it is reasonable to assume it is from the chemotherapy. If she is older and starts to get the effects after treatment, it's difficult to know if it's the chemotherapy or if it would have happened anyway at that time of life. I believe the treatments work equally well in both situations. Having said this, this is not general knowledge by all physicians, as the literature is not rich with the newest information regarding this topic.

Mindy Goldman, M.D.: We previously mentioned that for women getting chemotherapy, the symptoms of menopause may be more intense because of the acute onset. The treatments are the same however. For young women getting treatment, they tend to get their periods back after treatment. This is similar to women getting their natural periods in their late 40s or early 50s. It may be important for your breast cancer physicians to determine if you are menopausal because the other class of drugs called the aromatase inhibitors are only used in post-menopausal women. When women are on tamoxifen, they oftentimes have irregular periods and sometimes have no periods at all (amenorrhea), so it may be important to check an estradiol level to determine if the ovaries are recovering.

Charles Loprinzi, M.D.: As best we understand things, this probably only applies to women with ER/PR+ cancers. To be honest, it's not 100% certain that recurrence of menstrual periods is related to recurrence of breast cancer, although it's probably so. The reason I say this is that we know that younger women with newly diagnosed breast cancer (less than 35 years old) have a higher risk of getting a recurrence of their breast cancer. That is the group most likely to retain their menstrual periods, because they're young. It's not 100% known if the return of menses is the cause or the younger age.

Mindy Goldman, M.D.: For women with hormone-receptor-positive disease, there are some studies that suggest that shutting down the ovaries, or ovarian suppression, is as effective as chemotherapy. We know that the estrogen that is produced by the ovaries has some impact on breast cancer. What we don't know is whether we should be shutting down the ovaries in all premenopausal women with hormone-receptor-positive symptoms. There are large trials ongoing to help us answer that question.

When to expect menopause symptoms?

Question from Dogzmama: I am premenopausal but will start chemotherapy and tamoxifen within 2 weeks. How soon do menopause symptoms occur? What makes some people have worse symptoms than others?

Answers —Charles Loprinzi, M.D.: Almost certainly, the chemotherapy will be given first, and the tamoxifen will not be given until chemotherapy has been completed. Thus, talking about chemotherapy-induced hot flashes, the most important determinant of whether chemotherapy will cause this problem is related to the patient's age. If a woman is less than 35 years old, then the chance of chemotherapy causing such natural hot flashes would be quite low (less than 15-20%). If the patient is closer to the age of natural menopause, then the chances of developing symptoms from chemotherapy would be much higher, greater than 80%. With regards to tamoxifen, information from post-menopausal women shows that the main issue that increases the risk of hot flashes relates to two items: first, whether the women previously had moderate hot flashes when they went through menopause, and second, whether they went through estrogen therapy. In pre-menopausal women who are not having hot flashes when they start tamoxifen, the incidence and severity appears to be less then in post-menopausal women. As far as the timing, this is something that generally takes weeks to a couple of months to occur, as opposed to days.

Mindy Goldman, M.D.: Sometimes it's hard to predict because hot flashes are so variable in many women. If you look at natural menopause, some women seem to have few symptoms while others are significantly disabled by their menopausal symptoms.

Side effects of aromatase inhibitors permanent?

Question from TeriF: Are the side effects of aromatase inhibitors permanent?

Answers —Charles Loprinzi, M.D.: The main side effect of aromatase inhibitors is bone loss (osteoporosis). This occurs relatively gradually after the drug is started. When the drug is stopped, the bone thinning slows down and may even reverse a bit. With the thinner bones, however, the risk of fracture is present, and thus if this occurs, someone might consider this a more permanent problem. Another common symptom caused by aromatase inhibitors is joint pains. This is somewhat similar to what some women have when they go through menopause. The symptom of joint pains appears to affect up to 50% of women who take aromatase inhibitors, with up to 15% experiencing symptoms that cause drug cessation.

Mindy Goldman, M.D.: A common gynecological side effect from aromatase inhibitors is marked vaginal dryness. For some, it can be so severe the vagina feels like sand paper when they are sitting. This is because the aromatase inhibitors shut down all sources of estrogen, and the vagina is very rich in estrogen receptors. There are treatments for dryness and when one stops their aromatase inhibitor, many times their symptoms will become less severe.

Reason hot flashes continue long after menopause?

