The methods used for this review were applied to a larger systematic review of the association between menthol cigarette use and three smoking behaviors (Figure 1). Current results assess the Key Question (KQ), “Does menthol cigarette use have a differential impact on smoking cessation compared to non-menthol cigarette use?” The protocol for this systematic review was registered with the PROSPERO international prospective register of systematic reviews on March 22, 2016 and updated on January 10, 2019. The record is available at: ttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=119301.
The literature search identified 851 potentially relevant articles across sources with 838 articles from online databases and 13 additional articles through other sources. After independent review of titles and abstracts by two members of the research team, 428 references were excluded, resulting in 423 articles being screened at the full-text level (provided in SUPPLEMENTAL SECTION 1: References Included for Full-Text Review (n=423)). An additional 305 articles were excluded at the full-text level (provided in SUPPLEMENTAL SECTION 2: Excluded Studies Table (studies excluded at level 2 with reason for exclusion)), resulting in 118 relevant articles eligible for inclusion (provided in SUPPLEMENTAL SECTION 3: Included Studies List (n=118)). The weighted overall kappa for inter-rated reliability at level 2 screening was 0.96. Fifty-seven studies (seven of which were reported in paired studies) evaluated the association between menthol cigarette smoking and smoking cessation.
Smoking behaviors can vary across different population subgroups, suggesting that both individual and environmental factors influence smoking (7, 8). This review applied the Socio-Ecological Model created by McLeroy et al. (9) to guide consideration of the interrelationships between individuals and their social (micro-), physical (meso-), and policy (macro-) environments. This framework guided the sensitive analyses and further details on the conceptual framework are provided in SUPPLEMENTAL SECTION 4: Conceptual Framework.
Literature Search Methods
The search strategy included sources of published, peer-reviewed literature, theses and dissertations, and government and industry documents. The complete list of databases and search terms is provided in SUPPLEMENTAL SECTION 5: Search Strategy Overview.
Detailed descriptions of terminology used to organize and synthesize this review are provided in SUPPLEMENTAL SECTION 6: Terminology.
Inclusion and Exclusion Criteria
Inclusion and exclusion criteria were developed with review and input from external subject matter experts in tobacco research and systematic reviews. Reasons for exclusion of individual studies are provided in full in SUPPLEMENTAL SECTION 7: Inclusion/Exclusion.
Outcomes and Related Psychometrics
Included studies reported on at least one of the following outcomes: duration of abstinence, quit attempts (any quit attempts; number of quit attempts per person), rate of abstinence/quitting, change in smoking quantity/frequency, and return to smoking/relapse. Recognizing that not all the outcome measures are likely to be equally valid and reliable, this review examined the following Contextual Question (CQ) to provide additional information and context for the results, “Have measures used to examine cigarette smoking cessation been psychometrically assessed as valid and reliable?” Further details are provided in SUPPLEMENTAL SECTION 8: Contextual Question.
Complete study and sample characteristics are provided in the Evidence Tables in SUPPLEMENTAL SECTION 9: Study, Data Set, and Sample Characteristics and SUPPLEMENTAL SECTION 10: Evidence Tables, Sample Characteristics (Unadjusted [Table 10-1 and Table 10-2] and Adjusted [Table 10-3 and Table 10-4]).
ASSESSMENT OF INDIVIDUAL STUDY METHODOLOGY
The quality of the studies included in this systematic review was assessed at the study level using the Downs and Black checklist (10), as recommended by the Cochrane Collaboration (11) and provided in Table 12-1. Further details on the Downs and Black checklist and study quality are provided in SUPPLEMENTAL SECTION 11: Study Quality Assessments and SUPPLEMENTAL SECTION 12: Additional Study Quality Methods.
The strongest evidence to assess whether menthol cigarette use has a differential impact on smoking cessation compared to non-menthol cigarette use would be expected to be provided by longitudinal analyses that adjusted or controlled for key confounding factors – age, race/ethnicity, and gender – by inclusion criteria, modeling, or stratification. Longitudinal analytic results were considered the highest available evidence and, as such, were weighed more heavily in the strength of evidence analysis and qualitative synthesis below. In the absence of longitudinal analytic results, the highest level of available evidence was synthesized according to studies that controlled for the predefined demographic factors.
STRENGTH OF EVIDENCE EVALUATION
The overall strength of the body of evidence was assessed and graded as “high,” “moderate,” “low,” or “insufficient” using the Evidence-Based Practice Center (EPC) approach. Full details are provided in SUPPLEMENTAL SECTION 13: Strength of Evidence.
RESULTS: SMOKING CESSATION OR QUITTING BEHAVIORS
A total of 57 studies, reported in 64 unique references, evaluated the potential association between menthol cigarette use and smoking cessation. Table 1 below presents the five specific outcome measures for smoking cessation reported across adjusted and unadjusted studies; however, adjusted studies are considered a higher level of evidence in this synthesis. An overview of the psychometric findings for the measures of smoking cessation is presented in Table 8-1. A CQ evidence table, including reliability and validity data identified for each of the smoking-related outcome measures, is provided in Table 8-2.
Empirical data regarding reliability or validity qualified four of the five smoking cessation measures (duration of abstinence, quit attempts, rate of abstinence/quitting, change in smoking quantity/frequency) as “Acceptable.” Further detail on the non-systematic literature synthesis for psychometric assessment is provided in SUPPLEMENTAL SECTION 8: Contextual Question.
Synthesis of the Best Available Evidence
Summaries of the best available evidence — controlling for age, race/ethnicity, and gender — are presented by outcome measure below. Adjusted results by age, race/ethnicity, and gender subgroups are presented in SUPPLEMENTAL SECTION 14: Adjusted Subgroup Analyses by Outcome; unadjusted results from both the full sample and subgroups of age, race/ethnicity, and gender are presented in SUPPLEMENTAL SECTION 15: Unadjusted Results. Outcome measures are presented with a corresponding overview table for each outcome in the following order: duration of abstinence; quit attempts; rate of abstinence/quitting; change in smoking quantity/frequency; and return to smoking/relapse. Where two references reported the same data, the most recent publication was used as the data source.
Duration of Abstinence
Two studies, presented in Table 2, reported duration of abstinence.
Levy at al. (19) reported statistically significant lower odds of being a “recent” and “long-term” quitter for menthol compared with non-menthol smoking, across all models (AORs ranged from 0.92 to 0.97 across models). Cubbin et al. (20) reported duration of abstinence for six gender-race/ethnicity interactions, yielding only one significant finding that suggests that White female menthol smokers had been abstinent statistically significantly longer than White female non-menthol smokers (14.8 years vs. 12.5 years; p<0.01). Given the limited number of studies and the inconsistent findings reported for this measure, an association between menthol cigarette use and duration of abstinence is unclear and undefined in the evidence base.
Quit Attempts (Any quit attempts; Number of quit attempts per person)
Fourteen studies, as presented in Table 3, reported measures of quit attempts.
Kahende at al. (34) reported White menthol smokers had statistically significant lower odds than White non-menthol smokers of having made a past-year quit attempt (AOR=0.91, 95% CI: 0.84 to 0.99; p<0.05).
Nine studies found no difference between menthol and non-menthol smokers in terms of having made at least one quit attempt (within various timeframes), across all models and subgroup analyses/stratifications performed (14, 20, 31, 35-37, 40, 41, 46) . In addition, Stahre et al. (32) found no significant difference in the odds of using any type of quit aid between menthol and non-menthol current smokers, and menthol and non-menthol former smokers.
Three studies reported mixed findings. Levy et al. (19) reported that menthol users had statistically significant higher odds of past-year quit attempts than non-menthol users (AOR=1.03, 95% CI: 1.02 to 1.03; p<0.001); this result remained unchanged when adding nicotine dependence to the model. However, a third model (adjusting for additional, unspecified covariates) reported statistically significant lower odds of past year quit attempts among menthol users (AOR=0.98, 95% CI: 0.98 to 0.98). In Keeler et al. (29), the overall odds of past-year quit attempts between menthol and non-menthol smokers were no different. Both the 2017 and 2018 studies by Keeler at al. (29, 30) found Black menthol smokers were statistically significantly more likely to report past-year quit attempts than Black non-menthol smokers (2018: AOR=1.39, 95% CI: 1.16 to 1.67; p<0.001; 2017: AOR=1.37, 95% CI: 1.16 to 1.61; p=0.0002); however, no such differences were reported for other racial/ethnic subgroups.
The majority of the results from these fourteen studies reported no differences between menthol and non-menthol smoking in terms of quit attempts.
