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What is the best way to diagnose menopause?
No single test for menopause is highly sensitive and specific. The best predictors that a woman will enter menopause within 4 years include age at least 50 years, amenorrhea for 3 to 11 months, and menstrual cycle irregularity within 12 months (strength of recommendation [SOR]: B; based on multiple prospective cohort studies).
For diagnosing perimenopause, the level of follicle-stimulating hormone (FSH) is most useful for clinical situations in which the pretest probability, as based on history, is midrange (SOR: B, based on 1 systematic review and 2 cross-sectional studies).
Take an active approach, reassure patients they are experiencing a normal transition
Tsveti Markova, MD
Wayne State University, Detroit, Michigan
Women usually come to our practice when they start experiencing perimenopausal symptoms and seek relief. After ruling out clinically similar conditions like diabetes or thyroid disease, we can take an active approach of patient education. We reassure patients that they are experiencing a normal hormonal transition that can take 6 to 7 years. It is important to emphasize any needed lifestyle changes in such areas as smoking, substance use, diet and exercise, weight management, bone loss prevention, and bladder control. We can discuss with our patients ways of alleviating symptoms. In our practice, we do not frequently use hormonal lab tests (FSH, luteinizing hormone, estrogen), since they can be unreliable and do not usually affect our clinical approach. In addition to the perimenopausal syndrome, diagnosing the patient’s condition as “menopause” only describes cessation of fertility. We encourage women to use safe methods of contraception until they experience 12 months of amenorrhea. Before that time, barrier methods (IUDs, condoms, etc) are options of choice, since oral contraceptives may mask perimenopausal symptoms and invalidate any hormonal measurements.
Evidence summary
Since natural menopause is clinically defined as the final menstrual period, the best way to diagnose it is to retrospectively observe 12 consecutive months of amenorrhea. Several studies followed women longitudinally and found the characteristics that best predicted actual transition to menopause within 4 years were amenorrhea of between 3 and 12 months duration (sensitivity=0.16–0.32; specificity=0.98–1.0; positive likelihood ratio [LR+]=14.4–∞; negative likelihood ratio [LR–]=0.69–0.84), cycle irregularity within 12 months (sensitivity=0.65–0.66; specificity=0.77–0.85; LR+=2.84-4.17; LR–=0.42–0.84), and age≥50 years (sensitivity=0.35; specificity=0.98; LR+=15.4; LR–=0.66).1-3 Change in the amount of flow is more sensitive but less specific (sensitivity=0.81; specificity=0.30; LR+=1.15; LR–=0.65).3 A woman’s global perception of being perimenopausal can also be useful for “rulingin” transition to menopause within the next several years (sensitivity=0.18; specificity=1; LR+=∞; LR–=0.82).1,5 No studies were identified that prospectively studied the usefulness of laboratory or radiologic findings among perimenopausal women for predicting transition to postmenopausal state.
Because the perimenopause marks the entry into the menopausal transition, whether a woman has entered perimenopause is often the more relevant diagnosis to be made. Factors often used to diagnose perimenopause include age, maternal age at menopause, vasomotor and vaginal symptoms, FSH level, and a patient’s global perception of being perimenopausal. Other proposed methods include vaginal ultrasound to measure ovarian volume and number of antral follicles and assays for inhibins, but currently the test characteristics for these are inferior to less invasive and less costly methods.
Age alone can be a useful predictor for perimenopause; most women have either entered or completed the menopausal transition by age 50, and almost all by age 55.
The TABLE summarizes test characteristics for a variety of symptoms and lab assays to diagnose perimenopause. No one test is highly sensitive and specific. Typical symptoms of hot flashes, night sweats, and vaginal dryness are about as specific as laboratory tests, but are generally less sensitive.1,4,6-7 Self-perceived menopausal status is moderately to highly sensitive, but the range of specificity estimates are wide. The LR+and LR–for FSH, which are of midhigh magnitude, would suggest it to be the best single diagnostic test.4,6,7 However, because laboratory tests are usually ordered after some determination of pretest probability based on history and physical, FSH may be of less utility where the pretest probability for perimenopause is already high, such as the case of a 52-year-old woman seeking “confirmation” for perimenopausal symptoms. FSH levels are highly varied within individuals during perimenopause; and further variation due to body-mass index and ethnicity make defining diagnostic thresholds difficult.8
TABLE
Symptoms and laboratory tests for diagnosing perimenopause
| SYMPTOM/LAB TEST | SENSITIVITY | SPECIFICITY | LR+ | LR– |
|---|---|---|---|---|
| Elevated FSH*4,6,7 | 0.65–0.74 | 0.79–0.94 | 3.06–11.32 | 0.29–0.45 |
| Inhibin (immunoreactive)4 | 0.07 | 0.96 | 1.90 | 0.97 |
| Inhibin A4 | 0.61 | 0.54 | 1.31 | 0.73 |
| Inhibin B4 | 0.46 | 0.78 | 2.05 | 0.70 |
| Hot flashes1,4 | 0.22–0.59 | 0.83–0.91 | 2.12–4.06 | 0.54–0.87 |
| Night sweats4 | 0.20–0.50 | 0.74–0.87 | 1.90 | 0.67–0.92 |
| Vaginal dryness4 | 0.11–0.29 | 0.80–0.97 | 1.48–3.79 | 0.92 |
| Self-perceived perimenopausal status1,4 | 0.77–0.95 | 0.39–0.64 | 1.53–2.13 | 0.10–0.36 |
| LR+, likelihood ratio if the test is positive; LR–, likelihood ratio if the test is negative; FSH, follicle-stimulating hormone. | ||||
| *Two studies defined elevated FSH as=20 IU/L, one study defined elevated FSH as=24 IU/L. | ||||
Recommendations from others
The American Academy of Family Physicians, American College of Physicians, and American College of Obstetricians and Gynecologists do not address the diagnosis of menopause in any recommendations.
