- Open Access
Pain in midlife women: a growing problem in need of further research
Women's Midlife Health volume 8, Article number: 4 (2022)
More than 10% of American adults experience some level of daily pain, and nearly 40 million (17.6%) experience episodes of severe pain annually. Women are particularly impacted by both episodic and chronic pain with higher prevalence and a greater level of pain-related disability compared to men. Midlife is a critical period for women during which the frequency of pain complaints begins to increase. Although pain is known to be influenced and controlled by sex hormones, it has not been widely recognized as a symptom of the menopausal transition outside of the menopause research community. The recent thematic series in this journal has specifically highlighted pain related conditions including rheumatoid arthritis, migraine and abdominal pain for which the significance among midlife women is not typically recognized. The studies presented in this thematic series present a small fraction of relevant, understudied questions regarding pain and its impact on women in midlife. Addressing the gaps in knowledge will require longitudinal studies that consider the emergence of pain symptomatology in relation to midlife trajectories of other symptoms and health determinants, as well as further study of new and emerging therapies.
Over the last two decades, the rising prevalence of pain and the related opioid epidemic have led to increased interest in better understanding the epidemiology and mechanisms of pain [1,2,3]. More than 10% of American adults experience some level of daily pain, and nearly 40 million (17.6%) experience severe levels of pain annually [2, 4, 5]. The prevalence of pain increases with age, in part due to the increasing prevalence of medical conditions which cause pain, such as arthritis and diabetes [6, 7]. Thus, the public health burden of pain is expected to increase dramatically with the demographic shift of the U.S. population to older ages. Furthermore, poorly controlled episodic pain can transform into chronic pain disorders (defined as 15 or more days of pain per month for 3 or more months), which are associated with significant disability and morbidity [2, 4, 8].
Women are particularly impacted by both episodic and chronic pain with higher prevalence and a greater level of pain-related disability compared to men [9, 10]. The pain related conditions with higher female preponderance affect a broad range of organs and body regions [11, 12]. These include fibromyalgia, chronic fatigue syndrome, complex regional pain syndrome, abdominal pain (irritable bowel syndrome), interstitial cystitis/bladder pain syndrome, chronic pelvic pain of uncertain origin, migraine and orofacial pain/TMJ disorders. These conditions tend to emerge during the reproductive years and often subside in late life although, despite their frequency, these conditions have been significantly understudied in all age groups.
Further, dysmenorrhea, a common pain phenomenon of reproductive age women has been suggested as a key contributing factor to the higher prevalence of pain disorders in women than men. Dysmenorrhea has been associated with enhanced pain sensitivity which may increase risk of developing pain conditions in midlife and beyond [13, 14].
Prior work has largely been limited to studies of sex differences in chronic pain while the primary biological mechanisms that mediate gender differences in pain expression have been understudied  and remain controversial . Recently, the increasing trend in prevalence of pain and the current opioid epidemic have led to a new emphasis on better understanding mechanisms that underlie the disproportionate burden of pain disorders in women. Studies have explored sex hormones, immunologic markers, and functional brain imaging among others in order to elucidate possible factors related to sex differences [5, 8, 16, 17].
The existing literature suggests that midlife is a critical period for women during which the frequency of pain complaints begins to increase. Midlife women experience increasing prevalence of chronic pain symptoms (aches and pains, headache, genitourinary pain) even in the absence of newly diagnosed chronic conditions [18, 19]. Though the significant burden of pain symptoms in midlife women has long been recognized, few studies have addressed the epidemiology and mechanisms of pain in midlife women. Particularly lacking are longitudinal studies of pain trajectories across midlife. The critical need to fill this knowledge gap is underscored by the fact that the highest increase in opioid prescribing and opioid related overdose mortality has been among women in their 40s, 50s and 60s [3, 20].
