ࡱ> _Fwbjbj .jA\jA\xx @!@!@!T!T!T!8!"dT!S #++++E-E-E-NRPRPRPRPRPRPR$VoY6tR@!E-#-"E-E-E-tR ++WySKNKNKNE-\ 8+@!+NRKNE-NRKNKNV2Q@(!Q+Б48DrQ(:RS0SQ YJYQY@!QKNE-E-E-tRtRKNE-E-E-SE-E-E-E-YE-E-E-E-E-E-E-E-E-x> :Poremeaji seksualnih funkcija uzrokovani lijekovima Nataaa Mrduljaa-uji Uvod Seksualna disfunkcija (SD) ozbiljan je zdravstveni problem povezan s kvalitetom ~ivota sa zna ajnim utjecajem na ~ivot pacijenta i njegovog partnera. Prema ameri kim studijama seksualne smetnje mogu se o ekivati kod oko 30% muakaraca i 40% ~ena. Kod ~ena naj eai problem predstavlja smanjena seksualna ~elja s prevalencijom od 22%. Klasifikacija DSM - 5 (Dijagnosti ki i statisti ki priru nik za duaevne poremeaje 5) smetnje seksualne ~elje u ~ena zajedno sa smetnjama uzbuenja svrstava u jedan, zajedni ki poremeaj. Kod muakaraca naj eai problem je prijevremena ejakulacija (PE), s prevalencijom od 21%, mada se oni ak i eae javljaju lije niku zbog erektilne disfunkcije (ED). Analiza SD u osam europskih zemalja pokazala je da ak 34% ~ena i 15% muakaraca izvjeatavaju o niskoj spolnoj ~elji, dok studija Laumann i Nicolosi (2005) na 29 zemalja airom svijeta, ka~e da je u odrasloj populaciji (od 40 do 80 godina), u ~ena prevalencija niske spolne ~elje od 26 do 43%, a u muakaraca od 12,5 do 28%. Lijekovi mogu utjecati na poremeaj svih faza seksualnog odgovora: ~elju, uzbuenje i orgazam - ejakulaciju. Uglavnom izazivaju negativne nuspojave (sni~enu funkciju), osim rijetkih izuzetaka (npr. antiparkinsonici koji poja avaju spolni nagon stimulacijom dopaminskih receptora). Seksualne nuspojave eae se spominju u psihotropnih lijekova (antipsihotici, antidepresivi, modulatori raspolo~enja/antiepileptici, anksiolitici), antihipertenziva, opioida (npr. morfin, tramadol, buprenorfin), hormona (oralni kontraceptivi, antiandrogeni..), SERM-ova, u indometacina, antihistaminika, H2 blokatora i antiemetika (metoklopramid). Najva~niji neurotransmiteri povezani sa seksualnim odgovorom su: dopamin (medijalna preopti ka regija hipotalamusa, mezolimbi ki put i nukleus accumbens) koji djeluje stimulirajue na ~elju, uzbuenje i orgazam, serotonin (hipokampus i amigdala) koji inhibira seksualnu ~elju, orgazam i ejakulaciju, prolaktin koji negativno utje e na sve seksualne funkcije direktno, preko prolaktinskih receptora u hipotalamusu (~elja, uzbuenje) ili indirektno, sni~avanjem lu enja estrogena i testosterona i noradenalin koji povisuje sposobnost uzbuenja preko svog utjecaja na centralne receptore i inhibira erekciju vezujui se na periferne alfa 1 receptore. Koji su mehanizmi djelovanja lijekova na seksualne funkcije? Prije svega odnose se na direktni u inak na katekolaminsku transmisiju i promjene u adrenergi no-kolinergi noj ravnote~i, te na neuroendokrini sustav. Poremeaji seksualnih funkcija vezani su za blokadu dopaminskih receptora, poveanje koncentracije prolaktina i nespecifi no centralno sedativno djelovanje (antihistaminski i antikolinergi ni u inci) koji vode smanjenoj seksualnoj aktivnosti openito (poviaeni prolaktin npr. djeluje na sve faze seksualne reakcije). U terapiji antidepresivima smetnje seksualne ~elje, orgazma i ejakulacije uklju uju poviaeni serotonin, osobito preko 5-HT2 i 5-HT3 receptora. Periferni efekt blokade alfa adrenergi kih receptora odgovoran je za dilataciju arterija u penisu (blokada alfa 1 i vjerojatno alfa 2 adrenergi kih i muskarinskih receptora) i povezan je s ED i prijapizmom kod upotrebe antipsihotika. Neki lijekovi (npr. antiepileptici), s obzirom na svoj metabolizam, uzrokuju porast aktivnosti hepatalnog mikrosomatskog enzimskog sustava (citokrom P450). Poti e se metabolizam spolnih hormona i poja ava proizvodnja SHBG-a (engl. Sex Hormone Binding Globulin), ato reducira razinu aktivnog spolnog hormona (testosterona) u cirkulaciji i smanjuje spolnu ~elju. Hiperprolaktinemija je va~na, ali zanemarena nuspojava antipsihoti nog lije enja. Prolaktin je poviaen prilikom koriatenja lijekova koji antagonisti ki djeluju na dopaminske receptore (klorpromazin, haloperidol, risperidon, sulpirid, cisaprid, metoklopramid) i lijekova koji sni~avaju koncentraciju dopamina (metildopa, rezerpin, estrogeni i opijati). esta je u konvencionalnih antipsihotika i u nekih atipi nih antipsihotika (risperidon i amisulprid), a rjea je u drugih atipi nih antipsihotika (aripiprazole, klozapin, olanzapin, kvetiapin, ziprasidon). Seksualna disfunkcija se mo~e javiti kao nuspojava lije enja mnogih bolesti. U naaoj svakodnevnoj praksi javlja se u lije enju: kardiovaskularnih bolesti (arterijske hipertenzije, zatajenja srca), benigne hiperplazije prostate, karcinoma prostate, adjuvantne terapije karcinoma dojke, Parkinsonove bolesti, LUTS-a (engl. low urinary tract symptoms  simptoma donjeg mokranog trakta), kroni ne boli, epilepsije, psihijatrijskih bolesti (anksioznih poremeaja, depresije, psihoza, bipolarnog poremeaja i sl.), te koriatenju hormonalne kontracepcije. Kod veine navedenih stanja vrlo esto je teako razlikovati u kojoj mjeri je SD posljedica osnovne bolesti, kao dio klini ke slike ili lije enja. SD u terapiji sr ano-~ilnih bolesti Dostupni podaci (Baumhakel i sur., 2011; Manolis i sur., 2008) ukazuju na to da je arterijska hipertenzija rizi ni faktor za SD, s obzirom na to da je muaka i ~enska seksualna disfunkcija prevalentnija u hipertenzivnih nego u normotenzivnih pojedinaca. Seksualne nuspojave antihipertenziva esto dovode do odustajanja od terapije bez znanja lije nika. Prema tome, prije uklju ivanja terapije, trebalo bi utvrditi postoji li ve u pacijenta ED jer ovaj problem mo~e biti povezan s hipertenzijom, koronarnom arterijskom bolesti (CAD  engl. coronary arterial disease), sr anim zatajenjem i aeernom bolesti. Ako je tome tako, onda se u terapiju mogu uklju iti inhibitori fosfodiesteraze -5 (PDE-5). Jedina iznimka je pacijent s CAD koji u terapiji ima nitrate, kada je kontraindicirano korisiti ove lijekove. Tiazidi, neselektivni antagonisti aldosteronskih receptora i beta blokatori mogu izazvati ED. Dok beta blokatori, kao ato su metoprolol, pindolol i atenolol snizuju razinu testosterona i FSH i na taj na in uzrokuju erektilnu disfunkciju, neselektivni beta blokatori (propranolol, sotalol...) direktno djeluju na penilne vaskularne glatke miaine stanice uzrokujui vasokonstrikciju preko alfa adrenergi ke stimulacije ato vodi do smanjene perfuzije korpora kavernosa. Od beta blokatora iznimka je visoko selektivni nebivolol koji ne samo da ima manju incidenciju ED od ostalih beta blokatora, nego i povoljno djeluje na erekciju oslobaanjem duai nog oksida u endotelu krvnih ~ila, s posljedi nom vazodilatacijom penilnih arterija i poviaenim protokom krvi u kavernoznim tijelima. Blokatori kalcijevih kanala ini se da nemaju negativna djelovanja na ED osim verapamila. ACE inhibitori i blokatori angiotenzinskih receptora imaju neutralan ili pozitivan utjecaj na ED. Za razliku od spironolaktona, eplerenon nema seksualnih nuspojava