The North American Menopause Society states that estradiol and FSH are of limited value in confirming perimenopause due to extreme monthly fluctuations. They say perimenopausal women are not protected from unplanned pregnancy until amenorrhea of at least 1 year’s duration or consistently elevated FSH levels (>30 IU/L) are demonstrated. Confirmation of perimenopause relies on medical history and symptoms.
The American Association of Clinical Endocrinologists recommends a detailed history, exam, and measurement of FSH. The diagnosis of menopause is confirmed by FSH levels >40 IU/L; however, they note in perimenopause, FSH elevation is intermittent and not reliable for establishing the onset of menopause.
1 Dudley EC, Hopper JL, Taffe J, Guthrie JR, Burger HG, Dennerstein L. Using longitudinal data to define the perimenopause by menstrual cycle characteristics. Climacteric 1998;1:18-25.
2 Brambilla DJ, McKinlay SM, Johannes CB. Defining the perimenopause for application in epidemiologic investigations. Am J Epidemiol 1994;140:1091-1095.
3 Taylor SM, Kinney AM, Kline JK. Menopausal transition: predicting time to menopause for women 44 years or older from simple questions on menstrual variability. Menopause 2004;11:40-48.
4 Bastian LA, Smith CM, Nanda K. Is this woman perimenopausal? JAMA 2003;289:895-902.
5 Taffe J, Dennerstein L. Time to the final menstrual period. Fertil Steril 2002;78:397-403.
6 Cooper GS, Baird DD, Darden FR. Measures of menopausal status in relation to demographic, reproductive, and behavioral characteristics in a populationbased study of women aged 35–49 years. Am J Epidemiol 2001;153:1159-1165.
7 Flaws JA, Langenberg P, Babus JK, Hirshfield AN, Sharara FI. Ovarian volume and antral follicle counts as indicators of menopausal status. Menopause 2001;8:175-180.
8 Randolph JF, Jr, Sowers M, Gold EB, et al. Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status. J Clin Endocrinol Metab 2003;88:1516-1522.
No single test for menopause is highly sensitive and specific. The best predictors that a woman will enter menopause within 4 years include age at least 50 years, amenorrhea for 3 to 11 months, and menstrual cycle irregularity within 12 months (strength of recommendation [SOR]: B; based on multiple prospective cohort studies).
For diagnosing perimenopause, the level of follicle-stimulating hormone (FSH) is most useful for clinical situations in which the pretest probability, as based on history, is midrange (SOR: B, based on 1 systematic review and 2 cross-sectional studies).
Take an active approach, reassure patients they are experiencing a normal transition
Tsveti Markova, MD
Wayne State University, Detroit, Michigan
Women usually come to our practice when they start experiencing perimenopausal symptoms and seek relief. After ruling out clinically similar conditions like diabetes or thyroid disease, we can take an active approach of patient education. We reassure patients that they are experiencing a normal hormonal transition that can take 6 to 7 years. It is important to emphasize any needed lifestyle changes in such areas as smoking, substance use, diet and exercise, weight management, bone loss prevention, and bladder control. We can discuss with our patients ways of alleviating symptoms. In our practice, we do not frequently use hormonal lab tests (FSH, luteinizing hormone, estrogen), since they can be unreliable and do not usually affect our clinical approach. In addition to the perimenopausal syndrome, diagnosing the patient’s condition as “menopause” only describes cessation of fertility. We encourage women to use safe methods of contraception until they experience 12 months of amenorrhea. Before that time, barrier methods (IUDs, condoms, etc) are options of choice, since oral contraceptives may mask perimenopausal symptoms and invalidate any hormonal measurements.
Evidence summary
Since natural menopause is clinically defined as the final menstrual period, the best way to diagnose it is to retrospectively observe 12 consecutive months of amenorrhea. Several studies followed women longitudinally and found the characteristics that best predicted actual transition to menopause within 4 years were amenorrhea of between 3 and 12 months duration (sensitivity=0.16–0.32; specificity=0.98–1.0; positive likelihood ratio [LR+]=14.4–∞; negative likelihood ratio [LR–]=0.69–0.84), cycle irregularity within 12 months (sensitivity=0.65–0.66; specificity=0.77–0.85; LR+=2.84-4.17; LR–=0.42–0.84), and age≥50 years (sensitivity=0.35; specificity=0.98; LR+=15.4; LR–=0.66).1-3 Change in the amount of flow is more sensitive but less specific (sensitivity=0.81; specificity=0.30; LR+=1.15; LR–=0.65).3 A woman’s global perception of being perimenopausal can also be useful for “rulingin” transition to menopause within the next several years (sensitivity=0.18; specificity=1; LR+=∞; LR–=0.82).1,5 No studies were identified that prospectively studied the usefulness of laboratory or radiologic findings among perimenopausal women for predicting transition to postmenopausal state.
Because the perimenopause marks the entry into the menopausal transition, whether a woman has entered perimenopause is often the more relevant diagnosis to be made. Factors often used to diagnose perimenopause include age, maternal age at menopause, vasomotor and vaginal symptoms, FSH level, and a patient’s global perception of being perimenopausal. Other proposed methods include vaginal ultrasound to measure ovarian volume and number of antral follicles and assays for inhibins, but currently the test characteristics for these are inferior to less invasive and less costly methods.
Age alone can be a useful predictor for perimenopause; most women have either entered or completed the menopausal transition by age 50, and almost all by age 55.
The TABLE summarizes test characteristics for a variety of symptoms and lab assays to diagnose perimenopause. No one test is highly sensitive and specific. Typical symptoms of hot flashes, night sweats, and vaginal dryness are about as specific as laboratory tests, but are generally less sensitive.1,4,6-7 Self-perceived menopausal status is moderately to highly sensitive, but the range of specificity estimates are wide. The LR+and LR–for FSH, which are of midhigh magnitude, would suggest it to be the best single diagnostic test.4,6,7 However, because laboratory tests are usually ordered after some determination of pretest probability based on history and physical, FSH may be of less utility where the pretest probability for perimenopause is already high, such as the case of a 52-year-old woman seeking “confirmation” for perimenopausal symptoms. FSH levels are highly varied within individuals during perimenopause; and further variation due to body-mass index and ethnicity make defining diagnostic thresholds difficult.8
TABLE
Symptoms and laboratory tests for diagnosing perimenopause
| SYMPTOM/LAB TEST | SENSITIVITY | SPECIFICITY | LR+ | LR– |
|---|---|---|---|---|
| Elevated FSH*4,6,7 | 0.65–0.74 | 0.79–0.94 | 3.06–11.32 | 0.29–0.45 |
| Inhibin (immunoreactive)4 | 0.07 | 0.96 | 1.90 | 0.97 |
| Inhibin A4 | 0.61 | 0.54 | 1.31 | 0.73 |
| Inhibin B4 | 0.46 | 0.78 | 2.05 | 0.70 |
| Hot flashes1,4 | 0.22–0.59 | 0.83–0.91 | 2.12–4.06 | 0.54–0.87 |
| Night sweats4 | 0.20–0.50 | 0.74–0.87 | 1.90 | 0.67–0.92 |
| Vaginal dryness4 | 0.11–0.29 | 0.80–0.97 | 1.48–3.79 | 0.92 |
| Self-perceived perimenopausal status1,4 | 0.77–0.95 | 0.39–0.64 | 1.53–2.13 | 0.10–0.36 |
| LR+, likelihood ratio if the test is positive; LR–, likelihood ratio if the test is negative; FSH, follicle-stimulating hormone. | ||||
| *Two studies defined elevated FSH as=20 IU/L, one study defined elevated FSH as=24 IU/L. | ||||
Recommendations from others
The American Academy of Family Physicians, American College of Physicians, and American College of Obstetricians and Gynecologists do not address the diagnosis of menopause in any recommendations.
The North American Menopause Society states that estradiol and FSH are of limited value in confirming perimenopause due to extreme monthly fluctuations. They say perimenopausal women are not protected from unplanned pregnancy until amenorrhea of at least 1 year’s duration or consistently elevated FSH levels (>30 IU/L) are demonstrated. Confirmation of perimenopause relies on medical history and symptoms.
The American Association of Clinical Endocrinologists recommends a detailed history, exam, and measurement of FSH. The diagnosis of menopause is confirmed by FSH levels >40 IU/L; however, they note in perimenopause, FSH elevation is intermittent and not reliable for establishing the onset of menopause.
No single test for menopause is highly sensitive and specific. The best predictors that a woman will enter menopause within 4 years include age at least 50 years, amenorrhea for 3 to 11 months, and menstrual cycle irregularity within 12 months (strength of recommendation [SOR]: B; based on multiple prospective cohort studies).
For diagnosing perimenopause, the level of follicle-stimulating hormone (FSH) is most useful for clinical situations in which the pretest probability, as based on history, is midrange (SOR: B, based on 1 systematic review and 2 cross-sectional studies).
Take an active approach, reassure patients they are experiencing a normal transition
Tsveti Markova, MD
Wayne State University, Detroit, Michigan
Women usually come to our practice when they start experiencing perimenopausal symptoms and seek relief. After ruling out clinically similar conditions like diabetes or thyroid disease, we can take an active approach of patient education. We reassure patients that they are experiencing a normal hormonal transition that can take 6 to 7 years. It is important to emphasize any needed lifestyle changes in such areas as smoking, substance use, diet and exercise, weight management, bone loss prevention, and bladder control. We can discuss with our patients ways of alleviating symptoms. In our practice, we do not frequently use hormonal lab tests (FSH, luteinizing hormone, estrogen), since they can be unreliable and do not usually affect our clinical approach. In addition to the perimenopausal syndrome, diagnosing the patient’s condition as “menopause” only describes cessation of fertility. We encourage women to use safe methods of contraception until they experience 12 months of amenorrhea. Before that time, barrier methods (IUDs, condoms, etc) are options of choice, since oral contraceptives may mask perimenopausal symptoms and invalidate any hormonal measurements.
