Carpal Tunnel Syndrome
Repetitive Use and Trauma
CTS is more common in persons whose wrists and hands are exposed to repeated mechanical stress or repetitive trauma. Many studies have reported that occupational exposure to activities such as use of chainsaws or jackhammers, quarry drilling, or assembly line work increases the risk of CTS by 2- to 21-fold (Palmer 2011; Walter 2002). A study of 347 workers in a hospital and two manufacturing plants reported that working with forceful hand exertion 20-60% of the time was associated with about a 3-fold greater risk of CTS (Burt 2013).
Studies examining possible links between prolonged use of a computer keyboard or mouse and CTS have failed to consistently demonstrate significant correlation between the two. A 2014 analysis of six published CTS studies reported that computer use was non-significantly associated with higher rates of CTS (Mediouni 2014). One large study of 5658 Danish technical workers reported that while long hours of computer keyboard use was not associated with higher incidence of CTS, using a right-handed computer mouse 20 hours or more per week was associated with a significantly higher risk of right-handed CTS (Andersen 2003). Also, another researcher found that high cumulative computer keyboard strokes may increase CTS risk (Eleftheriou 2012).
CTS may also occur among musicians using repetitive hand movements, especially those who play keyboard instruments such as the piano, organ, or accordion (Wilson 2014; Lederman 2006).
At least 18 published studies have reported an association between higher body mass index (BMI) and CTS risk (Bland 2005b). A comprehensive review of the published literature on CTS found that being overweight or obese was associated with a 40% increased chance of developing CTS (Spahn 2012). A study of the correlation between work-related hand effort and CTS found that among those with a BMI ≥ 30 (the cutoff point for obesity), there was over 3 times the odds that increased exertion would be associated with CTS (Burt 2011). This same research team later found that obese healthcare and factory workers were more than 3 times as likely to develop CTS over a 2-year follow-up period (Burt 2013). In another study, obesity increased the risk of severe CTS of unknown origin by 60%. In this study, each point increase in BMI was associated with a 9% higher risk of severe CTS; however, this elevated risk was not apparent in people over age 60 (Seror 2013). Similarly, another study reported that higher BMI was significantly associated with higher risk of CTS in 3005 adults younger than 63 years; little relationship between higher BMI and CTS was seen however in 1150 subjects over age 63 (Bland 2005b).
The mechanisms by which obesity contributes to CTS are not completely understood (Bland 2005a; Bland 2005b), and interestingly, an intervention study found that weight loss alone did not improve CTS (Kurt 2008).
Diabetes and Metabolic Syndrome
Between 11% and 25% of diabetics have CTS (Papanas 2010; Fitzgibbons 2008; Redmond 2009). CTS may occur with greater frequency in diabetics because of a number of factors, including damage to nerves resulting from high blood sugar, greater stiffness of connective tissue, and blood vessel inflammation (Dyck 1996; Ibrahim 2012; Sugimoto 2008).
A prospective survey of 676 patients found that type II diabetes increased the risk of severe CTS by 72% (Seror 2013). A study of over 100 patients with confirmed CTS found that 75% had metabolic syndrome, a condition highly correlated with future development of diabetes and cardiovascular disease. This is roughly three times the rate that would be expected in the general population. CTS patients with metabolic syndrome had more severe CTS as judged by electrophysiological parameters compared to those without CTS (Balci 2007; Beltran-Sanchez 2013). Similar results were observed in a Turkish study (Onder 2013). A population study that examined the health records of over one million people found that several factors associated with diabetes and metabolic syndrome, including gout, hypertension, and obesity, were correlated with CTS (Tseng 2012). In a case control study, CTS patients were found to have a significantly higher rate of glucose metabolism abnormalities compared to controls. The authors concluded that pre-diabetes may be a significant factor in CTS, including idiopathic CTS (Plastino 2011).
Readers may also consult the Diabetes protocol for more information.
A strong association between CTS and rheumatoid arthritis (RA) has been observed for decades (Stevens 1992; Chamberlain 1970; Barnes 1967). The incidence of CTS in people with RA is estimated to be about 10-20% (Barnes 1967; Ashworth 2013b). CTS in RA is believed to be a result of carpal tunnel narrowing that occurs due to thickening of structures in the wrist joint (Karadag 2012; Mayo Clinic 2014).
Readers may consult the Rheumatoid Arthritis protocol for information about the disease and its treatment.
