Although women are prescribed opioid medications for pain more frequently than their male counterparts, that doesn't mean that their pain management needs are being met.
Roughly 1 in 4 Americans are living with chronic non-cancer pain, and the majority of them are women. Several chronic pain conditions (such as dysmenorrhea, vulvodynia, dyspareunia, and pelvic pain) are women-specific. Other chronic pain conditions, including fibromyalgia,1 irritable bowel disorder,2 migraine,3 arthritic conditions,4 complex regional pain syndrome,5 and some inflammatory conditions,6 are more prevalent in women. In aggregate, women are more likely than men to acquire a chronic pain condition in their lifetime. Moreover, research has shown that women’s pain is more intense, occurs more frequently, and lasts for a longer duration of time than it does for men.7 In short, pain tends to be a more severe and more complex problem for women.
Women are more likely than men to seek medical attention for a health problem, but this does not always translate into better care. Opioid drugs are one of the most common forms of chronic pain treatment in the US, with empirical data showing that women are prescribed opioids more often for their chronic pain than are men.8,9 On average, women are also taking higher doses of opioids than men.8-10 Indeed, epidemiological studies show that while prescription opioid use in the US has increased significantly for both sexes, women are leading the pack. This fact raises two important questions: Why are women prescribed opioids more often than men, and what are the consequences of this treatment disparity?
One is cautioned from concluding that women are prescribed opioids more often than men because they have more pain. Surprisingly, pain intensity is not the major predictor for opioid prescription. Rather, findings from multiple studies suggest that patient behaviors observed by the physician during the office visit powerfully influence the likelihood that the physician will write the patient an opioid prescription. What are the patient behaviors that lead to opioid prescription? Negative affect,11 psychological distress,11 and pain behaviors12 (eg, grimacing or bracing) all predict receipt of opioids—and more so for women. Furthermore, anxiety,13 depression,13 and painrelated dysfunction14 have all been shown to predict opioid prescription and opioid use in women. As such, psychological and behavioral factors appear to influence the pharmaceutical chronic pain treatment women receive. Importantly, opioids are not approved to treat such psychological or behavioral concerns, so the pathway between psychological and behavioral factors and opioids is a curious one. The logic of the prescribing provider may be a well-intended assumptionthat pain amelioration with opioids will lead to reduced psychological distress and improved function. However, one need only to look at the data to discover that this assumption is unsupported.
Chronic pain tends to be a condition that is managed, rather than cured. Given this longterm trajectory, the need for proper assessment and treatment of psychological comorbidities and distress in women is underscored. Chronic pain is stressful. For most people, the consequences of living with chronic pain serve to compound the stress. To illustrate a few examples, a person with chronic pain may experience interpersonal difficulties as his or her ability to fulfill a family role is diminished, financial difficulties may arise or worsen as work capacity may be compromised and as medical bills increase, and a patient’s sense of self-worth may be diminished by a decline in function. Now a person must deal with the experience of their pain as well as the life impact of their pain.
Because the experience of pain is stressful and absorbs a significant portion of coping reserves, one’s ability to cope with the many other life stresses is reduced. As stress increases and adaptive coping diminishes, psychological distress and comorbidities are more likely to be expressed. And under these conditions, physical pain will increase in tandem, thus completing a bad cycle of pain-distress-pain.
It’s unsurprising that stress/distress and pain are so closely related. The International Association for the Study of Pain (IASP) defines pain as “an unpleasant sensory and an emotional experience associated with actual or potential tissue damage”. Chronic pain is pain that persists beyond three months of expected healing in the case of injury, or pain that simply lasts for three months in the case of idiopathic pain. The IASP definition reminds us that our psychological experience is built into the very definition of pain. Indeed, cognitive, emotional, and behavioral factors powerfully influence the experience of pain, our level of distress regarding pain, the trajectory of pain, and response to pain treatments. This may be more true for women, given that women’s brains are wired to be more attuned to the emotional aspects of situations.15, 16 Women with chronic pain may have greater levels of psychological distress.16-19
Perhaps the most important thing physicians and other pain care providers can do for their female chronic pain patients is to properly assess their ability to cope with their pain and other life stresses. Generally, referral to a pain psychologist is optimal, if such local resources exist (see sidebar). The pain psychologist will assess coping patterns and develop a plan to help the patient self-manage her own physiological and psychological stress responses. Research shows that cognitive, emotional, and behavioral factors strongly influence pain and response to pain treatment. Therefore, the cognitive, emotional, and behavioral factors must be treated so that the patient is empowered with the understanding, skill set, and support to make concrete changes that lead to improved quality of life and reduced need for pain medication. In other words, patients can learn to address some of the underlying factors that maintain or promote pain, rather than passively taking medication and remaining dependent on clinicians to provide them with ‘relief’.
