Bikalutamidning tibbiy qo'llanilishi - Medical uses of bicalutamide

The tibbiy maqsadlarda foydalanish ning bikalutamid, a steroid bo'lmagan antiandrogen (NSAA), davolashni o'z ichiga oladi androgenga bog'liq sharoitlar va gormon terapiyasi ta'sirini blokirovka qilish androgenlar. Bunday ko'rsatmalar davolashni o'z ichiga oladi prostata saratoni erkaklarda, teri va sochlarning holati kabi husnbuzar, seboreya, hirsutizm va soch to'kilishi ayollarda, yuqori testosteron darajasi ayollarda, gormon terapiyasi yilda transgender ayollar, kabi balog'at yoshini to'suvchi oldini olish uchun balog'at yoshi yilda transgender qizlar va davolash uchun erta balog'at yoshi o'g'il bolalar va davolash uzoq muddatli erektsiya erkaklarda. Bundan tashqari, davolashda ba'zi bir ahamiyatga ega bo'lishi mumkin parafiliyalar va giperseksualizm erkaklarda.

Prostata saratoni

Bikalutamid asosan prostata saratoni erta va rivojlangan davolashda ishlatiladi.[1] U kuniga 50 mg dozada tasdiqlangan kombinatsiyalangan davolash bilan gonadotropinni chiqaradigan gormon analogi (GnRH analogi) yoki davolashda orkiektomiya (ya'ni jarrohlik yoki tibbiy kastratsiya) D2 bosqichi metastatik prostata saratoni (mPC),[2][3] va a monoterapiya davolash uchun kuniga 150 mg dozada C yoki D1 bosqichi mahalliy darajada rivojlangan prostata saratoni (LAPC).[2][4][5][6] Garchi samarali bo'lsa ham mPC va LAPC, bikalutamid endi davolash uchun ko'rsatilmagan mahalliy prostata saratoni (LPC) prostata saratoni (EPC) sinovida salbiy natijalar tufayli.[5] Yangisini kiritishdan oldin NSAA enzalutamid 2012 yilda,[7] bikalutamid deb hisoblanadi parvarish standarti prostata saratonini davolashda antiandrogen va bu ko'rsatkich uchun hali ham keng qo'llaniladi.[8][7][9] Ilgari antiandrogenlarga nisbatan steroidal antiandrogen (SAA) siproteron asetat (CPA) va NSAAlar flutamid va nilutamid, bicalutamide ning yaxshilangan profilini ko'rsatadi samaradorlik, bag'rikenglik va xavfsizlik,[10][7][11][12] va shu sababli prostata saratonini davolashda ularning o'rnini asosan egalladi.[2][13][14][10][15][16][17]

1940-yillarning boshlarida erkaklardagi prostata saratoni o'sishi jarrohlik kastratsiya bilan regressiya qilinganligi yoki yuqori dozali estrogen juda past darajadagi qon aylanishini keltirib chiqaradigan terapiya testosteron va ma'muriyati bilan tezlashdi ekzogen testosteron.[18][19] O'shandan beri androgenlar testosteron va dihidrotestosteron (DHT) funktsiyasi sifatida trofik omillar uchun prostata bezi, rag'batlantiruvchi hujayraning bo'linishi va ko'payish va ishlab chiqarish to'qima o'sishi va prostata bezi saratoni fonida stimulyatsiyaga olib keladigan bezlarning kattalashishi o'smalar va kasallikning rivojlanishining sezilarli darajada tezlashishi.[20] Ushbu kashfiyotlar natijasida, androgen etishmovchiligini davolash (ADT), turli xil usullar bilan, shu jumladan jarrohlik kastratsiyasi, yuqori dozada estrogenlar, SAAlar, GnRH analoglari, NSAAlarva androgen biosintezi inhibitörleri (masalan, abirateron asetat ), prostata saratoni davolashning asosiy usuli bo'ldi.[18] Garchi ADT prostata o'smalarini qisqartirishi yoki barqarorlashtirishi va shu sababli prostata saratoni rivojlanishini sezilarli darajada sekinlashtirishi va umrini uzaytirishi mumkin, umuman davolash mumkin emas. Dastlab kasallikning rivojlanishini sekinlashtiradigan samarali bo'lsa-da, eng rivojlangan prostata saratoni bemorlari oxir-oqibat chidamli bo'lib qoladilar ADT va prostata saratoni o'sishi qisman progressivligi sababli yana tezlasha boshlaydi mutatsiyalar ichida androgen retseptorlari (AR) natijasida bikalutamid kabi preparatlar aylanadi AR antagonistlar agonistlar.[21]

Fikrlash uchun asosni bir necha kuzatuvlar tashkil etadi estrodiol blokadasi (CAB), unda kastratsiya va an NSAA birlashtirilgan.[22] Kastratsiya singari juda past darajadagi androgenlar prostata saratoni hujayralarining o'sishini sezilarli darajada rag'batlantirishga va kasallikning rivojlanishini tezlashtirishga qodir ekanligi aniqlandi.[23] Kastratsiya gonadalar tomonidan androgenlarni ishlab chiqarishni to'xtatib, aylanma testosteron miqdorini 95% ga kamaytirsa ham,[24] tomonidan past darajadagi androgenlar ishlab chiqarilishi davom etmoqda buyrak usti bezlari, va bu aylanma testosteronning qoldiq darajasini hisobga oladi.[25] Bundan tashqari, prostata bezi darajasi aniqlandi DHTprostata tarkibidagi asosiy androgen bo'lgan kastratsiyadan so'ng dastlabki qiymatlarining 40-50% gacha qoladi.[25][26] Buning sababi aylanma zaifni qabul qilish hisobiga aniqlangan buyrak usti androgenlari kabi dehidroepiandrosteron (DHEA) va androstenedion (A4) prostata va ularning de novo testosteronga aylanishi va DHT.[25][26][27] Shunday qilib, prostata bezi ichida androjen signalizatsiyasi kastratsiya bilan ham davom etadi.[25][26][27]

Ilgari, jarrohlik adrenalektomiya va shunga o'xshash erta androgen biosintezi inhibitörleri ketokonazol va aminoglutetimid Kastratsiyaga chidamli prostata saratonini davolashda muvaffaqiyatli ishladilar.[24][18][28][29] Ammo adrenalektomiya yuqori darajadagi invaziv usul hisoblanadi kasallanish, ketokonazol va aminoglutetimid nisbatan yuqori toksiklikka ega va davolashning har ikkala usuli ham qo'shimchani talab qiladi kortikosteroidlar, ularni ko'p jihatdan unideal qilish.[18][30][31][32] Ning rivojlanishi KABINA bilan NSAAlar bikalutamid va enzalutamid singari va abirateron asetat singari yangi va toqatli androgen biosintezi inhibitörleri bilan, avvalgi usullarni almashtirgan invaziv bo'lmagan, qulay va yaxshi muhosaba qilingan terapiyalarga imkon berdi.[29][33]

Keyingi klinik tadqiqotlar shuni ko'rsatdiki, yuqori dozalarda monoterapiya NSAAlar ishlatilganidan ko'ra KABINA prostata saratoni bilan kasallangan erkaklarda hayotni uzaytirishda kastratsiyaga teng keladi.[10][18][34][35] Bundan tashqari, NSAA monoterapiya umuman yaxshiroq muhosaba qilinadi va katta bilan bog'liq hayot sifati kastratsiyadan ko'ra,[36][37][38][39] bu testosteron darajasi kamaymasligi bilan bog'liq deb o'ylashadi NSAA monoterapiya va shu sababli kengaytirilgan darajalar biologik faol va foydali metabolitlar estrogenlar va kabi testosteronning neyosteroidlar saqlanib qolgan.[38][39][40][41][42] Shu sabablarga ko'ra, NSAA monoterapiya kastratsiyaning muhim muqobiliga aylandi va KABINA prostata saratonini davolashda.[43][44][45]

Bikalutamid boshlanganda testosteron alevlenmesi ta'sirini kamaytirish uchun ishlatilishi mumkin GnRH agonist terapiya.[46][47]

Bikalutamid kabi estrogen bilan birikmasi etinilestradiol sulfanat shakli sifatida ishlatilgan KABINA va bikalutamidni jarrohlik yoki tibbiy kastratsiya bilan birlashtirishga alternativa sifatida.[48]

Teri va soch holati

Shuningdek qarang: Flutamid § Teri va sochlarning holati va Nilutamid § Teri kasalliklari

Androgenlar testosteron va DHT ichida hal qiluvchi rol o'ynaydi patogenez bir qator dermatologik holatlar shu jumladan husnbuzar, seboreya, hirsutizm (ayollarda yuz / tana sochlarining haddan tashqari o'sishi), va soch to'kilishi (androgenik alopesiya).[49] Buni namoyish qilishda ayollar to'liq androgen befarqligi sindromi (CAIS) ishlab chiqarmaydi sebum yoki husnbuzarni rivojlantiring va juda ozi yo'q tanasi, umumiy, yoki aksillar sochlari.[50][51] Bundan tashqari, erkaklar tug'ma 5a-reduktaza II tip etishmovchiligi, 5a-reduktaza bo'lish ferment testosteronning teridagi androgen ta'sirini sezilarli darajada kuchaytiradi, ozgina miqdorda husnbuzarlarga ega emas yuz sochlari, tanadagi sochlarning kamayishi va erkaklarning sochlari to'kilishi holatlari qayd etilmagan.[52][53][54][55][56] Aksincha, giperandrogenizm Masalan, ayollarda polikistik tuxumdon sindromi (PCOS) yoki tug'ma buyrak usti giperplaziyasi (CAH), odatda akne va hirsutizm bilan bog'liq virilizatsiya (erkalash) umuman olganda.[49] Yuqorida aytib o'tilganlarga muvofiq, antiandrogenlar yuqorida aytib o'tilganlarni davolashda juda samarali ekanligi aniqlandi androgenga bog'liq teri va sochlarning holati.[57][58]

Kuniga 25 mg bikalutamid monoterapiyasi bilan davolangan 37 yoshli ayolda bosh terisi soch zichligini yaxshilash.[59] Chap davolashdan oldin, o'ng esa 6 oylik terapiyadan keyin.[59]

Klinik tadkikotlarda past dozali bikalutamid ayollarda hirsutizmni davolashda samarali ekanligi aniqlandi.[60][61][62][63][64][65][66] Tadqiqotlardan birida dori-darmonlarga yaxshi muhosaba qilingan, barcha bemorlarda soch zichligi sezilarli darajada pasaygan va klinik jihatdan sezilarli yaxshilanish kuzatilgan Ferriman - Gallvey ballari 3 oyda 41,2% ga va 6 oyda 61,6% ga kamaygan (22,0 ± 5,1 dan 8,6 ± 3,5 gacha).[67][68][62] 2013 yilgi tekshiruv natijalariga ko'ra, "Bikalutamidning past dozasi (kuniga 25 mg) hirsutizmni davolashda samarali ekanligi ko'rsatilgan IH va PCOS. Bu hech qanday jiddiy yon ta'sirga ega emas [yoki olib kelishi mumkin] tartibsiz davrlar."[61] 2017 yilda bikalutamidning a bilan birikmasi tug'ilishni nazorat qilish uchun estrodiol a da baholandi III bosqich klinik sinov bilan kasallangan ayollarda og'ir hirsutizmni davolash uchun PCOSva faqatgina tug'ruqni nazorat qilishning birlashtirilgan tabletkasidan ancha samarali ekanligi aniqlandi.[69][70][64] Bundan tashqari, bikalutamidning xavfsizligi va nojo'ya ta'sirlarni keltirib chiqarishi ko'rsatildi, faqat o'sishining sezilarli o'sishi bundan mustasno umumiy xolesterin va past zichlikdagi lipoprotein darajalar.[64] 2019 yilda o'tkazilgan tadqiqotda bikalutamid ayollarda bosh terisi sochlarini davolashda samarali ekanligi haqida xabar berilgan.[59]

