Chronic pain syndromes like fibromyalgia, chronic pelvic pain, interstitial cystitis/bladder pain syndrome, and chronic migraine cause significant disability and impair quality of life for many women. Evaluation of chronic pain can be complex because women often have overlapping syndromes as well as comorbid anxiety and depression. Multidisciplinary care including nonpharmacologic treatments like exercise and mindfulness-based therapies as well as pharmacologic medications improve function and decrease pain. With their wide knowledge base, primary care providers are well-equipped to primarily manage chronic pain in their women patients.
Key points
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Chronic pain and chronic pain syndromes are more common in women.
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Comorbid anxiety and depression frequently occur in chronic pain syndromes.
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Multidisciplinary care can decrease pain and improve quality of life for all the chronic pain syndromes.
Chronic noncancer pain is common in adults across the world and women have higher rates of chronic pain than men. , Data from the 2021 National Health Interview survey showed that 22% of women and 19.7% of men in the United States have chronic pain. More importantly, 7.6% of women have high impact pain (pain that disrupts daily functioning). Higher rates of pain and painful conditions continue as women age. Compared to patients with other chronic diseases, patients with chronic pain conditions have higher levels of psychological distress, lower health related quality of life scores and incur health care costs 3 times higher than matched controls.
Chronic pain conditions (fibromyalgia, irritable bowel syndrome, and migraine) are more common in women. Many theories exist on why women have more pain than men, but no clear etiology has been found. Studies on gender differences in pain are often preclinical, contradictory or inconclusive without enough convincing evidence to change clinical practice. Gender differences in pain are likely from a complex interaction of genetic, physiologic, psychological, and social factors.
Gender bias in health care and research may also play a role in how studies are reported and how patients are treated. Few studies compare pain in men to women, but women are often compared to men (andronormativity). Some studies also demonstrate hegemonic masculinity in which masculine attributes are idealized as the norm against which both men and women are judged. Women are more often described as being hysterical, emotional, or complainers. Women with chronic pain are more often assigned psychological rather than somatic causes for their pain and their narratives often focus on having to prove they are in pain to health care providers.
In most pain syndromes, no clear etiology exists so treatment cannot be standardized. Because women often have multiple coexisting pain syndromes, it can take longer to elicit a patient’s full history and do a physical. Multidisciplinary treatment has consistently been shown to decrease pain scores and improve quality of life. Education about chronic pain is beneficial and often gives a patient reassurance that something horrible (ie, cancer, multiple sclerosis) is not present. Nonpharmaceutical treatments (exercise, dietary changes, mindfulness-based therapies, and physical therapy) are helpful in most chronic pain disorders and can provide substantial relief in some patients. Pharmaceutical medications are available but often do not provide complete pain relief, so setting patient expectations is important. Opioids are not recommended for most pain disorders because they are not helpful and have a poor benefit to risk ratio. Comorbid anxiety and depression are common and when present, worsen pain’s impact on daily life. Although specialty care may be required, primary care physicians are well trained to primarily manage most pain syndromes and comorbid disorders.
Fibromyalgia
Fibromyalgia is a common chronic pain syndrome with a prevalence of 2% to 5% in women in the United States. The incidence of fibromyalgia increases with age, with the highest rates of incidence in patients more than 45 years of age. Current data points to abnormal central pain processing as the etiology of the syndrome. Evidence supports an imbalance in inhibitory neurotransmitters (serotonin, norepinephrine) and excitatory neurotransmitters (Substance P, glutamate). Because of abnormal pain processing, hyperalgesia (increased sensitivity to painful stimuli) as well as allodynia (sensitivity to normally nonpainful stimuli) are common in fibromyalgia.
Patients with fibromyalgia have widespread pain. Other common symptoms include fatigue (up to 90%), sleep disturbance (up to 75%), headaches, morning stiffness, and cognitive issues. Comorbidities are common, with higher rates of depression, anxiety, headache syndromes, and irritable bowel syndrome than seen in the general population. Patients with fibromyalgia will have a normal physical examination without evidence of synovitis or inflammatory disease.
