Premature ovarian insufficiency associated with hypertension and hemodynamic, autonomic, morphological and cardiac functional effects - hormonal replacement therapy and physical training as countermeasures

• Grant number: 24/15589-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2025
• End date: September 30, 2028
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Principal Investigator: Hugo Celso Dutra de Souza
• Grantee: Ana Catarine da Veiga Oliveira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Introduction: We know little about the ability of hormone replacement therapy (HRT) to prevent or mitigate cardiovascular autonomic imbalances and adverse adaptations in cardiac morphology and functionality, inflammatory and oxidative stress profiles after premature ovarian failure (POF), and even less about the severity of these imbalances when associated with systemic arterial hypertension (SAH). Similarly, little is known about the beneficial effects of regular physical exercise on this condition. Clinical studies conducted in our laboratory have shown that aerobic physical training in hypertensive women, before and after physiological ovarian failure or physiological menopause (PM), was effective in attenuating autonomic imbalances, more specifically, baroreflex sensitivity (BRS) and autonomic modulation of heart rate variability (HRV) and blood pressure (BPV). Our hypothesis is that hypertensive women who have had POF, even when undergoing HRT, may present cardiovascular autonomic and cardiac morphofunctional impairments that are even more severe than those observed in hypertensive women with preserved ovarian function. In this case, aerobic physical training as a countermeasure may play an important role. Objectives: 1) To investigate whether HRT for at least two years in normotensive women with POI prevents metabolic, autonomic, cardiovascular, morphofunctional and cardiac impairments, as well as impairments in the inflammatory and oxidative stress profiles; 2) to evaluate whether hypertensive women with POI who undergo HRT present more severe impairments than those observed in hypertensive women with preserved ovarian function; 3) to compare the hemodynamic, autonomic, morphofunctional and cardiac impairments, as well as in the inflammatory and oxidative stress profiles of women with POI (55-65 years) who underwent HRT up to ¿ 51 years, normotensive and hypertensive, with those of women of the same age group who also underwent PM up to ¿ 51 years; and 4) to identify and quantify the effects of aerobic physical training on the aforementioned parameters, but mainly on cardiac morpho functionality and cardiovascular autonomic control, focusing on BRS and autonomic modulation of HRV and BPV. Methods: To this end, 240 women will be distributed into two large groups: a normotensive group (N=120) and a hypertensive group (N=120). Each large group will be subdivided into four smaller groups (N=30): women between 25 and 45 years old with preserved ovarian function; women between 25 and 45 years old, but who had POI between 25 and 39 years old and have been on HRT for at least two years; women between 55 and 65 years old who had physiological menopause; and women between 55 and 65 years old who had POI between 25 and 39 years old, but undergoing HRT until ¿ 51 years old. All groups will undergo the following experimental procedures at two different times, i.e., before and after the 16-week aerobic physical training period on a motorized treadmill; anthropometric assessment; complete blood count; lipid profile; hormone levels (estrogen, progesterone, FSH, LH and anti-mullerian hormone); echocardiography; cardiopulmonary exercise test; autonomic assessment by means of analysis of BRS and HRV and BPV; serum levels of catecholamines, inflammatory markers and oxidative stress.