Ayollarda husnbuzarlarni davolashda hirsutizmdan tashqari bikalutamiddan foydalanish mumkin.[71][72][73][74] Flutamid odatda past dozalarda ham husnbuzar alomatlarini 80 yoki 90% ga kamaytirishi aniqlandi, shu bilan birga bir necha tadkikotlar aknening to'liq tozalanishini ko'rsatdi.[75][76][77] Bir tadqiqotda, bu 3 oy ichida husnbuzar ballarini 80% ga kamaytirdi, aksincha SAA spironolakton shu davrda simptomlar atigi 40% ga kamaydi.[77][78][79] Bikalutamid antandrogen ta'siriga ega, bu flutamid bilan taqqoslanadigan yoki undan kattaroqdir va shu kabi terapevtik foyda keltirishi kutilgan.[80][36] Seboreik va soch to'kilishi kabi androgenga bog'liq bo'lgan boshqa teri va soch kasalliklari ham bikalutamid bilan davolanishi mumkin.[81] Akne bilan bir qatorda, flutamid seboreya va androgenga bog'liq bosh terisi to'kilishining 80% yoki undan ko'p pasayishiga olib kelishi aniqlandi.[82] Bundan tashqari, tug'ruqni nazorat qilish uchun estrodiol tabletka bilan birgalikda, flutamid bilan davolash, bitta kichik tadqiqotda soch to'kilishidan aziyat chekadigan deyarli barcha ayollarda kosmetik jihatdan maqbul sochlar zichligi oshishiga olib keldi.[77] Bikalutamid - bu ayollarda androgenga bog'liq teri va sochlarning holatini davolash uchun flutamidga jozibali alternativ, chunki flutamid jiddiy xavfga ega jigar toksikligi,[83][84] qaysi bikalutamid bilan bo'lishmaydi.[74][72][85]

Flutamid va bikalutamid kabi antiandrogenlar erkaklarga xosdir teratogenlar bu erkakni ayollashtirishi mumkin homila antiandrogen ta'siriga bog'liq.[57][86][87] Shu sababli, ular tomonidan tavsiya etilmaydi BIZ. Oziq-ovqat va dori-darmonlarni boshqarish ayollarda foydalanish uchun.[88] Ushbu xavf tufayli antiandrogenlarni faqat reproduktiv yoshdagi ayollarni etarli kontratseptsiya bilan birgalikda davolash uchun qo'llash tavsiya etiladi.[57][86][87] Tug'ilishni nazorat qilish tabletkalari, tarkibida estrogen va a progestin, odatda bu maqsadda ishlatiladi.[57] Bundan tashqari, tug'ilishni nazorat qilish tabletkalari o'zlari funktsional antiandrogen hisoblanadi va androgenga bog'liq teri va soch holatlarini davolashda mustaqil ravishda samarali bo'ladi; shuning uchun ular bunday holatlarni davolashda antiandrogen ta'sirini sezilarli darajada oshirishi mumkin.[57][89]

Transgender gormoni terapiyasi

Shuningdek qarang: Ayollashtiruvchi gormon terapiyasi § Nonsteroid antiandrogenlar va Nilutamid § Transgender gormoni bilan davolash

Bikalutamid antiandrogen sifatida ishlatiladi ayollarni gormonlarni davolash uchun transgender ayollar va a balog'at yoshini to'suvchi o'spirinda transgender qizlar.[90][91][92][93][94][95][96][97] Uni transgender ayollarda an bilan birgalikda ishlatish mumkin estrogen va yolg'iz.[90][92][98] Dori to'g'ridan-to'g'ri ta'sirini bloklaydi androgenlar kabi testosteron va dihidrotestosteron tanada va o'z-o'zidan ishlatilganda, shuningdek, sezilarli darajada ko'payishiga olib keladi estradiol darajalar.[90][97] Natijada, bikalutamid sabab bo'ladi demaskinizatsiya va qo'shimcha ravishda targ'ib qilishi mumkin feminizatsiya, estrogenni bir vaqtda ishlatmasdan ham.[90][92][98] Bu nuqsonli ayollarda paydo bo'ladigan narsalarga o'xshashdir AR sababli to'liq androgen befarqligi sindromi.[99] Ularda bikalutamidning demaskulinlashtiruvchi va ayollashtiruvchi ta'siri tug'ilish paytida erkak tayinlangan o'z ichiga oladi ko'krak rivojlanishi,[92][98][100][101][102] kamaytirilgan soch turmagi,[103] mushak massasining pasayishi,[104] ayol o'zgarishlar yog 'tarqalishi, kamaydi jinsiy aloqada bo'lish,[104] va kamaytirilgan o'z-o'zidan erektsiya.[105] Bikalutamidning kuniga 25 dan 50 mg gacha bo'lgan dozalari ishlatilgan va transgender ayollarda foydalanish uchun tavsiya etilgan.[91][90][106][96][92] Shu bilan birga, bikalutamidning past dozalari ham bunday maqsadlar uchun samarali bo'lishi mumkin.[94]

Boshqa antioksidantlardan farqli o'laroq, monoterapiya sifatida ishlatilganda bikalutamid sezilarli darajada oshadi testosteron va tug'ilish paytida erkak tayinlangan shaxslarda estradiol darajasi va shuning uchun bilvosita bo'lishi mumkin estrogenik transgender ayollarda ta'siri.[90][107][97] Bu transgender ayollarda ma'qul, chunki bu feminizatsiyani rivojlantirishga yordam beradi.[90][107][92][98] Shu bilan birga, bikalutamid ko'paymaydi jinsiy gormon darajalari, agar anning etarli dozalari bilan birlashtirilsa antigonadotropin kabi a GnRH analog, estrogen yoki progestogen, tufayli salbiy teskari aloqa ushbu dorilarning jinsiy gormon ishlab chiqarishga ta'siri.[46][108][109] Bikalutamid androgen darajasini pasaytirmagani uchun, uni saqlab qolishda yordam berishni istagan transgender ayollar uchun bu juda qulay antiandrogen bo'lishi mumkin. jinsiy aloqada bo'lish, jinsiy funktsiya va / yoki unumdorlik, kabi testosteron va uning metabolitlarini kuchli darajada bostiradigan antiandrogenlar sifatida CPA va GnRH modulyatorlar, ushbu funktsiyalarni katta darajada buzishi mumkin.[110][111][112] Bikalutamid testosteron miqdorini oshirishga qodir bo'lsa-da, blokirovka qilinganligi sababli ushbu testosteronning ta'siri yo'q AR bikalutamid tomonidan.[93]

Neyman va boshq. (2017, 2019) bikalutamidni a sifatida o'rgangan balog'at yoshini to'suvchi o'spirinda transgender qizlar.[92][98]:477 U yakka o'zi va estrogen bilan birgalikda baholandi.[92][98] Bemorlar o'rtacha yoshi 15,8 (14 yoshdan 18,4 yoshgacha) bo'lgan 14 transgender qiz bo'lib, ular 2013-2017 yillarda 50 mg / kunlik bikalutamid bilan davolangan, ulardan 7 nafari kuzatuvga qaytgan.[92][98] Odamlarda antiandrogen sifatida samaradorlikni ko'rsatishdan tashqari, bikalutamid monoterapiyasi estradiol darajasini oshirdi va ikkilamchi ta'sir sifatida feminizatsiyani kuchaytirdi.[92][98] Bunga ko'krak bezi rivojlanishi kiradi Teri bosqichi O'rtacha 5,7 oylik davolanishdan so'ng bemorlarning 86 foizidan 2 va 3tasi, ettinchi qiz 12,5 oylik ikkinchi kuzatuvida Tanner ko'krakning 3-bosqich rivojlanishini ko'rsatdi.[92][98] Bemorlarda testosteron darajasi 524 dan 619 ng / dL, estradiol darajasi esa 26 dan 61 pg / ml gacha bo'lgan.[92][98] Jigar funktsiyasini sinash ijro etildi va e'tiborga loyiq emas edi.[92][98] Garchi GnRH analoglar - bu transgender o'spirinlarda balog'at yoshini oldini olish uchun birinchi darajali davolash usuli, ular juda qimmatga tushadi va ko'pincha ularni rad etishadi tibbiy sug'urta.[92][98] Tadqiqotchilarning fikriga ko'ra, bikalutamid muqobil alternativani anglatadi GnRH transgender qizlarda balog'atga etishish bloki sifatida analoglar.[92][98]

Transeksüel ayollarda bikalutamidni antiandrogen sifatida baholash bo'yicha tadqiqotlar hozirgi kunda juda cheklangan.[90][113][92][98] Qanday bo'lmasin, bikalutamid giperandrogenizm sababli hirsutizmga chalingan ayollarda (shu jumladan, III bosqich sud jarayoni)[60][61][64] va balog'at yoshiga etmagan bolalarda,[114][115][116][97] va demaskinizatsiya va feminizatsiya - prostata saratoni bilan davolash qilingan erkaklarda bikalutamidning yaxshi hujjatlashtirilgan ta'siri.[103][117][118] Bundan tashqari, bikalutamid bilan bir xil ta'sir mexanizmiga ega bo'lgan nilutamid, chambarchas bog'liq antiandrogen, transgender ayollarda kamida beshta kichik klinik tadkikotlarda baholandi.[107][108][109][119][120][121] U kuniga 300 mg yuqori dozada, xuddi shu dozada prostata saratoni davolashda monoterapiya sifatida ishlatilgan.[107][108][109][119][120][121] Prostata bezi saratonini davolashda bikalutamidning mos keladigan monoterapiya dozasi kuniga 150 mg ni tashkil qiladi.[2][4][5] Flutamid, shuningdek, transgender ayollarda antandrogen sifatida ishlatilgan va kamida ikkita davolash markazi uning tez-tez ishlatilishini xabar qilgan.[91][107][122]