koji ponekad ograni avaju primjenu spironolaktona. Uz ostalo, eplerenon je djelotvoran u hipertenziji, gdje smanjuje oboje, hipertrofiju lijevog ventrikla i proteinuriju (dva sna~na markera poveanog KV rizika). Va~no je za svakog lije nika koji tretira hipertenzivne pacijente da se upozna sa SD (kroz bolju edukaciju i specifi ne seminare) za pravu skrb ovih pacijenata. Znanje o djelovanju lijekova na erektilnu funkciju i o velikoj ulozi endotela u penilnoj funkciji moglo bi popraviti pacijentovo prihvaanje na znanosti zasnovanog (EB-engl. evidence based) tretmana kardiovaskularnih bolesti. U slu aju kada je ED rezultat antihipertenzivne terapije, ordinarijus mo~e ili dodati PDE5 inhibitore ili zamijeniti dosadaanju terapiju s blokatorom angiotenzinskih receptora (Baumhakel i sur., 2011). ED je povezana s ishemijskom sr anom bolesti i mo~e biti rani marker za tihu koronarnu arterijsku bolest. Mo~e se pojaviti prije koronarne arterijske bolesti i simptomati na je, s vremenskim prozorom od 3 do 5 godina. Izmeu 50 i 70% muakaraca s koronarnom arterijskom bolesti ima ED. Jedna i druga dijele iste rizi ne faktore i endotelijalna disfunkcija im je zajedni ki nazivnik. U 30% pacijenata sa zatajenjem sr ane funkcije (CHF, engl. congestive heart failure) registriran je kompletni nedostatak seksualne aktivnosti. U pacijenata koji boluju od CHF i imaju stabilnu sr anu funkciju, seksualna funkcija openito nije kontraindicirana i trebalo bi je ohrabriti kao oblik fizikalne terapije umjerenog intenziteta. U inkovita terapija ED u ovih pacijenata trebala bi se zasnivati na izboru kardio-vaskularnih lijekova s najni~im djelovanjem na pacijentovu erektilnu funkciju i koriatenju PDE5 inhibitora. PDE5 inhibitori poboljaavaju endotelijalnu funkciju, toleranciju napora, smanjuju pluni vaskularni otpor i tlak u plunoj arteriji i povisuju sr ani index. Ipak, prije negoli ato lije imo pacijente sa zatajenjem srca s PDE5 inhibitorima, pacijentima bi trebalo procijeniti rizik sr anog dogaaja za vrijeme seksualne aktivnosti. PDE5 inhibitori su sigurni i korisni u terapiji ED u pacijenata sa zatajenjem srca. Popravak ED s PDE5 inhibitorima povezan je s poboljaanjem kvalitete ~ivota i redukcije depresije. Studije sveu iliata Rutgers pokazuju da statini poboljaavaju ED kod muakaraca koja je neuralne etiologije. Statini poveavaju razinu duai nog oksida (NO) koji je vazodilatator te poveavaju razinu endotelnih progenitornih stanica u krvi koje su va~ne u oateenju endotela. Klini ke studije upuuju da statini mogu poboljaati simptome ED, bez obzira na lipidni status pacijenta. Ovi lijekovi imaju mnogostruka djelovanja, stoga je teako razlu iti u kolikoj mjeri je njihov u inak sekundarna posljedica smanjenja lipida u krvi ili je nastao putem drugih mehanizama. SD u terapiji psihofarmacima i antiepilepticima Anksiolitici mogu djelovati na sve faze seksualnog odgovora (~elju, uzbuenje i orgazam) i njihovo djelovanje ovisi o dozi lijeka. Ukoliko uspjeano smanjuju anksioznost, onda mogu biti i korisni u rjeaavnju seksualnih poremeaja (npr. davanje malih doza benzodiazepina prije seksualnog odnosa mo~e ubla~iti anksioznost). Seksualna disfunkcija (Holt i sur., 2011) je esta i nedovoljno prepoznata u ljudi s te~im psihi kim bolestima i povezana je s antipsihoti kim tretmanom. Istra~ivanjem pacijenata na tipi nim i atipi nim antipsihoticima uo eno je da su SD u estala nuspojava. ED je naju estalija meu muakarcima na antipsihoticima i zna ajno