Effects of sequential combined transdermal and oral hormone replacement therapies on serum lipid and lipoproteins in postmenopausal women

Abstract

The aim of this study was to compare the effects of sequential combined transdermal and oral postmenopausal hormone replacement therapies on serum lipid-lipoprotein profiles risk markers for cardiovascular disease. A prospective randomize study was designed: Ninety-six healthy nonhysterectomised postmenopausal women were randomized to receive either transdermal continuous 17beta-estradiol, 0.05 mg/d (Estraderm TTS, Novartis, Basel, Switzerland), with transdermal sequential norethisterone acetate, 0.25 mg/d (Estragest TTS, Novartis, Basel, Switzerland), or oral continuous conjugated equine estrogens, 0.625 mg/d (Premarin 0.625 mg, Wyeth, Philadelphia, U.S.A.), with oral sequential medroxyprogesterone acetate, 10 mg/d (Farlutal 5 mg, Deva, Istanbul, Turkey). 84 women completed the trial, 42 in oral and 42 in the transdermal group. The serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoproteins AI and apolipoproteins B at 6 months after starting treatment were compared with baseline values for both therapies. Both oral and transdermal therapies significantly reduced serum levels of total cholesterol (208-190 mg/dL and 216-199 mg/dL, respectively, p=0.0001) and LDL-cholesterol (128-112 mg/dL and 140-127 mg/dL, respectively, p=0.001). The serum levels of triglycerides did not show any significant change with oral therapy, whereas this lipid fell (128-101 mg/dL, p=0.0001) significantly with transdermal therapy. We found significant decrease in HDL-cholesterol with transdermal therapy while there was no significant change with oral therapy. Apolipoproteins AI, the major protein component of HDL2 subfraction, was increased by oral therapy and lowered by transdermal therapy. As a conclusion, we have found that serum total cholesterol and LDL-cholesterol were lowered by both therapies, with no significant differences between treatments, whereas there were significant differences between treatments according to effects on serum triglycerides and apolipoproteins AI.

Effects of Intranasal Estradiol Treatment on Serum Paraoxonase and Lipids in Healthy, Postmenopausal Women

“…An improvement in lipid profi le has been indicated in most of the studies that deal with the effect of HT on lipid metabolism [11,[30][31][32] . There are different effects of HT on lipid-lipoprotein profi les due to routes of administration.…”

“…There are different effects of HT on lipid-lipoprotein profi les due to routes of administration. Although transdermal estrogen decreases TG levels by avoiding the hepatic fi rst-pass effect [33] , the oral route had a more favorable effect on lipid metabolism than the transdermal route, except TGs [11,34,35] . In this current cross-sectional study, a signifi cantly higher HDL level was observed in intranasal 17 ␤ -estradiol (300 g/day) users with regard to women not on HT.…”

“…It has been shown that postmenopausal hormone therapy (HT) improves lipid-lipoprotein profi les [11,12] . There are several ways of estrogen use in clinical practice: transdermal, subcutaneous, oral and intranasal 17 ␤ -estradiol that is a relatively novel application form.…”

The Short-Term Effects of Different Regimens of Hormone Replacement Therapy on Left Ventricular Structure and Performance in Healthy Postmenopausal Women

“…As aforementioned in the Introduction, estrogen receptors have been shown throughout the cardiovascular system including the myocardium [1][2][3][4], and also estrogen has a reducing constrictor effect on the vascular endothelium and improves endothelium-dependent vasodilation in both the peripheral and coronary vasculatures [5][6][7][8][9][10]. The cardioprotective effects of estrogen may not only depend on its beneficial effects on lipoprotein levels, which were well documented [17,24,25], and atherosclerosis, which was induced by estrogen deficiency [26][27][28][29], but also its effects on other aspects of the cardiovascular system. Nevertheless, many questions remain about risk and benefits of estrogen/progestin use in postmenopausal women.…”

Does 2-Methoxyestradiol Represent the New and Improved Hormone Replacement Therapy for Atherosclerosis?

“…Initiation of the atherogenic response is promoted by hypercholesterolemia because chronic high levels of cholesterol in the bloodstream lead to prolonged retention of low-density lipoproteins in the subendothelial space. 4,5 The renin-angiotensin system (RAS) modulates several components of atherosclerotic process, including inflammation, oxidative stress, and hypertrophy of the vascular wall, 6 and estrogen modulates most of, if not all, the components of the RAS cascade, including the synthesis of angiotensin II (Ang II), the key mediator of the RAS, and the 2 receptor subtypes (AT 1 and AT 2 ) that mediate Ang II action. Both animal 7 and clinical studies 8 demonstrate that estrogen inhibits angiotensin-converting enzyme activity, resulting in decreased levels of Ang II in the circulation and in specific tissues, including the aorta.…”