Transeksüel gormon terapiyasi uchun nilutamidning klinik tadkikotlarida, estrogen bilan birgalikda emas, balki yakka o'zi berilgan dori 8 hafta ichida yosh transgender ayollarda (19 yoshdan 33 yoshgacha) kuzatiladigan klinik feminizatsiya belgilarini keltirib chiqardi.[109] Ushbu o'zgarishlarga ko'krak bezi rivojlanishi, sochlarning pasayishi,[108] o'z-o'zidan erektsiya pasayishi va jinsiy aloqada bo'lish,[119] va ijobiy psixologik va hissiy o'zgarishlar.[119][123] Ko'krak rivojlanishining belgilari, masalan, ko'paygan ko'krak bezi sezgirligi, sochlarning pasayishi bilan bir qatorda, feminizatsiyaning dastlabki ko'rsatkichlari bo'lgan va 6 hafta ichida barcha mavzularda sodir bo'lgan.[121][109][119] Nilutamid o'z-o'zidan ikki baravar ko'paydi luteinizan gormon (LH) va testosteron darajasi va uch baravar estradiol darajasi.[108][109][120] Kuniga 100 mkg qo'shimchalar og'zaki etinilestradiol nilutamid terapiyasiga 8 xaftadan so'ng o'sishni bekor qildi LH, testosteron va estradiol darajasi va ayol / kastrat oralig'ida keskin bostirilgan testosteron darajasi.[108][109] Ushbu natijalar asosida nafaqat nilutamid, ayniqsa, nilutamid va estrogen kombinatsiyasi transgender ayollarda antiandrogen ta'sirini va feminizatsiyani keltirib chiqarish nuqtai nazaridan samarali hisoblanadi.[108][109]

Nilutamid transgender gormoni terapiyasi uchun samarali ekanligi aniqlangan bo'lsa-da, prostata saratoni davolashda va ayniqsa klinik jihatdan unchalik jiddiy bo'lmagan boshqa ko'rsatmalar uchun nilutamiddan foydalanish endi dorilarning o'ziga xos nojo'ya ta'sirlari tufayli bekor qilinmoqda. eng muhimi, kasallanishning yuqori darajasi interstitsial pnevmonit.[20][124][125] Bu o'sib borishi mumkin bo'lgan salbiy ta'sir o'pka fibrozi va o'limga olib kelishi mumkin.[126] Gepatotoksisitning haddan tashqari xavfi tufayli flutamid endi tavsiya etilmaydi jigar etishmovchiligi prostata saratoni bilan kasallangan erkaklarda.[127][122][83][128] Shu sababli, yangi va xavfsizroq NSAAlar bikalutamid singari asosan flutamid va nilutamid o'rnini egalladi va endi buning o'rniga tegishli ko'rsatkichlar uchun ishlatiladi.[15][16][17] Selektiv sifatida AR antagonistlar, flutamid, nilutamid va bikalutamidning ta'sir mexanizmi bir xil, bikalutamid esa shunga o'xshash yoki kattaroqdir samaradorlik antandrogen sifatida flutamid va nilutamidga.[129]

Bikalutamidning kuniga 50 mg va undan yuqori dozalarda jigar fermentlarining ko'payishi va gepatotoksikoz xavfi kichikligi ma'lum.[90][93][61][85][130] Natijada, shunday qilish tavsiya etiladi jigar funktsiyasi testlari (LFT) vaqti-vaqti bilan bajariladi.[93][106][131] Tavsiya etilgan protseduralardan biri - LFTni bir oyda, ikki oyda, so'ngra har 6 oyda bir umr davomida tekshirish.[131] Jigar fermentlarini ko'tarish xavfi va jigar etishmovchiligi bikalutamid bilan qaraganda ancha kichikroq ko'rinadi CPA,[85] bu transgender ayollarda eng ko'p ishlatiladigan antiandrogen hisoblanadi Evropa va dunyoning boshqa joylarida.[107][132][133] In Qo'shma Shtatlar, qaerda yagona mamlakatlardan biri CPA tibbiy foydalanish uchun tasdiqlanmagan,[134][135] transgender ayollarda nisbatan zaif va selektiv bo'lmagan antiandrogen spironolakton odatda keng qo'llaniladi.[136][137][138] Bikalutamid - bu transgender ayollarda ushbu antiandrogenlarga qulay alternativa.[90][93][91] Bu juda ham ko'p kuchli dan CPA va spironolakton an AR antagonist.[92][139] Biroq, CPA erkaklarda testosteron darajasi kontekstida bikalutamidga qaraganda ancha kuchli antiandrogen hisoblanadi, chunki uning past dozalarda testosteron miqdorini sezilarli darajada bostirishi qo'shimcha ta'sir ko'rsatadi.[140][141] O'zlarining kerakli natijalariga erisha olmaydigan yoki bunga qodir bo'lmagan transgender ayollarda toqat qil The yon effektlar boshqa antiandrogenlarning klinisyenlari ba'zan bikalutamidni kiritadilar yoki unga o'tadilar.[91][92]

Erkak erta balog'at yoshi

Bikalutamid an bilan birgalikda ishlatiladi aromataza inhibitori kabi anastrozol yoki letrozol davolashda periferik erta balog'at yoshi yosh bolalarda.[142][143][144][114] Kombinatsiya tufayli erkaklar periferik erta yoshdagi balog'at yoshini davolash uchun ishlatilgan oilaviy erkaklar bilan cheklangan erta balog'at yoshi (FMPP, aks holda testotoksikoz deb ataladi) va ozroq darajada Makkun-Olbrayt sindromi.[143][145] Holbuki antigonadotropik kabi dorilar GnRH modulyatorlar va progestogenlar kabi siproteron asetat va medroksiprogesteron asetat odatda davolash uchun ishlatiladi markaziy erta balog'at yoshi, ushbu dorilar periferik erta yoshdagi balog'atga etishishda kam yoki umuman samarasiz, chunki bu balog'at yoshiga etmagan balog'at yoshidan mustaqil gonadotropin sekretsiya.[143] Buning o'rniga, androgen va estrogenlar periferik erta yoshdagi balog'atga etishish davrida to'g'ridan-to'g'ri inhibe qilinishi kerak. jinsiy gormon retseptorlari antagonistlari va sintez inhibitörleri.[143] Bikalutamidning dozasi kuniga bir marta 2 mg / kg (yoki 20 dan 30 kg gacha bo'lgan yoki 45-65 funtgacha bo'lgan o'g'il bolalarda 40-60 mg gacha) dozani erkaklar periferik erta yoshdagi balog'at yoshida qo'llash tavsiya etiladi.[144] Bikalutamid bu holatdagi androgenlarning ta'sirini blokirovka qilish uchun, aromataza inhibitori esa estrogenlar darajasini pasaytirish uchun ishlatiladi.[143] Davolashning maqsadi keyingi rivojlanishning oldini olishdir ikkilamchi jinsiy xususiyatlar va, ayniqsa, o'sish sur'atlarini sekinlashtirish va oxirgi kattalarni yaxshilash uchun balandlik.[143]

Periferik nogironlikning nodir tabiati tufayli, kasallikni davolashda ishlatiladigan dorilar faqat oz sonli bemorlarda cheklangan darajada o'rganilgan.[144][143][146] Sanoat homiysi bo'lgan bikalutamidni ishlatadigan eng katta va yagona tadqiqot, II bosqich, ko'p markazli, xalqaro, ochiq yorliq, bitta qo'l klinik sinov nomi bilan tanilgan Bicalutamide va Anastrozol Ttakrorlash Testotoksikoz (BATT) tadqiqotida 14 yosh bolalarda 12 oy davomida 12,5-100 mg / kunlik bikalutamid va 0,5-1,0 mg / kun anastrozol kombinatsiyasi baholandi. FMPP.[142][147][143][148][149][116][146] O'g'il bolalarning o'rtacha yoshi 4 ± 2 yoshni, 2 yoshdan 9 yoshgacha bo'lgan yoshni tashkil etdi.[142][116][146] Boshlang'ich bosqichda o'g'il bolalar o'rtacha 23 ± 6 kg (52 ± 12 funt), vazni 17-35 kg (37 dan 77 funt) gacha bo'lgan.[146] O'g'il bolalardagi testosteronning o'rtacha umumiy darajasi dastlabki bosqichda 277 ± 208 ng / dL ni tashkil etdi va 6 oyda 523 ± 258 ng / dL va 12 oyda 427 ± 243 ng / dL ga oshdi.[142][116][146] O'g'il bolalarda estradiolning o'rtacha umumiy darajasi boshlang'ich bosqichda 3,8 pg / ml ni tashkil etdi va 6 va 12 oyda nisbatan o'zgarmadi (mos ravishda 2,5 pg / ml va 3,5 pg / ml).[142][116][146] Bikalutamidning dozasi kuniga 12,5 mg dan boshlangan va keyinchalik qon aylanishini ushlab turish uchun zarur bo'lganda sozlash bilan oshirilgan (R) 5 dan 15 mg / ml gacha bo'lgan maqsad oralig'ida -bikalutamid kontsentratsiyasi.[150][142][116][146] Ushbu diapazon (R) prostata saratoni bilan kasallangan kattalar erkaklarida kuniga 30 dan 100 mg gacha bikalutamid bilan erishilgan bikalutamid darajasi.[146][142][4] 12 oylik o'g'il bolalarda bikalutamidning o'rtacha dozasi kuniga 60 ± 29 mg ni tashkil etdi, 86% bolalar 50 yoki 100 mg / kunlik bikalutamidda.[116] Darajalari (R) -bikalutamid dozalari bilan mutanosib bo'lgan va o'g'il bolalarning yoshi yoki vazni bilan bog'liq bo'lmagan.[116]

In BATT sud jarayoni, o'sish tezligi kamaydi, suyak yoshi taraqqiyot sekinlashdi, tajovuzkorlik kamaydi va erkalash, orqali o'lchanadi Tannerni sahnalashtirish ning pubik sochlar va jinsiy a'zolar, keyingi taraqqiyotga o'xshamadi.[143][151][152][116][146] Biroq, o'sish sur'atlarining pasayishi mo''tadil bo'lib, unga etishmayotgan edi statistik ahamiyatga ega (p = 0.053).[143][147][116][146] Aksincha, suyak pishib etish darajasining pasayishi xuddi shunga o'xshash mo''tadil deb ta'riflangan bo'lsa-da, suyak yoshining xronologik yoshga nisbati sezilarli darajada kamaydi (p < 0.0001).[143][147][116][146] Oddiy balog'atga etishish davrida chiziqli o'sish va skeletning kamol topishi asosan o'g'il va qiz bolalardagi testosteron emas, balki estradiol tufayli yuzaga keladi va shu sababli bu balog'atamid va anastrozol birikmasi bilan bu balog'atga etmagan balog'atga etishish nazariy jihatdan asosan aromataza inhibitori bilan bog'liq bo'ladi. bikalutamidda.[153][154] Moyak O'g'il bolalar kuzatilgan yil davomida hajmi biroz oshdi.[116] A Giyohvand moddalarga qarshi yangi dastur uchun bikalutamid FMPP ichida Qo'shma Shtatlar asosida taqdim etildi BATT sinov ma'lumotlari.[142][146][155] Biroq, ariza tomonidan tasdiqlanmagan Oziq-ovqat va dori-darmonlarni boshqarish, bu samaradorlikning etarli dalillarini keltirmadi.[142][146][155] Bikalutamidni ishlatish uchun ko'rsatma berilmagan bo'lsa-da, bikalutamid dorilar yorlig'i tadqiqot natijalarini o'z ichiga olgan holda yangilandi.[142][146] Xususida yon effektlar, Tadqiqotda bikalutamid va anastrozol birikmasi tasvirlangan yaxshi muhosaba qilinadi yo'q bilan xavfsizlik tashvishlar.[150] Biroq, jinekomastiya, bikalutamidga tegishli bo'lib, o'g'il bolalarning deyarli yarmida kuzatilgan.[143][151][116][146] Bundan tashqari, bitta holat yumshoq jigar fermentlarining ko'tarilishi (14 dan 1; 7%), ehtimol bikalutamid bilan bog'liq bo'lgan, kuzatilgan, ammo terapiyani to'xtatmasdan o'z-o'zidan hal qilingan.[142][146]

