Background: Cardiovascular diseases (CVDs) are the leading cause of
women’s mortality, linked to aging and reduced estrogen during menopause.
Estrogen replacement therapy (ERT) is suggested for CVDs prevention. Yet, its
timing initiation remains contentious. Thus, we aimed to evaluate the effect of
early and late estrogen therapy on cardiac function and lipid metabolism in
ovariectomized old female Wistar rats. Methods: Fifty randomized female
Wistar rats were included in 5 groups (n = 10, 18 months old): (1) Sham, (2) 10
weeks post ovariectomy (Ovx-10 w), (3) 10 weeks post Ovx + early estrogen
replacement therapy (Ovx 10 w-early ERT), (4) 20 weeks post Ovx (Ovx-20 w) and
(5) Ovx 20 w-late ERT. Three days (early ERT) or 10 weeks (late ERT) after
surgery 17- estradiol was given (5 µg/kg/day), and 10 weeks
after the start of ERT, we assessed cardiac function by echocardiography,
electrocardiography, and cardiac catheterization. Estradiol, cholesterol,
triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein
(LDL) levels were determined. Cardiac histology was performed with Masson’s
staining. Results: Ovariectomy (Ovx) increases left ventricle internal
systolic diameter (0.4 vs 0.3 cm, *p = 0.020) and decreases
shortening fraction (40 vs 54 %, *p = 0.030) regardless of
therapy. ERT prevents the increase in left ventricle mass after 10 weeks post-Ovx
and the ejection fractionreduction after 20 weeks. Lower P wave amplitudes (18.8
vs 24.2 ms, *p = 0.013) were found in the Ovx-20 w group. A
longer duration of the QRS complex after 20 weeks post-Ovx with and without ERT
was found (32.5 and 32.1 vs 28.3 ms, *p = 0.003; *p =
0.007). Diastolic blood pressure was higher 20 weeks post-Ovx (86 vs 76
mmHg, *p = 0.047), regardless of ERT. The left ventricle (LV) –dP/dt
was decreased in Ovx groups without ERT (–750 vs –1320 mmHg, *p = 0.034). An increase in LV collagen deposition was found in the Ovx 10 w group
vs Sham (9.58 vs 4.54 %, *p = 0.028). Early ERT
avoids the increase in body weight, cholesterol and LDL caused by Ovx.
Conclusions: Ovariectomy causes time-dependent alterations in lipid
metabolism, morphology, electrical activity, and heart contractile function.
Early but not late ERT prevents some of these effects.