Differential response to estrogen challenge test in women with and without premenstrual dysphoria

This study tested the hypothesis that brain sensitivity to normal fluctuations in gonadal hormones is increased in women with premenstrual dysphoria. For this purpose, the effect of a common gonadal hormonal challenge on the sensitivity of the brain was investigated in 13 women with premenstrual dysphoria and 12 asymptomatic controls. The estrogen challenge test, comprising estradiolbenzoate 0.04 mg/kg, was given as an intramuscular gluteal injection between 0700 and 1000h on day 3 or 4 of the menstrual cycle; blood was sampled at 0, 0.6, 6.5, 24, 32, 48, 56, 72, 96, 120, and 144h and analyzed for estradiol, FSH and LH. Serum estradiol levels after the injection and the corresponding FSH responses were similar between the study groups; however, the LH responses were significantly different. Women with premenstrual dysphoria had a relatively stronger negative feedback response (p=0.014) up to the point of nadir LH levels (maximal negative feedback), but displayed higher LH levels at the nadir (p=0.01), more LH surge-like reactions (p=0.047), and a 50% higher area under the curve (AUC) for LH (p=0.03) than controls. The LH response in women with premenstrual dysphoria was related to the VAS-rated symptoms; the negative increment (AOC) correlated to luteal phase "bloating" (r(s)=0.73; p=0.0069) whereas the AUC of LH correlated to "irritability" (r(s)=0.58; p=0.040). A significant interaction term between study group and changes in LH during the negative feedback phase (32-0h), with regard to luteal phase "irritability" was found (test for interaction p=0.005). For the premenstrual dysphoria group, ratings of "depressed mood"were related to baseline FSH levels (r(s)=0.60; p=0.034), and to the AUC of FSH during the negative feedback phase (r(s)=0.58; p=0.043). Women with premenstrual dysphoria displayed a gonadotrophin response to estradiol challenge that differed from that of controls, and was correlated to symptom severity.