Key result
Early but not late estrogen replacement attenuates ischemic events and LDL increases in aged rats.
Why the study?
Estrogen replacement therapy is suggested for CVD prevention, yet the timing of its initiation remains contentious.
Does early versus late estrogen replacement therapy improve cardiac function and lipid metabolism in ovariectomized aged female Wistar rats?
RCT (n=50)
Randomized into 5 groups
No
Does early versus late estrogen replacement therapy improve cardiac function and lipid metabolism in ovariectomized aged female Wistar rats?
Absolute Event Rate: 0.4% vs 0.3%
p-value: p=0.020
In an aged rat model of ovariectomy, early but not late initiation of estrogen replacement therapy prevented adverse cardiac remodeling, contractile dysfunction, and lipid alterations.
Should not change clinical estrogen timing; hypothesis-generating for menopause models in humans.
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-β 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.
No takes yet. Share an insight, caveat, or question.
Ramírez‐Hernández et al. (2024) conducted an RCT in Ovariectomy-induced cardiac dysfunction and dyslipidemia (n=50). 17-β estradiol vs. Sham and ovariectomy without therapy was evaluated on Left ventricle internal systolic diameter (p=0.020). Early, but not late, estrogen replacement therapy prevented ovariectomy-induced increases in cholesterol, LDL, and collagen deposition, and attenuated ischemic events in aged female rats.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: