- Email: [email protected]
Nonhormonal Treatment of Menopausal Symptoms
JNP
NONHORMONAL TREATMENT OF MENOPAUSAL SYMPTOMS There are many reasons a woman may choose to not take hormone replacement therapy (HRT) for
as long as 5 years) and wane after about 1 year after menopause. However, some symptoms have been demonstrated to cause problems for as long as 30 years.2
Physiology
PRESCRIPTION PAD Maren S. Mayhew
menopausal symptoms. She may have a contraindication, increased risk for problems, or a personal preference. Much of the research on nonhormonal treatment was done in women with contraindications, such as breast cancer survivors, and most are fairly short-term studies. This column discusses the medications recommended by the North American Menopause Society for treatment of menopause symptoms.1 However, these medications are not approved by the US Food and Drug Administration for this use. The most common problematic symptoms of menopause are vasomotor symptoms, such as hot flashes and night sweats. Other symptoms are dizziness, mood disorders, sleep disturbances, headaches, difficulty concentrating, memory impairment, general malaise, rapid, irregular heartbeat, atrophic vaginitis, bladder irritability, myalgias, and arthralgias. Most of these have a central nervous system component. These symptoms can have a significant negative effect of a woman's quality of life. These symptoms are most severe during the perimenopausal phase (which may last
384
The Journal for Nurse Practitioners - JNP
The basic hormonal change in menopause is loss of estrogen.2 Estrogen has many effects on the body, many of which are not completely understood. Loss of estrogen alters the activity of the noradrenergic and serotonergic systems by affecting the levels of the neurotransmitters in the brain. This affects the hypothalamic thermoregulatory center, causing hot flashes. Both norepinephrine and serotonin play central roles in central thermoregulation. Serotonin and norepinephrine are 2 of 3 neurotransmitters (along with dopamine) in the brain that are affected in depression3; a proper balance of the 3 is needed to avoid depression. While depression is not a result of menopause, depression is very common in perimenopausal and menopausal women and may coexist with menopausal symptoms and may be affected by the hormonal influence on neurotransmitters.
Treatment Many centrally acting medications have been used to relieve the symptoms of menopause. An unfortunate characteristic of centrally acting medications is that they have a high rate of adverse reactions. Most of these are mild and may resolve with continued use. However, when treating symptoms rather than a serious illness, it is often difficult to get a patient to accept a medication that is going to cause symptoms of its own. However, centrally
May 2008
Table 1. Important Characteristics and Effects of Recommended Medications Medication
Alertness
Weight
Clonidine
Somnolence*
No effect
No relationship
Depression
Gabapentin
Somnolence
Gain
Can cause
Paroxetine
Somnolence
Gain
Treatment
Venlafaxine
Insomnia**
Loss
Treatment
*Can also cause insomnia. **Can also cause somnolence.
acting medications such as antihypertensives, anticonvulsants, and antidepressants have proven helpful for some women. • Antihypertensives. Clonidine has been shown to have a modest effect on hot flashes. Its mechanism of action is to stimulate inhibitory alpha norepinephrine receptors. If a woman has menopausal symptoms and hypertension, it is sensible to try clonidine if not contraindicated.4 Frequent adverse reactions include constipation, dry mouth, drowsiness, and dizziness. Gastrointestinal distress, headache, and nervousness are also seen. A potentially serious problem may be the development of symptomatic hypotension.3 • Anticonvulsants. Gabapentin increases levels of GABA, an inhibitory neurotransmitter. How it affects hot flashes is not understood, but it can be effective.4 Gabapentin may cause depression. Other common reactions include dizziness, ataxia, and peripheral edema.3 • Antidepressants. A number of antidepressants have been studied.2 While all selective serotonin reuptake inhibitors (SSRIs) have been researched, paroxetine (Paxil) appears to be the most effective and is the only SSRI currently recommended for use in menopause. Paroxetine is different from the other SSRIs in that it is also anticholinergic. Anticholinergic adverse effects include sedation, dry mouth, constipation, urinary retention, and tachycardia. Citalopram (Celexa) may also be effective and could be used if the patient is unable to tolerate the side effects of paroxetine. Citalopram (Celexa), fluoxetine (Prozac), and sertraline (Zoloft) are more likely to cause insomnia than other products. These drugs may cause weight loss, whereas paroxetine may cause
