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18 ve studies, increased in two, and unchanged in 12 LDL levels were unchanged or reduced in 14 of the 15 studies in which they were measured Thus, the limited information available would suggest a neutral effect of T therapy on lipid pro les A doubleblind, placebo-controlled study involving 108 healthy men receiving transdermal T failed to show any signi cant difference between groups in serum levels of lipids and apolipoprotein during 36 months of treatment [197] In a 24-week, multicenter, randomized, parallel-group study, Dobs et al [198] compared transdermal and intramuscular administration of androgens in 58 men and did not detect any signi cant difference in HDL levels or in the ratio of total cholesterol to HDL in either group, regardless of the mode of therapy We have already cited on p 234 the results of the meta-analysis by Isidori et al [88], which concluded there was a signi cant decrease of serum total cholesterol on T therapy in aging men, whatever the T level, while no signi cant effect could be demonstrated on LDL cholesterol, and a signi cant decrease in HDL cholesterol was observed only in the aging men with baseline serum T >10 nmol/L Thus, the present data, taken together, suggest that T therapy within the physiologic range is not associated with signi cant worsening of the lipid pro le

87 Ibid 88 Wayne Freedman, Pollution in China Could Impact Our Air, KGO-TV, November 7, 2007, http://abclocalgocom/ kgo/story section=news/environment&id=5747398 89 Michelle L Bell et al, Global Impacts of Particulate Matter Air Pollution, Environmental Research Letters (2007): 2, http://www ioporg/EJ/abstract/1748-9326/2/4/045026 90 Keith Bradsher and David Barboza, Pollution from Chinese Coal Casts a Global Shadow, New York Times, June 11, 2006 91 Ibid 92 Ibid 93 Scott Barrett, Barrett Proposal: A Multitrack Climate Treaty System, Belfer Center for Science and International Affairs, September 5, 2007, http://belfercenterksgharvardedu/experts/ 1294/scott_barretthtml 94 Steve Gelsi, Bush Calls For Halt in Greenhouse Gas Growth by 2025, MarketWatch, April 16, 2008, http://wwwmarketwatchcom/news/story/bush-calls-halt-greenhouse-gas-growth/ stor yaspx guid=%7B4E95F81E - 4F34 - 4AE9 - 80A7 - 723 DB5FE9B80%7D&dist=msr_3 95 The Search for Clean Coal, Globe-Net, May 28, 2008, http:// wwwclimatebizcom/feature/2008/05/28/the - search - clean coal page=0%2C2 96 Coal Mining, in The Coal Resource: A Comprehensive Overview of Coal (London: World Coal Institute, 2005) 97 Search for Clean Coal 98 Mobile Sources, Environmental Protection Agency, http://www epagov/oms/invntory/overview/pollutants/indexhtm 99 For example, varied discount rates applied to the costs of global warming for 100 years can generate widely different cost scenarios 100 Gas Prices Dominate the Public s Economic News Agenda, News Interest Index, Pew Research Center for the People & the Press, June 19, 2008, http://people-pressorg/report/431/ gas-prices-public-agenda 101 State of the World 2008: Innovations for a Sustainable Economy, Worldwatch Institute, http://wwwworldwatchorg/ stateoftheworld

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digital rectal examination (DRE) should promote the early diagnosis, and thus potential cure, of most unmasked prostate cancers identi ed during T therapy Certainly, all men presenting for possible T therapy who are found to have an abnormal PSA level or abnormal DRE should rst undergo prostate biopsy, and there should also be a low threshold for biopsy if the PSA level rises substantially or if there is a change on DRE, such as the development of a nodule, asymmetry, or areas of increased rmness Although a history of prostate cancer has been considered an absolute contraindication to T therapy, this point is now under active debate for men who are deemed cured In follow-up studies of tens of thousands of men it appears that the risk of having prostate cancer is also high in the PSA range of 2 4 ng/mL, which implies that the commonly accepted cut-off value of PSA of 4 ng/mL as safe may not be valid [192] Meanwhile the majority of the prostate cancer experts agree that, rather than the absolute value of PSA, its velocity during the observational period is of importance, and that an increase of PSA of more than 05 ng/mL/year over two following years is an indication for a prostate biopsy and withdrawal from Treplacement therapy [193] The present recommendations are as follows: biopsy is recommended if the PSA velocity exceeds 02 05 ng/mL/year in men with a total PSA level less than 25 ng/mL/year, or if the PSA velocity is greater than 075 ng/mL/year and the total PSA is above 4 ng/mL [194] A strict adherence to these guidelines is essential

The belief that T is a risk factor for cardiac disease is based on the observation that men have both a higher incidence of cardiovascular events and higher T levels than women However, few, if any, data support a causal relation between higher T levels and heart disease [199 202] Indeed, several studies suggest that higher T levels may actually have a favorable effect on the risk of cardiovascular disease [203,204] Evidence that T therapy may be bene cial for men with cardiac disease was provided by English et al, who found that 22 men with chronic stable angina who were treated with transdermal T therapy had greater angina-free exercise tolerance than 24 placebo-treated controls [205] However, it is unknown how this observation may relate to cardiovascular risk during long-term T supplementation In a study

102 Ibid 103 Ibid 104 Meredith A Giordano and Aaron TWolf, The World s International Freshwater Agreements: Historical Developments and Future Opportunities, Atlas of International Freshwater Agreements, http:// wwwtransboundarywatersorstedu/publications/atlas/ 105 Monica Prasad, On Carbon, Tax and Don t Spend, New York Times, March 25, 2008, http://wwwnytimescom/2008/03/25/ opinion/25prasadhtml 106 The Elusive Negawatt, Economist, May 8, 2008, http://www economistcom/displaystorycfm story_id=11326549 107 Introduction, Carbon Tax Center, http://wwwcarbontaxorg/ introduction/#why (last accessed June 16, 2008) 108 Joseph E Stiglitz Stands Up for a Carbon Tax, Courrier International, December 12, 2007, http://europecourrierinter nationalcom/eurotopics/articleasp langue=uk&publication=12/ 12/2007&cat=REFLECTIONS&pi=1

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