Evidence summary
Since natural menopause is clinically defined as the final menstrual period, the best way to diagnose it is to retrospectively observe 12 consecutive months of amenorrhea. Several studies followed women longitudinally and found the characteristics that best predicted actual transition to menopause within 4 years were amenorrhea of between 3 and 12 months duration (sensitivity=0.16–0.32; specificity=0.98–1.0; positive likelihood ratio [LR+]=14.4–∞; negative likelihood ratio [LR–]=0.69–0.84), cycle irregularity within 12 months (sensitivity=0.65–0.66; specificity=0.77–0.85; LR+=2.84-4.17; LR–=0.42–0.84), and age≥50 years (sensitivity=0.35; specificity=0.98; LR+=15.4; LR–=0.66).1-3 Change in the amount of flow is more sensitive but less specific (sensitivity=0.81; specificity=0.30; LR+=1.15; LR–=0.65).3 A woman’s global perception of being perimenopausal can also be useful for “rulingin” transition to menopause within the next several years (sensitivity=0.18; specificity=1; LR+=∞; LR–=0.82).1,5 No studies were identified that prospectively studied the usefulness of laboratory or radiologic findings among perimenopausal women for predicting transition to postmenopausal state.
Because the perimenopause marks the entry into the menopausal transition, whether a woman has entered perimenopause is often the more relevant diagnosis to be made. Factors often used to diagnose perimenopause include age, maternal age at menopause, vasomotor and vaginal symptoms, FSH level, and a patient’s global perception of being perimenopausal. Other proposed methods include vaginal ultrasound to measure ovarian volume and number of antral follicles and assays for inhibins, but currently the test characteristics for these are inferior to less invasive and less costly methods.
Age alone can be a useful predictor for perimenopause; most women have either entered or completed the menopausal transition by age 50, and almost all by age 55.
The TABLE summarizes test characteristics for a variety of symptoms and lab assays to diagnose perimenopause. No one test is highly sensitive and specific. Typical symptoms of hot flashes, night sweats, and vaginal dryness are about as specific as laboratory tests, but are generally less sensitive.1,4,6-7 Self-perceived menopausal status is moderately to highly sensitive, but the range of specificity estimates are wide. The LR+and LR–for FSH, which are of midhigh magnitude, would suggest it to be the best single diagnostic test.4,6,7 However, because laboratory tests are usually ordered after some determination of pretest probability based on history and physical, FSH may be of less utility where the pretest probability for perimenopause is already high, such as the case of a 52-year-old woman seeking “confirmation” for perimenopausal symptoms. FSH levels are highly varied within individuals during perimenopause; and further variation due to body-mass index and ethnicity make defining diagnostic thresholds difficult.8
TABLE
Symptoms and laboratory tests for diagnosing perimenopause
| SYMPTOM/LAB TEST | SENSITIVITY | SPECIFICITY | LR+ | LR– |
|---|---|---|---|---|
| Elevated FSH*4,6,7 | 0.65–0.74 | 0.79–0.94 | 3.06–11.32 | 0.29–0.45 |
| Inhibin (immunoreactive)4 | 0.07 | 0.96 | 1.90 | 0.97 |
| Inhibin A4 | 0.61 | 0.54 | 1.31 | 0.73 |
| Inhibin B4 | 0.46 | 0.78 | 2.05 | 0.70 |
| Hot flashes1,4 | 0.22–0.59 | 0.83–0.91 | 2.12–4.06 | 0.54–0.87 |
| Night sweats4 | 0.20–0.50 | 0.74–0.87 | 1.90 | 0.67–0.92 |
| Vaginal dryness4 | 0.11–0.29 | 0.80–0.97 | 1.48–3.79 | 0.92 |
| Self-perceived perimenopausal status1,4 | 0.77–0.95 | 0.39–0.64 | 1.53–2.13 | 0.10–0.36 |
| LR+, likelihood ratio if the test is positive; LR–, likelihood ratio if the test is negative; FSH, follicle-stimulating hormone. | ||||
| *Two studies defined elevated FSH as=20 IU/L, one study defined elevated FSH as=24 IU/L. | ||||
Recommendations from others
The American Academy of Family Physicians, American College of Physicians, and American College of Obstetricians and Gynecologists do not address the diagnosis of menopause in any recommendations.
The North American Menopause Society states that estradiol and FSH are of limited value in confirming perimenopause due to extreme monthly fluctuations. They say perimenopausal women are not protected from unplanned pregnancy until amenorrhea of at least 1 year’s duration or consistently elevated FSH levels (>30 IU/L) are demonstrated. Confirmation of perimenopause relies on medical history and symptoms.
The American Association of Clinical Endocrinologists recommends a detailed history, exam, and measurement of FSH. The diagnosis of menopause is confirmed by FSH levels >40 IU/L; however, they note in perimenopause, FSH elevation is intermittent and not reliable for establishing the onset of menopause.
