Estropipate

Effects of estropipate treatment on plasma lipids and lipoprotein lipid composition in postmenopausal women.[Pubmed:1991799]

J Clin Endocrinol Metab. 1991 Feb;72(2):283-6.

It is generally believed that the cardioprotective benefit of long term treatment of postmenopausal women with estrogen results in part from its capacity to increase high density lipoprotein (HDL) and lower low density lipoprotein (LDL) concentrations. The extent to which the various estrogens employed in replacement treatment affect the composition of lipoproteins, however, is not known. For this reason, we have examined the impact of one such preparation, the synthetic estrone Estropipate (1.25 mg/day), on lipoprotein levels and composition in six postmenopausal women. After 6 months of treatment, whole plasma triglyceride (pretreatment, 135 +/- 63; posttreatment, 143 +/- 56 mg/dL), cholesterol (pretreatment, 232 +/- 14; posttreatment, 216 +/- 29 mg/dL), and HDL-C (pretreatment, 57.8 +/- 14.8; posttreatment, 55.6 +/- 13.2) were unchanged. However, plasma free (unesterified) cholesterol (FC) fell (pretreatment, 73.4 +/- 6.2; posttreatment, 53.7 +/- 9.3 mg/dL; P less than 0.05) and lecithin (L) rose significantly (pretreatment, 2.12 +/- 0.29; posttreatment, 2.47 +/- 0.34 mumol/mL; P less than 0.01). The consequence of these changes was a significant decline in the plasma FC/L ratio (pretreatment, 0.91 +/- 0.17; posttreatment, 0.68 +/- 0.12; P less than 0.01) to levels observed in healthy menstruating women. The calculated lipoprotein particle size was unchanged in very low density lipoproteins and increased significantly (P less than 0.05) in LDL after Estropipate therapy. Since qualitatively altered lipoproteins enriched in FC and an increased FC/L ratio in plasma are both associated with increased coronary risk, the improvement noted in these parameters after Estropipate therapy indicates that its use may be beneficial despite the lack of change in whole plasma lipids.

Estrogen regulation of the cytochrome P450 3A subfamily in humans.[Pubmed:15282264]

J Pharmacol Exp Ther. 2004 Nov;311(2):728-35.

This study examines the possible role of estrogen in regulating the expression of the human CYP3A subfamily: CYP3A4, CYP3A5, CYP3A7, and CYP3A43. To accomplish this goal, mRNA was quantified from human livers and endometrial samples, and total CYP3A protein levels were evaluated by Western immunoblot analysis of the liver samples. The human endometrial samples were from premenopausal and postmenopausal women. The premenopausal endometrium was either in the proliferative or secretory phase, whereas for the postmenopausal endometrium samples, the women had been treated with either a placebo or Estropipate, an estrogen substitute. After analyses, CYP3A4 mRNA was shown to have lower hepatic expression in females than in males. In the endometrium, CYP3A4 and CYP3A43 are down-regulated by estrogen, whereas CYP3A5 is expressed at higher levels during the secretory phase. CYP3A7 was not detected in the endometrium. In addition, the CYP3A subfamily showed increased mRNA expression in the liver as age increased. The expression levels of total CYP3A protein and total CYP3A mRNA showed good correlation. Despite apparent regulation of CYP3A4 mRNA expression by estrogen, the effects of estrogen may be overshadowed by additional regulators of gene expression.