1. Recognize hormonal influence on migraine headache.

2. Individualize therapy for women with migraine headache during the perimenopausal period.

3. Cite diagnostic criteria for fibromyalgia.

4. Discuss the role of central sensitization in symptoms associated with fibromyalgia.

5. Recognize and care for patients with fibromyalgia.

Perimenopausal Issues in Headache
Jan Lewis Brandes, MD, Assistant Clinical Professor, Department of Neurology, Vanderbilt University, and Director, Nashville Neuroscience Group, Nashville, TN

Perimenopause and menopause: menopause begins when woman has not menstruated for 12 consecutive months; critical time in woman’s life, when she is at peak demand for intellectual and social functioning; estrogen levels fluctuate during perimenopause (levels often higher in perimenopausal than premenopausal period); estrogen receptors present in periaqueductal gray matter of midbrain; increase in receptors may play important role for migraineur in perimenopausal period; perimenopausal period characterized by age (47 yr of age average), menstrual irregularity, hot flushes, night sweats, changes in mood, and irritability; diagnosis dependent on history; laboratory tests of no value in determining whether woman in perimenopause

Hormonal influence: hormones can improve, worsen, or have no impact on migraine; history of hormonal influence important in addressing migraine in perimenopause; rethink diagnosis of migraine if onset of headache at >50 yr of age, onset of headache with menstruation, or onset or worsening of headache with oral contraceptive (OC) use (clue that extended-use OCs should not be prescribed); information about headache during pregnancy and lactation important in predicting how woman may respond to hormone replacement therapy (HRT; may be critical to keep woman at 50 to 70 pg/mL); history of fertility management (use of clomiphene [eg, Clomid]); endometrial ablation (little data about impact on menstrual periods or migraine); mother’s history not predictive for daughter (family history more relevant to headache associated with malignancy); predictors of perimenopause—age most reliable; symptomatology; hematocrit; thyrotropin (TSH); blood tests (eg, follicle-stimulating hormone [FSH], estrogen, inhibin) least reliable; anxiety and depression often dramatically worsen; sleep fragmentation and changes in sexual functioning can occur during perimenopause

Hormonal treatment regimens: consider patient’s hormonal status and influence on migraine attack; hormone replacement therapy (HRT)—assess patient’s risk factors for breast cancer, osteoporosis (has loss of bone mineral density from lack of estrogen gone undetected?), and vascular issues; reasonable to consider HRT if migraine attacks thought to be hormonally triggered; strategies—stratify therapy; instruct patient to treat headache at beginning of attack; short-term menstrual prevention; adjunctive hormonal therapies with HRT, estrogen replacement therapy (ERT), or OCs; considerations in prescribing HRT—attempt to establish triggering event; consider risk factors (eg, family history of colon cancer); sleep fragmentation and risk for fracture; data show women with history of premenstrual syndrome (PMS) develop increase in migraine frequency when prescribed HRT; study—≈13.7% of women affected by headache in perimenopause; onset preceded menopause in 82% of cases; surgical menopause shown to worsen headache; headache improved in two-thirds of women who had physiologic menopause (≈50% of that group worsened with use of HRT, whereas ≈10% of patients experienced no change); patient’s history key to individualizing therapy; OCs—data show cyclic HRT worsens headache; lack of evidence about effect on migraine and long-term health effects of continuous dosing; provides cycle regulation and contraception; does not appear to have significant adverse effects

Meta-analysis vs Women’s Health Initiative (WHI): HRT shown to prevent fractures and reduce risk for colon cancer (≈20%); WHI did not carefully evaluate cognitive function in women on HRT; meta-analysis showed verbal memory, vigilance, reasoning, and motor speed improved in symptomatic women; data show increase in nonfatal stroke (study did not control for hypertension and hyperlipidemia); consider woman’s risk for thromboembolic events and breast cancer when prescribing HRT; individualize hormonal treatment—increase or decrease dosage, and/or change route; consider adjunctive therapy; discontinue regimen if not effective; use caution with injectable contraceptives in women with uterus (effect on endometrium); small study showed statistical benefit over baseline when combination of 2 phytoestrogens used; ≈50% of women taking danazol improved; tamoxifen shown to improve headache in some women and worsen it in others

Conclusion: hormonal history most important issue when addressing perimenopausal symptoms; consider patient’s risk factors for adverse events with use of HRT, ERT, or OCs; perimenopause time when woman requires support; issues surrounding WHI findings made women reluctant to consider therapy, even though it is likely their best option for perimenopausal symptoms

Fibromyalgia
Dawn A. Marcus, MD, Associate Professor, Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA

Diagnosis: patient’s pain drawing (identifies areas of pain, numbness, or burning) crucial in making diagnosis; important to identify all areas of pain, even if headache patient’s only complaint; fibromyalgia or fibrositis previously used as “wastebasket diagnosis”; in 1990, American College of Rheumatology developed specific diagnostic criteria; diagnostic criteria—chronic pain for 3 mo; widespread pain affecting left and right side of body, above and below waist; pain in 11 of 18 tender points when exerting 4 kg of pressure (using dolorimeter or thumb); ask patient to rate severity of pain (scale from 0-10; 0, just pressure; 10, excruciating pain) on tender points; record pain score for each tender point on pain drawing; discriminating level 11 tender points with pain scores of 2; 50% of surveyed patients with fibromyalgia complained of headache; fibromyalgia overview—≈5 to 6 million people in United States have fibromyalgia; more common in women than men (ratio dependent on study); no specific diagnostic test; rule out other medical conditions; not just young woman’s disease; prevalence greater in older people

Fibromyalgia and chronic headache: commonly occur together; do not allow patient to focus attention on one symptom alone; entire pain picture needs to be addressed and treated; data show 5% of general population has fibromyalgia; ≈17% of migraineurs have fibromyalgia, and patients with transformed migraine more likely to have fibromyalgia; approximately one-third of patients with frequent headaches have symptoms of fibromyalgia; prevalence of migraine in fibromyalgia—76% of patients seen for treatment of fibromyalgia reported troublesome headaches; 85% reported impact of headache substantial or severe; migraine primary type of headache among patients with fibromyalgia; only small percentage of patients had analgesic overuse-associated headache; evidence supports fibromyalgia and headache as comorbid conditions

Causes of fibromyalgia: diagnosis not validated by diagnostic tests (eg, blood test, x-ray); patients often told symptoms signs of stress; stress important factor in pain problems, but not cause of symptoms; pathophysiology—studies support peripheral and central changes in central nervous system (CNS; reassure patients symptoms not imagined and/or complaints not unreasonable); many different receptors and neurotransmitters important for chronic pain and headache; N-methyl-D-aspartic acid (NMDA) receptors important for temporal summation (wind-up); repeated activation of CNS makes patient more susceptible and sensitive, leading to firing of pain signals; skin biopsy—substantial and significantly increased prevalence of NMDA receptors in skin of patient with fibromyalgia, compared to controls; supports claims of greater sensitivity to painful sensations by patients with fibromyalgia; unmyelinated neurons in patients with fibromyalgia different from those in normal individuals; central sensitization—important factor in chronic pain; with increased stimulation, CNS becomes more sensitive and more prone to sending pain messages; may be reason symptoms occur together; some central sensitization factors can be changed (eg, sleep disturbances, psychologic factors, stress), but others cannot (eg, genetic factors); fibromyalgia increases pain sensitivity; studies confirm patients with fibromyalgia have lower pain threshold and more likely to interpret nonpain signals as painful; patients have enhanced temporal summation (supported by NMDA receptor study); more sensitive to pain, including subthreshold pain; increased pain sensitivity enhanced by stress; data show brain of patient with fibromyalgia more activated when subjected to pain stimuli, compared to control subjects; pain dysregulation—data show 40% of patients with chronic headache had widespread painful tender points; location and severity of tender points similar in patients with fibromyalgia and headache

Treatment: patients with fibromyalgia generally highly motivated to feel better; focus assessment on symptoms that can be effectively treated (not possible to treat all symptoms); perform and document tender point examination; have patient fill out fibromyalgia-impact questionnaire and identify disabling symptoms (eg, fatigue, sleep, bowel problems, anxiety, headache); documentation of tender point count (number of positive tender points) and tender point score (sum of all points) tracks patient’s progress and provides motivation; multidisciplinary approach recommended (eg, pain psychologist, stress management, cognitive rest)

Medications: benefits modest; cannot rely on medications as primary therapy; analgesics—limited benefit; studies consistently show analgesics no better than placebo (one study showed some benefit with combination of tramadol and acetaminophen); avoid nonsteroidal anti-inflammatory drugs and opioids (adverse side effects add to patient’s problems); antidepressants—duloxetine and pregabalin only medications approved for fibromyalgia; studies show most antidepressants do not work well for patients with fibromyalgia; duloxetine and milnacipran (not available in United States) associated with good efficacy; moderate efficacy with amitriptyline; duloxetine study—patients treated with 20, 60, or 120 mg for 3 mo; patients switched to 60 or 120 mg for 3 additional months; significant improvement in pain severity with 60- or 120-mg dose; improvement seen 1 wk after taking medication and maintained for 6 mo; analgesic benefits independent of depression; patients with sleep, mood, and anxiety problems often helped; pregabalin study—patients treated with 300 to 600 mg daily bid; treated in open-label fashion; patients who responded continued in double-blind treatment with previously effective dose of pregabalin or switched to placebo; loss of response in 61% with placebo, compared to 30% with pregabalin at study conclusion

Exercise: primary treatment modality; start with aerobic exercise and strengthening exercises; studies show aerobic exercise 3 times weekly and strengthening exercises 2 times weekly provides cardiovascular benefits, decreases pain, and improves quality of life and function