Prostatic Hyperplasia and Prostatic Cancer

consumption฀correlates฀more฀clearly฀than฀current฀cigarette฀smoking฀with฀the฀development฀ of฀benign฀prostatic฀hyperplasia฀BPH;฀however,฀at฀35฀or฀more฀cigarettesday฀the฀risk฀for฀ BPH฀was฀found฀to฀be฀increased฀OR฀=฀1.45;฀CI:฀1.07–1.97.฀Moderate฀alcohol฀consump- tion฀and฀avoidance฀of฀smoking฀may฀beneit฀BPH฀ [419] . Prostatic฀cancers฀are฀not฀among฀the฀neoplasias฀primarily฀caused฀by฀smoking.฀However,฀ a฀few฀follow-up฀studies฀ [420–422] ฀indicate฀that฀smoking฀may฀increase฀the฀risk฀slightly฀by฀ 18.฀In฀heavy฀smokers฀40฀or฀more฀cigarettesday,฀the฀relative฀risk฀rises฀to฀51฀or฀80฀ [422] .฀One฀study฀performed฀in฀more฀than฀340,000฀men฀revealed฀risk฀increases฀of฀21฀£25฀ cigarettesday฀and฀of฀45฀³26฀cigarettesday,฀indicating฀that฀cigarette฀smoking฀should฀ also฀be฀viewed฀as฀a฀risk฀factor฀for฀prostatic฀cancer฀ [423] .฀A฀Canadian฀study฀has฀conirmed฀ an฀increased฀risk฀for฀prostatic฀cancer฀among฀smokers฀OR฀=฀2.31;฀CI:฀1.09–4.89,฀with฀a฀ high฀BMI฀increasing฀the฀risk฀still฀further฀ [424] . A฀raised฀leptin฀level฀may฀be฀important฀for฀prostatic฀growth฀and฀angiogenesis,฀especially฀ since฀ prostatic฀ tissue฀ contains฀ leptin฀ receptors฀ [425] .฀ An฀ association฀ between฀ smoking฀ habits฀and฀the฀development฀of฀prostatic฀cancer฀was฀not฀conirmed฀in฀22,071฀men฀partici- pating฀in฀the฀Physicians’฀Health฀Study:฀the฀relative฀risks฀for฀prostate฀cancer฀were฀1.14฀CI:฀ 1.00–1.30฀for฀past฀smokers฀and฀1.10฀CI:฀0.84–1.44฀for฀current฀smokers฀20฀or฀more฀ cigarettesday฀ [426] .

7.6.6 Fertility Disorders

The฀literature฀contains฀growing฀evidence฀to฀indicate฀that฀smoking฀is฀harmful฀to฀both฀male฀ and฀female฀fertility฀because฀the฀carcinogens฀and฀mutagens฀present฀in฀cigarette฀smoke฀reach฀ the฀germline฀cells฀ [427] .฀In฀men,฀smoking฀diminishes฀semen฀quality,฀including฀sperm฀con- centration,฀motility฀and฀morphology.฀The฀associations฀between฀male฀smoking฀and฀semen฀ quality฀can฀be฀demonstrated฀more฀clearly฀in฀“healthy”฀men฀than฀in฀men฀from฀infertility-clinic฀ populations฀ [428] .฀The฀changes฀in฀semen฀quality฀were฀already฀evident฀in฀men฀above฀the฀age฀ of฀22฀years฀ [428] .฀However,฀these฀results฀have฀not฀been฀conirmed฀in฀a฀clinical฀trial฀in฀mar- ried฀couples฀ [429] .฀In฀a฀study฀conducted฀in฀young฀soldiers฀from฀the฀Czech฀Republic,฀smoking฀ was฀ found฀ to฀ produce฀ changes฀ in฀ sperm,฀ including฀ X฀ and฀ Y฀ chromosome฀ aggregation,฀ reduced-linearity฀of฀sperm฀motion,฀and฀more฀“round-headed”฀sperm฀see฀Fig.฀ 7.6 ฀ [430] . In฀women,฀cigarette฀smoking฀has฀been฀associated฀with฀an฀increase฀in฀the฀average฀time฀ to฀conception฀–฀5.1฀months฀for฀current฀smokers฀compared฀with฀4.3฀months฀for฀women฀who฀ never฀smoked฀ [431] .฀Since฀cotinine฀enters฀the฀follicular฀luid,฀the฀likelihood฀that฀the฀nico- tine฀metabolite฀has฀a฀tubal฀effect฀in฀normal฀ovulatory฀cycles฀is฀considered฀minimal฀and฀has฀ been฀rejected฀ [432,฀433] . Ovarian฀ function฀ and฀ fertility฀ were฀ assessed฀ in฀ a฀ cohort฀ of฀ 499฀ women,฀ and฀ ฀gonadotrophin-stimulated฀ovarian฀function฀was฀found฀to฀be฀reduced฀in฀smokers฀compared฀ with฀non-smokers฀ [434] .฀A฀history฀of฀increasing฀tobacco฀exposure฀was฀associated฀with฀ decreasing฀serum฀oestradiol฀levels,฀number฀of฀retrieved฀oocytes฀and฀number฀of฀embryos,฀ with฀the฀result฀that฀smoking฀adversely฀affected฀the฀implantation฀rate฀and฀ongoing฀preg- nancy฀rate฀ [434] .฀The฀increased฀miscarriage฀rate฀in฀smokers฀is฀also฀evidently฀attributable฀ to฀cadmium฀and฀polyaromatic฀hydrocarbons,฀which฀inluence฀trophoblast฀differentiation฀ [435] .฀It฀is฀currently฀under฀discussion฀whether฀nicotine฀also฀has฀such฀effects฀see฀Chap.฀8.฀ Investigations฀in฀11,888฀women฀have฀failed฀to฀establish฀unequivocally฀whether฀simultane- ous฀smoking฀and฀coffee฀intake฀inluence฀fecundity฀ [436] .฀Another฀study฀of฀this฀question฀ concluded฀that฀moderate฀smoking,฀coffee฀drinking฀and฀alcohol฀consumption฀do฀not฀have฀a฀ deleterious฀effect฀on฀fecundity฀ [437] ,฀but฀only฀259฀women฀were฀included฀in฀this฀study.