Rate of abstinence/quitting (including but not limited to prolonged abstinence [PA], point prevalence abstinence [PPA], identifiable cigarette type [menthol versus non-menthol] smoked before quitting, and being a former smoker [versus current smoker])
Twenty-eight studies (from 31 references), presented below in Table 4, reported on rate of abstinence/quitting outcomes.
Four studies found that menthol smokers had statistically significantly lower odds of quitting than non-menthol smokers: two studies reported 7-day PPA (between weeks 14 and 26 (62); and at the previous 7 days and at week 7 (27)). Additionally, two studies examined cessation at different time points (one year abstinence from purchasing a pack of cigarettes (53); and abstinence at three to six week follow-up (43)).
Fifteen studies (from 16 references) found no difference in the rate of abstinence between menthol and non-menthol smokers, both overall and within subgroup analyses, in terms of: 7-day PPA in six studies (23, 24, 63-66); 30-day PPA in one study (42); quit rates from baseline to follow-up in three studies from four references (41, 46, 50, 61); cessation of greater than 3 months in two studies (29, 30); PA in two studies (69, 70); and, past-year abstinence in one study (55).
Nine studies (from 11 references), reported mixed significance (47, 49, 52, 54, 56-59, 68, 71, 75). Using NHIS data, Sulsky et al. (54) found that White menthol and non-menthol regular and daily smokers were no different in odds of past-year abstinence; similar results were observed in Black menthol and non-menthol daily smokers. Using TUS-CPS data, the authors found no significant difference in one- to three-year abstinence between White menthol and non-menthol smokers (both regular and daily). For other race/ethnicities, no difference was detected between menthol and non-menthol use in terms of abstinence among regular and daily smokers. However, for Black daily (AOR=0.89, 95% CI: 0.81 to 0.98) and regular (AOR=0.87, 95% CI: 0.80 to 0.95) smokers, menthol use was statistically significantly associated with lower odds of abstinence.
Reitzel et al. (68) found that menthol and non-menthol smokers were no different in terms of short-term abstinence for the overall sample. However, among White participants, menthol use predicted a statistically significant decrease in short-term abstinence (β=−1.56, SE=0.79; χ2=3.96; p=0.05) as well as 7-day PPA (β=−1.60, SE=0.79; χ2(1) = 4.06; p = .04; n = 132). No such differences were reported for either outcome among Black participants (short-term abstinence: β=0.54, SE=0.55; p=0.33; and 7-day PPA: β=1.00, SE=0.67; p=0.11).
Blot et al. (56) found that White menthol smokers had statistically significant greater odds of having quit compared with non-menthol smokers (AOR=1.55, 95% CI: 1.41 to 1.70); however, Black menthol and non-menthol smokers were no different.
Trinidad et al. (52) reported that, among White, Black, Asian-American/Pacific Islander, and Hispanic participants, menthol smoking was associated with statistically significant lower odds of abstinence greater than 6 months (AORs ranged from 0.28 to 0.48). However, among Native American/Alaskan native participants, menthol and non-menthol smokers were no different in terms of the odds of abstinence greater than 6 months.
Delnevo et al. (57, 58) reported on the odds of being a former smoker across five racial/ethnic subgroups and the following five sample restrictions (according to past and current smoking status): Former smokers who quit within the past 5 years and all current smokers (regardless of quit attempt history); former smokers who quit within the past 5 years and all current smokers (regardless of quit attempt history), both of whom currently do not use other tobacco products; former smokers who quit within the past 5 years and current smokers who reported ever having made a quit attempt; former smokers who quit within the past 5 years and current smokers who reported ever having made a quit attempt, both of whom currently do not use other tobacco products; and, past 12-month cigarette smokers who made a quit attempt or quit (i.e., former smokers). Among the overall sample, across four of the five restrictions, menthol cigarette smokers were statistically significantly less likely than non-menthol smokers to be former smokers with AORs ranging from 0.90 to 0.92.
Black menthol smokers were statistically significantly less likely to be former smokers compared to Black non-menthol smokers in all five restrictions with AORs ranging from 0.68 to 0.81. White menthol, versus non-menthol, smokers were statistically significantly less likely to be a former smoker across three restrictions. However, Hispanic menthol and non-menthol smokers were no different across four of the five restrictions; and, were statistically significantly less likely to be a former smoker in one restriction.
In Reitzel’s ‘Project Mom’ (71, 75), menthol cigarette use did not predict continuous abstinence from smoking. However, among White women, menthol smokers were statistically significantly less likely to maintain continuous abstinence compared to non-menthol smokers (AOR=0.19, 95% CI: 0.04 to 0.89).