je viae izra~ena u tipi nih nego u atipi nih antipsihotika. Za razliku od toga, nije pronaena statisti ka zna ajnost u ~elji, ejakulaciji/orgazmu i iznad svega u ukupnim zbrojevima testova za seksualne disfunkcije. Atipi ni antipsihotici su relativno sigurniji lijekovi, osim po pitanju ED. SD u ovih pacijenata je dijelom uzrokovana hiperprolaktinemijom. Atipi ni antipsihotici kao ato su klozapin, olanzapin, risperidon, razli iti psihostimulansi i amfetamini imaju antagonisit ko djelovanje na adrenergi ke alfa-1 receptore i ini se da je to osnova za prijapizam izazvan lijekovima. Prolaktin je prolazno poviaen tokom stresa, prilikom stimulacije bradavica, u snu, pri fizi koj aktivnosti i seksualnom odnosu. Simptomi hiperprolaktinemije uklju uju ginekomastiju, galaktoreju, seksualnu disfunkciju, infertilnost, oligomenoreju i amenoreju. Studije ka~u da je stopa prevalencije oligomenoreje/amenoreje 45% i galaktoreje 19% u ~ena tretiranih konvencionalnim antipsihoticima. Najvei utjecaj na pojavu hiperprolaktinemije ima sulpirid, a slijede risperidon, haloperidol, olanzapin, te klozapin. Hiperprolaktinemija izazvana tipi nim antipsihoticima i risperidonom mo~e izravno oslabiti seksualni interes i erektilnu funkciju, pa bi pitanja o simptomima koji mogu biti posljedica hiperprolaktinemije trebala biti rutinska (promjene veli ine dojki, laktacija, seksualna ~elja i funkcija te menstrualni ciklus). Kod takvih pacijenata mo~emo smanjiti dozu lijeka, zamijeniti lijek ili dodati dopaminski agonist bromokriptin (2-8 mg/dnevno). Aripiprazol (Mete i sur., 2016) je antipsihotik povezan s manjim nuspojavama u usporedbi s drugim antipsihoticima. To je atipi ni antipsihotik druge generacije, odobren za terapiju shizofrenije i manije u bipolarnom poremeaju tipa 1. Za razliku od drugih antipsihotika, ima veliki agonisti ki afinitet za D2 i D3 receptore. Ima takoer 5-HT1A parcijalnu agonisti ku i 5-HT2A antagonisti ku aktivnost ato mo~e poja ati seksualnu aktivnost. Prva je ili druga linija terapije, esto koriatena zbog tog ato manje od drugih antipsihotika djeluje na: poveanje te~ine, pospanost, dislipidemiju, insulinsku rezistenciju, hiperprolaktinemiju i ekstrapiramidalne simptome. D2 parcijalni dopaminergi ki agonizam aripiprazola bi mogao objasniti zaato njegovo koriatenje obi no ne uzrokuje SD i mo~e ak i vratiti seksualnu funkciju kada ga dodamo drugom antipsihotiku (Mesa i sur., 2013). Opisani su i slu ajevi poviaene seksualne ~elje (Cheon i sur., 2013) i vee preokupacije seksom nakon uzimanja aripiprazola. Dvije su mogue strategije terapije, dodavanje aripiprazola kod reguliranog pacijenta s hiperprolaktinemijom i prelazak na terapiju aripiprazolom kod pacijenta koji nije dobro reguliran. Farmakoloaka terapija s potencijalom vraanja seksualne funkcije koja je izazvana antipsihoti nim tretmanom mo~e popraviti prihvaanje i redovito uzimanje terapije i kvalitetu ~ivota naaih pacijenata, posebno onih koji su mlai i na terapiji su prve psihoti ne epizode. Rutinska pitanja o seksualnim simptomima prije propisivanja antipsihotika, kao i na kontroli iznad svega e poboljaati zadovoljstvo i prihvaanje terapije. Serotonergi ki mehanizmi jednako su va~ni kao i dopaminergi ki u seksualnom funkcioniranju. Dok tipi ni antipsihotici blokiraju D2 receptore i tako stimuliraju poja anu sekreciju prolaktina uzrokujui SD, atipi ni antipsihotici koji su serotonin-dopamin antagonisti, induciraju njihove seksualne nuspojave kroz serotoninske