Publications

Nontoxic naturally occurring metabolite of estrogen namely 2-methoxyestradial (2ME2) found in serum and urine has been shown to be antitumorigenic in various tumor models including the prostate. A recent study conducted in breast cancer cells showed growth stimulatory effect of 2ME2 when used at low concentrations (10-750 nM). Studies from our laboratory has demonstrated prostate tumor preventive ability of 50 mg/kg 2-ME2. In this study we show that concentrations of 2-ME2 as low as 1 µM is sufficient to inhibit proliferation and induce apoptosis in androgen responsive LNCaP cells. In addition oral administration of doses lower than 50 mg/kg prevented prostate tumor development in LNCaP xenograft model. The observed tumor growth inhibition was associated with induction of apoptosis, increased expression of Wee1 kinase and p34cdc2. In addition administration of 25 mg/kg 2-ME2 prevented tumor development significantly that is associated with reduction in serum PSA levels.

INTRODUCTION

Erectile dysfunction (ED) and cardiovascular disease (CVD) share pathophysiological mechanisms and often co-occur. Yet it is not known whether ED provides an early warning for increased CVD or other causes of mortality.

AIM

We sought to examine the association of ED with all-cause and cause-specific mortality.

METHODS

Prospective population-based study of 1,709 men (of 3,258 eligible) aged 40-70 years. ED was measured by self-report. Subjects were followed for a mean of 15 years. Hazard ratios (HR) were calculated using the Cox proportional hazards regression model.

MAIN OUTCOME MEASURES

Mortality due to all causes, CVD, malignant neoplasms, and other causes.

RESULTS

Of 1,709 men, 1,284 survived to the end of 2004 and had complete ED and age data. Of 403 men who died, 371 had complete data. After adjustment for age, body mass index, alcohol consumption, physical activity, cigarette smoking, self-assessed health, and self-reported heart disease, hypertension, and diabetes, ED was associated with HRs of 1.26 (95% confidence interval [CI] 1.01-1.57) for all-cause mortality, and 1.43 (95% CI 1.00-2.05) for CVD mortality. The HR for CVD mortality associated with ED is of comparable magnitude to HRs of some conventional CVD risk factors.

CONCLUSIONS

These findings demonstrate that ED is significantly associated with increased all-cause mortality, primarily through its association with CVD mortality.