Question from BevP: I have been having severe hot flashes since menopause (age 55). Now I'm 72. Effexor doesn't help. Why do some women have never-ending hot flashes for the rest of their lives? I thought they were supposed to only happen during the few years around menopause.

Answers —Charles Loprinzi, M.D.: Dr. Goldman knows the answer!

Mindy Goldman, M.D.: Although it is true that most women's hot flashes resolve by about 3-5 years after menopause, about 15% of women persist in having hot flashes throughout their menopausal years. For many of these women, the severity of hot flashes may not be as great as when they first went into menopause.

Charles Loprinzi, M.D.: It's unknown as to why these women continue to have persistent hot flashes. Some women who are overweight or particularly underweight may have more trouble with hot flashes than others.

Mindy Goldman, M.D.: We think that hot flashes are due to loss of estrogen and its effect on certain parts of the brain that have temperature control mechanisms, but the reality is even in 2008, we're not 100% sure what causes a hot flash. Because of this, it's harder to predict who will be in that 15% of women who do continue to have hot flashes throughout the remainder of their lives.

Bone density test if period has not returned?

Question from Tulip: Should you have a bone density test if you are 40 and your period has not returned post ACT chemotherapy?

Answers —Charles Loprinzi, M.D.: Bone density is recommended to be obtained around the time of menopause. If a woman at age 40 has not had menstrual periods for a year or more after finishing chemotherapy, then it seems reasonable to get a bone mineral density test around that time. There are not hard and fast guidelines around this, however.

Mindy Goldman, M.D.: Women reach peak bone density at around 30-35 and all women have a gradual decline in bone density after that. The major rate of loss, 2-3% per year, is in the immediate years after menopause. If she is going through menopause at an earlier age (10 years earlier than expected), it will be important to do things like weight-bearing exercise and taking calcium supplementation in order to maintain her bone density and hopefully prevent osteoporosis.

Tips to increase memory?

Question from BeckyM: Is there anything I can do to increase my memory? I forget words I have known for over 40 years when I am trying to have a conversation.

Answers —Mindy Goldman, M.D.: Many women may notice changes in concentration, memory recall, and memory in general after they've gone through menopause. There is certainly a lot of controversy over the role of estrogen in memory changes and brain function. There are also many complicating factors that can affect memory. Many women may not be sleeping well, partly because hot flashes are disturbing sleep and chronic lack of sleep affects mood, overall functioning memory, and concentration. Aside from hormone replacement therapy, which is controversial in its role in brain function and memory, there haven't been good-quality studies done that have looked at this. There are some herbal therapies that are thought to improve blood flow to the brain, but the data on these are very poor. Certainly, getting adequate rest and exercise and maintaining weight are all important in the menopausal years and may help to improve brain function.

Charles Loprinzi, M.D.: This seems like a good time to comment upon chemotherapy-associated brain function. There is a phenomenon that has been labeled as "chemo brain" or "chemo fog." For a couple of decades, patients have been noting this as a problem. The exact nature of this problem is not known currently; however more is being learned as medical studies are being done to address this issue. Interesting things related to it include that patients' complaints of brain function do not match well with tests of brain function. Women who do very well on tests actually have complaints of less function. One of the things that has come up is that it appears that women have to use more brain function to solve the same problems that they used to solve with less brain function. This has been shown in sophisticated images of the brain as women are asked to perform some sort of brain function (like remembering things or doing a math function). We do not currently have good antidotes to recommend people take. Men have this problem too. :-)

Long-term effects of antidepressants for hot flashes?

Question from Teresa: I have been taking Effexor XR to help with hot flashes after taking hormones that I had to quit "cold turkey." Are there any long-term effects from taking an antidepressant if I don't need it for depression?

Answer —Charles Loprinzi, M.D.: Of interest, Effexor (chemical name: venlafaxine) was the first of the antidepressants reported to be effective for treating hot flashes. Relatively low doses of the drug (oftentimes much lower than needed for depression) are effective. Also, the effect of this drug on hot flashes is much faster (days to a week), than the antidepressant effects of this type of medication (weeks to a month or so). I know I haven't addressed your question yet! As far as the long term side effects, I'm not aware of there being any long term side effects of using these drugs for hot flashes. I would not expect any more side effects of these drugs when used for hot flashes than when used for depression. I will say that some women do have symptoms when they stop these drugs, especially when they stop them rather abruptly. These symptoms include agitation and feeling uneasy. Therefore, weaning off these drugs slowly is recommended.