mehanizme. Na ovaj na in mo~emo objasniti da pojava SD nije zna ajno razli ita. Opijati imaju vei afinitet za opijatne receptore od endorfina. Kao dugotrajni efekt na mozgu atakora, istra~iva i su uo ili da metadon reducira mo~dane (kortikalne) alfa adrenergi ne receptore. Alfa adrenergi ka opstrukcija uzrokuje ishemijski prijapizam. Vee doze metadona i dulje trajanje metadonske terapije povezano je s veom ED. Spontane erekcije mogu se dogaati kao kompenzatorne na nuspojave metadona na ED nakon brzog ustezanja istog, posredovano alfa adrenergi kim receptorima. Brz prekid metadona mo~e uzrokovati prijapizam. U terapiji mo~e pomoi fluoxetin i pentoxifylline 400-800/dan. Uloga antiepileptika/stabilizatora raspolo~enja u seksualnom funkcioniranju ostaje nejasna, mada je SD kod njihovog koriatenja uobi ajena nuspojava (Yang i sur., 2013). Simptomi uklju uju ED, hiposeksualnost, hiperseksualnost i ejakulatornu disfunkciju. Klasi ni antiepileptici kao valproat i enzim inducirajui antiepileptici mogu uzrokovati sni~enje libida. Topiramat, pregabalin i gabapentin mogu izazvati SD, dok okskarbazepin, lamotrigin i levetiracetam mogu poboljaati seksualnu funkciju. Valproat smanjuje libido i uzbuenje u pacijenata s bipolarnim poremeajem. Karbamazepin reducira razinu slobodnog testosterona u pacijenata s epilepsijom i tako doprinosi oateenom libidu u nekih pacijenata. On takoer inducira mikrozomalne enzime i tako reducirajui efektivnu plazma koncentraciju lijekova koji se skupa koriste (haloperidol) reducira i njihovu efikasnost. Ovo mo~e indirektno poboljaati seksualne nuzefekte ovih lijekova. Mada terapija za SD koja je povezana s antiepilepticima ostaje nejasna, prebacivanje na drugi antiepileptik mo~e biti opcija. ak do 70% bolesnika s depresijom mo~e imati seksualne disfunkcije koje mogu biti simptom osnovne bolesti ili pak nuspojava farmakoterapije antidepresivima. Depresija i terapija antidepresivima povezani su sa SD u ~ena i muakaraca uklju ujui orgazam i poteakoe uzbuivanja, hipoaktivnu seksualnu ~elju, preuranjenu ejakulaciju, erektilne poteakoe i dispareuniju. SD se spominje kao esti razlog neodr~avanja i prekida terapije antidepresivima. Tablica 1. Seksualne nuspojave antidepresiva AntidepresivSDfluoksetin (Portal, Prozac, Fluval..)galaktoreja, smanjenje libida sertralin (Zoloft, Sonalia, Asentra, Halea..)poremeaj ejakulacije u vidu odgoene ejakulacije, smanjenje libida.paroksetin (Seroxat, Paroxetin, Deprozel..)ED i poremeaj ejakulacijecitalopram (Citalon, Starcitin..)ED i prijapizamtricikli ki antidepresiviporemeaj erektilne i ejakulatorne funkcije (nema zna ajne razlike meu pojedinim antidepresivima iz ove skupine)venlafaksin (Velafax, Alventa, Zanfexa) poremeaj orgazma, ejakulacije i erektilna disfunkcijaklomipramin (Anafranil), imipraminsmanjenje libida i ED, poremeaj orgazma, galaktoreja i amenorejatrazodon (Trittico)prijapizamMAO-inhibitoriED i poremeaj ejakulacijereboksetin (Edronax)u dozama veim od 8 mg/dan dovodi do ED Tricikli ki antidepresivi, fluoksetin i paroksetin (SSRI-selektivni inhibitori ponovne pohrane serotonina) i venlafaksin (SNRI  selektivni inhibitor ponovne pohrane serotonina i noradrenalina) meu antidepresivima naj eae uzrokuju seksualne disfunkcije (smanjena ~elja, ED, poremeaji orgazma i ejakulacije) dok se antidepresivi koji ne utje u na serotoninsku neurotransmisiju najrjee povezuju sa seksualnom disfunkcijom kao nuspojavom lijeka (mirtazapin - Mirzaten, Calixta, bupropion - Wellbutrin i moklobemid  Aurorix). Nadalje, neki od spomenutih antidepresiva koriste se u terapiji SD, induciranoj sa SSRI i SNRI - kod postojanja seksualnih smetnji preporu a se sniziti dozu antidepresiva, zamijeniti lijek mirtazapinom, bupropionom, ili moklobemidom ili dodati bupropion redovito. Bupropion (Patel i sur., 2016) predstavlja inhibitora ponovne pohrane NA i DA, potencijalno omoguava poja avanje djelovanja uobi ajenih antidepresiva kao ato su SSRI. Nema utjecaja na serotonin, histamin, acetilkolin ili adrenalin receptore  zbog toga nije povezan sa zna ajnom sedacijom, kognitivnim, antikolinergi kim gastrointestinalnim ili hipotenzivnim nuspojavama. Prema istra~ivanjima popravlja seksualnu funkciju u pacijenata u kojih je seksualna disfunkcija inducirana uzimanjem SSRI. Openito se dobro podnosi, ima vrlo niske stope seksualne disfunkcije i ini se da prije izaziva gubitak te~ine nego dobitak. Vortioksetin, (Sanchez i sur., 2016) noviji antidepresiv za terapiju depresije major (MDD, engl. major depressive disorder), antagonist je 5-HT3, 5-HT7 i 5-HT1D receptora, 5-HT1B rec parcijalni agonist, 5-HT1A receptor agonist i serotonin (5-HT) transporter (SERT) inhibitor. Poja ava serotonergi ku, noradrenergi ku, dopaminergi ku, kolinergi ku, histaminergi ki i glutamatergi ku neurotransmisiju u strukturama mozga povezanim s MDD. Vortioxetine  profil nuspojava je sli an SSRI, s naj eaim smetnjama od strane GI trakta, meutim, niska incidencija seksualne disfunkcije i poremeaja spavanja mo~e se pripisati modulaciji vortioksetinskih receptora. SD mo~e biti prevenirana ili tretirana nuspojava antidepresiva (Taylor i sur., 2013). Pacijente treba rutinski pitati o seksualnoj funkciji da se problemi prepoznaju na vrijeme. Treba naglasiti ulogu lije nika u tom procesu jer pacijenti uglavnom izbjegavaju zapo eti razgovor o toj temi. Ukoliko se seksualna funkcija ignorira, mo~e podr~ati depresiju, ugroziti terapijski ishod i voditi nesuradljivosti. `irok je spektar strategija za noaenje s ovim problemom, uklju ujui bihevioralni, psiholoaki i farmakoloaki pristup. Za muakarce s antidepresivima induciranom ED, dodatak sidenafila ili tadanafila ini se efikasna strategija. Za ~ene s antidepresivima induciranom seksualnom disfunkcijom, dodatak bupropiona u veim dozama ini se pristup koji za sada najviae obeava. SD u terapiji bolnih stanja Bolno stanje samo po sebi utje e negativno na sve faze seksualnog odgovora. Meutim, uo eno je da i neki lijekovi koje u tim stanjima koristimo djeluju negativno na seksualnu funkciju. Kod psihotropnih lijekova ranije su spomenuti opijati i njihovo djelovanje na seksualnu funkciju. Ostali analgetici, posebno nesteroidni antireumatici (NSAR) povezuju se s ED u manjem broju slu ajeva. U literaturi se spominje ciklobenzaprine, koji u nas nije registriran. To je oralni lijek, indiciran za terapiju boli povezanu sa spazmima miaia u akutnim muskulo-koatanim okolnostima. Spada u skupinu miainih relaksatora, spazmolitika. Strukturno je sli an triciklicima (npr. amitriptilinu) i ima sli ne nuspojave (pospanost u 39%, vrtoglavicu u 27% i suha usta u 11% pacijenata). Bolna ejakulacija se kao nuspojava javlja u tricikli kih antidepresiva i antipsihotika, a opisani su slu ajevi iste kod koriatenja cyclobenzaprina. Reakcija je reverzibilna i rjeaava se prestankom uzimanja lijeka (Kraus, 2015) SD u lije enju BPH i LUTS-a SD je potencijalna nuspojava lijekova (La Torre i sur., 2016). koje