Serum estrogen levels and prostate cancer risk in the prostate cancer prevention trial: a nested case–control study

OBJECTIVE: Finasteride reduces prostate cancer risk by blocking the conversion of testosterone to dihydrotestosterone. However, whether finasteride affects estrogens levels or change in estrogens affects prostate cancer risk is unknown. METHODS: These questions were investigated in a case-control study nested within the prostate cancer prevention trial (PCPT) with 1,798 biopsy-proven prostate cancer cases and 1,798 matched controls. RESULTS: Among men on placebo, no relationship of serum estrogens with risk of prostate cancer was found. Among those on finasteride, those in the highest quartile of baseline estrogen levels had a moderately increased risk of Gleason score < 7 prostate cancer (for estrone, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.06-2.15; for estradiol, OR = 1.50, 95% CI = 1.03-2.18). Finasteride treatment increased serum estrogen concentrations; however, these changes were not associated with prostate cancer risk. CONCLUSION: Our findings confirm those from previous studies that there are no associations of serum estrogen with prostate cancer risk in untreated men. In addition, finasteride results in a modest increase in serum estrogen levels, which are not related to prostate cancer risk. Whether finasteride is less effective in men with high serum estrogens, or finasteride interacts with estrogen to increase cancer risk, is uncertain and warrants further investigation

Time trends in municipal distribution patterns of cancer mortality in Spain

BACKGROUND: New disease mapping techniques widely used in small-area studies enable disease distribution patterns to be identified and have become extremely popular in the field of public health. This paper reports on trends in the geographical mortality patterns of the most frequent cancers in Spain, over a period of 20 years. METHODS: We studied the municipal spatial pattern of stomach, colorectal, lung, breast, prostate and urinary bladder cancer mortality in Spain across four quinquennia, spanning the period 1989-2008. Case data were broken down by town (8073 municipalities), period and sex. Expected cases for each town were calculated using reference rates for each five-year period. For map plotting purposes, smoothed municipal relative risks were calculated using the conditional autoregressive model proposed by Besag, York and Mollié, with independent data for each quinquennium. We evaluated the presence of spatial patterns in maps on the basis of models, calculating the variance in relative risk corresponding to the structured spatial component and the unstructured component, as well as the proportion of variance explained by the structured spatial component. RESULTS: The mortality patterns observed for stomach, colorectal and lung cancer were maintained over the 20 years covered by the study. Prostate cancer and the tumours studied in women showed no defined spatial pattern, with the single exception of stomach cancer. The trend in spatial fractional variance indicated the possibility of a change in the spatial pattern in breast, bladder and colorectal cancer in women during the last five-year period. The paper goes on to discuss ways in which spatio-temporal data are depicted in the case of cancer, and review the risk factors that may possibly influence the respective tumours’ spatial patterns. CONCLUSION: In men, the marked geographical patterns of stomach, colorectal, lung and bladder cancer remained stable over time. Breast, colorectal and bladder cancer in women show signs of the possible appearance of a spatial pattern in Spain and should therefore be monitored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2407-14-535) contains supplementary material, which is available to authorized users

20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol, a novel natural product for prostate cancer therapy: activity in vitro and in vivo and mechanisms of action

We recently isolated 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH3-PPD), a natural product from Panax notoginseng, and demonstrated its cytotoxicity against a variety of cancer cells. Here we report the effects of this compound in vitro and in vivo on human prostate cancer cells, LNCaP (androgen-dependent) and PC3 (androgen-independent), in comparison with three structurally related ginsenosides, ginsenoside Rh2, ginsenoside Rg3, and 20(S)-protopanaxadiol. Of the four test compounds, 25-OCH3-PPD was most potent. It decreased survival, inhibited proliferation, induced apoptosis, and led to G1 cell cycle arrest in both cell lines. It also decreased the levels of proteins associated with cell proliferation (MDM2, E2F1, cyclin D1, and cdks 2 and 4) and increased or activated pro-apoptotic proteins (cleaved PARP, cleaved caspase-3, -8, and -9). In LNCaP cells, 25-OCH3-PPD inhibited the expression of the androgen receptor and prostate-specific antigen. Moreover, 25-OCH3-PPD inhibited the growth of prostate cancer xenograft tumours. Combining 25-OCH3-PPD with conventional chemotherapeutic agents or with radiation led to potent antitumour effects; tumour regression was almost complete following administration of 25-OCH3-PPD and either taxotere or gemcitabine. 25-OCH3-PPD also demonstrated low toxicity to noncancer cells and no observable toxicity in animals. In conclusion, our preclinical data indicate that 25-OCH3-PPD is a potential therapeutic agent against both androgen-dependent and androgen-independent prostate cancer