Either the 2016 American College of Rheumatology ( https://www.fpmx.com.au/resources/office/New_Clinical_Fibromyalgia_Diagnostic_Criteria.pdf ) or the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Taxonomy criteria can be used to make the diagnosis of fibromyalgia. These are 80% sensitive and 74% sensitive respectively for diagnosing fibromyalgia. Laboratory testing is not required for the diagnosis of fibromyalgia but is useful in excluding other disorders.
Nonpharmacologic treatments should be the focus of therapy because they are more effective than pharmacologic treatments. Simply establishing the diagnosis of fibromyalgia can improve satisfaction with health and decrease health care utilization. , The National Fibromyalgia Foundation has helpful resources if patients desire web-based education ( https://www.fmaware.org/ ).
Cognitive behavioral therapy is an effective treatment of fibromyalgia. , It reduces pain, disability, and fatigue and improves health related quality of life. Exercise should be recommended for all patients with fibromyalgia. Aerobic and resistance exercise decreases depression and pain and improves quality of life, fatigue and sleep. , Studies involving lower intensity exercise or having a goal of 50% maximum heart rate had lower attrition rates and better symptom improvement. , Meditative movement therapies (Tai Chi, yoga) improve overall function, sleep, depression, and fatigue Studies support the benefits of mindfulness-based interventions, hypnosis, electromyographic (EMG) biofeedback, and hydrotherapy. Although many patients use cannabis products for treatment of their fibromyalgia more research needs to be done to see if these products are clinically effective.
Pharmacologic therapy is available for patients who do not have desired improvement with nonpharmacologic interventions. However, the effect sizes of many medications are modest, with a small number of patients achieving a 30% reduction in pain. Cyclobenzaprine is a muscle relaxer, but the chemical structure is similar to tricyclic antidepressants (TCAs). It produces a modest improvement in global functioning. TCAs offer effective treatment of fibromyalgia, with amitriptyline being the most studied. Three meta-analyses have found a moderate to large effect on pain reduction. , , The selective norepinephrine reuptake inhibitors (SNRIs) duloxetine and milnacipran have a small to moderate effect on pain reduction. , A systematic review of 5 studies found that pregabalin reduces pain versus placebo. Opioids and nonsteroidal anti-inflammatory medications are not recommended because of side effect profile and ineffectiveness.
Chronic pelvic pain
Chronic pelvic pain (CPP) has a world-wide prevalence of up to 26% In the United States, it accounts for 40% of laparoscopies and 12% of hysterectomies. The American College of Obstetrics and Gynecology describes CPP as pain symptoms perceived to originate from the pelvic organs/structures typically lasting more than 6 months. It is often associated with negative cognitive, behavioral, sexual, and emotional consequences as well as with symptoms suggestive of lower urinary tract, sexual, bowel, pelvic floor, myofascial or gynecologic dysfunction. Women with CPP have higher rates of sleep disorders, prior physical and/or sexual abuse and in a specialty CPP clinic, one-third screened positive for post-traumatic stress disorder (PTSD). Comorbid anxiety and depression is also common. Imaging studies show increased activation in pain centers and decreased gray matter volume, which is seen in other chronic pain conditions. ,
The most common causes of CPP include musculoskeletal pelvic floor pain, irritable bowel syndrome, interstitial cystitis, chronic uterine pain (leiomyoma, endometriosis, adenomyosis) and peripheral neuropathy (nerve entrapment syndromes). Musculoskeletal disorders are often underdiagnosed and were found in 50% to 90% of patients at CPP centers. In women who have no identifiable cause, their pain can be part of other pain syndromes like fibromyalgia.
Because of the broad differential, a standardized history and examination form can be helpful. https://osher.ucsf.edu/sites/osher.ucsf.edu/files/inline-files/Chronic_Pelvic_Pain.pdf . A psychosocial assessment using standardized questionnaires like the patient health questionnaire (PHQ) and general anxiety disorder (GAD) 7 can identify comorbid depression and anxiety.
Physical examinations can be painful and emotionally difficult for patients with CPP. The examination should be chaperoned and fully explained to the patient before beginning. The musculoskeletal examination should include a full examination of the spine, sacroiliac joints, and hips. The abdominal examination can evaluate tenderness and abdominal wall trigger points. The genitourinary examination begins with an external examination. A moistened cotton swab can be used to identify painful areas on the thighs or external genitalia. A single digit internal examination can evaluate tenderness of the pelvic floor muscles, urethra, and bladder. A bimanual examination should be done to evaluated uterine and adnexal abnormalities and finally a speculum examination can visualize the vagina and cervix.