Gandhi et al. (47) found no difference between White menthol and non-menthol smokers in odds of abstinence at both four weeks and six months. Black menthol smokers had statistically significant lower odds of abstinence compared to Black non-menthol smokers at both time points, four weeks (measured by 7-day PPA) (AOR=0.32, 95% CI: 0.16 to 0.62) and at 6 months post-quit (AOR=0.48, 95% CI: 0.25 to 0.90). Hispanic menthol smokers had statistically significant lower odds of abstinence at four weeks compared to Hispanic non-menthol smokers (AOR=0.43, 95% CI: 0.1 to 0.9); at six months, Hispanic menthol and non-menthol smokers were no different in odds of abstinence.
Gundersen et al. (59) suggested no significant difference in being a former smoker between menthol and non-menthol smokers in the overall sample, nor among Black smokers. However, odds of being a former smoker were statistically significantly higher for White menthol compared to White non-menthol smokers (AOR=1.17, 95% CI: 1.00 to 1.36; p<0.05). Odds of being a former smoker were statistically significantly lower for Hispanic menthol compared to Hispanic non-menthol smokers (AOR=0.61, 95% CI: 0.39 to 0.97; p=0.04), and for non-White menthol compared to non-White non-menthol smokers (AOR=0.55, 95% CI: 0.43 to 0.71; p<0.01).
Okuyemi et al. (49) reported no significant difference in odds of quitting between menthol and non-menthol smokers among adults ≥50 years of age; however, in adults <50 years of age, the odds of quitting for menthol smokers were statistically significantly lower for menthol smokers (AOR=2.02, 95% CI: 1.03 to 3.95).
Across the 28 studies, the majority of studies (15 studies) found no difference between menthol and non-menthol smokers in the rate of abstinence. Four studies reported that menthol smokers were statistically significantly less likely to quit smoking and nine studies reported results of mixed significance based on various stratifications. Overall, the evidence for this outcome was inconsistent for the association between menthol cigarette use and the rate of abstinence/quitting.
Change in Smoking Quantity/Frequency
Two studies (from four references), presented in Table 5, provided adjusted analysis of change in smoking
One study, from two references (46, 50) reported no difference between menthol and non-menthol cigarette users for changes in smoking frequency. One study (from two references) reported mixed significance. Reitzel et al. (71, 75) found that Black female menthol, versus non-menthol, smokers reported substantially less cigarette reduction (measured by CPD) over the course of 26 (β=3.82, SE=3.77; p=0.02; n=71). But no difference was found in changes in smoking frequency for the overall sample.
The overall evidence base for this outcome was limited by the small number of included studies, and the mixed significance of findings across studies precludes clear conclusions from the available evidence.
Return to Smoking/Relapse
Two studies, presented in Table 6, provided analyses of return to smoking/relapse.
In Muench and Juliano (74), menthol smokers were at a statistically significant greater risk of lapsing compared with non-menthol smokers, in both the univariate regression (AOR=3.474, p<0.05) and lapse survival curve analyses (HR=2.798, Wald statistic=2.79; p=0.048). Pletcher et al. (41), reported that young adult menthol smokers had a statistically significant higher likelihood of returning to smoking, compared to non-menthol smokers (AOR=1.89, 95% CI: 1.17 to 3.05; p=0.009).
The results from the two included studies suggest a higher likelihood of menthol smokers returning to smoking. However, the small number of studies—neither of which is based on a nationally representative sample—limit the generalizability of the association between menthol cigarette use and returning to smoking/relapse.
SENSITIVITY ANALYSES (ADJUSTED RESULTS)
Three sensitivity analyses were conducted in order to test whether the results differed after more stringent inclusion and exclusion criteria were applied. Overall, results from the sensitivity analyses suggested little to no change. Full details on the sub-group analysis and sensitivity analyses are provided in SUPPLEMENTAL SECTION 16: Sensitivity Analyses (Adjusted Results).