The dearth of studies regarding pain in midlife women has contributed to under-diagnosis of specific pain disorders even in the setting of pain complaints. The consequence is poor management of pain in midlife women . This is further compounded by the fact that midlife is also associated with increasing occurrence of a multitude of physical and psychological symptoms that can have complex interactions with pain complaints [19, 22]. Beyond the proximal effects of untreated pain, poor management of midlife pain may have long-term effects on later life health of women by limiting physical activity and functioning [23, 24]. Finally, pain presents a particular challenge for midlife women given its adverse impact on functioning during a time in the life-course that is marked by a high level of family and work demands .
For women, midlife is marked by the hormonal changes of the menopausal transition (M.T.) . Though pain is known to be influenced and controlled by sex hormones, it has not been widely recognized as a symptom of the M.T. outside the menopause research community [18, 26]. Studies that have examined pain prevalence across the life span have not typically focused on the M.T [2, 3, 6]. Most work regarding symptoms associated with hormonal changes in the M.T. have focused primarily on the cardinal menopausal symptoms; vasomotor symptoms, or symptoms related to sleep and mood [22, 27, 28]. In comparison, relatively few studies have examined the occurrence of pain across the M.T. in relation to hormone changes. Further, studies which have examined pain during the M.T. have generally focused on pelvic pain or on non-specific, generic pain (e.g., broadly musculoskeletal or total pain), without distinctions between types of pain affecting different organs or parts of the body [18, 19, 26].
Current knowledge regarding the epidemiology of pain in midlife women is limited by several methodologic factors. Many studies are based on pain clinic populations which have well defined pain phenotypes but lack adequate consideration of important midlife characteristics including the M.T. Conversely, most studies of the M.T. include detailed hormonal and biomarker data but not specific characterization of pain symptoms. With the exception of the Study of Women’s Health Across the Nation (SWAN) and the Seattle Midlife Women’s Health Study, no longitudinal studies have examined changes in pain related complaints across the stages of the M.T. Another limitation in the field is related to challenges to adequately capturing pain complaints and operationalizing them as pain disorders within population based studies. As pain complaints are common in a high percent of the population, it is important to parse out not only the frequency but also the intensity of pain and interference of pain with activities of daily living . Further, accurate and reliable characterization of pain complaints is complicated by temporal variations. Ascertainment of complaints multiple times per day, over multiple days may be required to optimize characterization of pain symptoms. Emerging methods that apply mobile technology such as smart phone apps are a promising strategy that should advance the study of pain mechanisms [29, 30].
Historically, the literature has focused on studies of pain defined broadly, or on sub-types of pain traditionally associated with the M.T. The recent thematic series in the journal Women’s Midlife Health (WMHL) specifically highlighted pain related conditions that while common and troublesome in midlife women are not typically recognized by the broader medical and research community as particularly burdensome at this time of life. Two of these articles are reviews that focus on rheumatoid arthritis  and migraine , pain causing conditions that can occur in either sex at any age. While not typically considered causes of midlife pain symptoms, both disorders tend to have a female predominance that peaks in midlife. These reviews indicate that although both conditions have been linked to hormonal changes in women there is not a clear understanding of the specific mechanisms that play a role in their pathophysiology and presentation. Symptom presentation of both rheumatoid arthritis and migraine appears to change with fluctuating hormonal states, and both generally improve in high and rising endogenous estrogen states (pregnancy) and worsen with hormonal fluctuations during the M.T [31, 32]. Nevertheless, treatment of both joint pain and migraine headache with exogenous estrogens has shown inconsistent results [33,34,35].
The under-recognition of rheumatoid arthritis (R.A.) in women during midlife and particularly the lesser recognized non-immunologic mechanisms and their complications which contribute either directly or indirectly to pain in R.A. are discussed in Chancay et al. . Most R.A. treatment and management is focused on controlling the inflammatory components of the disease. The authors argue that recognizing the non-inflammatory contributors of R.A. pain, such as mechanical pain, fibromyalgia, and psychosocial factors creates an opportunity for more optimal treatment within the biopsychosocial model [31, 36]. The article highlights that midlife may be a critical period during which more complete “whole woman” approaches to managing R.A. may be important.
Another pain condition in need of a “whole woman” approach to diagnosis and treatment is migraine, a central nervous system condition in which the cardinal symptom, severe headache, typically begins in the teens and early 20’s. Although migraine is typically recognized as a leading pain condition in women during the reproductive years, the review by Pavlovic  emphasizes that migraine prevalence and symptom frequency peak during midlife. The hormonal regulation of migraine has been recognized since ancient times, although primarily with respect to the prominence of peri-menstrual attacks . However, midlife and the M.T. in particular create a specific challenge for women with migraine as fluctuating hormonal cycles decrease the predictability of attacks. As noted in the review, this has important consequences for treatment and quality of life. Migraine treatment in midlife women is further complicated by the fact that treatment with exogenous estrogen containing compounds is controversial given that migraine has been associated with increased stroke risk [38, 39]. Consequently, strict guidelines limit use of estrogen containing contraceptives in women with migraine older than 35 years of age . Given that cardiovascular risk rises in midlife and that many women are unable to tolerate or have unmet needs in migraine treatment, new emerging therapeutic approaches for migraine are particularly relevant for this age group.
The potential long-term pathophysiologic consequences of migraine were explored in the original study by Newman-Norlund et al. , illustrating the potential relevance of some emerging therapeutic modalities for active treatment of migraine in midlife women. Researchers assessed changes in cortical and subcortical brain volume on MRI in 12 patients with chronic migraine before and after treatment with sphenopalatine nerve blocks; a highly specialized in-office procedure. They observed potential correlations between changes in areas of cortex involved in pain processing and markers of pain pre- and post-treatment. Despite the small sample size, this is an important treatment study, which adds to our growing understanding of treatment-related brain changes associated with headache recovery in women with migraine. The fact that all women in the study had history of migraine for over a decade suggests the possibility of recovery even in long established disease states .
A fourth article in the thematic series addresses abdominal pain, a common pain symptom not typically perceived as a hallmark of midlife . This study from the Seattle Midlife Women’s Health Study examines whether abdominal pain experienced at midlife is due to aging or to hormonal changes related to the M.T . The authors assessed how changes in severity of abdominal pain change in relation to age, stage of the M.T., perceptions of stress and to both hormonal and stress related biomarkers. The Seattle study is uniquely poised to address this question, as it is one of the few established longitudinal cohorts of women that followed several hundred women for over two decades while they transitioned from the late reproductive phase of life into the postmenopausal years. The study has previously examined back and joint pain showing that they were predominantly related to age, but not to MT-related factors . Consistent with the literature, the Callan et al. manuscript reported decreases in abdominal pain with increasing age . They extended prior work showing that estrogen and testosterone are associated with lower severity of abdominal pain , while anxiety and perceived stress were associated with higher severity of abdominal pain.
Overall, the WMHL thematic series on pain illustrates several important themes regarding pain in midlife women. They show that pain is a common symptom among midlife women and that they experience pain in many domains beyond those commonly recognized as related to the M.T. While some sub-types of pain newly emerge in midlife, many common forms of pain, such as headache and abdominal pain, can worsen in midlife. The studies presented in this thematic series present a small fraction of relevant, understudied questions regarding pain in women’s midlife.
The midlife is clearly an essential time of not only hormonal transition but of emerging symptoms that likely impact future health outcomes. The influence of sex hormones on pain in midlife women is still under investigation. There is increasing recognition that psychological and social factors play an important role in pain. Further work is needed to examine both racial and ethnic disparities as well as socioeconomic factors related to the presentation of pain symptoms, and to diagnosis and management of pain disorders. Access to treatment in midlife women is of utmost importance given the pervasiveness and burden on a population level and the under-recognition in clinical practice [6, 8]. Furthermore, the treatment interruptions due to the ongoing COVID-19 pandemic are exacerbating these problems and creating a need for novel therapy alternatives using emergent technologies such as telemedicine. Incorporation of these new modalities into treatment plans of midlife women is of particular urgency [44, 45].
