After the heart and estrogen/progestin replacement study and the women's health initiative study, the prospect of hormone replacement therapy (HRT) on cardiovascular diseases (CVD) has changed dramatically. These findings led to various attempts to search for alternatives for classical HRT, e.g. phytoestrogens. The flavanone 8-prenylnaringenin (8-PN) was identified as a phytoestrogen with strong estrogen receptor-α activity. As the pituitary and the liver are targets for estrogen action, we assessed the effect of ovariectomy (OVX) and long-term treatment (3 months) with 17-β estradiol benzoate (E₂B) and 8-PN on pituitary and liver functions in adult OVX rats. Tested doses were 6.8 and 68.4 mg/kg body weight (BW) of 8-PN and 0.17 and 0.7 mg/kg BW of E₂B. Our results demonstrate that 8-PN and E₂B decreased BW and increased uterus weight. The high doses of E₂B and 8-PN increased serum GH and decreased serum IGF-1 levels. E₂B dose dependently decreased cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) concentrations in OVX rats. The high dose of 8-PN showed an estrogenic activity regarding cholesterol and LDL regulation but had no effect on HDL concentrations. By contrast, the low dose of 8-PN augmented HDL levels compared with intact rats. Triglyceride levels were raised in response to the high E₂B dose but unaffected by 8-PN treatment. Taken together, 8-PN displays an anti-atherosclerotic profile that appears to be even more beneficial than the one displayed by E₂B, and thus might demonstrate a remarkable potential for the prevention of CVD associated with estrogen deficiency.

Hormone replacement therapy (HRT) has been used for several decades to treat menopausal discomforts. However, in the light of recent studies that draw attention to the potential hazards of conventional HRT, various attempts have been undertaken to search for alternatives to classical HRT. Phytoestrogens are claimed to be capable of positively influencing menopausal symptoms, including hot flushes. We designed a long-term study of 3 months to assess the effects of subcutaneous and orally fed 17β-estradiol (E2), as well as the actions of resveratrol (RES) on pituitary function in female rats. Our results have demonstrated that RES binds with a 10-fold lower affinity to estrogen receptor (ER)-α than to ERβ. The data from the in vivo study revealed that a dosage of 5 μg and 50 μg RES/kg bodyweight per day given to ovariectomized (OVX) rats achieved serum levels of 1.0 and 8.1 μM respectively. Long-term treatment of OVX rats with RES revealed no estrogenic potential on pituitary function in vivo as assessed by LH and prolactin secretion and by regulation of mRNAs for LHα, LHβ, and GnRH receptor. Subcutaneous treatment with E2 in silastic capsules exerted stronger effects on LH and prolactin secretion, as well as on LHβ, LHα, GnRH receptor, and ERβ mRNA regulation compared with orally applied estradiol benzoate despite comparable serum levels. Levels of aryl hydrocarbon receptor (AhR) mRNA in the pituitary were increased following OVX and attenuated by long-term E2 treatment, whereas RES did not modulate AhR mRNA expression.