The effect of estradiol and selective estrogen receptor modulators on lipid profile in the ovariectomized rat model

Menopause can increase the risk of cardiovascular diseases, diabetes mellitus, and metabolic syndrome, principally due to estrogen deficiency. In the current experiment, protective effects of selective estrogen receptor modulators (SERMs) and estradiol (E2), alone and combined, were evaluated in a rat model of menopause.

Forty-eight female Wistar rats underwent ovariectomy to induce a menopause model. Then, the animals were subjected to receive SERMs including tamoxifen (TAM), raloxifene (RAL), and bazedoxifene (BZA) and E2. Finally, serum and liver tissue samples were collected post-treatment for experimental analysis.

The induction of menopause by ovariectomy reduced the body weight of animals and altered their food intake. TAM, RAL, ethinyl E2 (EE2), and BZA/conjugated estrogens (BZA/CE) improved the ovariectomy-induced elevation of total cholesterol and low-density lipoprotein (LDL) cholesterol significantly. In this regard, the lowering effects of SERMs were significantly greater than EE2. The increased levels of triglycerides were also alleviated by RAL, EE2, and BZA/CE but not TAM. Moreover, the combination of SERMs, especially BZA/CE therapy, had significantly increasing effects on high-density lipoprotein (HDL) cholesterol levels, in a more effective manner than E2 therapy alone. Low-density lipoprotein receptor gene and protein expression levels were also significantly increased by SERMs. The HDL2 subfraction was found to be significantly enhanced in TAM, RAL, and BZA/CE therapy.

The therapy with SERMs, alone or in combination with E2, may be efficiently utilized instead of E2 replacement therapy in post-menopausal conditions.