Addressing these gaps in knowledge will require longitudinal studies that consider the emergence of pain symptomatology in relation to midlife trajectories of other symptoms and health determinants, as well as further study of new and emerging therapies. In addition to development of traditional therapeutics, more holistic approaches are needed for effective study and treatment of pain in midlife women. Further, efforts are needed to better understand environmental and occupational risk factors for pain and interventions to ameliorate them. Finally, the association of pain with significant opioid related morbidity and mortality in midlife women [3, 20], suggests the need to better understand how pain symptomatology and its response to treatment change in midlife. Increased research regarding sex differences in response to treatment is essential. This will not only improve pain treatment for women but will further our understanding of the pathophysiology of pain. This increased knowledge may have ramifications for both sexes throughout the lifespan.
Availability of data and materials
Goldberg DS, McGee SJ. Pain as a global public health priority. BMC Public Health. 2011;11. https://doi.org/10.1186/1471-2458-11-770.
Kennedy J, Roll JM, Schraudner T, Murphy S, McPherson S. Prevalence of persistent pain in the U.S. adult population: new data from the 2010 national health interview survey. J Pain. 2014;15(10):979–84. https://doi.org/10.1016/j.jpain.2014.05.009.
Campbell CI, et al. Age and gender trends in long-term opioid analgesic use for noncancer pain. Am J Public Health. 2010;100(12):2541–7. https://doi.org/10.2105/AJPH.2009.180646.
Johannes CB, Le TK, Zhou X, Johnston JA, Dworkin RH. The prevalence of chronic pain in United States adults: results of an internet-based survey. J Pain. 2010;11(11):1230–9. https://doi.org/10.1016/j.jpain.2010.07.002.
Von Korff M, et al. United States National Pain Strategy for population research: concepts, definitions, and pilot data. J Pain. 2016;17(10). https://doi.org/10.1016/j.jpain.2016.06.009.
Gureje O, Von Korff M, Simon GE, Gater R. Persistent pain and well-being: a World Health Organization study in primary care. J Am Med Assoc. 1998;280(2):147–51. https://doi.org/10.1001/jama.280.2.147.
Simon GE, et al. Association between obesity and psychiatric disorders in the US adult population. Arch Gen Psychiatry. 2006;63(7):824–30. https://doi.org/10.1001/archpsyc.63.7.824.
Pitcher MH, Von Korff M, Bushnell MC, Porter L. Prevalence and profile of high-impact chronic pain in the United States. J Pain. 2019;20(2):146–60. https://doi.org/10.1016/j.jpain.2018.07.006.
Fillingim RB, King CD, Ribeiro-Dasilva MC, Rahim-Williams B, Riley JL. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain. 2009;10(5):447–85. https://doi.org/10.1016/j.jpain.2008.12.001.
Bartley EJ, Fillingim RB. Sex differences in pain and stress. Neurosci Pain, Stress Emotion. 2016:77–95 Elsevier.
Belfer I. Pain in women. Agri. 2017;29(2):51–4. https://doi.org/10.5505/agri.2017.87369 Turkish Society of Algology.
Craft RM, Mogil JS, Aloisi AM. Sex differences in pain and analgesia: the role of gonadal hormones. Eur J Pain. 2004;8(5):397–411. https://doi.org/10.1016/j.ejpain.2004.01.003.
Iacovides S, Avidon I, Baker FC. What we know about primary dysmenorrhea today: a critical review. Hum Reprod Update. 2015;21(6):762–78. https://doi.org/10.1093/HUMUPD/DMV039.
Chen CX, Kwekkeboom KL, Ward SE. Self-report pain and symptom measures for primary dysmenorrhoea: a critical review. Eur J Pain. 2015;19(3):377–91. https://doi.org/10.1002/EJP.556.
Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci. 2012;13(12):859–66. https://doi.org/10.1038/nrn3360.
Gross J, Gordon DB. The strengths and weaknesses of current US policy to address pain. Am J Public Health. 2019;109(1). https://doi.org/10.2105/AJPH.2018.304746.
Pavlovic JM, Akcali D, Bolay H, Bernstein C, Maleki N. Sex-related influences in migraine. J Neurosci Res. 2017;95(1–2):587–93. https://doi.org/10.1002/jnr.23903.
Harlow SD, et al. It is not just menopause: symptom clustering in the study of Women’s health across the nation. Women’s Midlife Heal. 2017;3. https://doi.org/10.1186/s40695-017-0021-y.
Gibson CJ, Li Y, Bertenthal D, Huang AJ, Seal KH. Menopause symptoms and chronic pain in a national sample of midlife women veterans. Menopause. 2019;26(7):708–13. https://doi.org/10.1097/GME.0000000000001312.
Gibson CJ, Li Y, Huang AJ, Rife T, Seal KH. Menopausal symptoms and higher risk opioid prescribing in a national sample of women veterans with chronic pain. J Gen Intern Med. 2019. https://doi.org/10.1007/s11606-019-05242-w.
Thomas AJ, Mitchell ES, Woods NF. The challenges of midlife women: themes from the Seattle midlife Women’s health study. Women’s Midlife Heal. 2018;4(1). https://doi.org/10.1186/s40695-018-0039-9.
Hoga L, Rodolpho J, Gonçalves B, Quirino B. Women’s experience of menopause: a systematic review of qualitative evidence. JBI database Syst Rev Implement Rep. 2015;13(8):250–337. https://doi.org/10.11124/jbisrir-2015-1948.
Dugan SA, Gabriel KP, Lange-Maia BS, Karvonen-Gutierrez C. Physical activity and physical function: moving and aging. Obstet Gynecol Clin N Am. 2018;45(4):723–36. https://doi.org/10.1016/j.ogc.2018.07.009 W.B. Saunders.
Farris SG, et al. Pain worsening with physical activity during migraine attacks in women with overweight/obesity: a prospective evaluation of frequency, consistency, and correlates. Cephalalgia. 2017. https://doi.org/10.1177/0333102417747231.
Harlow SD, et al. Executive summary of the stages of reproductive aging workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause. 2012;19(4):387–95. https://doi.org/10.1097/gme.0b013e31824d8f40.
Dugan SA, Lewis TT, Everson-Rose SA, Jacobs EA, Harlow SD, Janssen I. Chronic discrimination and bodily pain in a multiethnic cohort of midlife women in the study of women’s health across the nation. Pain. 2017;158(9). https://doi.org/10.1097/j.pain.0000000000000957.
Seritan AL, Iosif AM, Park JH, Deatheragehand D, Sweet RL, Gold EB. Self-reported anxiety, depressive, and vasomotor symptoms: a study of perimenopausal women presenting to a specialized midlife assessment center. Menopause. 2010;17(2):410–5. https://doi.org/10.1097/gme.0b013e3181bf5a62.
Greenblum CA, Rowe MA, Neff DF, Greenblum JS. Midlife women: symptoms associated with menopausal transition and early postmenopause and quality of life. Menopause. 2013;20(1):22–7. https://doi.org/10.1097/gme.0b013e31825a2a91.
Thomas JG, et al. Ecological momentary assessment of the relationship between headache pain intensity and pain interference in women with migraine and obesity. Cephalalgia. 2016;36(13). https://doi.org/10.1177/0333102415625613.
May M, Junghaenel DU, Ono M, Stone AA, Schneider S. Ecological momentary assessment methodology in chronic pain research: a systematic review. J Pain. 2018;19(7):699–716. https://doi.org/10.1016/j.jpain.2018.01.006 Churchill Livingstone Inc.
