Clinical Briefs-By Louis Kuritzky, MD
Clinical Briefs-By Louis Kuritzky, MD
Estrogen Replacement Therapy and Ovarian Cancer Mortality in U.S. Women
The preponderance of epidemiologic data associates both endometrial and breast cancer with postmenopausal estrogen replacement therapy (ERT). The relationship of ovarian cancer to ERT is less clear. Recent case-control studies have suggested an increased risk with ERT, especially of long duration. Rodriguez and colleagues investigated the association between ERT and ovarian cancer mortality in a large population of female participants in the Cancer Prevention Study II (n = 676,526). Data were accrued over 14 years of observation, and include almost 1000 ovarian cancer deaths.
Even users of ERT had a slightly increased rate of ovarian cancer mortality (rate ratio = 1.23). This positive association increased in strength with duration of ERT use, so that persons using ERT for more than 10 years had an approximately 2-fold increase in relative risk. When coupled with the earlier case-control studies, this current report strengthens the concerns that ERT, especially of long duration, increases the risk of ovarian cancer mortality. Nonetheless, since total lifetime risk of ovarian cancer mortality is relatively small (< 2%), other potential favorable effects of ERT in other tissue compartments must be taken into account in the risk-benefit analysis. Additionally, the effect of concomitant progestational treatment has not been comprehensively addressed.
Rodriguez C, et al. JAMA. 2001;285: 1460-1465.
Effects of A Low-Molecular Weight Heparin on Thrombus Regression and Recurrent Thromboembolism in Patients with Deep-Vein Thrombosis
Low molecular weight heparin (LMWH) has been found to be as useful as traditional unfractionated heparin (HEP) for early management of deep vein thrombosis (DVT) or pulmonary embolism (PE), but offers the advantage that monitoring activated partial thromboplastin. (APPT) is not necessary. Meta-analysis of earlier trials has suggested that LMWH affords a greater likelihood of thrombus regression, as well as a reduced rate of clinical recurrence. The current trial (n = 1137) was developed to explore the relative efficacy of LMWH and HEP in reference to thromboembolic recurrence and thrombus regression, assessed by venography.
LMWH, whether administered once or twice daily, demonstrated statistically significantly greater likelihood of thrombus regression (relative likelihood = 1.3 compared to HEP). LMWH was also significantly less likely to be associated with recurrent thromboembolic events.
Breddin and colleagues conclude that LMWH is more effective than unfractionated heparin in reduction of thrombus size, recurrent DVT, and new pulmonary embolism.
Breddin HK, et al. N Engl J Med. 2001;344:626-631.
Effects of Vitamin E on Lipid Peroxidation in Healthy Persons
There is much debate about the perceived potential benefit of antioxidant therapies, including vitamin E, upon cardiovascular, oncologic, and neurologic end points. Oxidized LDL has been particularly associated with progressive atherosclerotic vascular damage. It has been postulated that vitamin E might reduce the ability of lipids to become oxidized, yet a model for quantification of such an oxidation protective effect has been lacking until recently. Meagher and colleagues used 2 newly developed quantitative markers of lipid peroxidation status: isoprostanes and 4-hydroxynonenenal (4-HNE). Subjects received doses of vitamin E ranging from 200-2000 IU daily for 8 weeks (n = 30).
Irrespective of dose used, there was no demonstrable effect of vitamin E supplementation on markers of lipid peroxidation. Recent large data sets, such as the HOPE trial, also failed to demonstrate a beneficial effect of vitamin E supplementation on cardiovascular end points. Meagher et al question the potential benefit of supplemental vitamin E consumption.
Meagher EA, et al. JAMA. 2001;285: 1178-1182.
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