1 Dudley EC, Hopper JL, Taffe J, Guthrie JR, Burger HG, Dennerstein L. Using longitudinal data to define the perimenopause by menstrual cycle characteristics. Climacteric 1998;1:18-25.
2 Brambilla DJ, McKinlay SM, Johannes CB. Defining the perimenopause for application in epidemiologic investigations. Am J Epidemiol 1994;140:1091-1095.
3 Taylor SM, Kinney AM, Kline JK. Menopausal transition: predicting time to menopause for women 44 years or older from simple questions on menstrual variability. Menopause 2004;11:40-48.
4 Bastian LA, Smith CM, Nanda K. Is this woman perimenopausal? JAMA 2003;289:895-902.
5 Taffe J, Dennerstein L. Time to the final menstrual period. Fertil Steril 2002;78:397-403.
6 Cooper GS, Baird DD, Darden FR. Measures of menopausal status in relation to demographic, reproductive, and behavioral characteristics in a populationbased study of women aged 35–49 years. Am J Epidemiol 2001;153:1159-1165.
7 Flaws JA, Langenberg P, Babus JK, Hirshfield AN, Sharara FI. Ovarian volume and antral follicle counts as indicators of menopausal status. Menopause 2001;8:175-180.
8 Randolph JF, Jr, Sowers M, Gold EB, et al. Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status. J Clin Endocrinol Metab 2003;88:1516-1522.
1 Dudley EC, Hopper JL, Taffe J, Guthrie JR, Burger HG, Dennerstein L. Using longitudinal data to define the perimenopause by menstrual cycle characteristics. Climacteric 1998;1:18-25.
2 Brambilla DJ, McKinlay SM, Johannes CB. Defining the perimenopause for application in epidemiologic investigations. Am J Epidemiol 1994;140:1091-1095.
3 Taylor SM, Kinney AM, Kline JK. Menopausal transition: predicting time to menopause for women 44 years or older from simple questions on menstrual variability. Menopause 2004;11:40-48.
4 Bastian LA, Smith CM, Nanda K. Is this woman perimenopausal? JAMA 2003;289:895-902.
5 Taffe J, Dennerstein L. Time to the final menstrual period. Fertil Steril 2002;78:397-403.
6 Cooper GS, Baird DD, Darden FR. Measures of menopausal status in relation to demographic, reproductive, and behavioral characteristics in a populationbased study of women aged 35–49 years. Am J Epidemiol 2001;153:1159-1165.
7 Flaws JA, Langenberg P, Babus JK, Hirshfield AN, Sharara FI. Ovarian volume and antral follicle counts as indicators of menopausal status. Menopause 2001;8:175-180.
8 Randolph JF, Jr, Sowers M, Gold EB, et al. Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status. J Clin Endocrinol Metab 2003;88:1516-1522.
Evidence-based answers from the Family Physicians Inquiries Network
What are the best therapies for acute migraine in pregnancy?
No randomized controlled trials of pharmacologic therapy for acute migraine in pregnant women are available. Three treatment studies suggest that nonpharmacological therapies (combinations of skin warming, relaxation, biofeedback, and physical therapy) were effective for pain relief (strength of recommendation [SOR]: C, poor-quality cohort and case-control studies). Practice guidelines and most review articles recommend acetaminophen as the first-line therapy (SOR: C, expert opinion). Treatment modalities, including medications, should be chosen based on both effectiveness for nonpregnant patients and established pregnancy safety from surveillance studies.
It is helpful to test nonpharmacologic treatments during the prepregnancy period
Tricia C. Elliott, MD
Department of Family Medicine, Baylor College of Medicine, Houston, Tex
For young women diagnosed with migraine, begin discussing with them during the family planning period treatment options for acute migraine in pregnancy. Trials of approved medications and nonpharmacologic treatments can be given at this time to evaluate their efficacy and to give the patient time to feel comfortable with them. It is especially important to test nonpharmacologic treatments during the prepregnancy period.
In my own experience as a physician, and as a young woman with a long-standing history of migraine, biofeedback and relaxation techniques work better when the patient is first exposed during pain-free or subacute pain periods. For moderate to severe migraineurs, it is difficult to institute these techniques during a full-blown attack. For such patients, experience with safer treatment modalities before pregnancy would allow greater success for treatment of acute migraine during pregnancy.
Evidence summary
Eighteen percent of all women report migraines.1 As estrogen levels increase early in pregnancy, many women report an increase in headache or new-onset headache. As estrogen levels stabilize in the second and third trimester, 60% to 70% of women with migraine report reduction in symptoms.1,2
Nonpharmacologic treatment. A small case series of electromyograph (EMG) biofeedback and relaxation techniques on 5 pregnant women showed that 4 became headache-free.3 It is impossible to say whether it was the intervention, natural disease progression, or the attention received from the therapist that produced this result. Two studies were published together evaluating thermal biofeedback, relaxation training, and physical therapy exercises. The first, a cohort study, showed decrease in symptoms for 15 of 19 women. The second, a small randomized controlled trial, compared 11 women using the combination treatment with 14 control women who received attention from the therapist but no other intervention. More than 72% of the treatment arm improved, compared with nearly 29% of the attention control group.4 Interpretation of these studies is limited by small sample size and testing in settings with specialized resources that are not found in every community.
