The AMPP Study was approved by the Albert Einstein College of Medicine Institutional Review Board. The AMPP Study was modeled on the methods of the American Migraine Studies I [17] and II [18], described in detail elsewhere [16] and briefly summarized herein. In 2004, a screening survey was mailed to a stratified random sample of 120,000 U.S. households encompassing 257,339 household members [16]. The questionnaire was completed by the head of the household, who reported the total number of household members and the number of household members experiencing at least occasional self-defined “severe headache”. Each household member with severe headaches was asked to complete a questionnaire that included questions the AMS/AMPP diagnostic module which allows for assignment of migraine based upon on modified ICHD-2 criteria. This module has been demonstrated to have a sensitivity of 100% and specificity of 82% for the diagnosis of migraine [19]. No significant changes occurred between ICHD-2 and ICHD-3beta that are related to the criteria used in this study.
A random sample of 24,000 of the adult (i.e., ≥18 years of age) respondents to the 2004 survey who self-reported active (i.e., past 12 months) “severe headache” were asked to participate in an annual longitudinal follow up study. They completed questionnaires annually from 2005-2009. We used the 2009 AMPP Study survey because complete data were available to describe subtypes of menstrual migraine and it included the HIT-6 (with paid permission for use) as well as the MIDAS.
In the 2009 survey, respondents answered questions about headache symptoms, frequency, severity, menstrual status and whether they had headache/migraine associated with menstruation, employment status (i.e., working for pay full- or part-time, unemployed, retired, a student, a homemaker, disabled, a volunteer, on medical or maternity leave, or “other”) and completed the MIDAS [20] and HIT-6 questionnaire [21]. 17,052 females were mailed the 2009 AMPP Study questionnaire and 71.4% (n = 12,180) were completed and returned (Figure 1).
Respondents were asked to indicate the number of days they had headache in the preceding three months and the number of days with their “most severe type of headache” over the preceding year. A total of 5,134 female respondents of the 2009 AMPP Study survey met criteria for episodic migraine and were considered active cases (i.e., defined as having at least one migraine in the previous 12 months and an average of <15 headache days per month over the preceding 3 months). Of these, 1,697 were eligible for this analysis which included the following: aged 18 to 60 years, had at least one menstrual cycle in the preceding two months, and responded to the questions used to determine menstrual migraine status.
Menstrual migraine subgroups
The diagnostic criteria for migraine in association with menses have not been firmly established; as a consequence in ICHD-3beta [2] (Table 1) the criteria remain in the Appendix, indicating that they are not yet fully accepted, but intended for further study. We could not apply ICHD-3beta criteria as written because we relied on self-reported recall of headaches associated with menses, a common approach both in large scale epidemiological studies and in clinical care. Our large scale study does not include daily diaries as recommended by ICHD-3beta criteria in order to establish a diagnosis.
The AMPP Study questionnaire asked, “Which statements best describe your headaches in relation to your period?” Respondents were classified into three mutually exclusive groups based on their responses. Women who selected “all of my headaches are related to my menstrual cycle (my headaches ONLY happen around the time of my period from two days before to three days after the start of menstruation)” were assigned to the self-reported predominantly menstrual migraine (MM) group. Women who selected “I am MORE LIKELY to get headaches with my period but they also occur at other times of the month” were assigned to the self-reported menstrually-associated migraine (MAM) group unless they also endorsed the MM statement. Finally, women who selected “my headaches are NOT related to my menstrual cycle” were assigned to the self-reported menstrually-unrelated migraine (MUM) group if they did not also endorse the MM or MAM statement. Another difference between how we defined our subgroups and ICHD-3beta criteria is that we did not require women to endorse “I get headaches with at least two of every three periods” as these data were not collected.
We did not exclude women who endorsed more than one response option. Of respondents who endorsed the response “My headaches ONLY happen around the time of my period [from two days before to three days after the start of menstruation]” about one third also endorsed “I am MORE LIKELY to get headaches with my period but they also occur at other times of the month”. Simultaneous endorsement of both statements most likely occurs in women who have predominantly MM with occasional migraine and/or headaches at other times. Accordingly, we assigned these women to the self-reported predominantly MM group (MM). This decision and its potential consequences are considered in the discussion. “I am MORE LIKELY to get headaches with my period but they also occur at other times of the month” and “my headaches are NOT related to my menstrual cycle” were both endorsed by 4.1% of the cases and these women were assigned into the MAM group. This is likely conservative since these cases likely decreased the strength of observed associations.