koristimo u BPH i LUTS-u. Uobi ajena je povezanost izmeu LUTS-a i ED (patofizioloaki  poremeaj NO puta, poja anog kontraktilnog signala, autonomno, adrenergi ka hiperaktivnost i pelvi ka atheroskleroza). Alfa blokatori (alfa 1 adrenergi ki antagonisti) i 5-ARI (5 alfa reduktaza inhibitor ili testosteron 5 alfa reduktaza inhibitor) mogu posebno uzrokovati ED, poremeaje ejakulacije i redukciju seksualne ~elje. Od alfa blokatora silodosin (kod nas nije registriran) ima najviau incidenciju SD. Perzistirajue seksualne nuspojave nakon prekida finasterida su nedavno prijavljene. Ipak, za ovo su potrebne daljnje studije. SD u lije enju ca prostate, ca dojke i hormonalnoj terapiji SD u terapiji ca prostate (Schover, 2015) prvenstveno sjln 8>@tz|n*zPR򱪱wmwhfB*KHph&&&hf5B*KHph&&& hf5\ hf\ hf5hfB*ph&&& h8KH\ hKH\ h!#KH\ hfKH\h!#hfB*php0 *hf5h!#hf5h!#hP5 h5 hBIhf hBIhhhfhf5CJaJ&lnpj$(8.:..4*CFNRRS $dha$9$dh^`a$ :$dha$ 9$dh^a$$dha$dhRf !!X#Z#b##h$b&d&'(P((>+F+8.:........./|0@1B1224 99::";ླྀ஧|qhf5B*\ph&&&hfB*KHph&&&hf6B*ph&&&hfB*CJaJphp0he h70hf heKH\h70hfKH\ hf5hfB*php0 hf6 hf\hBI hf0J(6 hf0J(hfhfB*\ph&&&hfB*ph&&&hf5B*ph&&&,";$;;;< <`<b<d<>>?"A.AAAB CC&C(CCCDDD&FFFHHBJDNFNRRSUUUUUU\\\쮧{hfB*CJKH\aJphp0 hf5h!# hf6 hpKH\ h70hf heKH\h70hfKH\hf6KH\ hfKH\hfB*KH\php0hfB*KHph&&&hfB*\ph&&&hfhfB*ph&&&hf5B*\ph&&&-SU,dpsx~ 9dh$If^9dh^$dha$ $dha$ :$dha$\\,dDdNd\djdldffjjjjjkhkjkvkkkkklzmooppssssxxyyyyz~ VX|~ֆ؆ *hfB*ph&&&hfB*ph&&&hf5B*ph&&&hfB*KH\php0hfB*CJKH\aJphp0hfB*CJaJphp0 heKH\h70hfKH\ hfKH\hfhf0J'6\; X~JSkd$$If0#$.44 lap 9dh$If^Skd$$If0#$.44 lap~؆TtJSkd$$If0#$.44 lap 9dh$If^Skd,$$If0#$.44 lap؆ RTrtNPDFZ\z|܊ފ,.2h(8ʎ":Nʐ ^`rt:<h³­"hRthf5CJOJQJ\aJ heKHh70hf5B*KHphp0h70hfKH hfKH hf\hf5B*\ph&&&hfB*\ph&&&hfB*php0hfhfB*ph&&&bx *,4jnhjprtʓʓʃ{{{ohfmHnHsHtHhfB*ph&&&hfB*CJKH\aJphp0hf6KH\ h%0vKH\h%0vh%0vKH\$h70hfB*CJKH\aJphp0h70hfKH\ hfKH\hfB*CJaJphp0U h70hf hez5 hf5hfhfB*KH\php0+ lnjlnprtxz|~$a$gd}Z$a$ $dh`a$ :$dha$$dha$ $dha$e odnosi na androgen-deprivacijsku terapiju (ADT) kod koje se javlja gubitak ~elje, ED i promjena kvalitete orgazma, te distres zbog ginekomastije i feminiziranog rasporeda tjelesne masti. ak i nakon 3-4 mjeseca od prekida terapije, spolna ~elja u muakarca je sni~ena i prisutna su nepovratna oateenja erektilnog tkiva u penisu. Erekcija se ne oporavlja u oko polovice muakaraca, ak iako je ADT bio diskontinuiran. Mada intermitentna ADT dopuata do neke mjere oporavak seksualne funkcije, treba oko 9-12 mjeseci da se razina serumskog testosterona oporavi nakon prekida ADT. U oko polovice muakaraca zaostaje permanentna erektilna disfunkcija. Ovim pacijentima i njihovim partnerima treba ponuditi optimisti na i istinita o ekivanja o seksualnosti za vrijeme hormonske terapije. Naaa kultura smatra da hormoni imaju apsolutnu mo da kontroliraju ~elju i funkciju umjesto da ih vidi kao jedan faktor u kompleksnoj interakciji seksualnih vjerovanja i iskustava, odnosa meu partnerima i vjeatina u noaenju s kroni nom bolesti. Hormonalna kontracepcija mo~e utjecati na ~ensku seksualnu funkciju. Ipak, seksualne nuspojave hormonalnih kontraceptiva nisu dovoljno dobro prou avane. ini se da postoji mijeaani utjecaj na libido, s malim postotkom ~ena koji imaju iskustvo porasta ili smanjenja, a veina nema iskustvo promjene. Estrogen i progesteron (Shah i sur., 2010) u kombinaciji smanjuju testosteron i povisuju SHBG (engl.sex hormone binding globulin) bez konzistentnog utjecaja na libido. Samo progesteron mo~e u malom broju smanjiti