Sumatriptan and other agents. Six studies have evaluated sumatriptan use in pregnancy.5 All were designed to evaluate teratogenicity and harm. None evaluated treatment efficacy in pregnancy. One prospective controlled cohort study showed an increase in miscarriage rates that did not reach statistical significance.6 No trials showed an increased risk in birth defects compared with the general population.
A single case report on the use of intravenous magnesium sulfate and prochlorperazine reported that the combination was effective for aborting a prolonged (6-day) migraine with aura for a pregnant woman.7
Safety in pregnancy. The US Food and Drug Administration (FDA) assigns fetal risk categories to all drugs based on controlled studies in humans, animal reproduction studies, and surveillance studies.8 Though no data exist on the effectiveness of other medications for migraine in pregnancy, it is reasonable to select drugs for both effectiveness for nonpregnant patients and established safety as determined by the FDA’s fetal risk summary. The TABLE shows commonly used drugs for acute migraine and their pregnancy risk category classification.
TABLE
Pregnancy risk category of abortive drugs for migraine
| MEDICATION | PREGNANCY RISK CATEGORY |
|---|---|
| Acetaminophen | B |
| Ibuprofen | B/D* |
| Naproxen | B/D* |
| Acetaminophen/oxycodone | B |
| Acetaminophen/codeine | C |
| Meperidine | B |
| Prochlorperazine | C |
| Sumatriptan | C |
| Butalbital/aspirin/caffeine | C/D* |
| Ergotamine/caffeine | X |
| A=Controlled human studies show no risk; B=No evidence of risk in humans, but no controlled studies; C=Risk to humans has not been ruled out; D=Positive evidence of risk to humans from human or animal studies; X=Contraindicated in pregnancy. | |
| *Category changes to D if used in 3rd trimester. | |
| Source: Briggs et al 2002.7 | |
Recommendations from others
Practice guidelines published by the American Academy of Neurology recommend acetaminophen as first-line therapy based on its established safety in surveillance studies, although it is of questionable efficacy for nonpregnant patients. They also recommend nonpharmacologic treatment as an acceptable option in pregnancy.9 Most review articles also recommend acetaminophen alone or in combination with codeine as the treatment of first choice.1,10
1. Silberstein SD. Migraine and pregnancy. Neurol Clin 1997;15:209-231.
2. Maggioni F, Alessi C, Maggino T, Zanchin G. Headache during pregnancy. Cephalalgia 1997;17:765-769.
3. Hickling EJ, Silverman DJ, Loos W. A non-pharmacological treatment of vascular headache during pregnancy. Headache 1990;30:407-410.
4. Marcus DA, Scharff L, Turk DC. Nonpharmacological management of migraines in pregnancy. Psychosom Med 1995;57:527-535.
5. Hilaire ML, Cross LB, Eichner SF. Treatment of migraine headaches with sumatriptan in pregnancy. Ann Pharmacother 2004;38:1726-1730.
6. Shuhaiber S, Pastuszak A, Schick B, et al. Pregnancy outcome following first trimester exposure to sumatriptan. Neurology 1998;51:581-583.
7. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. 6th ed. Philadelphia, Pa: Lippincott, Williams, and Wilkins; 2002.
8. Rozen TD. Aborting a prolonged migrainous aura with intravenous prochlorperazine and magnesium sulfate. Headache 2003;43:901-903.
9. Silberstein SD. Practice parameter: Evidence-based guidelines for migraine headache (an evidence based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55:754-762.
10. Gladstone JP, Eross EJ, Dodick DW. Migraine in special populations. Treatment strategies for children and adolescents, pregnant women, and the elderly. Postgrad Med 2004;115:39-44,47-50.
No randomized controlled trials of pharmacologic therapy for acute migraine in pregnant women are available. Three treatment studies suggest that nonpharmacological therapies (combinations of skin warming, relaxation, biofeedback, and physical therapy) were effective for pain relief (strength of recommendation [SOR]: C, poor-quality cohort and case-control studies). Practice guidelines and most review articles recommend acetaminophen as the first-line therapy (SOR: C, expert opinion). Treatment modalities, including medications, should be chosen based on both effectiveness for nonpregnant patients and established pregnancy safety from surveillance studies.
It is helpful to test nonpharmacologic treatments during the prepregnancy period
Tricia C. Elliott, MD
Department of Family Medicine, Baylor College of Medicine, Houston, Tex
For young women diagnosed with migraine, begin discussing with them during the family planning period treatment options for acute migraine in pregnancy. Trials of approved medications and nonpharmacologic treatments can be given at this time to evaluate their efficacy and to give the patient time to feel comfortable with them. It is especially important to test nonpharmacologic treatments during the prepregnancy period.
In my own experience as a physician, and as a young woman with a long-standing history of migraine, biofeedback and relaxation techniques work better when the patient is first exposed during pain-free or subacute pain periods. For moderate to severe migraineurs, it is difficult to institute these techniques during a full-blown attack. For such patients, experience with safer treatment modalities before pregnancy would allow greater success for treatment of acute migraine during pregnancy.
