Differences in free estradiol and sex hormone-binding globulin in women with and without premenstrual dysphoric disorder

Context: Over the years, different hypotheses involving the ovarian steroid hormones have been proposed to explain the luteal phase occurrence of severe premenstrual syndrome symptoms. Although it had been strongly suspected that differences in the concentrations of the ovarian steroids may underlie the mood and psychological imbalance of this disorder, the evidence for this hypothesis has been inconsistent and remains controversial. Objective: Our objective was to measure the ovarian steroid hormones across the menstrual cycle in women with and without luteal phase symptoms consistent with premenstrual dysphoric disorder (PMDD). Design: We measured estradiol (E2), progesterone, and SHBG in women with and without PMDD using a cross-sectional and prospective experimental design. Participating women underwent 2-month self-assessment symptom screening and 1-month hormonal evaluation. Results: Overall means for LH, progesterone, E2, peak E2, and free E2 were not different between groups. Across the menstrual cycle, overall percent free E2 was significantly lower and SHBG significantly greater in the PMDD group compared with controls (1.39 ± 0.26 vs. 1.50 ± 0.28, P = 0.03; 61.4 ± 25.1 vs. 52.4 ± 21.3 nmol/liter, P = 0.046, respectively). During the luteal phase, free E2 was significantly lower in the PMDD group compared with controls (PMDD 7.6 ± 7.0 vs. controls 8.9 ± 8.4 pmol/liter; P = 0.032). For both follicular and luteal phases, SHBG was significantly higher in the PMDD group (follicular phase 60.5 ± 31.7 vs. 51.4 ± 38.2 nmol/liter, P = 0.047; luteal phase 65.1 ± 32.3 vs. 55.1 ± 38.9 nmol/liter, P = 0.03). In both groups, SHBG significantly increased from the follicular to luteal phase. Conclusion: Luteal phase concentrations of free E2, percent free E2, and SHBG differ significantly between women with and without PMDD.