PMDD patients were significantly older (mean age 37.4 years ± 4.4) than their control counterparts (mean age 28.6 years ± 6.4; Student t29 = 4.48, p < .01).
Baseline Biochemical Analyses
Mean baseline serum MgT concentrations were within the normal reference range in all subjects, and there were no significant differences between women with PMDD and healthy control subjects (.79 ± .09 mmol/L and .75 ± .10 mmol/L, respectively, reference range .75-1.00 mmol/L). Mean RBC MgT, MBC-C MgT, and MBC-T MgT measures also were not different between patients and healthy control subjects at baseline (). Similarly, there were no differences between patients and control subjects in baseline urinary Mg excretion or any other urinary measure (); however, the mean baseline 24-hour urinary magnesium output was below the lower limit of the reference range in both patients (2.14 ± .53 mmol/24 hour) and healthy control subjects (2.35 ± .60 mmol/24 hr; reference range 3.0 - 4.25 mmol/24 hour).
Mean (±SD) Magnesium Blood Measures at Pre, Post, and the Day after Receiving Mg Infusion
Mean (± SD) 24-Hour Urinary Measures Before and After Magnesium (Mg) Infusion
None of the following baseline blood measures were found to be abnormal in study subjects or significantly different between patients and healthy control subjects: TSH, fT4, cortisol, FSH, and LH.
Biochemical Measures Following Magnesium Infusion
We found no statistically significant differences in (mean ± SD) urinary % Mg retention between patients (31.5 ± 25) and control subjects (27.5 ± 19; ). By the end of the 4-hour infusion of Mg, mean serum MgT had increased significantly in both women with PMDD and in healthy control subjects. Repeated-measures ANOVA results revealed a significant time effect [F(2,56) = 112, p < .001] for serum MgT, with concentrations peaking at the end of the infusion and returning to baseline levels by the next morning in all subjects. Post hoc testing revealed significant time effects for before and after infusion comparisons (t56 = 14.1, p < .01) and for after infusion versus day 2 comparisons (t56 = 12.7, p < .01). Neither diagnosis nor time-by-diagnosis effects were discovered, however. During the double-blind trial, no significant changes in serum Mg were observed after the placebo infusions conducted in women with PMDD. Thus, repeated-measures ANOVA results revealed a significant time by treatment effect for serum MgT in the women with PMDD [F(2,16) = 37.5, p < .01].
Figure 3 Mean magnesium retention in women with premenstrual dysphoric disorder (PMDD; n = 16) and healthy control subjects (HC; n = 14). No statistically significant differences were found in mean % Mg retention (± SEM) between women with PMDD and HC. (more ...)
There were no significant time, diagnosis, or time-by-diagnosis effects in mean RBC and MBC-C MgT concentrations over the course of the study (preinfusion, postinfusion, and 24 hours postinfusion) as analyzed by repeated-measures ANOVA.
For MBC-T MgT, there was a significant time effect [F(2,52) = 6.1, p < .01], reflecting a decrease in MBC-T MgT postinfusion, but no diagnosis or time-by-diagnosis effects. Measures of MgT and Ca obtained in 24-hour urine collections before and after infusion of intravenous Mg () showed a time effect [F(1,28) = 152, p < .01; F(1,27) = 5.5, p < .05, respectively], reflecting an increase in Mg and Ca excretion, but no diagnosis or time-by-diagnosis effects. Similarly, women with PMDD and control subjects did not differ in the urinary excretion of creatinine over time.
Of the 12 PMDD patients studied under double-blind conditions, 2 were asymptomatic at the time of Mg infusion. Hence all biochemical analyses were performed twice, first for all PMDD patients and again for only those PMDD patients who were symptomatic during the study cycle. Significant findings did not differ in the two analyses.
Mood and Behavioral Ratings
As expected, healthy control subjects initially had low scores on the BDI, STAI, PMTS-O, PMTS-S, and VAS. The intravenous administration of Mg was not associated with any mood changes in healthy control subjects.
In the open-label Mg infusions with the first six PMDD patients, we observed significant improvement in mean mood symptoms postinfusion as assessed by VAS (; note that this figure shows only irritability; we found similar results with the other mood and physical symptoms). There was a significant time-by-diagnosis effect, with PMDD patients achieving substantial reductions in mood scores during and immediately after Mg infusion, compared with control subjects, whose mood scores did not change significantly (). Post hoc Bonferroni t tests showed the significant improvement in symptoms to occur by 90 min and to continue throughout the Mg infusion and 24 hours after the end of the magnesium infusion. In addition, syndrome-based mood ratings revealed a significant time-by-diagnosis effect, with PMDD patients experiencing reductions in mood symptoms immediately after Mg infusion compared with control subjects, who remained asymptomatic throughout the study [BDI, F(1,18) = 28.7, p < .001; STAI, F(1,18) = 17.8, p < .001; PMTS-O, F(1,18) = 338, p < .001; PMTS-S, F(1,18) = 10.2, p < .01]. This significant effect was maintained after post hoc analyses with Bonferroni t tests [BDI, t (18) = 6.68, p < .01; STAI, t (18) = 5.59, p < .01; PMTS-O, t (18) = 22, p < .01; and PMTS-S, t (18) = 3.9, p < .01]. Under double-blind conditions in the 10 symptomatic PMDD patients receiving placebo and Mg infusions (), however, there was neither a treatment (Mg vs. placebo) nor time-by-treatment effect found for any of these mood and behavioral measures. In addition there were no statistically significant differences between women with (n = 6) and women without (n = 6) Mg deficiency in their symptom severity.
Figure 4 Improvement of irritability associated with magnesium (Mg) infusion during open and double-blind crossover trials. Open Mg trial: repeated-measures analysis of variance (ANOVA) of the first six time points revealed significant time-by-diagnosis effects (more ...)
Mood Measures in Symptomatic PMDD Women Pre, Post, and the Day After Receiving Magnesium and Placebo (Mean±SD)
We observed no significant correlations between the percent retention of Mg and symptom improvement (as measured by the BDI, STAI, PMTS-O, PMTS-S, or VAS) immediately after Mg infusion or the day after the infusion. There were no correlations between VAS symptoms and serum Mg or the percent Mg retention after corrections for multiple comparisons.