OBJECTIVE: Estrogen supplementation is considered a reliable therapeutic 
approach to symptoms of vasomotor dysregulation (hot flashes) associated with 
the menopausal transition and sex hormone deprivation. Implication of changes in 
central neurotransmission in the pathogenesis of hot flashes has prompted the 
off-label use of serotonergic and γ-aminobutyric acid-ergic drugs as a 
therapeutic alternative, claiming similarity of outcomes to those of estrogen 
treatment.
METHODS: Using telemetric recordings in a rat model of estrogen deficit-induced 
vasomotor dysregulation, we compared the long- and short-term effects of 
estrogen supplementation and treatment with neuropharmaceuticals (venlafaxine, 
desvenlafaxine, fluoxetine, agomelatine, gabapentin) on endpoints of 
thermoregulation.
RESULTS: Among the tested drugs, only fluoxetine was capable to emulate the 
restorative action of estradiol on the diurnal oscillations in skin temperature 
and control of heat dissipation. Unlike estradiol, several of the tested 
compounds produced marked transient decreases in skin temperature within the 
first 2 hours of application while being unable to restore physiological diurnal 
patterns of thermoregulation.
CONCLUSIONS: Our findings suggest that in this animal model of impaired 
thermoregulation, neuropharmaceuticals may simulate therapeutic effects by 
eliciting immediate but transient hypothermia, which is not associated with the 
recovery of physiological control of heat dissipation. Therefore, short-term 
monitoring of drug actions in this disease model may considerably bias readouts 
of drug discovery for menopausal vasomotor symptoms.