Bikalutamid va anastrozolni davolashda haqiqiy samaradorligi va xavfsizligini aniqroq aniqlash uchun qo'shimcha tadqiqotlar o'tkazish zarur FMPP.[147] Uchun uzoq muddatli natijalar yo'q BATT o'rganish hali nashr etilgan, ammo tadqiqotda ikkala o'g'il bolalarning 5 yillik kuzatuvi nashr etildi va samaradorligi to'g'risida xabar berildi.[143][151][152][156][149] Tadqiqot barcha o'g'il bolalar voyaga yetguncha davom etishi va kelajakda qo'shimcha nashrni rejalashtirish bilan davom etishi ko'zda tutilgan.[149][143] Ga qo'shimcha ravishda BATT o'qish, turli xil ish bo'yicha hisobotlar va seriyali bikalutamidning erkaklar periferik prekusiyali balog'at yoshidagi aromataza inhibitori bilan birgalikda nashr etilgan.[115][157][158][156][159][160][161][162][163][164] Ushbu hisobotlarda xuddi shunday natijalar ta'riflangan BATT o'rganish.[165][156]

Erkaklarning periferik erta yoshdagi balog'at yoshini davolashda bikalutamidga alternativalar kiradi spironolakton, siproteron asetat va ketokonazol.[143][144] Anastrozol bilan bikalutamid spironolakton va birikmasidan ustun hisoblanadi testolakton periferik erta yoshdagi balog'at yoshida, samaradorligi yuqori va yon ta'siri kamroq.[115][156] Bu bikalutamid spironolaktonga qaraganda ancha kuchli va selektiv antiandrogen ekanligiga mos keladi.[116][156][92] Bikalutamid bilan dozalash osonroq bo'ladi, chunki spironolakton bilan 12 soatlik oraliqda kuniga ikki marta, kuniga bir marta yuborish kerak.[147][143][156] Shu sabablarga ko'ra, bikalutamid kasallikni davolashda spironolakton o'rnini egalladi.[97]:2139 Bikalutamid bilan taqqoslash uchun kuniga bir marta 5 mg / kg (yoki 20 dan 30 kg gacha bo'lgan yoki 45 dan 65 funtgacha bo'lgan o'g'il bolalarda 100 dan 150 mg gacha) spironolaktonning yuqori dozasi erkakning periferik erta yoshdagi balog'atidan foydalanish uchun tavsiya etiladi.[144]

Uzoq muddatli erektsiya

Antiandrogenlar sezilarli darajada engillashtirishi va oldini olishlari mumkin priapizm (ehtimol og'riqli jinsiy olatni erektsiya to'rt soatdan ko'proq davom etadigan) penisning to'g'ridan-to'g'ri blokadasi orqali AR.[166][167] Shunga muvofiq, bikalutamid past dozalarda (har kuni 50 mg dan yoki haftada bir yoki ikki martadan kam) bir qator holatlarda erkaklarda takrorlanadigan priapizmni sezilarli darajada nojo'ya ta'sirlarsiz bartaraf etish uchun topilgan.[168][169][170] va bu ko'rsatkich uchun ishlatiladi yorliqdan tashqari.[171][172] Xabar qilingan holatlarda, libido, qattiq erektsiya, potentsial jinsiy aloqa, orgazm va sub'ektiv ejakulyatsion hajm barchasi buzilmagan yoki o'zgarishsiz qolgan va bicalutamid kuniga 25 mg yoki undan kam dozada yuborilganda jinekomastiya rivojlanmagan.[168][169][170] Ba'zi jinekomastiya va ko'krak bezi sezuvchanligi kuniga 50 mg dan davolangan bitta bemorda paydo bo'lgan, ammo dozasi ikki baravar kamayganda sezilarli darajada yaxshilangan.[170] Ushbu mavzularda kuzatilgan bikalutamidning bardoshlik darajasi profilnikiga qaraganda ancha qulay deb hisoblanadi GnRH analoglar va estrogenlar (ular ushbu holatni davolashda ham qo'llaniladi).[168][169] Biroq, muvaffaqiyatli va yaxshi muhosaba qilingan bo'lsa-da, juda kam holatlar qayd etilgan.[173] Bikalutamidning priapizmga ta'sirchanligiga qaramay, kichik klinik tadqiqotlar shuni ko'rsatdiki, kuniga 50 mg dozada bikalutamid monoterapiyasi hech qanday ta'sir ko'rsatmadi tungi erektsiya prostata saratoni bilan kasallangan erkaklarda.[37][174]

Jinsiy og'ish

The antigonadotropik antiandrogenlar CPA, medroksiprogesteron asetat (MPA) va GnRH analoglarning barchasi davolash uchun keng qo'llanilgan parafiliyalar (masalan, pedofiliya ) va giperseksualizm erkaklarda.[175][176] Ular androgen miqdorini kastrat yoki kastratga yaqin darajada bostiradilar va kamaytirishda yuqori samaradorlikka ega jinsiy istaklar, qo'zg'alish va xatti-harakatlar.[175] Bundan tashqari, ular davolash uchun ishlatiladi jinsiy huquqbuzarlar vositasi sifatida kimyoviy kastratsiya ehtimolini kamaytirish maqsadida retsidiv jinoyat.[175]

Ular parafiliya va giperseksualizmni davolashda o'rganilmagan bo'lsa ham, NSAAlar flutamid va bikalutamid kabi ushbu ko'rsatkichlar uchun potentsial dorilar sifatida taklif qilingan va antigonadotropik antiandrogenlarga nisbatan yuqori toqatlilik va xavfsizlikka ega bo'lishi mumkin.[175][177][178][179] Misol tariqasida, chunki NSAAlar estrogen darajasini kamaytirmang, antigonadotropik antiandrogenlardan farqli o'laroq, ular saqlanib qoladi suyak mineral zichligi (BMD) va juda kam yoki umuman xavfi yo'q osteoporoz va bog'liq suyak sinishi.[175][177][180] Shu bilan birga, estrogen signalini to'sqinlik qilish sababli, jinekomastiyaning sezilarli darajada uchrashi bilan bog'liq NSAAlar.[175] Monoterapiyadan foydalanishdan tashqari, NSAAlar boshlanishi paytida jinsiy aloqani vaqtincha bostirish uchun himoya qilingan GnRH dastlabki testosteron alevlenmesi bilan bog'liq bo'lgan ortib borayotgan androgen signalizatsiyasining oldini olish orqali agonist davolash.[176]

Parafiliya va giperseksualizmni selektiv usulda davolash AR antagonistlar aftidan sog'lom strategiya, bu amalda haqiqatga to'g'ri kelmasligi mumkin.[37] Ajablanarlisi shundaki, jinsiy buzilishning kamligi yoki umuman yo'qligi, shu jumladan jinsiy aloqani yo'qotish va pasayish jinsiy faoliyat, ning klinik tadkikotlarida kuzatilgan NSAA monoterapiya.[37][5] Buning izohi shu NSAAlar androgen darajasini pasaytirmang va estrogenlar va neyosteroidlar kabi testosteron metabolitlari erkaklarda jinsiy aloqa va funktsiyani saqlash uchun juda muhim ahamiyatga ega bo'lishi mumkin.[38][39][40][41][42] Shunga muvofiq, testosteron mahalliy hisoblanadi aromatiklangan estradiolga miya bo'ylab keng tarqaladi va estradiol ko'plarning vositachisi bo'lib ko'rinadi markaziy testosteronning harakatlari.[57] Shu sabablarga ko'ra antigonadotropik antiandrogenlardan farqli o'laroq, NSAA monoterapiya parafiliya va giperseksualizmni boshqarishda cheklangan foydali bo'lishi mumkin.[37] Ning qo'shilishi NSAAlar kabi antigonadotropik antiandrogenlarga GnRH analoglari ba'zi foydali bo'lishi mumkin, ammo, ayniqsa og'ir holatlarda.[176][181] Qanday bo'lmasin, hozirda etarli dalillar mavjud emas va shu sababli qo'shimcha tadqiqotlar o'tkazilishi kerak.[177]