7.7 Disorders of Mineral Metabolism and Bone

For฀several฀years,฀an฀association฀has฀been฀suspected฀between฀smoking฀and฀disorders฀of฀ mineral฀metabolism,฀and฀studies฀have฀recently฀been฀published฀which฀demonstrate฀a฀signii- cant฀effect฀of฀decades฀of฀smoking฀on฀calcium฀metabolism฀and฀hence฀on฀bone฀density.฀In฀ this฀context,฀the฀key฀hormones฀are฀25-hydroxyvitamin฀D฀25-OH-D฀and฀parathyroid฀hor- mone฀PTH฀ [438–443] .฀Adrenocortical,฀anterior฀pituitary฀and฀thyroid฀hormones฀are฀also฀ adversely฀affected฀ [444–446] . Clinical฀ studies฀ in฀ recent฀ years฀ have฀ focussed฀ on฀ the฀ harmful฀ effects฀ of฀ smoking฀ in฀ women.฀Investigations฀in฀rats฀indicate฀that฀nicotine฀has฀no฀adverse฀consequences฀in฀terms฀of฀ bone฀mineral฀density฀or฀fracture฀tendency฀ [447] .฀When฀rats฀were฀treated฀with฀extremely฀ high-dose฀nicotine฀infusions฀2.5-fold฀higher฀concentrations฀than฀the฀average฀in฀smokers,฀ no฀changes฀were฀produced฀in฀serum฀concentrations฀of฀calcium,฀25-OH-D฀and฀1,25-dihy- droxyvitamin฀D฀1,25-OH 2 -D;฀however,฀serum฀phosphorus฀and฀PTH฀concentrations฀were฀ increased฀ [448] .฀ It฀ is฀ further฀ conceivable฀ that฀ various฀ tobacco฀ smoke฀ constituents,฀ such฀ as฀cadmium,฀hydroquinone,฀thiocyanate฀and฀nitrosamines,฀exert฀an฀inluence฀on฀calcium฀ metabolism฀ [449–451] .

7.7.1 Vitamin D and Oestrogen Metabolism

Smoking฀ causes฀ reductions฀ in฀ 25-OH-D,฀ osteocalcin฀ [452] ฀ and฀ PTH฀ which฀ cannot฀ be฀ explained฀in฀terms฀of฀other฀lifestyle฀factors฀ [453] .฀The฀decline฀in฀PTH฀levels฀is฀evidently฀ 80 70 60 50 40 30 20 10 AI SV SZ TSZ MS TMS Smoker Nonsmoker Fig. 7.6 ฀฀฀Sperm฀analysis฀of฀ smokers฀S;฀n฀=฀10฀and฀ non-smokers฀NS;฀n฀=฀15฀ [430] .฀AI฀abstinence฀interval฀in฀ days,฀p฀฀0.02;฀SV฀semen฀ volume฀ml;฀SZ฀semen฀cells฀ 10 7 ml;฀TSZ฀total฀sperm฀count฀ per฀sample฀10 7 ml;฀p฀฀0.001;฀ MS฀motile฀sperm฀;฀TMS฀ total฀motile฀sperm฀10 6 ml;฀฀ p฀฀0.02.฀The฀p-values฀ indicate฀signiicance฀for฀the฀ comparison฀S฀vs.฀NS