A systematic review of dietary, nutritional, and physical activity interventions for the prevention of prostate cancer progression and mortality

PURPOSE: Given the long-term, although potentially fatal, nature of prostate cancer, there is increasing observational evidence for the reduction in disease progression and mortality through changes in lifestyle factors. METHODS: We systematically reviewed dietary, nutritional, and physical activity randomized interventions aimed at modifying prostate cancer progression and disease-specific mortality, including a detailed assessment of risk of bias and methodological quality. RESULTS: Forty-four randomized controlled trials of lifestyle interventions, with prostate cancer progression or mortality outcomes, were identified. Substantial heterogeneity of the data prevented a meta-analysis. The included trials involved 3,418 prostate cancer patients, median 64 men per trial, from 13 countries. A trial of a nutritional supplement of pomegranate seed, green tea, broccoli, and turmeric; a trial comparing flaxseed, low-fat diet, flaxseed, and low-fat diet versus usual diet; and a trial supplementing soy, lycopene, selenium, and coenzyme Q10, all demonstrated beneficial effects. These trials were also assessed as having low risk of bias and high methodological quality (as were seven other trials with no evidence of benefit). The remaining trials were either underpowered, at high or unclear risk of bias, inadequately reported, of short duration or measured surrogate outcomes of unproven relationship to mortality or disease progression, which precluded any benefits reported being reliable. CONCLUSION: Large, well-designed randomized trials with clinical endpoints are recommended for lifestyle modification interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10552-015-0659-4) contains supplementary material, which is available to authorized users

Declines in sexual activity and function predict incident health problems in older adults: prospective findings from the English Longitudinal Study of Ageing

The objective of this study was to investigate cross-sectional and longitudinal associations between declines in sexual activity and function and health outcomes in a large population-based sample of older adults. Data were from 2577 men and 3195 women aged ≥ 50 years participating in the English Longitudinal Study of Ageing. Past-year changes in sexual desire, frequency of sexual activity, and ability to have an erection (men)/become sexually aroused (women) were assessed at baseline by self-completion questionnaire. Health outcomes (self-rated health, limiting long-standing illness, doctor-diagnosed diseases of the vascular system, and cancer) were self-reported at baseline (2012/2013) and 4-year follow-up (2016/2017). Data were analyzed using logistic regression, adjusted for sociodemographics, health behaviors, and depressive symptoms. Prospectively, men who reported a decline in sexual desire had higher odds of incident limiting long-standing illness (OR 1.41, 95% CI 1.04–1.91) and incident cancer (OR 1.63, 95% CI 1.06–2.50) than those who maintained their sexual desire. Men who reported a decline in the frequency of sexual activities had higher odds of deterioration in self-rated health (OR 1.47, 95% CI 1.04–2.08) and incident limiting long-standing illness (OR 1.69, 95% CI 1.20–2.37). In women, a decline in frequency of sexual activities was associated with deterioration of self-rated health (OR 1.64, 95% CI 1.07–2.51). Erectile dysfunction was longitudinally associated with poorer health outcomes including incident cancer (OR 1.73, 95% CI 1.11–2.70), coronary heart disease (OR 2.29, 95% CI 1.29–4.07), and fair/poor self-rated health (OR 1.66, 95% CI 1.19–2.32). Practitioners should be mindful that a decline in sexual activity, desire, or function in older age may be an important indicator of future adverse health outcomes