Adabiyotlar

  1. ^ Bagatelle C, Bremner WJ (2003 yil 27-may). Sog'liqni saqlash va kasallikdagi androgenlar. Springer Science & Business Media. 25- betlar. ISBN  978-1-59259-388-0.
  2. ^ a b v d Lemke TL, Uilyams DA (2008). Foyening tibbiy kimyo tamoyillari. Lippincott Uilyams va Uilkins. 121, 1288, 1290-betlar. ISBN  978-0-7817-6879-5. Arxivlandi asl nusxasidan 2017 yil 8 sentyabrda.
  3. ^ Klotz L, Schellhammer P (2005 yil mart). "Kombinatsiyalangan androgen blokadasi: bikalutamid uchun holat". Prostata saratoni klinikasi. 3 (4): 215–9. doi:10.3816 / cgc.2005.n.002. PMID  15882477.
  4. ^ a b v Cockshott identifikatori (2004). "Bikalutamid: klinik farmakokinetikasi va metabolizmi". Klinik farmakokinetikasi. 43 (13): 855–878. doi:10.2165/00003088-200443130-00003. PMID  15509184. Ushbu ma'lumotlar to'g'ridan-to'g'ri glyukuronidatsiya tez tozalanadigan asosiy metabolik yo'l ekanligini ko'rsatadi (S) -bikalutamid, holbuki gidroksillanish, so'ngra glyukuronidlanish sekin tozalanadigan uchun asosiy metabolik yo'ldir (R) -bikalutamid.
  5. ^ a b v d Vellington K, Keam SJ (2006). "Bicalutamide 150mg: uning mahalliy darajada rivojlangan prostata saratoni davolashda qo'llanilishini ko'rib chiqish" (PDF). Giyohvand moddalar. 66 (6): 837–50. doi:10.2165/00003495-200666060-00007. PMID  16706554. S2CID  46966712. Arxivlandi (PDF) asl nusxasidan 2016 yil 28 avgustda.
  6. ^ Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ (sentyabr 1997). "Prostatit karsinomasi rivojlangan bemorlar uchun estrodiol androgen blokadasida flutamid bilan taqqoslaganda bikalutamidning klinik foydalari: er-xotin ko'r, randomizatsiyalangan, ko'p markazli sinovning yakuniy hisoboti. Casodex Combination Study Group". Urologiya. 50 (3): 330–6. doi:10.1016 / S0090-4295 (97) 00279-3. PMID  9301693.
  7. ^ a b v Vogelzang NJ (sentyabr 2012). "Enzalutamid - prostata bezi metastatik saratonini davolashda katta yutuq". Nyu-England tibbiyot jurnali. 367 (13): 1256–7. doi:10.1056 / NEJMe1209041. PMID  23013078. S2CID  32314622. Dastlabki steroid bo'lmagan antiandrogen agentlari - flutamid, nilutamid va bikalutamid2 - metastatik kastratsiyaga chidamli prostata saratoni holatlarida kastratsiyadan kam samaraliroq ekanligi isbotlangan, ammo bikalutamid hanuzgacha o'rtacha darajada samarali sekonder gormon terapiyasi sifatida keng qo'llanilmoqda, chunki uning xavfsizligi juda yaxshi .
  8. ^ Regitz-Zagrosek V (2012 yil 2 oktyabr). Farmakologiyada jinsiy va jinsi farqlari. Springer Science & Business Media. 575– betlar. ISBN  978-3-642-30725-6. Arxivlandi asl nusxasidan 2016 yil 24 iyunda.
  9. ^ Horvich A (2010 yil 11 fevral). Prostata saratonini tizimli davolash. Onkologiya yilnomalari. 17 Suppl 10. OUP Oksford. 44– betlar. doi:10.1093 / annonc / mdl262. ISBN  978-0-19-956142-1. PMID  17018726.
  10. ^ a b v Chabner BA, Longo DL (8 Noyabr 2010). Saraton ximioterapiyasi va bioterapiya: printsiplari va amaliyoti. Lippincott Uilyams va Uilkins. 679-680 betlar. ISBN  978-1-60547-431-1. Strukturaviy nuqtai nazardan antiandrogenlar steroidal, jumladan, siproteron [asetat] (Androkur) va megestrol [asetat] yoki steroid bo'lmagan, shu jumladan flutamid (Eulexin, boshqalar), bikalutamid (Casodex) va nilutamid (Nilandron) deb tasniflanadi. Steroidal antiandrogenlar kamdan kam qo'llaniladi.
  11. ^ Weber GF (2015 yil 22-iyul). Saraton kasalligining molekulyar davolash usullari. Springer. 318– betlar. ISBN  978-3-319-13278-5. Flutamid va nilutamid bilan taqqoslaganda, bikalutamid Androgen retseptorlari uchun 2 baravar ko'paygan, yarim umr uzoqroq va toksikligi sezilarli darajada kamaygan. Flutamidga nisbatan qulayroq xavfsizlik profiliga asoslanib, bikalutamid prostata bezining rivojlangan metastatik karsinomasini davolash uchun Gonadotropinni chiqaruvchi gormon analogi bilan kombinatsiyalangan davolashda qo'llaniladi.
  12. ^ Kolvenbag GJ, Blackledge GR (1996 yil yanvar). "Bikalutamidning dunyo miqyosidagi faolligi va xavfsizligi: qisqacha sharh". Urologiya. 47 (1A Suppl): 70-9, munozara 80-4. doi:10.1016 / s0090-4295 (96) 80012-4. PMID  8560681. Bikalutamid - bu kuniga bir marta qabul qilish qulayligi, prostata saratoni bilan bog'liq faollik va mukammal xavfsizlik profilini ta'minlovchi yangi antiandrogen. U samarali va flutamidga qaraganda yaxshiroq bardoshlik xususiyatiga ega bo'lganligi sababli, bikalutamid prostand bezi saratoniga chalingan bemorlarni davolash uchun kastratsiya bilan birgalikda antiandrogen terapiyasining birinchi to'g'ri tanlovini anglatadi.
  13. ^ Kaliks RA, Del Giglio A (2008). "Ilg'or prostata saratonini boshqarish" (PDF). Revista da Associação Medica Brasileira. 54 (2): 178–82. doi:10.1590 / S0104-42302008000200025. PMID  18506331. Arxivlandi (PDF) asl nusxasidan 2017 yil 10 mayda.
  14. ^ Payen O, Top S, Vessieres A, Brule E, Lauzier A, Plamont M, McGlinchey MJ, Myuller-Bunz H, Jouen G (2011). "Flotamid va bikalutamidning steroid bo'lmagan antiandrogenlari ferrotsenil hosilalarining sintezi va biologik faolligi". Organometalik kimyo jurnali. 696 (5): 1049–1056. doi:10.1016 / j.jorganchem.2010.10.051. Kiproteron asetat klinik jihatdan qo'llanilgan birinchi steroidal antiandrogenlardan biri bo'lgan, ammo uning yon ta'siri, ayniqsa progestin va glyukokortikoid retseptorlari bilan o'zaro ta'siri, bu preparatni nilutamid [3,4], flutamid [3,4], steroid bo'lmagan antiandrogenlarga qaraganda kamroq mashhur qildi. ] va bikalutamid [8].
  15. ^ a b Gulley JL (2011). Prostata saratoni. Demos tibbiy nashriyoti. 81– betlar. ISBN  978-1-935281-91-7. Arxivlandi asl nusxasidan 2016 yil 25 aprelda.
  16. ^ a b Moser L (2008 yil 1-yanvar). Prostata saratonini davolashdagi tortishuvlar. Karger tibbiyot va ilmiy nashrlari. 41-42 betlar. ISBN  978-3-8055-8524-8. Arxivlandi asl nusxasidan 2016 yil 16 mayda.
  17. ^ a b Gulley JL (2011 yil 20-dekabr). Prostata saratoni. Demos tibbiy nashriyoti. 505– betlar. ISBN  978-1-935281-91-7.
  18. ^ a b v d e Figg V, Chau CH, Kichik EJ (14 sentyabr 2010). Prostata saratoni bilan dori-darmonlarni boshqarish. Springer Science & Business Media. 56, 71-72, 75, 93 betlar. ISBN  978-1-60327-829-4.
  19. ^ Kavoussi P, Costabile RA, Salonia A (17 oktyabr 2012). Klinik urologik endokrinologiya: erkaklar salomatligi tamoyillari. Springer Science & Business Media. 7–7 betlar. ISBN  978-1-4471-4404-5.
  20. ^ a b Denis LJ, Griffits K, Kayzari AV, Merfi GP (1999 yil 1 mart). Prostata saratoni bo'yicha darslik: patologiya, diagnostika va davolash: patologiya, diagnostika va davolash. CRC Press. 55, 279-280 betlar. ISBN  978-1-85317-422-3. Arxivlandi asl nusxasidan 2016 yil 3 iyunda.
  21. ^ Balk SP (sentyabr 2002). "Androgen retseptorlari androgenga bog'liq bo'lmagan prostata saratoni uchun maqsad". Urologiya. 60 (3 qo'shimcha 1): 132-8, munozara 138-9. doi:10.1016 / S0090-4295 (02) 01593-5. PMID  12231070.
  22. ^ Sarosdi MF (1999). "Qanday rivojlangan prostata saratoni estrodiol blokirovkasida foydalanish uchun eng maqbul antiandrogen? Birinchi va ikkinchi avlod antiandrogenidan o'tish". Saratonga qarshi dorilar. 10 (9): 791–6. doi:10.1097/00001813-199910000-00001. PMID  10587288.
  23. ^ Dasgupta P, Kirby RS (27 dekabr 2011). Prostata saratoni ABC. John Wiley & Sons. 52- betlar. ISBN  978-1-4443-3437-1.
  24. ^ a b Bruskewitz R (2012 yil 6-dekabr). Prostata atlasi. Springer Science & Business Media. 5, 190-bet. ISBN  978-1-4615-6505-5.
  25. ^ a b v d Denis L (2012 yil 6-dekabr). Prostata saratonida antiandrogenlar: Maxsus endokrin davolash kaliti. Springer Science & Business Media. 128, 158, 203-betlar. ISBN  978-3-642-45745-6.
  26. ^ a b v Luo S, Martel C, Chen C, Labrie C, Candas B, Singh SM, Labrie F (dekabr 1997). "Flutamid yoki Casodex bilan kunlik dozalash maksimal antiandrogen ta'siriga ega". Urologiya. 50 (6): 913–9. doi:10.1016 / S0090-4295 (97) 00393-2. PMID  9426723.
  27. ^ a b Gautier S, Martel C, Labrie F (oktyabr 2012). "Steroid lotinlari androgen retseptorlari sof antagonistlari sifatida". Steroid biokimyosi va molekulyar biologiya jurnali. 132 (1–2): 93–104. doi:10.1016 / j.jsbmb.2012.02.006. PMID  22449547. S2CID  28982450.
  28. ^ Lupulesku A (1990 yil 24 oktyabr). Saraton kasalligini davolashda gormonlar va vitaminlar. CRC Press. 113– betlar. ISBN  978-0-8493-5973-6.
  29. ^ a b Petrovich Z, Baert L, Brady LW (2012 yil 6-dekabr). Prostata karsinomasi: menejmentdagi yangiliklar. Springer Science & Business Media. 687– betlar. ISBN  978-3-642-60956-5.
  30. ^ Held-Warmkessel J (2006). Prostata saratoni bilan bog'liq dolzarb muammolar: hamshiralik istiqboli. Jones va Bartlett Learning. 275– betlar. ISBN  978-0-7637-3075-8.
  31. ^ Steckler T, Kalin N, Reul J (2005 yil 25-fevral). Stress va miya haqida qo'llanma 2-qism: Stress: integral va klinik jihatlar. Elsevier. 442– betlar. ISBN  978-0-08-055331-3.
  32. ^ Hong WK, Holland JF (2010). Holland-Frei saraton kasalligi 8. PMPH-AQSh. 939– betlar. ISBN  978-1-60795-014-1.
  33. ^ Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA (25 avgust 2011). Kempbell-Uolsh urologiyasi: Ekspert bilan maslahatlashing Premium nashri: Kengaytirilgan onlayn xususiyatlar va chop etish, 4 jildli to'plam. Elsevier sog'liqni saqlash fanlari. 2938-2939, 2946-betlar. ISBN  978-1-4160-6911-9. Arxivlandi asl nusxasidan 2016 yil 5 mayda.
  34. ^ Mydlo JH, Godec CJ (29 sentyabr 2015). Prostata saratoni: Ilmiy va klinik amaliyot. Elsevier Science. 516-521, 534-540-betlar. ISBN  978-0-12-800592-7. Arxivlandi asl nusxasidan 2017 yil 8 sentyabrda.
  35. ^ Strauss III JF, Barbieri RL (2013 yil 28-avgust). Yen & Jaffening reproduktiv endokrinologiyasi: fiziologiya, patofiziologiya va klinik boshqaruv. Elsevier sog'liqni saqlash fanlari. 688– betlar. ISBN  978-1-4557-5972-9. Bikalutamidni qabul qiladigan erkaklarda suyak zichligi yaxshilanadi, ehtimol bu estradiolning 146% ko'payishi va estradiol erkaklarda suyak zichligining asosiy vositachisi ekanligi bilan ikkinchi darajali bo'ladi.