Menopause, Pregnancy, and Female Hormones
CTS is more common in women than men, and there is an apparent correlation with female sex hormones, although the exact nature of the relationship remains unclear (Kim, Hann 2010; Ferry 2000). The age of peak incidence of CTS in women is 40-60 years, which coincides with menopause (Mattioli 2008; Ashworth 2013b). An early observational study found that 17 of 53 (32%) women whose ovaries had been removed (oophorectomy) had CTS. In contrast, only 10% of premenopausal women in this study had CTS. Nerve conduction studies were abnormal in 14 of the oophorectomized women with CTS but normal in all but one of the premenopausal women. Also, symptoms were of greater severity in the oophorectomized women (Pascual 1991). Another study concluded that earlier age at menopause may increase CTS risk (Kaplan 2008). A small, uncontrolled study found that hormone replacement therapy (HRT) was effective for relieving CTS symptoms, though no nerve conduction tests were reported, and the author acknowledged the possibility of a placebo effect with HRT (Hall 1992).
CTS risk is also heightened during pregnancy, although pregnancy-related CTS is typically mild (Mondelli 2007). During pregnancy, the incidence of clinical CTS has been reported to be as high as 62% (Padua 2010). The exact cause of pregnancy-related CTS is not completely understood, but it may be related to hormonal fluctuations and accompanying fluid retention, increased weight, and/or changes in blood sugar metabolism (Osterman 2012). One study that measured improvement in CTS symptoms as well as wrist and hand functionality from pregnancy to one-year postpartum found that 40% of women experienced improvement in both measures a year after delivery (Mondelli 2007).
A large epidemiologic study compared the records of 1264 women with CTS to an equal number of women without CTS and observed that women over age 40 who had taken oral contraceptives were 38% more likely to develop CTS (Ferry 2000).
For a detailed discussion of women’s hormonal health, refer to the Female Hormone Restoration protocol.
Aromatase inhibitors (eg, anastrozole [Arimidex]), used to treat estrogen receptor-positive breast cancer (Nishihori 2008), have been associated with an increased risk of CTS. A study of over 6000 postmenopausal women who took either anastrozole or tamoxifen (Nolvadex, a selective estrogen receptor modulator) during breast cancer treatment found a highly significant difference in the rate of CTS between the two groups over a median follow-up period of over eight years. Although CTS was rare in both groups, it occurred in 2.6% of the women treated with anastrozole and 0.7% of those treated with tamoxifen. This study found that CTS rates were significantly higher in those who had previously taken HRT as well as those who had prior chemotherapy (Sestak 2009). Additionally, a case report described the onset of CTS in six women after initiation of aromatase inhibitor treatment, which was relieved when their medication was switched to tamoxifen (Nishihori 2008).
Anti-estrogen therapy, also called hormonal therapy, is used to prevent breast cancer recurrence following successful treatment; tamoxifen is often used in this setting. In a study of 4657 women who underwent successful breast cancer treatment and remained disease-free after taking tamoxifen for 2-3 years, subjects either continued taking tamoxifen or changed their treatment to the aromatase inhibitor exemestane (Aromasin). After a median 7.5-year follow-up period, women taking exemestane had over five times the chance of developing CTS during treatment than those taking tamoxifen (Mieog 2012).
CTS appears to occur frequently in individuals with hypothyroidism (low thyroid hormone levels) (Kececi 2006). A study of over one million patient records found that hypothyroidism was correlated with CTS, and more so in individuals under the age of 39 compared to older people (Tseng 2012). The reasons for these higher rates in people with hypothyroidism are not well understood. Some research suggests that hypothyroidism may increase CTS risk by interfering with proper nerve function (Kececi 2006). However, it is not clear whether treating hypothyroidism will improve CTS symptoms; one study reported that the majority of patients treated with thyroid hormone replacement sufficient to return their thyroid hormone levels to normal continued to experience CTS symptoms (Palumbo 2000).
Other Potential Risk Factors
Trauma or burn injuries to the forearm or wrist are also potential causes of CTS (LeBlanc 2011; Hassan 2008). Leukemia, tumors, amyloidosis, sarcoidosis, or certain infections may also cause CTS (LeBlanc 2011; Hassanpour 2006; Von Glehn 2012).
CTS is relatively rare among children, but is seen in some genetic syndromes (Van Meir 2003; White 2010; Kwon 2011). Other causes of childhood CTS include wrist trauma and bone malformation (Van Meir 2003; Leduc 2014; Potulska-Chromik 2014; Davis 2014).