www.npjournal.org
weight gain. Frequent SSRI adverse effects are nausea, headache, diarrhea, constipation, dry mouth, and sexual dysfunction. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor that appears to be the most effective of all of the nonhormonal treatments of menopausal symptoms.2 Frequent adverse reactions are nausea and vomiting, dry mouth, headache, insomnia or somnolence, and sweating. It can also cause sexual dysfunction. Table 1 lists several medications and their effects. One should look at the complete person when prescribing a medication for menopausal symptoms. Consider the other symptoms the woman is experiencing. Most women do not have hot flashes without any other symptoms. Insomnia, hypertension, and depression are common. Choice of medication should take these factors into account. While these medications may be helpful, they are far from an ideal treatment of menopause symptoms. HRT remains more effective, but much research remains to find a better treatment. References 1. North American Menopause Society. Treatment of menopauseassociated vasomotor symptoms: position statement of the North American Menopause Society. Menopause. 2004;11:11-33. 2. Rapkin, AJ. Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment. Am J Obstetr Gynecol. 2007;196:97-106. 3. Edmunds MW, Mayhew MS. Pharmacology for the primary care provider. 2nd ed. St Louis, MO: Mosby; 2004. 4. Loprinzi CL, Stearns V, Barton D. Centrally active nonhormonal hot flash therapies. Am J Med. 2005;118(12B):118S-123S.
Maren Mayhew, MS, ANP, GNP, is the author and editor of Pharmacology for Primary Care Providers, a textbook for NPs published by Mosby. She can be reached at marenmayhew@ comcast.net. This is a monthly column on medication news and controversies.Suggestions for topics are welcome. 1555-4155/08/$ see front matter © 2008 American College of Nurse Practitioners doi: 10.1016/j-nupra.2008.03.018
The Journal for Nurse Practitioners - JNP
385
NONHORMONAL TREATMENT OF MENOPAUSAL SYMPTOMS There are many reasons a woman may choose to not take hormone replacement therapy (HRT) for
as long as 5 years) and wane after about 1 year after menopause. However, some symptoms have been demonstrated to cause problems for as long as 30 years.2
Physiology
PRESCRIPTION PAD Maren S. Mayhew
menopausal symptoms. She may have a contraindication, increased risk for problems, or a personal preference. Much of the research on nonhormonal treatment was done in women with contraindications, such as breast cancer survivors, and most are fairly short-term studies. This column discusses the medications recommended by the North American Menopause Society for treatment of menopause symptoms.1 However, these medications are not approved by the US Food and Drug Administration for this use. The most common problematic symptoms of menopause are vasomotor symptoms, such as hot flashes and night sweats. Other symptoms are dizziness, mood disorders, sleep disturbances, headaches, difficulty concentrating, memory impairment, general malaise, rapid, irregular heartbeat, atrophic vaginitis, bladder irritability, myalgias, and arthralgias. Most of these have a central nervous system component. These symptoms can have a significant negative effect of a woman's quality of life. These symptoms are most severe during the perimenopausal phase (which may last
384
The Journal for Nurse Practitioners - JNP
The basic hormonal change in menopause is loss of estrogen.2 Estrogen has many effects on the body, many of which are not completely understood. Loss of estrogen alters the activity of the noradrenergic and serotonergic systems by affecting the levels of the neurotransmitters in the brain. This affects the hypothalamic thermoregulatory center, causing hot flashes. Both norepinephrine and serotonin play central roles in central thermoregulation. Serotonin and norepinephrine are 2 of 3 neurotransmitters (along with dopamine) in the brain that are affected in depression3; a proper balance of the 3 is needed to avoid depression. While depression is not a result of menopause, depression is very common in perimenopausal and menopausal women and may coexist with menopausal symptoms and may be affected by the hormonal influence on neurotransmitters.