  36. ^ a b Fradet Y (fevral 2004). "Bikalutamid (Casodex) prostata saratoni davolashda". Saraton kasalligiga qarshi kurash bo'yicha mutaxassis. 4 (1): 37–48. doi:10.1586/14737140.4.1.37. PMID  14748655. S2CID  34153031.
  37. ^ a b v d e Iversen P, Melezinek I, Shmidt A (2001 yil yanvar). "Nonsteroid antiandrogenlar: prostata saratoni rivojlangan, jinsiy qiziqish va funktsiyasini saqlab qolishni istagan bemorlar uchun terapevtik variant" BJU xalqaro. 87 (1): 47–56. doi:10.1046 / j.1464-410x.2001.00988.x. PMID  11121992. S2CID  28215804.
  38. ^ a b v Wibowo E, Schellhammer P, Wassersug RJ (2011 yil yanvar). "Erkakning normal faoliyatidagi estrogenning roli: prostata saratoni bilan og'rigan bemorlarning androgen etishmovchiligini davolash bo'yicha klinik ta'siri". Urologiya jurnali. 185 (1): 17–23. doi:10.1016 / j.juro.2010.08.094. PMID  21074215.
  39. ^ a b v Motofei IG, Rowland DL, Popa F, Kreienkamp D, Paunica S (2011 yil iyul). "Heteroseksual va gomoseksual prostata saratoni bilan kasallangan bemorlarda bikalutamid bilan dastlabki tadqiqotlar: erkaklar gomoseksual qo'zg'alishida androgenlarning mumkin bo'lgan ta'siri". BJU xalqaro. 108 (1): 110–5. doi:10.1111 / j.1464-410X.2010.09764.x. PMID  20955264. S2CID  45482984.
  40. ^ a b Wibowo E, Wassersug RJ (sentyabr 2013). "Estrogenning kastrlangan erkaklarning jinsiy qiziqishiga ta'siri: prostata saratoni bilan og'rigan bemorlarning androgen-deprivatsiya terapiyasiga ta'siri". Onkologiya / gematologiya bo'yicha tanqidiy sharhlar. 87 (3): 224–38. doi:10.1016 / j.critrevonc.2013.01.006. PMID  23484454.
  41. ^ a b Chedrese PJ (2009 yil 13-iyun). Reproduktiv endokrinologiya: Molekulyar yondashuv. Springer Science & Business Media. 233– betlar. ISBN  978-0-387-88186-7. Arxivlandi asl nusxasidan 2017 yil 5 sentyabrda.
  42. ^ a b King SR (2008). "Emerging roles for neurosteroids in sexual behavior and function". Andrologiya jurnali. 29 (5): 524–33. doi:10.2164/jandrol.108.005660. PMID  18567641. S2CID  8834769.
  43. ^ Anderson J (2003 yil mart). "The role of antiandrogen monotherapy in the treatment of prostate cancer". BJU xalqaro. 91 (5): 455–61. doi:10.1046 / j.1464-410X.2003.04026.x. PMID  12603397. S2CID  8639102.
  44. ^ Boccardo F (August 2000). "Hormone therapy of prostate cancer: is there a role for antiandrogen monotherapy?". Onkologiya / gematologiya bo'yicha tanqidiy sharhlar. 35 (2): 121–32. doi:10.1016/S1040-8428(00)00051-2. PMID  10936469.
  45. ^ Kolvenbag GJ, Iversen P, Newling DW (2001). "Antiandrogen monotherapy: a new form of treatment for patients with prostate cancer". Urologiya. 58 (2 Suppl 1): 16–23. doi:10.1016/s0090-4295(01)01237-7. PMID  11502439.
  46. ^ a b Shlomo Melmed (1 January 2016). Uilyams Endokrinologiya darsligi. Elsevier sog'liqni saqlash fanlari. 752– betlar. ISBN  978-0-323-29738-7. GnRH analogues, both agonists and antagonists, severely suppress endogenous gonadotropin and testosterone production [...] Administration of GnRH agonists (e.g., leuprolide, goserelin) produces an initial stimulation of gonadotropin and testosterone secretion (known as a "flare"), which is followed in 1 to 2 weeks by GnRH receptor downregulation and marked suppression of gonadotropins and testosterone to castration levels. [...] To prevent the potential complications associated with the testosterone flare, AR antagonists (e.g., bicalutamide) are usually coadministered with a GnRH agonist for men with metastatic prostate cancer.399
  47. ^ Sugiono M, Vinkler MH, Okeke AA, Benni M, Gillatt DA (2005). "Bicalutamide vs cyproterone acetate in preventing flare with LHRH analogue therapy for prostate cancer—a pilot study". Prostata saratoni va prostata kasalliklari. 8 (1): 91–4. doi:10.1038 / sj.pcan.4500784. PMID  15711607. S2CID  9151853.
  48. ^ Wolfgang Hinkelbein; Kurt Miller; Thomas Wiegel (7 March 2013). Prostatakarzinom — urologische und strahlentherapeutische Aspekte: urologische und strahlentherapeutische Aspekte [Prostate carcinoma — urological and radiotherapeutic aspects: urological and radiotherapeutic aspects]. Springer-Verlag. 99- betlar. ISBN  978-3-642-60064-7.
  49. ^ a b Zouboulis CC, Degitz K (2004). "Androgen action on human skin -- from basic research to clinical significance". Eksperimental dermatologiya. 13 Suppl 4: 5–10. doi:10.1111/j.1600-0625.2004.00255.x. PMID  15507105. S2CID  34863608.
  50. ^ Shalita AR, Del Rosso JQ, Webster G (21 March 2011). Acne Vulgaris. CRC Press. 33– betlar. ISBN  978-1-61631-009-7. Arxivlandi asl nusxasidan 2016 yil 9 dekabrda.
  51. ^ Zouboulis CC, Katsambas AD, Kligman AM (28 July 2014). Pathogenesis and Treatment of Acne and Rosacea. Springer. 121–21 betlar. ISBN  978-3-540-69375-8. Arxivlandi from the original on 10 December 2016.
  52. ^ Marks LS (2004). "5alpha-reductase: history and clinical importance". Urologiya bo'yicha sharhlar. 6 Suppl 9: S11–21. PMC  1472916. PMID  16985920.
  53. ^ Sloane E (2002). Biology of Women. O'qishni to'xtatish. 160–16 betlar. ISBN  0-7668-1142-5.
  54. ^ Hanno PM, Guzzo TJ, Malkowicz SB, Wein AJ (26 January 2014). Penn Clinical Manual of Urology E-Book: Expert Consult - Online. Elsevier sog'liqni saqlash fanlari. 782– betlar. ISBN  978-0-323-24466-4.
  55. ^ Harper C (1 August 2007). Interters. Berg. 123–23 betlar. ISBN  978-1-84788-339-1.
  56. ^ Blume-Peytavi U, Whiting DA, Trüeb RM (26 June 2008). Soch o'sishi va buzilishi. Springer Science & Business Media. pp. 161–162, 181. ISBN  978-3-540-46911-7.
  57. ^ a b v d e f Diamanti-Kandarakis E, Tolis G, Duleba AJ (1995). "Androgens and therapeutic aspects of antiandrogens in women". Journal of the Society for Gynocologic Investigation. 2 (4): 577–92. doi:10.1177/107155769500200401. PMID  9420861. S2CID  32242838. Androgen receptors have been detected in many areas including the cortex, pituitary, hypothalamus, preoptic area, septum, amygdala, thalamus, and brain stem.79,80 These receptors appear to be identical to other ARs and may be activated by both testosterone and 5α-DHT. In the cortex and pituitary, androgens do not undergo significant aromatization, and it appears that the effects of androgens on these tissues are mediated by ARs. In contrast, most of the effects of androgens on the hypothalamus and limbic system are thought to be mediated by estrogen receptors rather than AR.78 This concept, the aromatization hypothesis, has been validated in studies of the brain of the female subhuman primate.
  58. ^ Katsambas AD, Dessinioti C (2010). "Hormonal therapy for acne: why not as first line therapy? facts and controversies". Dermatologiya klinikalari. 28 (1): 17–23. doi:10.1016/j.clindermatol.2009.03.006. PMID  20082945.
  59. ^ a b v Fernandez-Nieto D, Saceda-Corralo D, Rodrigues-Barata R, Hermosa-Gelbard A, Moreno-Arrones O, Jimenez-Cauhe J, Ortega-Quijano D, Vano-Galvan S (November 2019). "Oral bicalutamide for female pattern hair loss: A pilot study". Dermatol Ther. 32 (6): e13096. doi:10.1111/dth.13096. PMID  31579984. S2CID  203652305.
  60. ^ a b Williams H, Bigby M, Diepgen T, Herxheimer A, Naldi L, Rzany B (22 January 2009). Dalillarga asoslangan dermatologiya. John Wiley & Sons. pp. 529–. ISBN  978-1-4443-0017-8. Arxivlandi asl nusxasidan 2016 yil 2 mayda.
  61. ^ a b v d Erem C (2013). "Update on idiopathic hirsutism: diagnosis and treatment". Acta Clinica Belgica. 68 (4): 268–74. doi:10.2143/ACB.3267. PMID  24455796. S2CID  39120534.
  62. ^ a b Rabe T, Albring C, Blume-Peytavi U, Egarter C, Geisthövel F, König K, Kuhl H, Merkle E, Mueck AO, Reisch N, Schüring A, Stute P, Toth B, Wildt L, Zouboulis CC (2015). "Hirsutismus – Medikamentöse Therapie Gemeinsame Stellungnahme der Deutschen Gesellschaft für Gynäkologische Endokrinologie und Fortpflanzungsmedizin e.V. und des Berufsverbands der Frauenärzte e.V." [Hirsutism – Medicinal treatment. Joint statement of the German Society of Gynaecological Endocrinology and Reproductive Medicine and the Professional Association of Gynaecologists]. Journal für Reproduktionsmedizin und Endokrinologie (nemis tilida). 12 (3): 102–149. ISSN  1810-2107.
  63. ^ Müderris II, Bayram F, Ozçelik B, Güven M (February 2002). "New alternative treatment in hirsutism: bicalutamide 25 mg/day". Ginekologik endokrinologiya. 16 (1): 63–6. doi:10.1080/gye.16.1.63.66. PMID  11915584. S2CID  6942048.
  64. ^ a b v d Moretti C, Guccione L, Di Giacinto P, Simonelli I, Exacoustos C, Toscano V, Motta C, De Leo V, Petraglia F, Lenzi A (2018 yil mart). "Polikistik tuxumdon sindromi va shiddatli xirsutizmdagi kombinatsiyalangan og'iz kontratseptsiyasi va bikalutamid: ikki marta ko'r tasodifiy boshqariladigan sinov". J. klinikasi. Endokrinol. Metab. 103 (3): 824–838. doi:10.1210 / jc.2017-01186. PMID  29211888. S2CID  3784055.
  65. ^ Müderris, II; Öner, G (2009). "Hirsutizm Tedavisinde Flutamid ve Bikalutamid Kullanımı" [Flutamide and Bicalutamide Treatment in Hirsutism]. Turkiye Klinikleri Journal of Endocrinology-Special Topics (turk tilida). 2 (2): 110–2. ISSN  1304-0529.
  66. ^ Costanzo Giulio Moretti, Laura Guccione, Paola Di Giacinto, Amalia Cannuccia, Chiara Meleca, Giulia Lanzolla, Aikaterini Andreadi, Davide Lauro (2016), Efficacy and Safety of Myo-Inositol Supplementation in the Treatment of Obese Hirsute PCOS Women: Comparative Evaluation with OCP+Bicalutamide Therapy, pp. 1325–1326, doi:10.1210/endo-meetings.2016.RE.5.SUN-153 (inactive 2020-11-10), archived from asl nusxasi on 2020-02-01CS1 maint: mualliflar parametridan foydalanadi (havola) CS1 maint: DOI 2020 yil noyabr holatiga ko'ra faol emas (havola)
  67. ^ Bigby M, Herxheimer A, Naldi L, et al. (2014 yil 5-iyun). Dalillarga asoslangan dermatologiya. Vili. 1904- bet. ISBN  978-1-118-35762-0.
  68. ^ Shapiro J (12 November 2012). Hair Disorders: Current Concepts in Pathophysiology, Diagnosis and Management, An Issue of Dermatologic Clinics. Elsevier sog'liqni saqlash fanlari. 187- betlar. ISBN  978-1-4557-7169-1.