Sleeping pills, supplements for insomnia?

Question from CVera: I'm on Arimidex and Bonefos. I have joint pains and at times insomnia. Insomnia is really a problem. Can I take sleeping pills? Or herbal supplements like melatonin?

Answers —Charles Loprinzi, M.D.: Arimidex (chemical name: anastrozole) is one of the aromatase inhibitors. As previously mentioned, this can cause bone pains, or arthralgias, and in up to 15% of people these can be significant enough for patients to want to stop the drug. Options include temporarily stopping the drug versus switching to a different aromatase inhibitor or to tamoxifen. The insomnia is not necessarily related to the Arimidex or the bone-strengthening medication Bonefos (chemical name: clodronate). (This latter medication is not available in the United States, so I suspect you come from Canada or another country where it is available.) Having said the above, treatment of the insomnia could be decided independent of the fact you are taking any of these medications. There is hypnosis and other mind/body measures that have been studied as treatment for insomnia. There are other sleep-help things such as not napping and getting plenty of exercise during the day (not right before bed time). In addition, there are medications that can be taken. These include Benadryl, or prescription sleeping medications, or herbal type medicines such as melatonin. These work to varying degrees, with none of them being fabulous.

Mindy Goldman, M.D.: It's helpful to understand a little bit more about the insomnia. If you think it's due to joint pain and being uncomfortable when trying to sleep, then approaching joint pain may be beneficial. Sometimes, herbal products like glucosamine may be helpful or talking to the oncologist may be helpful. If the insomnia is due to hot flashes, treating the hot flashes would be appropriate. Sleeping meds are available, but drugs like Ambien (chemical name: zolpidem) should be used in the short term as long-term use may be addicting.

Okay to remove IUD if no period?

Question from CynthiaA: After mastectomy, I had chemotherapy and now am on tamoxifen 10 mg. June 2006 was my last period. I had an IUD installed in Oct. 2004 and would like to have it removed. Is this a wise decision? I am 51. What should I ask the gynecologist? Should I have any tests?

Answers —Mindy Goldman, M.D.: Certainly, in a 51-year-old, even without breast cancer treatment, the natural pregnancy chance at that age is incredibly low. Given the breast cancer treatment, it is reasonable to pull the IUD. Women who are on tamoxifen may have their menstrual cycle suppressed and so checking a blood level of estrogen can be helpful to know if someone is pre- or post-menopausal. In your situation, given your age, it is reasonable to just pull the IUD.

Charles Loprinzi, M.D.: I might just add that 10 mg tamoxifen is lower than the usual recommended 20 mg per day. I assume you're taking two of the 10 mg tablets per day.

Supplements safe for hormone-postive?

Question from Sherry: Are herbal supplements safe for survivors of hormone-sensitive breast cancer? Some products claim to "balance hormones" or replace and/or increase hormone levels to manage menopause symptoms. Can you identify or direct us to a source that can identify which supplements are actually protective/effective/safe and which are dangerous?

Answers —Charles Loprinzi, M.D.: Supplements are a complex subject. A big part of the complexity is that herbal supplements are not regulated. Thus, it is not very clear what is contained in different supplements. Some supplements, over time, have actually been shown to have estrogen in them. There are plant supplements, such as soy, which contain phytoestrogen, which is just a term that means plant estrogen. There is controversy as to whether or not this is beneficial versus detrimental versus neutral in terms of breast cancer risk. My own take on this issue of soy intake in a person with a prior history of breast cancer is that it's reasonable for them to ingest soy in their diet (if they like soy products), but I do not recommend soy supplements.

Mindy Goldman, M.D.: One resource that may be helpful is NCCAM, the National Center for Complementary and Alternative Medicine. It's a division of NIH and has a fair amount of information on some of the popular herbs as well as research that's been done. Again, most of these are not studied specifically in breast cancer patients, so we don't truly know about safety and efficacy in many of these herbs.

Tips to ease vaginal dryness?

Question from RZehr: I'm 50 and feel like the Sahara Desert. Is this something I just have to deal with or can I get help? I never suffered this until I got off tamoxifen, started taking Arimidex and had my hysterectomy. My doctor says I just need to have a lot of sex with my husband to keep things lubricated. Besides having lots of sex, is there anything else I can do to help ease this severe situation?

