Characteristics of PMS and probable PMDD cases and controls at baseline are presented in . PMS and PMDD cases were slightly younger than controls and had a significantly higher mean BMI at baseline (p
0.001 for all). Current and former smoking was also significantly more common in PMS and PMDD cases compared with controls, as was ever use of OC (p
0.0001 for all). Approximately 16% of both PMS and PMDD cases reported having had a diagnosis of depression at baseline compared with 7.5% of controls (p
0.0001 for both). Use of antidepressant medications was also more common in both PMS and PMDD cases than in controls (p
Age-Standardized Characteristics of Premenstrual Syndrome (PMS) Cases, Probable Premenstrual Dysphoric Disorder (PMDD) Cases, and Controls at Baseline, NHS2a PMS Substudy, 1991–2001
We estimated age-adjusted and multivariable relative risks of PMS and probable PMDD by level of alcohol intake during adolescence and young adulthood (). Overall, age-adjusted RR suggested that alcohol use was positively associated with the incidence of PMS. For example, women whose first use of alcohol was before age 18 had a significant 92% higher risk of developing PMS than women never consuming alcohol (RR
1.92, 95% CI 1.45-2.54). After adjustment for other factors, however, results were substantially attenuated; control for pack-years of cigarette smoking explained most of the difference between age-adjusted and multivariable results. In multivariable analyses, results suggested that women who started drinking before age 18 had a modestly higher risk of developing PMS than those whose first alcohol use was at older ages (p
for trend among drinkers
0.02), but risk was not significantly different from that of nondrinkers.
Sixty-seven percent of PMS cases reported first using alcohol before the age at which their menstrual symptoms began. Among all cases and those controls reporting any menstrual symptoms, women who reported first using alcohol before the age at which their menstrual symptoms started had an RR of 1.18 compared with never drinkers (95% CI 0.86-1.62), whereas those reporting first alcohol use after the age of symptom onset had an RR of 0.88 (95% CI 0.62-1.23). The amount of alcohol consumed during each time period in adolescence and early adulthood was not linearly related to risk of PMS. Results further adjusted for smoking status at each specific age and total drinking-years were identical.
For most analyses, results for probable PMDD were slightly stronger than those for PMS (). For example, women whose first use of alcohol was before age 18 had an RR of 1.35 (95% CI 0.93-1.98) compared with never drinkers. However, as with PMS, we did not observe a linear relationship with quantity of alcohol use at any specific age and incidence of probable PMDD.
We also did not observe evidence of a linear relationship between alcohol intake in 1989, at baseline in 1991, and during follow-up and risk of incident PMS or probable PMDD (). At each time period, risk tended to be higher in former drinkers than in never drinkers and current drinkers. For example, women who were former drinkers in 1989 (i.e., had consumed alcohol during a previous time period but did not consume alcohol in 1989) had a 32% higher risk of PMS (95% CI 0.97-1.78) compared with women who had not consumed alcohol before 1989 (i.e., never drinkers). Results were slightly stronger for PMDD, suggesting a 60% higher risk of PMDD (95% CI 1.13-2.27) in former drinkers compared with never drinkers. Among current drinkers, results suggested that risk of PMS was inversely related to level of alcohol intake; at reference year, this trend was statistically significant (for PMS, p
0.006; for PMDD, p
0.02). Additional analyses evaluating beer, wine, and liquor intake separately did not suggest that risk differed by alcohol type (results not shown).
Alcohol Intake before Baseline and during Follow-Up and Risk of PMSa and Probable PMDD, NHS2 PMS Substudy, 1991–2001
To determine if long-term alcohol intake was differently related to risk than drinking during any single time period, we calculated total drinking-years for each woman, which took into consideration both duration of alcohol use and quantity at each age. Compared with never drinkers, women in the highest quintile of drinking-years, a level equivalent to one or more glasses of wine per day for ≥13 years, did not have a significantly higher risk of PMS. For probable PMDD, risk was significantly 50% higher in women in quintiles 3 and 4 compared with never drinkers but not in quintile 5 (p
0.52). Results pertaining to drinking pattern also did not suggest that women who used alcohol regularly in 1989 had an increased risk of developing PMS/PMDD.
In our analyses of potential effect modification, results stratified by BMI at reference year suggested the possibility of an increased risk of PMS and probable PMDD associated with alcohol use in leaner women (). For example, in women with BMI <25.0
, we observed a positive linear relationship between total drinking-years and risk of PMS. Compared with never drinkers, multivariable RR for quintiles 1–5 were 1.01, 1.10, 1.52, 1.63, and 1.74 (95% CI for quintile 5 vs. 1
1.11-2.72), respectively (p
0.002). In heavier women, risk was not associated with total drinking-years; compared with never drinkers, RR for quintiles 1–5 in this group were 1.03, 0.95, 0.89, 1.06, and 0.66 (95% CI for quintile 5 vs. 1
0.10), respectively (p
0.01). We also observed significantly higher risks of PMS in leaner women who first used alcohol before age 18 and before menstrual symptoms started but not in heavier women (results not shown). The relationship between age at first alcohol use and PMS was slightly higher in those with younger reference ages than older ages, but interactions were not statistically significant (results not shown).
Multivariable Relative Risks and 95% Confidence Intervals of PMS and Probable PMDD by Total Drinking-Years of Alcohol Stratified by Body Mass Index at Time of Diagnosis, NHS2a PMS Substudy, 1991–2001
Results from subanalyses limited to women not using OCs at baseline, never smokers, and women who had not received a diagnosis of depression before PMS diagnosis were very similar to the main analysis (results not shown).