Studies have shown that women are more influenced by their thoughts and expectations related to pain than are men.20, 21 For instance, women who expect pain relief from a placebo pill tend to experience greater pain relief than men.21 Some data suggest that women who are stressed by thinking negatively about their pain may be more likely to express proinflammatory cytokines in their blood following such a stressor.20 By working with a pain psychologist or pain coach, women may learn, in a structured way, how to harness the power of their thoughts and their expectations and to begin channeling this power in a positive way toward the goal of reducing pain and distress.
Chronic opioid use is not without varied iatrogenic consequences, such as constipation and tolerance. While a comprehensive review of these consequences is beyond the scope of this article, some relevant female-specific factors are highlighted here. For instance, chronic opioid use is associated with dysregulation of the endocrine system.21-24 Because the endocrine system influences the experience of pain, it is possible that opioid-induced endocrinopathy is a primary pathway by which pain worsens over time.
One study found that women of reproductive age who took opioids long term experienced opioid-induced amenhorrhea.23 Amenhorrhea carries risks of its own, including compromised bone health and infertility.25 A subset of reproductive age women on opioids maintain their fertility and providers should monitor these patients for pregnancy planning. Patients should be informed that opioids carry teratogenic risks, including low birth weight, premature birth, hypoxic-ischemic brain injury, prolonged QT syndrome, neonatal withdrawal syndrome, and neonatal death.26 When possible, patients should be weaned off opioids prior to pregnancy.
Opioids have been shown to disrupt levels of testosterone, estradiol, and dehydroepiandrosterone sulfate (DHEAS) in women. Even post-menopausal women can experience significant opioid-induced endocrinopathy on chronic opioid therapy.23 Providers should monitor patients’ hormone levels and may consider a baseline hormonal panel for women prior to initiating opioid therapy to be used as a reference point. The endocrine system is known to impact mood, cognition, insulin secretion, cardiovascular events, sexual function, bone loss and fracture risk (particularly in older women). Referral to an endocrinologist may benefit the patient. Physicians and clinicians may monitor for symptoms and may judiciously consider whether the potential benefit of opioids outweighs the known risks.
Lastly, women should understand the likely risks of treatment before treatment is initiated. Before opioids are prescribed, female patients should understand the relevant endocrine risks. Education regarding these treatment risks should be provided by the prescribing physician/clinician. Taking time to review the medication risks may provide the clinician with an opportunity to highlight some alternate evidence-based non-pharmacological treatment options, such as pain psychology and cognitive behavioral pain care, meditation, physical therapy, and gentle yoga.
Dr. Darnall is an assistant professor at Oregon Health & Science University. As a pain psychologist and pain researcher, her work has focused on sex/gender specific issues in chronic pain populations, and on improving pain care for women.
1. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. Jan 1995;38(1):19-28.
2. Payne S. Sex, gender, and irritable bowel syndrome: making the connections. Gend Med. Aug 2004;1(1):18-28.
3. Stewart WF, Shechter A, Rasmussen BK. Migraine prevalence. A review of population-based studies. Neurology. Jun 1994;44(6 Suppl 4):S17-23.
4. Symmons D, Turner G, Webb R, et al. The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new century. Rheumatology (Oxford). Jul 2002;41(7):793-800.
5. de Mos M, de Bruijn AG, Huygen FJ, Dieleman JP, Stricker BH, Sturkenboom MC. The incidence of complex regional pain syndrome: a population-based study. Pain. May 2007;129(1-2):12-20.