RESULTS OF META-ANALYSIS
All studies considered for meta-analyses controlled, at minimum, for age, gender, race/ethnicity. Menthol cigarette use was defined as either self-reported menthol use, current use, usual cigarette/brand used, or remaining with menthol cigarettes through the length of the study. Subgroup analyses were conducted to compare differences between study designs (prospective cohort and cross-sectional designs in abstinence [no duration]) and differences in measures (past year and ever quit attempt [ever quit attempts, any quit attempts between 2001 and 2005, and any quit attempts in the past 2, 3, or 5 years]). Further, sensitivity analyses were also completed according to race/ethnicity and abstinence verification (eCO verified), when possible. Pooled adjusted odds ratios (AORs) and 95% confidence intervals (CIs) with two-sided P values are reported from random-effects models utilizing the DerSimonian and Laird method (76) to measure the likelihood of reporting quit attempts and abstaining among menthol compared to non-menthol smokers. Pooled data for the meta-analyses were extracted for two outcome measures: quit attempts and duration of abstinence.
After screening all included adjusted studies, nine studies were included in the meta-analyses for quit attempts (14, 19, 29, 31, 34-36, 41, 46) and 12 studies for abstinence (23, 24, 27, 41, 47, 49, 56, 57, 59, 62, 64, 66). Full details are provided in SUPPLEMENTAL SECTION 17: Characteristics, Definitions, and Covariates of Studies Included in the Meta-Analysis and SUPPLEMENTAL SECTION 18: Forest Plots of Meta-Analyses.
Adjusted Odds of Reporting a Quit Attempt (Past Year or Ever)
Results from five studies (Figure 18-1) were pooled to measure the association of menthol use and past year quit attempts. Pooled results showed a statistically significant association between menthol, versus non-menthol, cigarette use and the increasing odds for past year quit attempts (OR=1.02, 95% CI: 1.01 to 1.03, p-value=0.003, I2=1%). However, the pooled result (Figure 18-2) from studies measuring ever quit attempts, any quit attempts between 2001 to 2005, and any quit attempt in the past 2, 3, or 5 years found no significant difference in the odds of making a quit attempt when comparing menthol and non-menthol smokers (OR=0.93, 95% CI, 0.82 to 1.05, p=0.23, I2=0%) (14, 41, 46). Results from two studies were pooled to measure for the association of menthol cigarette use and quit attempts (past year and quit attempts between 2001 and 2005) among Black participants (29, 46). Pooled results (Figure 18-4) showed a significant increase in the odds of Black menthol, versus non-menthol, smokers reporting quit attempts (OR=1.37, 95% CI: 1.17 to 1.61, p=0.00001, I2=14%). In contrast, among White menthol respondents in three studies (Figure 18-5), the odds of making a quit attempt were statistically significantly lower for menthol compared to non-menthol smokers (OR=0.95, 95% CI: 0.91 to 0.99, I2=0%) (29, 34, 46).
Adjusted Odds of Abstinence (No definition and 7-day PPA)
Data from four studies were pooled to measure the association of menthol use and abstinence (self-reported) with no specified duration of abstinence (41, 56, 57, 59). Recognizing the high heterogeneity balanced by the narrow confidence intervals, the pooled results showed no difference between menthol and non-menthol smokers in the odds of abstinence with no defined duration (Figure 18-6) (OR=0.96, 95% CI: 0.84 to 1.10, p=0.58, I2=71%).
Pooled data from three studies measuring the association of menthol use and abstinence with no specified duration of abstinence for Black and White menthol and non-menthol smokers were no different in terms of abstinence (56, 57, 59) (Figures 18-7 and 18-8) (OR=0.90, 95% CI: 0.73 to 1.10, p=0.29, I2=73%). Again, the heterogeneity was noted to be high. Individual meta-analysis results from four cohort studies measuring the association of menthol use and smoking abstinence measured by 7-day PPA are presented in Figure 18-9. When pooling results across these four studies, Black menthol smokers had statistically significantly lower odds of smoking abstinence 7-day PPA (OR=0.52, 95% CI: 0.38 to 0.70, p<0.0001, I2=0%) (Figure 18-10) (24, 27, 47, 49). These pooled results suggest an unclear association between cigarette type and abstinence. This may be due to the high heterogeneity among studies measuring this association, even when stratifying by study design and abstinence measures with specified duration.
STRENGTH OF EVIDENCE
Table 7a provides the SOE for the outcomes used in the current review to examine the association between menthol cigarette use and cessation outcomes. The adjusted data, treated as the higher level of evidence, were the primary source of data for this evidence synthesis and meta-analyses. Most measures were “indirect” and limited by the varying and/or undefined measures of abstinence. As presented in Table 7b, the overall strength of evidence for an association between menthol cigarette use and smoking cessation was graded as “low” based on deficiencies in the available evidence base.