Treatment of CPP should be multidisciplinary. Cognitive behavioral therapy is helpful for other pain syndromes but has not specifically been studied in CPP. Pelvic floor physical therapy can reduce pain. Although TCAs, SNRIs, and SSRIs are beneficial in other pain syndromes, they have not been studied in women with CPP. A recent randomized controlled trial (RCT) with gabapentin did not reduce pain in women with CPP. Opioids remain controversial, with some experts recommending weaning all women off of opioids for management of CPP and some recommending considering after multiple other treatment modalities have been tried. Small studies of abdominal wall and pelvic floor trigger point injection or peripheral nerve blocks have limited effectiveness. , Laparoscopic lysis of adhesions for management of CPP alone is not effective, and there is limited evidence for support of laparoscopic uterosacral nerve ablation and presacral neurectomy.
Interstitial cystitis/bladder pain syndrome
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain syndrome involving the urinary system. Although the term interstitial cystitis was previously used, there is no inflammation in most patients who have this disorder, therefore the new name IC/BPS is currently recommended. The American Urology Association defines IC/BPS as an unpleasant sensation (pain, pressure, and discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 weeks duration, in the absence of infection or other identifiable cause. Studies show a prevalence of 0.1% to 2.3% with a 5-fold women predominance. Symptoms can be daily, affected by social stress, diet, intercourse and prolonged sitting. Women often describe suprapubic, urethral, lower back or abdominal pain with bladder filling which is relieved with bladder emptying. Patients often have multiple low-volume voids per day to avoid bladder pain (whereas women with overactive bladder void multiple times a day to avoid incontinence).
The etiology is unknown and only 5% to 10% of women have visual and/or histologic changes on cystoscopy (Hunner lesions). Women with IC/BPS have higher rates of fibromyalgia, CPP, IBS, and migraines; therefore the cause of this syndrome is likely an interplay of immunologic and neurologic abnormalities affected by patient’s environment and genetics. As with other chronic pain syndromes, women should be evaluated and treated for anxiety and depression.
Using the genitourinary pain index ( https://elevation-physio.com/files/pdf/OCM-Female-GUPI.pdf ) and a voiding diary (file:///C:/Users/Owner/Downloads/diary_508.pdf) can be helpful to evaluate the extent of symptoms and to follow intervention efficacy. In a large survey, 96% of women with IC/BPS felt that foods could worsen their symptoms (citrus fruits, tomatoes, coffee, tea, carbonated beverages, artificial sweeteners, and spicy foods).
Examination should include the abdominal wall, hips, pelvic floor, bladder base and urethra as well as uterus and adnexal structures. Urinalysis and urine cultures are normal in IC/BPS, and abnormal results should result in further workup and/or consideration of a different etiology. Urologic guidelines recommend evaluation for incomplete bladder emptying in all patients. Cystoscopy is not required to make the diagnosis but should be considered if there are abnormal findings on examinations or urine evaluation or if patients do not respond to initial interventions. Urodynamics are not required for evaluation and can be painful for patients.
As with other chronic pain syndromes, there is not 1 treatment that will benefit all patients and patients often respond to multimodal care. In a large study of women, 45% had improvement with behavioral modifications (understanding bladder function, urge suppression techniques, management of fluid intake, avoiding dietary triggers). Another study showed that education on dietary triggers was helpful in reducing symptoms. Both the International Cystitis Association ( https://www.ichelp.org/understanding-ic/diet/the-ic-plate/ ) and the Interstitial Cystitis Network ( https://www.ic-network.com/ ) have dietary information on their websites. In women who have pelvic floor tenderness, pelvic floor physical therapy is recommended. Mindfulness based stress reduction improved pain self-efficacy and symptoms in women with IC/BPS.
