Menopause is an event resulting from the natural aging of the female organism, in which there is ovarian failure that, consequently, leads to hypoestrogenism. With the gradual decrease of estrogen (E2) levels, women become more susceptible to developing low-grade chronic inflammation. Low levels of E2 reduce the expression of genes that affect the balance between energy expenditure and consumption, in addition to negatively affecting carbohydrate and lipid metabolism. On the other hand, E2 has the ability to induce the expression of the HSP72 protein, one of the members of the 70 kDa family of heat shock proteins, which are anti-inflammatory and cytoprotective, and whose expression is modulated by different types of physiologically stressful situations, including heat stress. Therefore, during perimenopause, various homeostatic functions based on E2-dependent expression of HSP70 may collapse. In this study, we investigated the effects of aging in female mice, focusing on E2-mediated nitric oxide (NO)-induced heat shock response (HSR). We used female mice of the C57BL/6J strain: young (4 months) and aged (16 months) adult animals, being submitted to the following treatments: HS (heat shock treatment for 2 months once a week = 8 sessions with anesthesia) or SHAM (animals kept at room temperature and anesthetized only). We observed that, with regard to the muscular HSP70 content in the gastrocnemius muscle of adult and naturally aged females, there was a 59 % increase in the HS group as compared to the SHAM group in adult females; in the group of aged females, there was a 77 % increase in the HS group compared to the SHAM group (p=0.0341). Still with regard to HSP70 expression, we found a marked difference (p=0.0047) between the different ages of the animals that received the HS, indicating a more accentuated increase in the muscular concentrations of this protein in the aged females. As an effect of HS, we also observed an increase in 17β-Estradiol concentrations compared to the SHAM group (p=0.0467), being 83 % in the HS group (4 months) and 80 % in the HS group (16 months). In total, the results suggest a potential use of HS therapy as an alternative to hormone replacement therapy (HRT), especially its long-term safety has already been questioned. In addition, there are possible protective effects that are being re-established by the HSR pathway, until then suppressed due to the effects of aging/natural menopause of female metabolism, which reduces the metabolic capacity, among other effects, to maintain the hormonal status necessary for cytoprotective levels known.