  69. ^ Sarrafzadeh Y, Sarrafzadeh S, Sheibani A (2018). "Clinical Gynecologic Endocrinology and Infertility: A Literature Review" (PDF). Journal of Research in Medical and Dental Science. 6 (3): 220–225. doi:10.24896/jrmds.20186334 (harakatsiz 2020-11-10). ISSN  2347-2545.CS1 maint: DOI 2020 yil noyabr holatiga ko'ra faol emas (havola)
  70. ^ Neven AC, Laven J, Teede HJ, Boyle JA (January 2018). "A Summary on Polycystic Ovary Syndrome: Diagnostic Criteria, Prevalence, Clinical Manifestations, and Management According to the Latest International Guidelines". Semin. Reproduktsiya. Med. 36 (1): 5–12. doi:10.1055/s-0038-1668085. PMID  30189445.
  71. ^ Ascenso A, Marques HC (January 2009). "Acne in the adult". Tibbiy kimyo bo'yicha mini sharhlar. 9 (1): 1–10. doi:10.2174/138955709787001730. PMID  19149656.
  72. ^ a b Kaur S, Verma P, Sangwan A, Dayal S, Jain VK (2016). "Etiopathogenesis and Therapeutic Approach to Adult Onset Acne". Hindistonlik J Dermatol. 61 (4): 403–7. doi:10.4103/0019-5154.185703. PMC  4966398. PMID  27512185.
  73. ^ Xassun LA, Chaxal DS, Sivamani RK, Larsen LN (iyun 2016). "Akne davolashda gormonal vositalardan foydalanish". Semin Kutan Med Surg. 35 (2): 68–73. doi:10.12788 / j.sder.2016.027. PMID  27416311.
  74. ^ a b Azarchi S, Bienenfeld A, Lo Sicco K, Marchbein S, Shapiro J, Nagler AR (oktyabr 2018). "Ayollarda androgenlar: teri kasalliklarini gormonlarni modulyatsiya qiluvchi davolash usullari (II qism)". J. Am. Akad. Dermatol. 80 (6): 1509–1521. doi:10.1016 / j.jaad.2018.08.061. PMID  30312645.
  75. ^ Bettoli V, Zauli S, Virgili A (July 2015). "Is hormonal treatment still an option in acne today?". Br. J. Dermatol. 172 Suppl 1: 37–46. doi:10.1111/bjd.13681. PMID  25627824. S2CID  35615492.
  76. ^ Nguyen HL, Tollefson MM (2017). "Endocrine disorders and hormonal therapy for adolescent acne". Curr. Opin. Pediatr. 29 (4): 455–465. doi:10.1097/MOP.0000000000000515. PMID  28562419. S2CID  4640778.
  77. ^ a b v Diamanti-Kandarakis E (1999 yil sentyabr). "Ayollarda antiandrogen terapiyasining dolzarb jihatlari". Curr. Farm. Des. 5 (9): 707–23. PMID  10495361. Several trials demonstrated complete clearing of acne with flutamide [62,77]. Flutamide used in combination with an [oral contraceptive], at a dose of 500mg/d, flutamide caused a dramatic decrease (80%) in total acne, seborrhea and hair loss score after only 3 months of therapy [53]. When used as a monotherapy in lean and obese PCOS, it significantly improves the signs of hyperandrogenism, hirsutism and particularly acne [48]. [...] flutamide 500mg/d combined with an [oral contraceptive] caused an increase in cosmetically acceptable hair density, in sex of seven women suffering from diffuse androgenetic alopecia [53].
  78. ^ Uolter Braun Shelli; E. Dorinda Shelli (2001). Kengaytirilgan dermatologik terapiya II. V. B. Sonders. ISBN  978-0-7216-8258-7.
  79. ^ Adam Balen; Stiven Frenks; Roy Gomburg; Shon Kehoe (2010 yil oktyabr). Polikistik tuxumdon sindromining hozirgi boshqaruvi. Kembrij universiteti matbuoti. 132– betlar. ISBN  978-1-906985-41-7.
  80. ^ Blackledge GR (1996). "Clinical progress with a new antiandrogen, Casodex (bicalutamide)". Yevro. Urol. 29 Suppl 2: 96–104. doi:10.1159/000473847. PMID  8717470.
  81. ^ Lotti F, Maggi M (2015). "Teridagi androgen bilan bog'liq kasalliklarni gormonal davolash". European Handbook of Dermatological Treatments: 1451–1464. doi:10.1007/978-3-662-45139-7_142. ISBN  978-3-662-45138-0.
  82. ^ Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Hozirgi dorivor kimyo. 7 (2): 211–47. doi:10.2174/0929867003375371. PMID  10637363. S2CID  20732899.
  83. ^ a b Giorgetti R, di Muzio M, Giorgetti A, Girolami D, Borgia L, Tagliabracci A (mart 2017). "Flutamid ta'sirida gepatotoksiklik: axloqiy va ilmiy masalalar". Eur Rev Med Pharmacol Sci. 21 (1 ta qo'shimcha): 69-77. PMID  28379593.
  84. ^ Shaw JC (July 2002). "Hormonal therapies in acne". Mutaxassis Opin farmakoterusi. 3 (7): 865–74. doi:10.1517/14656566.3.7.865. PMID  12083987. S2CID  44388601.
  85. ^ a b v Thole Z, Manso G, Salgueiro E, Revuelta P, Hidalgo A (2004). "Antiandrogenlar tomonidan qo'zg'atilgan gepatotoksiklik: adabiyotlarni ko'rib chiqish". Urol. Int. 73 (4): 289–95. doi:10.1159/000081585. PMID  15604569. S2CID  24799765.
  86. ^ a b Iswaran TJ, Imai M, Betton GR, Siddall RA (May 1997). "An overview of animal toxicology studies with bicalutamide (ICI 176,334)". Toksikologik fanlar jurnali. 22 (2): 75–88. doi:10.2131/jts.22.2_75. PMID  9198005.
  87. ^ a b Smith RE (4 April 2013). Medicinal Chemistry – Fusion of Traditional and Western Medicine. Bentham Science Publishers. 306– betlar. ISBN  978-1-60805-149-6. Arxivlandi from the original on 29 May 2016.
  88. ^ "Bicalutamide". Amerika sog'liqni saqlash tizimi farmatsevtlari jamiyati. Arxivlandi asl nusxasidan 2016 yil 29 dekabrda. Olingan 8 dekabr 2016.
  89. ^ Adam Ostrzenski (2002). Gynecology: Integrating Conventional, Complementary, and Natural Alternative Therapy. Lippincott Uilyams va Uilkins. 86- betlar. ISBN  978-0-7817-2761-7.
  90. ^ a b v d e f g h men j Randolf JF (2018 yil dekabr). "Transgender ayollar uchun jinsni tasdiqlovchi gormon terapiyasi". Clin Obstet Gynecol. 61 (4): 705–721. doi:10.1097 / GRF.0000000000000396. PMID  30256230. ANDROGEN RECEPTOR BLOCKERS: Androgen receptor blockers bind directly to the androgen receptor and either competitively inhibit binding by testosterone or DHT, or irreversibly bind and induce variable antagonist/agonist effects. The prototype drug in this class is flutamide, a competitive inhibitor of the androgen receptor infrequently used clinically today due to complications including liver failure and death. Bicalutamide is a safer, longer acting alternative with a more favorable safety profile, although a small percentage of users will show elevated liver enzymes and rare cases of liver failure have been reported. Bicalutamide is approved for use in prostate cancer at an oral dose of 50 mg daily, but has been used in the treatment of hirsutism, polycystic ovary syndrome, precocious puberty, persistent erections, and in sex offenders. Studies in transwomen are quite limited, but bicalutamide appears to be effective and induces an actual increase in serum estradiol levels, a welcome adjunct effect in transwomen (Table 4). [...] TABLE 4. Available Antiandrogens/Androgen Suppressors and Routes of Administration: [...] Bicalutamide Oral 50 mg daily.
  91. ^ a b v d e Fishman, Sara L.; Paliou, Maria; Poretsky, Leonid; Hembree, Wylie C. (2019). "Endocrine Care of Transgender Adults". Transgender Medicine. Zamonaviy endokrinologiya. 143–163 betlar. doi:10.1007/978-3-030-05683-4_8. ISBN  978-3-030-05682-7. ISSN  2523-3785. Non-steroidal selective androgen receptor antagonists, developed as a treatment for androgen-sensitive prostate cancer, are occasionally used in transgender females who do not achieve their desired results or do not tolerate alternative drugs [52]. There are isolated reports of successful outcomes with flutamide (Eulexin), though reportedly not as effective as cyproterone acetate in reducing testosterone levels [12]. Both flutamide and bicalutamide (Casodex), in conjunction with oral contraceptive pills, have shown significant improvements in hirsutism in natal females with polycystic ovarian syndrome (PCOS) [53, 54, 55, 56, 57]. The use of these agents as antiandrogens in transgender patients has been limited by concerns of hepatotoxicity. However, at low doses, these agents have shown to be both well tolerated and effective when used for the treatment of hirsutism [57]. [...] Table 8.2: Antiandrogens: [...] Androgen receptor blocker: [...] Type: Bicalutamide. Route: Oral. Dose: 25–50 mg/day.
  92. ^ a b v d e f g h men j k l m n o p q r s Neyman A, Fuqua JS, Eugster EA (April 2019). "Bicalutamide as an Androgen Blocker With Secondary Effect of Promoting Feminization in Male-to-Female Transgender Adolescents". J O'smirlar salomatligi. 64 (4): 544–546. doi:10.1016/j.jadohealth.2018.10.296. PMC  6431559. PMID  30612811.
  93. ^ a b v d e Courtney Finlayson (3 August 2018). Pubertal Suppression in Transgender Youth. Elsevier sog'liqni saqlash fanlari. 81, 98-betlar. ISBN  978-0-323-56964-4. As a class, the antiandrogens (bicalutamide, flutamide, and nilutamide bind directly to the androgen receptor, thereby inhibiting its availability and increasing the receptors' degradation.50 The primary indication is for metastatic prostate cancer, although it has been used in the transfeminine population.52 These three agents differ primarily by pharmacokinetics, bicalutamide having the longest duration of action. While on the medication, testosterone levels are expected to rise dramatically but do not have an effect. Gynecomastia is a recognized side effect and could be desired in the transfeminine population. There are cases of fulminant hepatitis described, and it is recommended that transaminase levels are checked prior to initiation and then at 4-month intervals.53 The use of antiandrogens has not been rigorously studied in the gender nonconforming population, but its use is recommended for consideration in some transgender-health related publications.54-56 (p. 98) [...] Spironolactone, a weak androgen receptor antagonist, can also be used in [adolescent transgender girls] if GnRH agonists are not used. The medication, prescribed at dosing ranging from 100 to 300 mg/day orally,7 blunts the effect of androgens and can be helpful at slowing development of unwanted facial and body hair, or other masculinizing effects of male puberty. Other medications that suppress androgen action, including cyproterone acetate, flutamide, nilutamide, and bicalutamide, have been reported for use in transgender women as well.38 (p. 81)
