Fertility Disorders Urinary Tract Diseases

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 not฀inluenced฀by฀differing฀serum฀levels฀of฀calcium฀or฀phosphorus฀for฀review,฀see฀ [454] .฀ Smokers฀and฀non-smokers฀may฀behave฀very฀differently฀in฀terms฀of฀coffee,฀alcohol฀and฀ vitamin฀D฀intake฀and฀physical฀activity฀ [455] ,฀and฀reduced฀calcium฀intake฀may฀also฀lead฀to฀ an฀ increase฀ in฀ 1,25-OH 2 -D฀ via฀ a฀ reduction฀ in฀ oestrogen฀ levels฀ [453,฀ 456] .฀ Oestrogen฀ metabolism฀ is฀ increased฀ by฀ the฀ induction฀ of฀ 2-hydroxylation฀ of฀ oestradiol฀ in฀ the฀ liver฀ increased฀production฀of฀2-OH-oestrogens฀ [457] ,฀and฀smoking฀has฀a฀more฀pronounced฀ effect฀on฀the฀activity฀of฀orally฀than฀parenterally฀administered฀oestrogens฀ [458] .฀Oestrogens฀ are฀metabolised฀more฀rapidly฀in฀the฀liver฀of฀smokers,฀and฀this฀in฀turn฀may฀lead฀to฀reduced฀ PTH฀levels.฀Similarly,฀the฀raised฀cadmium฀burden฀in฀the฀kidneys฀may฀contribute฀to฀the฀ reduction฀in฀1,25-OH 2 -D฀ [459,฀460] .฀Owing฀to฀this฀reduction฀in฀1,25-OH 2 -D,฀less฀cal- cium฀would฀be฀absorbed฀ [461,฀462] ฀and฀taken฀up฀into฀bone.฀Reduced฀osteocalcin฀levels฀in฀ smokers฀diminish฀osteoblast฀activity,฀as฀has฀also฀been฀demonstrated฀in฀in฀vitro฀experiments฀ [463] .฀Calculated฀in฀terms฀of฀decades,฀bone฀density฀naturally฀declines฀signiicantly,฀even฀ without฀smoking,฀and฀25-OH-D฀levels฀correlate฀with฀bone฀density฀ [464,฀465] .฀According฀to฀ a฀study฀from฀Denmark,฀25-OH-D฀and฀1,25-OH 2 -D฀levels฀in฀smokers฀are฀reduced฀by฀10฀ and฀PTH฀levels฀by฀about฀20฀ [453] .฀These฀reduced฀levels฀were฀detected฀in฀50฀of฀smokers฀ [453] ,฀as฀also฀conirmed฀in฀another฀recently฀published฀study฀ [452] .฀Continued฀smoking฀ does฀not฀alter฀bone฀alkaline฀phosphatase฀and฀urinary฀hydroxyproline฀excretion฀ [452] .

7.7.2 Osteoporosis

Osteoporosis฀is฀assessed฀in฀terms฀of฀bone฀mineral฀density,฀and฀the฀common฀occurrence฀of฀ femoral฀neck฀fractures฀is฀important฀in฀this฀context฀ [466] .฀The฀inluence฀of฀smoking฀has฀ been฀a฀topic฀of฀controversial฀discussion฀in฀the฀past฀ [467] ,฀and฀research฀has฀focussed฀par- ticularly฀on฀postmenopausal฀women.฀An฀association฀between฀bone฀mineral฀density฀and฀ smoking฀was฀already฀demonstrated฀in฀the฀1980s฀ [467–470] .฀In฀summary,฀a฀moderate฀effect฀ of฀cigarette฀smoking฀was฀identiied฀on฀the฀reduction฀in฀bone฀mineral฀density฀of฀pre-฀and฀ post-menopausal฀women.฀The฀number฀of฀cigarettes฀smoked฀daily฀correlated฀approximately฀ with฀bone฀mineral฀density฀ [471] .฀This฀correlation฀was฀independent฀of฀body฀weight.฀A฀rela- tively฀large฀study฀in฀544฀men฀and฀822฀women฀detected฀decreases฀in฀hip฀bone฀mineral฀ density฀in฀smokers฀compared฀with฀non-smokers฀ [472] ,฀relecting฀the฀positive฀association฀ between฀smoking฀and฀decreased฀bone฀mineral฀density฀in฀old฀age. The฀anti-osteoporotic฀effect฀of฀hormone฀replacement฀therapy฀HRT฀with฀oestrogens฀ is฀ attenuated฀ by฀ smoking฀ whereas฀ the฀ anti-osteoporotic฀ effect฀ of฀ raloxifene฀ remains฀ unchanged฀ [473] .฀Female฀smokers฀with฀a฀low฀BMI฀have฀an฀increased฀risk฀for฀bone฀loss,฀ even฀during฀HRT฀ [474] .฀The฀ageing-related฀rise฀in฀IL-6฀levels฀is฀important฀for฀the฀patho- genesis,฀and฀IL-6฀is฀further฀increased฀by฀smoking฀ [475] . Men฀and฀women฀aged฀61–73฀years,฀born฀and฀residing฀in฀a฀rural฀area฀of฀England฀and฀at฀ risk฀for฀cardiovascular฀disease฀and฀osteoporosis,฀were฀compared฀with฀a฀control฀group฀in฀ terms฀of฀smoking฀habits฀ [476] .฀The฀data฀revealed฀reduced฀bone฀mineral฀density฀in฀men฀and฀ women฀who฀smoked฀see฀Fig.฀ 7.7 ,฀with฀greater฀decreases฀detected฀in฀the฀spine฀than฀in฀the฀ femoral฀neck.฀The฀subjects’฀build,฀drinking฀habits฀and฀physical฀activity฀were฀not฀associ- ated฀with฀the฀reduction฀in฀bone฀mineral฀density฀Fig.฀ 7.8 ฀ [476] .