6. Yacoub Wasef SZ. Gender differences in systemic lupus erythematosus. Gend Med. Aug 2004;1(1):12-17.
7. Unruh AM. Gender variations in clinical pain experience. Pain. May-Jun 1996;65(2-3):123-167.
8. Campbell CI, Weisner C, Leresche L, et al. Age and gender trends in long-term opioid analgesic use for noncancer pain. Am J Public Health. Dec 2010;100(12):2541-2547.
9. Cicero TJ, Wong G, Tian Y, Lynskey M, Todorov A, Isenberg K. Co-morbidity and utilization of medical services by pain patients receiving opioid medications: data from an insurance claims database. Pain. Jul 2009;144(1-2):20-27.
10. Williams RE, Sampson TJ, Kalilani L, Wurzelmann JI, Janning SW. Epidemiology of opioid pharmacy claims in the United States. J Opioid Manag. May-Jun 2008;4(3):145-152.
11. Wasan AD, Davar G, Jamison R. The association between negative affect and opioid analgesia in patients with discogenic low back pain. Pain. Oct 2005;117(3):450-461.
12. Turk DC, Okifuji A. What factors affect physicians’ decisions to prescribe opioids for chronic noncancer pain patients? Clin J Pain. Dec 1997;13(4):330-336.
13. Thielke SM, Simoni-Wastila L, Edlund MJ, et al. Age and Sex Trends in Long-Term Opioid Use in Two Large American Health Systems Between 2000 and 2005. Pain Med. Nov 25 2010;11:248-256.
14. Darnall B, Li H. Hysterectomy and predictors for opioid prescription in a chronic pain clinic sample. Pain Med. Feb 2011;12(2):196-203.
15. Canli T, Desmond JE, Zhao Z, Gabrieli JD. Sex differences in the neural basis of emotional memories. Proc Natl Acad Sci U S A. Aug 6 2002;99(16):10789-10794.
16. Cahill L. Sex- and hemisphere-related influences on the neurobiology of emotionally influenced memory. Prog Neuropsychopharmacol Biol Psychiatry. Dec 2003;27(8):1235-1241.
17. Edwards RR, Haythornthwaite JA, Sullivan MJ, Fillingim RB. Catastrophizing as a mediator of sex differences in pain: differential effects for daily pain versus laboratory-induced pain. Pain. Oct 2004;111(3):335-341.
18. Sullivan M, Tripp, DA, Santor, D. Gender differences in pain and pain behavior: the role of catastrophizing. Cog Ther Res. 2000;24:121—134.
19. Sullivan MJ, Thorn B, Haythornthwaite JA, et al. Theoretical perspectives on the relation between catastrophizing and pain. Clin J Pain. Mar 2001;17(1):52-64.
20. Darnall BD, Aickin, M., Zwickey, H. Pilot study of inflammatory responses following a negative imaginal focus in persons with chronic pain: Analysis by sex/gender. Gender Medicine. 2010;7(3):247-260.
21. Pud D, Cohen D, Lawental E, Eisenberg E. Opioids and abnormal pain perception: New evidence from a study of chronic opioid addicts and healthy subjects. Drug & Alcohol Dependence. May 20 2006;82(3):218-223.
22. Abs R, Verhelst J, Maeyaert J, et al. Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab. Jun 2000;85(6):2215-2222.
23. Daniell HW. Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of nonmalignant pain. J Pain. Jan 2008;9(1):28-36.
24. Vuong C, Van Uum SH, O’Dell LE, Lutfy K, Friedman TC. The effects of opioids and opioid analogs on animal and human endocrine systems. Endocr Rev. Feb 2010;31(1):98-132.
25. Rhodin A, Stridsberg M, Gordh T. Opioid endocrinopathy: a clinical problem in patients with chronic pain and long-term oral opioid treatment. Clin J Pain. Jun;26(5):374-380.
26. Hadi I, da Silva O, Natale R, Boyd D, Morley-Forster PK. Opioids in the parturient with chronic nonmalignant pain: a retrospective review. J Opioid Manag. Jan-Feb 2006;2(1):31-34.