libido i uzrokovati suhou vagine i dispareuniju. U postpartalnom periodu i za vrijeme laktacije, ove promjene su poja ane. Kod koriatenja IUD (engl. intra uterine device) nije uo en zna ajniji utjecaj na libido. Sama sterilizacija u ~ena openito ima pozitivan utjecaj na seksualnost ukoliko ~ena nije ambivalentna vezano za proceduru. Ipak, zdravstveni radnici trebaju imati saznanja da hormonalna kontracepcija mo~e imati negativna djelovanja na ~ensku seksualnost, radi adekvatnog savjetovanja. SD u terapiji inhibitorima aromataze (AI) u ~ena je uvelike podcijenjen problem (Baumgart i sur., 2013). Seksualna disfunkcija je tek skoro bila prepoznata kao visoko prevalentna nuspojava adjuvantne terapije ca dojke inhibitorima aromataze (smanjena seksualna ~elja, dispareunija, nedostatno vla~enje vagine, zna ajno viae od kontrolne skupine). ak 79% seksualno aktivnih ~ena koje su zapo ele terapiju AI razvilo je novi seksualni problem. Zaklju ak Seksualnost ini bitnu odrednicu kvalitete ~ivota velike veine ljudi. Seksualne nuspojave lijekova se mogu izbjei ukoliko znamo uzrokuje li odreeni lijek seksualne smetnje i koju vrstu nuspojava mo~emo o ekivati. Pacijente treba pitati konkretna pitanja jer oni sami uglavnom nisu spremni po eti govoriti o svojim seksualnim smetnjama (prema europskim istra~ivanjima svega 4% lije nika to radi). Jednostavnim pitanjem  Imate li kakvih seksualnih problema? mo~emo promijeniti dosadaanju praksu. Pacijente kojima ne mo~emo dovoljno pomoi u naaim ordinacijama mo~emo uputiti stru njacima, seksualnim terapeutima/savjetnicima.  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Tessler Lindau S, Schumm Ph, Laumann OE, Levinson W, O Muircheartaigh CA, Waite LJ. A study of sexuality and health among older adults in the united states. N Engl J Med. 2007; 357: 762 74.  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/?term=Yang Y%5BAuthor%5D&cauthor=true&cauthor_uid=26559937"Yang Y,  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/?term=Wang X%5BAuthor%5D&cauthor=true&cauthor_uid=26559937"Wang X. Sexual dysfunction related to antiepileptic drugs in patients with epilepsy.  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/26559937"Expert Opin Drug Saf. 2016;15:31-42. Waldinger MD.  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/26003261"Psychiatric disorders and sexual dysfunction. Handb Clin Neurol. 2015;130:469-89.  HYPERLINK "https://www.ncbi.nlm.nih.gov/pubmed/?term=Werneke U%5BAuthor%5D&cauthor=true&cauthor_uid=17087787"Werneke U,  HYPERLINK "https://www.ncbi.nlm.nih.gov/pubmed/?term=Northey S%5BAuthor%5D&cauthor=true&cauthor_uid=17087787"Northey S,  HYPERLINK "https://www.ncbi.nlm.nih.gov/pubmed/?term=Bhugra D%5BAuthor%5D&cauthor=true&cauthor_uid=17087787"Bhugra D. Antidepressants and sexual dysfunction.  HYPERLINK "https://www.ncbi.nlm.nih.gov/pubmed/17087787"Acta Psychiatr Scand. 2006;114:384-97.      PAGE 13 Klju ne poruke lijekovi mogu utjecati na poremeaj svih faza seksualnog odgovora: ~elju, uzbuenje i orgazam  ejakulaciju; seksualna disfunkcija se mo~e javiti kao nuspojava lije enja mnogih bolesti, prije svega u lije enju kardiovaskularnih, psihijatrijskih bolesti, epilepsije i kroni ne boli. Kod veine navedenih stanja vrlo esto je teako razlikovati je li i u kojoj mjeri SD posljedica osnovne bolesti, kao dio klini ke slike ili lije enja; PDE5 inhibitori su sigurni i korisni lijekovi u terapiji ED. 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