Evidence summary
Eighteen percent of all women report migraines.1 As estrogen levels increase early in pregnancy, many women report an increase in headache or new-onset headache. As estrogen levels stabilize in the second and third trimester, 60% to 70% of women with migraine report reduction in symptoms.1,2
Nonpharmacologic treatment. A small case series of electromyograph (EMG) biofeedback and relaxation techniques on 5 pregnant women showed that 4 became headache-free.3 It is impossible to say whether it was the intervention, natural disease progression, or the attention received from the therapist that produced this result. Two studies were published together evaluating thermal biofeedback, relaxation training, and physical therapy exercises. The first, a cohort study, showed decrease in symptoms for 15 of 19 women. The second, a small randomized controlled trial, compared 11 women using the combination treatment with 14 control women who received attention from the therapist but no other intervention. More than 72% of the treatment arm improved, compared with nearly 29% of the attention control group.4 Interpretation of these studies is limited by small sample size and testing in settings with specialized resources that are not found in every community.
Sumatriptan and other agents. Six studies have evaluated sumatriptan use in pregnancy.5 All were designed to evaluate teratogenicity and harm. None evaluated treatment efficacy in pregnancy. One prospective controlled cohort study showed an increase in miscarriage rates that did not reach statistical significance.6 No trials showed an increased risk in birth defects compared with the general population.
A single case report on the use of intravenous magnesium sulfate and prochlorperazine reported that the combination was effective for aborting a prolonged (6-day) migraine with aura for a pregnant woman.7
Safety in pregnancy. The US Food and Drug Administration (FDA) assigns fetal risk categories to all drugs based on controlled studies in humans, animal reproduction studies, and surveillance studies.8 Though no data exist on the effectiveness of other medications for migraine in pregnancy, it is reasonable to select drugs for both effectiveness for nonpregnant patients and established safety as determined by the FDA’s fetal risk summary. The TABLE shows commonly used drugs for acute migraine and their pregnancy risk category classification.
TABLE
Pregnancy risk category of abortive drugs for migraine
| MEDICATION | PREGNANCY RISK CATEGORY |
|---|---|
| Acetaminophen | B |
| Ibuprofen | B/D* |
| Naproxen | B/D* |
| Acetaminophen/oxycodone | B |
| Acetaminophen/codeine | C |
| Meperidine | B |
| Prochlorperazine | C |
| Sumatriptan | C |
| Butalbital/aspirin/caffeine | C/D* |
| Ergotamine/caffeine | X |
| A=Controlled human studies show no risk; B=No evidence of risk in humans, but no controlled studies; C=Risk to humans has not been ruled out; D=Positive evidence of risk to humans from human or animal studies; X=Contraindicated in pregnancy. | |
| *Category changes to D if used in 3rd trimester. | |
| Source: Briggs et al 2002.7 | |
Recommendations from others
Practice guidelines published by the American Academy of Neurology recommend acetaminophen as first-line therapy based on its established safety in surveillance studies, although it is of questionable efficacy for nonpregnant patients. They also recommend nonpharmacologic treatment as an acceptable option in pregnancy.9 Most review articles also recommend acetaminophen alone or in combination with codeine as the treatment of first choice.1,10
No randomized controlled trials of pharmacologic therapy for acute migraine in pregnant women are available. Three treatment studies suggest that nonpharmacological therapies (combinations of skin warming, relaxation, biofeedback, and physical therapy) were effective for pain relief (strength of recommendation [SOR]: C, poor-quality cohort and case-control studies). Practice guidelines and most review articles recommend acetaminophen as the first-line therapy (SOR: C, expert opinion). Treatment modalities, including medications, should be chosen based on both effectiveness for nonpregnant patients and established pregnancy safety from surveillance studies.
It is helpful to test nonpharmacologic treatments during the prepregnancy period
Tricia C. Elliott, MD
Department of Family Medicine, Baylor College of Medicine, Houston, Tex
For young women diagnosed with migraine, begin discussing with them during the family planning period treatment options for acute migraine in pregnancy. Trials of approved medications and nonpharmacologic treatments can be given at this time to evaluate their efficacy and to give the patient time to feel comfortable with them. It is especially important to test nonpharmacologic treatments during the prepregnancy period.
In my own experience as a physician, and as a young woman with a long-standing history of migraine, biofeedback and relaxation techniques work better when the patient is first exposed during pain-free or subacute pain periods. For moderate to severe migraineurs, it is difficult to institute these techniques during a full-blown attack. For such patients, experience with safer treatment modalities before pregnancy would allow greater success for treatment of acute migraine during pregnancy.
Evidence summary
Eighteen percent of all women report migraines.1 As estrogen levels increase early in pregnancy, many women report an increase in headache or new-onset headache. As estrogen levels stabilize in the second and third trimester, 60% to 70% of women with migraine report reduction in symptoms.1,2
Nonpharmacologic treatment. A small case series of electromyograph (EMG) biofeedback and relaxation techniques on 5 pregnant women showed that 4 became headache-free.3 It is impossible to say whether it was the intervention, natural disease progression, or the attention received from the therapist that produced this result. Two studies were published together evaluating thermal biofeedback, relaxation training, and physical therapy exercises. The first, a cohort study, showed decrease in symptoms for 15 of 19 women. The second, a small randomized controlled trial, compared 11 women using the combination treatment with 14 control women who received attention from the therapist but no other intervention. More than 72% of the treatment arm improved, compared with nearly 29% of the attention control group.4 Interpretation of these studies is limited by small sample size and testing in settings with specialized resources that are not found in every community.