Oral analgesics (phenazopyridine, acetaminophen, and non-steroidal anti-inflammatory drugs [NSAIDs]) can be prescribed. Although amitriptyline is recommended in guidelines , the studies show minimal improvement in symptoms. , Amitriptyline may be helpful in women who have other disorders that could benefit from a TCA. Although supported only by single small studies of low-quality evidence, some guidelines recommend gabapentin, montelukast, sildenafil, or hydroxyzine. ,
Pentosan polysulfate is the only Food and Drug Administration (FDA) approved medication for IC/BPS. It takes 3 to 6 months before a benefit is seen and is associated with a rare retinal pigmentary maculopathy. Therefore, patients will need retinal examinations before and periodically during treatment. Intravesicular installations (dimethyl sulfoxide [DMSO], lidocaine, and heparin), hydrodistension under anesthesia during cystoscopy, and treatment of Hunner lesions can improve pain in some patients. If other treatments are not helpful, intradetrussor injections of onobotulinum toxin A may help some. Major surgeries are rarely recommended and only for women who have not responded to all other therapies.
Chronic migraine
World-wide, migraine headaches are the #2 cause of years lived with disability for women and the #1 cause for women aged 15 to 49. 17% of women will have a migraine each year and the cumulative lifetime incidence is 43% (vs 6% and 18% in men). , Migraines often start at menarche and can increase in the mid-30s, and in perimenopause. Migraines often worsen with menstruation but can improve in pregnancy, breastfeeding women, and menopause. Women have longer migraines, higher rates of recurrence, more symptoms (nausea, vomiting, photophobia, and phonophobia) and more migraine with aura than men. ,
Migraines are classified into migraine without aura, migraine with aura, chronic migraine (headaches for >15 days a month) and migraine-overuse headache (headaches for >15 days a month in patients who take medications for headaches 10–15 days a month). For full details on the International classification of headache disorders criteria, see https://ihs-headache.org/en/resources/guidelines/ . This review will focus on chronic migraines. As with other chronic pain syndromes, higher rates of anxiety, depression, and sleep disorders are present, and these associations are more pronounced in women with chronic migraine versus episodic migraine. Women with migraines also have higher rates of cardiovascular disease and cardiovascular mortality.
The pathophysiology of migraine is unknown. Estrogen is a central neural stimulator. Migraines may occur with sudden decreases or fluctuating levels of estrogen as seen before menses or in perimenopause. Lower estrogen levels may make blood vessels more permeable to pain producing prostaglandins. In addition, estrogen increases serotonergic tone, and serotonin is an important pain modulator (decreases pain). , Other neuropeptides are likely involved, with calcitonin gene-related peptide (CGRP) levels increasing during migraines and returning to normal once migraines resolve.
A thorough history is often all that is needed to diagnose a migraine. Many migraines have triggers (stress, hormone levels, not eating, weather, and sleep disturbance). It is important to consider medication overuse headache in women with frequent headaches. This is often underdiagnosed and most often occurs with the following medicines (in order of frequency): opioids, butalbital containing analgesics, aspirin-acetaminophen-caffeine combinations, and triptans. Although it can be seen with NSAIDs, this group of medications is the least likely to cause medication overuse headaches. Taking the above medications for less than 10 days a month (or 15 days a month for acetaminophen, aspirin, or NSAIDs) effectively prevents overuse headaches. The treatment is to stop the inciting medication.
Although women with migraines have higher rates of strokes (11/100,000), taking combined oral contraceptives (COC) does not increase this risk unless women have migraine with aura. Taking COC increases risk of stroke 6-fold and is therefore contraindicated in women with migraine with aura. Women taking hormone replacement (either estrogen or estrogen and progesterone) have higher rates of migraine. However, women with migraines have higher rates of menopausal symptoms. Small studies evaluated the route and dosing of postmenopausal estrogen but have variable results. Variations in progesterone do not seem to influence migraines.
A neurologic examination should be normal. Neuroimaging modalities should only be ordered if a secondary cause of headache (tumor, infection) is considered. MRI is recommended over CT because of higher resolution and avoidance of ionizing radiation.
Effective treatments are available for chronic migraine. This is most likely to occur with multimodal care (behavioral treatments, nonpharmaceutical interventions, and pharmaceutical medications). Please see Table 1 for behavioral interventions and Table 2 for a list of medications effective for chronic migraine. Although there are many medications that can decrease migraine frequency, only the CGRP targeting therapies are specifically made for the treatment of migraine. Multiple studies have shown that this class of medication is safe, is at least as effective as other preventative therapies and has less side effects. The American Headache Society recently recommended that this class be first-line for the treatment of chronic migraines.
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