| Resumo: | The reproductive aging process in females consists in three major phases: the premenopause corresponding to the reproductive years, the perimenopause that consists in the transition to the final phase, the postmenopause that begins at menopause diagnosis. Postmenopause is known for both its distinctive hormonal and metabolic changes, primarily the well-known estrogen loss. This change triggers the loss of the protective effects that estrogen confers to women and raises the risk for the development of diseases, specifically, cardiovascular diseases by lipid profile alterations. This status has been mainly studied through assessments of differences between premenopause and postmenopause. However, it is reported that most of these changes occur earlier, especially during late perimenopause. For this reason, studies between perimenopause and postmenopause are of interest to better assess this transition. HIV infection results in the loss of cell-mediated immunity, which favors the acquisition of opportunistic infections that will irremediably cause the death of the patient. It is reported that over 32 million people have died due to HIV and approximately 37.9 million currently live with HIV-infection. However, thanks to the development and introduction of antiretroviral therapies (ART), which have shown to be effective on the control of the virus and the prevention of transmission to other individuals, HIV-infected patients experienced a great increase in both their quality of life and their life expectancy. Compared to the late 1990’s and early 2000’s, HIV-infected patients can now live over 50 years old and approach the same life expectancy as non-HIV individuals. However, HIV-infected patients now face new threats. HIV-infection, chronic inflammation and ART increases the risk of metabolic, cardiometabolic, neurocognitive and bone diseases due to their potential adverse effects. So, HIV-infected women adherent to antiretroviral therapy, have an increased life expectancy, which means that they are able to live long enough to reach menopause. This way, and additionally to their HIV and ART-inherent risk of disease, these women are now also susceptible to menopause-driven age-related diseases. In this study, we assessed the urinary metabolic profile of 74 HIV-infected women with similar chronological ages and close to the menopause (from 45 to 49 years old). The menopausal status of these women was defined according to their Antimüllerian hormone (AMH) levels (postmenopause and three consecutive groups of perimenopause, from closest to furthest from menopause onset). A non-targeted liquid chromatography and mass spectrometry-based metabolomics approach was conducted to assess the impact of the menopausal status on the metabolic profile. No metabolic differences were found between the postmenopause and the group of women furthest from menopause. However, metabolic differences between the furthest and closest groups from menopause were identified. These results prove that the most relevant metabolic changes can happen in late perimenopause. However, the metabolites responsible for the observed differences could not be identified and thus, further studies are required to corroborate these results. |