Treatment Many centrally acting medications have been used to relieve the symptoms of menopause. An unfortunate characteristic of centrally acting medications is that they have a high rate of adverse reactions. Most of these are mild and may resolve with continued use. However, when treating symptoms rather than a serious illness, it is often difficult to get a patient to accept a medication that is going to cause symptoms of its own. However, centrally
May 2008
Table 1. Important Characteristics and Effects of Recommended Medications Medication
Alertness
Weight
Clonidine
Somnolence*
No effect
No relationship
Depression
Gabapentin
Somnolence
Gain
Can cause
Paroxetine
Somnolence
Gain
Treatment
Venlafaxine
Insomnia**
Loss
Treatment
*Can also cause insomnia. **Can also cause somnolence.
acting medications such as antihypertensives, anticonvulsants, and antidepressants have proven helpful for some women. • Antihypertensives. Clonidine has been shown to have a modest effect on hot flashes. Its mechanism of action is to stimulate inhibitory alpha norepinephrine receptors. If a woman has menopausal symptoms and hypertension, it is sensible to try clonidine if not contraindicated.4 Frequent adverse reactions include constipation, dry mouth, drowsiness, and dizziness. Gastrointestinal distress, headache, and nervousness are also seen. A potentially serious problem may be the development of symptomatic hypotension.3 • Anticonvulsants. Gabapentin increases levels of GABA, an inhibitory neurotransmitter. How it affects hot flashes is not understood, but it can be effective.4 Gabapentin may cause depression. Other common reactions include dizziness, ataxia, and peripheral edema.3 • Antidepressants. A number of antidepressants have been studied.2 While all selective serotonin reuptake inhibitors (SSRIs) have been researched, paroxetine (Paxil) appears to be the most effective and is the only SSRI currently recommended for use in menopause. Paroxetine is different from the other SSRIs in that it is also anticholinergic. Anticholinergic adverse effects include sedation, dry mouth, constipation, urinary retention, and tachycardia. Citalopram (Celexa) may also be effective and could be used if the patient is unable to tolerate the side effects of paroxetine. Citalopram (Celexa), fluoxetine (Prozac), and sertraline (Zoloft) are more likely to cause insomnia than other products. These drugs may cause weight loss, whereas paroxetine may cause
www.npjournal.org
weight gain. Frequent SSRI adverse effects are nausea, headache, diarrhea, constipation, dry mouth, and sexual dysfunction. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor that appears to be the most effective of all of the nonhormonal treatments of menopausal symptoms.2 Frequent adverse reactions are nausea and vomiting, dry mouth, headache, insomnia or somnolence, and sweating. It can also cause sexual dysfunction. Table 1 lists several medications and their effects. One should look at the complete person when prescribing a medication for menopausal symptoms. Consider the other symptoms the woman is experiencing. Most women do not have hot flashes without any other symptoms. Insomnia, hypertension, and depression are common. Choice of medication should take these factors into account. While these medications may be helpful, they are far from an ideal treatment of menopause symptoms. HRT remains more effective, but much research remains to find a better treatment. References 1. North American Menopause Society. Treatment of menopauseassociated vasomotor symptoms: position statement of the North American Menopause Society. Menopause. 2004;11:11-33. 2. Rapkin, AJ. Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment. Am J Obstetr Gynecol. 2007;196:97-106. 3. Edmunds MW, Mayhew MS. Pharmacology for the primary care provider. 2nd ed. St Louis, MO: Mosby; 2004. 4. Loprinzi CL, Stearns V, Barton D. Centrally active nonhormonal hot flash therapies. Am J Med. 2005;118(12B):118S-123S.
Maren Mayhew, MS, ANP, GNP, is the author and editor of Pharmacology for Primary Care Providers, a textbook for NPs published by Mosby. She can be reached at marenmayhew@ comcast.net. This is a monthly column on medication news and controversies.Suggestions for topics are welcome. 1555-4155/08/$ see front matter © 2008 American College of Nurse Practitioners doi: 10.1016/j-nupra.2008.03.018
The Journal for Nurse Practitioners - JNP
385