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Objective: To assess the effect of low-dose conjugated equine estrogens (E) on circulating neurotransmitters and the efficacy for the treatment of psychological symptoms.Design: Controlled comparative clinical study.Setting: Endocrine Research Unit, Instituto Mexicano del Seguro Social, Mexico.Patient(s): Thirty postmenopausal women received conjugated equine E. Ten women acted as a comparison group.Intervention(s): Conjugated equine E, 0.312 mg/day, for 21 days per cycle during six cycles and added chlormadinone acetate, 2 mg/day, for the last 5 days of each cycle. Green scale for climateric women and Blatt-Kupperman Menopausal Index were used for measuring psychological well-being.Main Outcome Measure(s): Serum levels of dopamine (DA), noradrenaline, serotonin, and β-endorphin were quantified by specific assays at baseline and at the end of treatment.Result(s): Low baseline levels of DA, serotonin, and β-endorphin increased significantly (P<.001) from 181.9 ± 47.8 pg/mL to 202.9 ± 32.8 pg/mL (mean ± SD); from 206.4 ± 94.2 ng/mL to 279.2 ± 67.9 ng/mL; from 11.2 ± 1.8 pmol/L to 13.8 ± 2.4 pmol/L, respectively, after conjugated equine E. In parallel, augmented baseline noradrenaline levels diminished significantly (P<.05) from 30.2 ± 4.7 ng/mL to 24.0 ± 4.7 ng/mL. All neurotransmitter levels had a significant correlation with 17β-E2 concentrations at the end of the study. Alleviation of psychological symptoms was observed in all but eight treated women.Conclusion(s): Low-dose conjugated equine E associated with periodic administration of chlormadinone acetate elicited favorable changes in neurotransmitters and relieved psychological symptoms. [Copyright &y& Elsevier]