Sumatriptan and other agents. Six studies have evaluated sumatriptan use in pregnancy.5 All were designed to evaluate teratogenicity and harm. None evaluated treatment efficacy in pregnancy. One prospective controlled cohort study showed an increase in miscarriage rates that did not reach statistical significance.6 No trials showed an increased risk in birth defects compared with the general population.
A single case report on the use of intravenous magnesium sulfate and prochlorperazine reported that the combination was effective for aborting a prolonged (6-day) migraine with aura for a pregnant woman.7
Safety in pregnancy. The US Food and Drug Administration (FDA) assigns fetal risk categories to all drugs based on controlled studies in humans, animal reproduction studies, and surveillance studies.8 Though no data exist on the effectiveness of other medications for migraine in pregnancy, it is reasonable to select drugs for both effectiveness for nonpregnant patients and established safety as determined by the FDA’s fetal risk summary. The TABLE shows commonly used drugs for acute migraine and their pregnancy risk category classification.
TABLE
Pregnancy risk category of abortive drugs for migraine
| MEDICATION | PREGNANCY RISK CATEGORY |
|---|---|
| Acetaminophen | B |
| Ibuprofen | B/D* |
| Naproxen | B/D* |
| Acetaminophen/oxycodone | B |
| Acetaminophen/codeine | C |
| Meperidine | B |
| Prochlorperazine | C |
| Sumatriptan | C |
| Butalbital/aspirin/caffeine | C/D* |
| Ergotamine/caffeine | X |
| A=Controlled human studies show no risk; B=No evidence of risk in humans, but no controlled studies; C=Risk to humans has not been ruled out; D=Positive evidence of risk to humans from human or animal studies; X=Contraindicated in pregnancy. | |
| *Category changes to D if used in 3rd trimester. | |
| Source: Briggs et al 2002.7 | |
Recommendations from others
Practice guidelines published by the American Academy of Neurology recommend acetaminophen as first-line therapy based on its established safety in surveillance studies, although it is of questionable efficacy for nonpregnant patients. They also recommend nonpharmacologic treatment as an acceptable option in pregnancy.9 Most review articles also recommend acetaminophen alone or in combination with codeine as the treatment of first choice.1,10
1. Silberstein SD. Migraine and pregnancy. Neurol Clin 1997;15:209-231.
2. Maggioni F, Alessi C, Maggino T, Zanchin G. Headache during pregnancy. Cephalalgia 1997;17:765-769.
3. Hickling EJ, Silverman DJ, Loos W. A non-pharmacological treatment of vascular headache during pregnancy. Headache 1990;30:407-410.
4. Marcus DA, Scharff L, Turk DC. Nonpharmacological management of migraines in pregnancy. Psychosom Med 1995;57:527-535.
5. Hilaire ML, Cross LB, Eichner SF. Treatment of migraine headaches with sumatriptan in pregnancy. Ann Pharmacother 2004;38:1726-1730.
6. Shuhaiber S, Pastuszak A, Schick B, et al. Pregnancy outcome following first trimester exposure to sumatriptan. Neurology 1998;51:581-583.
7. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. 6th ed. Philadelphia, Pa: Lippincott, Williams, and Wilkins; 2002.
8. Rozen TD. Aborting a prolonged migrainous aura with intravenous prochlorperazine and magnesium sulfate. Headache 2003;43:901-903.
9. Silberstein SD. Practice parameter: Evidence-based guidelines for migraine headache (an evidence based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55:754-762.
10. Gladstone JP, Eross EJ, Dodick DW. Migraine in special populations. Treatment strategies for children and adolescents, pregnant women, and the elderly. Postgrad Med 2004;115:39-44,47-50.
1. Silberstein SD. Migraine and pregnancy. Neurol Clin 1997;15:209-231.
2. Maggioni F, Alessi C, Maggino T, Zanchin G. Headache during pregnancy. Cephalalgia 1997;17:765-769.
3. Hickling EJ, Silverman DJ, Loos W. A non-pharmacological treatment of vascular headache during pregnancy. Headache 1990;30:407-410.
4. Marcus DA, Scharff L, Turk DC. Nonpharmacological management of migraines in pregnancy. Psychosom Med 1995;57:527-535.
5. Hilaire ML, Cross LB, Eichner SF. Treatment of migraine headaches with sumatriptan in pregnancy. Ann Pharmacother 2004;38:1726-1730.
6. Shuhaiber S, Pastuszak A, Schick B, et al. Pregnancy outcome following first trimester exposure to sumatriptan. Neurology 1998;51:581-583.
7. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. 6th ed. Philadelphia, Pa: Lippincott, Williams, and Wilkins; 2002.
8. Rozen TD. Aborting a prolonged migrainous aura with intravenous prochlorperazine and magnesium sulfate. Headache 2003;43:901-903.
9. Silberstein SD. Practice parameter: Evidence-based guidelines for migraine headache (an evidence based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55:754-762.
10. Gladstone JP, Eross EJ, Dodick DW. Migraine in special populations. Treatment strategies for children and adolescents, pregnant women, and the elderly. Postgrad Med 2004;115:39-44,47-50.
Evidence-based answers from the Family Physicians Inquiries Network