Answers —Mindy Goldman, M.D.: This is a very common problem for women who are on aromatase inhibitors such as Arimidex (chemical name: anastrozole). For moisture, Replens may be helpful. There are also lubricants that we recommend for sexual activity. Some examples are Astroglide, Probe, or Silk. The role of local hormonal therapies in treating vaginal dryness for women with hormone-receptor-positive disease is a little controversial. Some of the standard estrogen creams used in menopausal women such as Premarin (chemical name: conjugated estrogens) or Estrace (chemical name: estradiol) could cause absorption into the blood stream if used in the standard doses that we treat menopausal women. The safety of that isn't known. There are a few types of therapies where there is little absorption of hormones into the blood steam. One option is the vaginal Estring (chemical name: estradiol). Many people use this as a first line to treat dryness. This however is based on pharmacy data showing little absorption into the blood stream and there aren't good studies that evaluate this in breast cancer patients. Another option is compounded testosterone. Testosterone is only United States Food and Drug Administration (FDA)-approved for men, but it is possible to make tiny doses in vaginal preparations that can be useful for women without the male-hormone-like side effects such as acne, hair growth, and oily skin. Finally, there is an estradiol insert called Vagifem that is also thought to have limited absorption, although there has been a recent study published specifically for women on aromatase inhibitors that shows a rise in estradiol when women used these products. So some oncologists feel that Vagifem should be contraindicated in breast cancer patients who are on aromatase inhibitors. We are actually doing a study at University of California, San Francisco, looking at the role of vaginal Estring or testosterone for women who have dryness who are on aromatase inhibitors.

Charles Loprinzi, M.D.: The one last thing to consider is to talk to your oncologist regarding the magnitude of benefit expected from the Arimidex you are taking. For some women the side effects might be more than the amount of benefit they might receive from the medication.

Okay to abruptly stop tamoxifen?

Question from Gazal Belgium: I'm a 5-year breast cancer survivor and have taken Nolvadex during these 5 years. I've had menopausal symptoms but still menstruate. Now it's time to stop the Nolvadex. What's better, to stop the medication gradually or to stop abruptly? What will/can be the effect of stopping the Nolvadex?

Answer —Charles Loprinzi, M.D.: Nolvadex is the brand name for the medication most well-known as tamoxifen. This can be stopped abruptly, as it takes weeks for this medication to get out of the body. Most oncologists, especially in the United States, stop this medication after 5 years of treatment, although there are some studies still ongoing with using this for up to 10 years. The menopausal symptoms that you are having may improve once this medication is stopped, although this cannot be said for certain. In fact, there are rare patients in whom the menopausal symptoms are worse when they're off this medication. Again, this is rare.

Nightmares a side effect of menopause?

Question from Eagles: Are nightmares a common side effect of menopause?

Answer —Mindy Goldman, M.D.: I am not aware of nightmares being a typical sign of menopause; however, many women notice sleep disruption and may not be able to enter into the deep REM phases of sleep. It may be possible that with disrupted sleep cycles, that normal dreaming doesn't occur. Women may experience nightmares, however, I'm not aware of research that's been done in this area.

Research on managing menopausal symptoms?

Question from MCec: Is there any new research happening on managing treatment-induced menopausal symptoms? If yes, in what direction and with what results?

Answers —Charles Loprinzi, M.D.: Yes, there are ongoing studies looking at ways of alleviating menopause-related problems in women with breast cancer and women who don't have breast cancer. We currently are completing approval on a clinical trial looking at pregabelin (brand name: Lyrica), which is a cousin medication of gabapentin (brand name: Neurontin). There are studies ongoing looking at paced breathing as a way to prevent hot flashes. There was an interesting report about an injection into a nerve in the neck (stellate ganglion block) for treating hot flashes. This latter item is very preliminary, and work is ongoing to try to better substantiate whether it does or does not help alleviate hot flashes. In addition, there are trials looking at vaginal dryness issues.

Mindy Goldman, M.D.: Because many of the alternatives to hormones that are being used to treat hot flashes have central effects within the brain, potentially many other drugs that affect neurotransmitters in the brain may be of benefit. Given that the survival rates from breast cancer have increased, quality of life issues are becoming much more important and I expect that we'll see many more studies coming out looking at alternatives to hormones in treating breast cancer patients. Certainly, in some women even the use of post-menopausal therapy may be considered although this is a controversial area. I would certainly not recommend this until all other options have been exhausted and not without discussing with your oncologist.