Chancay MG, Guendsechadze SN, Blanco I. Types of pain and their psychosocial impact in women with rheumatoid arthritis. Women’s Midlife Heal. 2019;5(1). https://doi.org/10.1186/s40695-019-0047-4.
Pavlović JM. The impact of midlife on migraine in women: summary of current views. Women’s Midlife Heal. 2020;6(1). https://doi.org/10.1186/S40695-020-00059-8.
Chen Q, Jin Z, Xiang C, Cai Q, Shi W, He J. Absence of protective effect of oral contraceptive use on the development of rheumatoid arthritis: a meta-analysis of observational studies. Int J Rheum Dis. 2014;17(7):725–37. https://doi.org/10.1111/1756-185X.12413.
Lane SJ, Heddle NM, Arnold E, Walker I. A review of randomized controlled trials comparing the effectiveness of hand held computers with paper methods for data collection. BMC Med Inform Decis Mak. 2006;6:23. https://doi.org/10.1186/1472-6947-6-23.
Chai NC, Peterlin BL, Calhoun AH. Migraine and estrogen. Curr Opin Neurol. 2014;27(3):315–24. https://doi.org/10.1097/WCO.0000000000000091.
Santoro N, Kravitz HM. The disruptive changes of midlife: a biopsychosocial adventure. Obstet Gynecol Clin N Am. 2018;45(4):xv–xvii. https://doi.org/10.1016/j.ogc.2018.08.001.
MacGregor EA. Classification of perimenstrual headache: clinical relevance. Curr Pain Headache Rep. 2012;16(5):452–60. https://doi.org/10.1007/s11916-012-0282-y.
Pavlović JM. Evaluation and management of migraine in midlife women. Menopause. 2018;25(8):927–9. https://doi.org/10.1097/GME.0000000000001104.
Tietjen GE, Maly EF. Migraine and ischemic stroke in women. A narrative review. Headache. 2020;60(5):843–63. https://doi.org/10.1111/head.13796 Blackwell Publishing Inc.
Lucas S. Migraine and other headache disorders: ACOG clinical updates in women’s health care primary and preventive care review summary volume XVIII, number 4. Obstet Gynecol. 2019;134(1):211. https://doi.org/10.1097/AOG.0000000000003322.
Newman-Norlund RD, Rorden C, Maleki N, Patel M, Cheng B, Androulakis XM. Cortical and subcortical changes following sphenopalatine ganglion blocks in chronic migraine with medication overuse headache: a preliminary longitudinal study. Women’s Midlife Heal. 2020;6(1):Dec. https://doi.org/10.1186/S40695-020-00055-Y.
Callan NGL, Mitchell ES, Heitkemper MM, Woods NF. Abdominal pain during the menopause transition and early postmenopause: observations from the Seattle midlife women’s health study. Women’s Midlife Heal. 2019;5(1):Dec. https://doi.org/10.1186/s40695-019-0046-5.
Mitchell ES, Woods NF. Pain symptoms during the menopausal transition and early postmenopause. Climacteric. 2010;13(5):467–78. https://doi.org/10.3109/13697137.2010.483025.
Shanthanna H, et al. Caring for patients with pain during the COVID-19 pandemic: consensus recommendations from an international expert panel. Anaesthesia. 2020;75(7):935–44. https://doi.org/10.1111/ANAE.15076.
Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet (London, England). 2021;397(10289):2082–97. https://doi.org/10.1016/S0140-6736(21)00393-7.
Dr. Pavlovic is funded by NIH/NIA K23AG049466. Dr. Derby is funded by NIH/NIA U19AG063720 and NIH/NIA 5U01AG012535.
Ethics approval and consent to participate
Consent for publication
Dr. Pavlovic has received consulting honoraria from Allergan, Alder, Biohaven, and Lundbeck; and has received travel support from the American Headache Society and North American Menopause Society.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Pavlović, J., Derby, C.A. Pain in midlife women: a growing problem in need of further research. womens midlife health 8, 4 (2022). https://doi.org/10.1186/s40695-022-00074-x