Number of migraine attacks and days with migraine/headache
Headache attack frequency was based on a response to a question about the number of days with headache (for most severe type of headache) in the past month, three months, and 12 months and converted to a measure of headaches per month. Headache-days in the past three months was taken from the response to a MIDAS question on the number of days with headache in the past three months (one migraine attack could last for multiple days).
Headache impact on functioning
We used the following migraine/headache impact measures: MIDAS (scored by grade), a MIDAS measure of lost productive time (LPT) [22,23] and the HIT-6 [21].
Migraine-related disability
The MIDAS is comprised of five questions related to impact of migraine/headache on functioning in defined roles (i.e., housework, work for pay, leisure time) [20] that are used to categorize severity into four grades based on total days of impaired functioning (i.e., Grade I or little or no disability, 0 to 5; Grade II or mild disability, 6 to 10; Grade III or moderate disability, 11 to 20; Grade IV or severe disability, ≥21, with an option of dividing Grade IV into IVA and IVB). The recall period for the MIDAS is three months, effectively covering three menstrual cycles.
Lost productive time
We used the two MIDAS work-for-pay questions to estimate lost productive time (LPT). These two questions ask about number of days of missed work in the past three months due to headache (absenteeism) and number of days while at work where productivity was reduced by half (presentism denoted as Half Days) or more because of headache.
Employment
Employment status was documented [22] for each respondent and defined as actively employed for pay (i.e., excludes those on short- or long-term medical leave) if they reported actively working enough hours to qualify for full- (≥35 hours) or part-time (20 to 34 hours) status in the previous two weeks. Individuals were defined as eligible for employment but “unemployed” if they reported they were either unemployed or on medical disability. For analysis, employment was defined as a binary variable (i.e., employed versus unemployed).
We also used the HIT-6, (with a licensing fee) which is comprised of six questions, to assess the impact of the most severe headache type on ability to function. Three questions are independent of headache frequency and three questions are related to frequency of headache attacks. It has a recall period of four weeks [21]. It should be noted that both MIDAS and HIT-6 impact measures do not specifically assess headache or migraine days related to menstruation, but all headache-days over an interval of 3 months and 1 month, respectively.
Analyses
The analysis was confined to women who both met criteria for migraine and had menstrual cycles in the two-month period before completing the 2009 AMPP Study survey. We compared the three subgroups defined by self-reported menstrual headache status (i.e., MM, MAM, MUM) on characteristics and measures of headache impact.
LPT was defined as: Missed Work Days + 0.5*(Workdays Where Productivity was Reduced by Half)
The LPT formula is for the number of missed workday equivalents in the three months before the survey. We assumed that a workday reduced by half or more is equivalent to working for half of a usual workday, an estimate that was validated in a previous diary study [20]. Based on previous experience [22,23] and given the non-normal distribution properties of work loss (i.e., a substantial proportion with no work loss), LPT was defined as two binary variables (i.e., < 0.5 LPT Days versus 0.5+ LPT days and < 2 LPT Days versus 2+ LPT days). For analysis, employment was defined as a binary variable (i.e., employed versus unemployed). We applied the standard scoring algorithm for HIT-6 items where responses are assigned values (i.e., Never = 6, Rarely = 8, Sometimes = 10, Very Often = 11, Always = 13) and summed for a total score. We stratified respondents using the standard cut-points. (i.e., <50 = little or no impact, and 50 to 55 for some impact, 56 to 59 for substantial impact, ≥60 for very severe impact). We completed regression analysis using cut-points above and below 56 (i.e., <56, ≥56) and 60 (i.e., <60, ≥60).
We used chi-square to compare the sociodemographic and headache characteristics of the three subgroups, and we used logistic regression (i.e., LPT, HIT-6 item variables) to analyze the relationship between menstrual migraine status and measures of headache impact, as previously defined. We completed separate logistic regression models for women who reported six or fewer headache-days in the past three months (i.e., an average of two headache-days per month) and for all women with EM (i.e., ≤45 headache-days in three months). Covariates were added in two sequential models that included: 1) age (18 to 29, 30 to 39, 40 to 49, 50 to 60); race (White, Black, Other); education (no high school diploma, high school diploma, some college or associates degree, bachelors degree, graduate degree); annual household income (< $22,500, $22,500to $39,999, $40,000 to $59,999, $60,000 to $89,999, ≥ $90,000), and age at migraine onset; and 2) number of attacks of the most severe type of headache in the past month. SAS version 9.2 was used for all analyses (SAS Institute Inc., Cary, NC).