Do we need clinical trials to test the ability of transdermal HRT to prevent coronary heart disease?

Abstract

CHD = coronary heart disease; CRP = C-reactive protein; HDL = high-density lipoprotein; HRT = hormone replacement therapy; PAI = plasminogen activator inhibitor.Available online http://cvm.controlled-trials.com/content/2/5/211The claim that postmenopausal hormone replacement therapy (HRT) reduces coronary heart disease (CHD) risk by 50% has until recently been a mantra in female health care and, to a lesser extent, in preventive cardiology [1]. This belief originated in the 1960s and is based on the logic that if the menopause causes CHD (a dubious proposal at best) then oestrogen replacement should prevent the disease. Plasma lipoprotein levels were an aspect of metabolism that was at the core of cardiovascular research at that time, and the changes in response to oestrogen were encouraging [2].A low incidence of CHD was subsequently shown in observational (nonrandomized) studies of HRT users [3]. This association was strengthened by the antiatherosclerotic effect of oestrogen demonstrated in fat-fed animals [4], which was consistent with the identification of this steroid as a powerful vasoactive agent.Administration of HRT through skin patches has become a common treatment option in postmenopausal women [5], resonating with the late 20th century distrust of 'pills'. By providing relatively stable blood hormone levels, it was expected to reduce side effects and improve compliance. The major disadvantages, aside from cost, are that patches may fall off or induce skin reactions. These problems have been minimized by advances such as 'matrix' patches that incorporate the steroid in the adhesive layer of the patch. Transdermal HRT is as effective as oral HRT in relieving climacteric symptoms, such as hot flushes, and has comparable effects on bone metabolism and bone density. Some women prefer patches and others prefer pills, and with such a complex and multisystem condition as the menopause it was always unlikely that any one therapy would emerge as a clear favourite.Transdermal and oral HRT differ in their impact on some CHD risk factors (Table 1). The long-standing view that oral HRT prevents CHD has been strongly challenged by recent randomized controlled trials [6]. Whereas a few years ago the question of interest was whether transdermal HRT could match the cardiovascular benefits of oral HRT, we have now entered a new phase in which the transdermal route might even be preferable. AbstractPostmenopausal hormone replacement therapy (HRT) with oral oestrogen was predicted to reduce coronary heart disease (CHD) risk by 50%. Randomized controlled trials show no such benefit, however, pointing instead to an initial increase in CHD events. Although the cardiovascular effects of transdermal HRT are largely unknown, improvements in arterial function are maintained when oestrogen is administered transdermally. Transdermal HRT also avoids the increased plasma levels of C-reactive protein (CRP) that are seen with oral HRT. However, the clinical significance of this general reduction in hepatic over-synthesis of plasma ...

Pharmacodynamic Evaluation of Oral Estradiol Nanoparticles in Estrogen Deficient (Ovariectomized) High-Fat Diet Induced Hyperlipidemic Rat Model

“…This high dose leads to increased hepatic synthesis of many proteins such as apolipoprotein A-1 (major component of HDL-C) and therefore, increases plasma levels of HDLs. However, this overdosing also leads to severe metabolic changes such as triglyceridemia (18,21) and this could be the reason that ES treatment did not make any difference in plasma TG levels, while nanoparticulate formulation significantly (p<0.001) decreased them (Fig. 2B).…”

“…Oral route is usually favoured because apart from the patient compliance, it also provides profound beneficial effect in increasing the HDL, a change that is often considered pivotal to have cardiovascular benefit (10,18). However, oral formulations of estradiol have poor systemic bioavailability because of hepatic first pass metabolism, which requires high doses to attain the required therapeutic levels.…”