Perimenopause is the transition period to menopause, which, in turn, marks the end of the
female reproductive period. During this stage, there is a significant decrease in serum 17β estradiol (E2), leading to cognitive, behavioral, metabolic, and biochemical impacts that tend
to improve with E2 hormone replacement therapy. Thus, this study aims to enhance the
understanding of the role of E2 deprivation and replacement in the face of perimenopause in
surgically induced menopausal rats through a multimodal analysis. To accomplish this, 68 adult
Wistar rats (200 ± 20g and 8 weeks of age) underwent bilateral oophorectomy or sham surgery
and were divided into four groups: a) non castrated + vehicle (NC + V), b) castrated + vehicle
(C + V), c) castrated + fluoxetine (C + FXT), and d) castrated + 17β-estradiol (C + E2). The
experiment was divided into two stages, with treatment initiated 15 days after the surgeries and
lasting for 28 days. Vehicle animals received 200 µL/day of peanut oil; those in the FXT group
received 5 mg/kg/day of fluoxetine, and the C + E2 group received 20 µg/day of E2. At the end
of the treatment, the animals were divided into two groups, the first for electrocorticographic
(ECoG) analysis, and the second group for mass variation, food intake, biochemical, liver
morphometryc, and behavioral analyses (elevated plus-maze and splash test). In ECoG,
hormonal deprivation increased delta wave power, and only the FXT treatment reversed this
effect. Castration also induced a reduction in theta oscillations compared to the intact group,
and only FXT was able to reverse this, although E2 promoted improvement. Hormonal
deprivation led to a decrease in alpha wave firing, which was not reversed by the treatments.
Regarding mass variation, at the end of the experiment, hormonal replacement resulted in less
weight gain compared to the other groups, even without a decrease in food intake. Furthermore,
E2 replacement increased the lipid profile (except for HDL) and the hepatic index compared to
the other groups. In terms of behavior, only grooming time was different, with hormonally
deprived animals spending less time grooming than intact ones, and no treatment had an effect
on this parameter. In this regard, we suggest that oophorectomy was effective in inducing
behavior similar to apathy, possibly linked to cognitive changes, and that treatments with FXT
and E2 showed promise in ECoG evaluation but not in behavior modulation. Furthermore, we
propose further studies to elucidate the changes caused by E2 hormone replacement therapy in
biochemistry and hepatic morphometric evaluation, as well as a more targeted assessment of
animal cognition.
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