  94. ^ a b Benjamin Vincent (21 June 2018). Transgender Health: A Practitioner's Guide to Binary and Non-Binary Trans Patient Care. Jessica Kingsley nashriyotlari. 158- betlar. ISBN  978-1-78450-475-5. Bicalutamide (Casodex®): This antiandrogen is used by some clinicians in the United States, it is not used in the UK. Its primary use is in the treatment of prostate cancer, but may effectively block testosterone production at much lower doses than are given in that context. Bicalutamide is associated with some risk of liver function abnormalities (Kolvenbag and Blackledge 1996), which are deemed acceptable in the context of prostate cancer but less so in gender affirming medical intervention because of the range of other options available (Deutsch 2017). (pp. 158–159) [...] There has been specific publication of a case of prostate cancer in a transgender woman, 41 years after accessing HRT (Miksad et al. 2006). In this case, oral bicalutamide and dutasteride were prescribed, which were effective in their antiandrogenic functions while also being maintainable with the patient's estrogen regimen. Indeed, bicalutamide may be an option as part of transfeminine HRT due to its antiandrogenic properties, such that synergy may be obtained in specific treatment circumstances. (p. 115–116)
  95. ^ Deutsch M (17 June 2016), Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People (PDF) (2nd ed.), University of California, San Francisco: Center of Excellence for Transgender Health, p. 28, In many countries, cyproterone acetate, a synthetic progestagen with strong anti-androgen activity is commonly used. Cyproterone has been associated with uncommon episodes of fulminant hepatitis.[12] Bicalutamide, a direct anti-androgen used for the treatment of prostate cancer, also has a small but not fully quantified risk of liver function abnormalities (including several cases of fulminant hepatitis); while such risks are acceptable when considering the benefits of bicalutamide in the management of prostate cancer, such risks are less justified in the context of gender affirming treatment.[13] No evidence at present exists to inform such an analysis.
  96. ^ a b Gooren, LJ (31 March 2011). "Clinical practice. Care of transsexual persons". Nyu-England tibbiyot jurnali. 364 (13): 1251–7. doi:10.1056/nejmcp1008161. PMID  21449788. Male-to-Female Transsexuals: Hormonal therapy is prescribed for male-to-female transsexuals to induce breast formation and a more female distribution of fat and to reduce male-pattern hair growth.19 To achieve these goals, the biologic action of androgens must be almost completely neutralized. Administration of estrogens suppresses gonadotropin output and therefore androgen production, but combining this treatment with a progestational agent, a gonadotropin-releasing-hormone (GnRH) analogue,20 or other medications that suppress androgen action (e.g., cyproterone acetate, flutamide, nilutamide, or bicalutamide) appears to be more effective.21 [...] Supplemental Table 1. Cross-sex hormone administration to transsexuals: Male-to-female transsexuals: 1) Drugs suppressing testosterone levels and/or testosterone action: Non-steroidal pure antiandrogens: flutamide 250 mg twice daily, nilutamide 150 mg twice daily, or the more recent bicalutamide 50 mg once daily (fewer side effects).
  97. ^ a b v d e Jameson JL, De Groot LJ (25 February 2015). Edndocrinology: Adult and Pediatric. Elsevier sog'liqni saqlash fanlari. pp. 2139, 2172, 2425–2426. ISBN  978-0-323-32195-2. Male-to-Female Transsexual Treatment. [...] For suppression of androgen secretion/action, several agents are available. In Europe, the most widely used drug is cyproterone acetate (usually 50 mg twice daily), a progestational compound with antiandrogenic properties. If not available, medroxyprogesterone acetate, 5 to 10 mg/day, is a less-effective alternative. Nonsteroidal anti-androgens, such as flutamide and nilutamide [and bicalutamide], are also used, but they increase gonadotropin secretion, causing increased secretion of testosterone and estradiol. The latter is desirable in this context, as it has feminizing effects. Spironolactone (up to 100 mg twice daily), a diuretic with antiandrogenic properties, has similar effects and is widely available.
  98. ^ a b v d e f g h men j k l m n Neyman, A; Fuqua, JS; Eugster, EA (dekabr 2017). "Bikalutamid Androgenni blokirovka qiluvchi vosita bo'lib, ayollarda (MTF) transgender o'spirinlarda erkaklarda feminizatsiyani rag'batlantirishning ikkinchi darajali ta'siriga ega". Pediatriyadagi gormonlar tadqiqotlari. 88: 1–628. doi:10.1159/000481424. PMID  28968603. Xulosa. Objectives: GnRH analogs are first-line treatment for halting pubertal development in gender variant youth. However, this medication is often denied by third party payors. The pure androgen receptor blocker bicalutamide represents a potential alternative approach to blocking puberty in natal males. Here, we describe the use of bicalutamide in MTF transgender patients. Methods: Medical records for patients with gender dysphoria (GD) followed in the pediatric endocrine clinic at Riley Hospital for Children were reviewed. All MTF transgender patients treated with bicalutamide were included. Variables evaluated comprised age, duration of follow up, timing of estrogen initiation, laboratory studies and physical exam findings including change in breast Tanner stage during treatment. Results: Of 77 patients with GD identified, 29 were MTF, of whom 14 (48%) aged 15.8 ± 1.9 years (range 12-18.4yr) were treated with bicalutamide 50 mg daily between 2013 and 2017. Of these, 3 were started on estrogen concurrently whereas 11 received bicalutamide alone, 7 of whom have returned for follow up thus far. After an average of 5.7±1.5 months, 86% of the patients (n=6) had breast development consisting of Tanner stage III in 4, Tanner stage II in 1, and Tanner stage III/11 of the right and left breast in 1. The 7th patient was noted to have Tanner Ill breasts at her 2nd follow-up clinic visit 12.5 months after starting bicalutamide. LFTs were obtained on 4 patients, estradiol on 3 patients and testosterone on 2 patients while exclusively taking bicalutamide. LFTs were unremarkable and concentrations of estradiol and testosterone were 26-61 pg/mL and 524-619 ng/dL, respectively. Conclusions: Bicalutamide is used in rare forms of precocious puberty in males and has a known side effect of gynecomastia. Here, we report the novel use of bicalutamide as a puberty blocker in MTF patients with GD in whom it also results in feminization by causing breast development. Additional studies are needed to further evaluate the potential role of bicalutamide in the therapeutic armamentarium for the treatment of transgender MTF adolescents.
  99. ^ Galani A, Kitsiou-Tzeli S, Sofokleous C, Kanavakis E, Kalpini-Mavrou A (2008). "Androgen insensitivity syndrome: clinical features and molecular defects". Hormones (Athens). 7 (3): 217–29. doi:10.14310/horm.2002.1201. PMID  18694860. S2CID  8232293.
  100. ^ Braunstein GD (September 2007). "Clinical practice. Gynecomastia". Nyu-England tibbiyot jurnali. 357 (12): 1229–37. doi:10.1056/NEJMcp070677. PMID  17881754.
  101. ^ Gentilini OD, Boccardo C (2015). "Male Breast Diseases". The Outpatient Breast Clinic: 431–446. doi:10.1007/978-3-319-15907-2_19. ISBN  978-3-319-15906-5.
  102. ^ Kanhai RC, Hage JJ, van Diest PJ, Bloemena E, Mulder JW (January 2000). "Short-term and long-term histologic effects of castration and estrogen treatment on breast tissue of 14 male-to-female transsexuals in comparison with two chemically castrated men". Amerika jarrohlik patologiyasi jurnali. 24 (1): 74–80. doi:10.1097/00000478-200001000-00009. PMID  10632490.
  103. ^ a b Higano CS (fevral 2003). "Androgenlardan mahrum etish terapiyasining nojo'ya ta'siri: toksikani kuzatish va minimallashtirish". Urologiya. 61 (2 ta qo'shimcha 1): 32-8. doi:10.1016 / S0090-4295 (02) 02397-X. PMID  12667885.
  104. ^ a b Lehne RA (2013). Hamshiralik parvarishi uchun farmakologiya. Elsevier sog'liqni saqlash fanlari. pp. 1297–. ISBN  978-1-4377-3582-6.
  105. ^ el-Rayes BF, Hussain MH (February 2002). "Hormonal therapy for prostate cancer: past, present and future". Saratonga qarshi terapiyani ekspertizasi. 2 (1): 37–47. doi:10.1586/14737140.2.1.37. PMID  12113064. S2CID  6869320. At 2-year follow-up, loss of spontaneous erections and sexual function occurred in 80 vs. 92% and 78 vs. 88% in the [flutamide, nilutamide and bicalutamide] versus CPA groups, respectively.
  106. ^ a b Libby, Valerie; Lee, Mabel; Liu, James H. (2019). "Transgender Health: Hormonal Management at 50 Years and Beyond". Maturitalar. 126: 34–37. doi:10.1016/j.maturitas.2019.04.220. ISSN  0378-5122. PMID  31239115.
  107. ^ a b v d e f Kreukels BP, Steensma TD, de Vries AL (1 July 2013). Jinsiy disforiya va jinsiy rivojlanishning buzilishi: parvarish va bilimdagi taraqqiyot. Springer Science & Business Media. 280- betlar. ISBN  978-1-4614-7441-8. Nonsteroidal antiandrogens, such as flutamide (50–75 mg/day) and nilutamide (150 mg/day), are also used, but they increase gonadotropin output with a rise of testosterone and estradiol; the rise of estradiol is a desirable effect in this context.
  108. ^ a b v d e f g Asscheman H, Gooren LJ, Peereboom-Wynia JD (1989). "Reduction in undesired sexual hair growth with anandron in male-to-female transsexuals—experiences with a novel androgen receptor blocker". Klinik va eksperimental dermatologiya. 14 (5): 361–3. doi:10.1111 / j.1365-2230.1989.tb02585.x. PMID  2612040. S2CID  45303518.
  109. ^ a b v d e f g h Rao BR, de Voogt HJ, Geldof AA, Gooren LJ, Bouman FG (1988). "Anti-androgenni qo'llashdagi afzalliklari va mulohazalari". Steroid biokimyosi jurnali. 31 (4B): 731–7. doi:10.1016/0022-4731(88)90024-6. PMID  3143862.
  110. ^ Gao Y, Maurer T, Mirmirani P (yanvar 2018). "Transgender odamlarda sochlarning buzilishini tushunish va ularga murojaat qilish". Am J Clin Dermatol. 19 (4): 517–527. doi:10.1007 / s40257-018-0343-z. PMID  29352423. S2CID  6467968. Steroid bo'lmagan antiandrogenlarga flutamid, nilutamid va bikalutamid kiradi, ular androgen darajasini pasaytirmaydi va jinsiy aloqa qobiliyatini va unumdorligini saqlamoqchi bo'lgan shaxslar uchun qulay bo'lishi mumkin [9].
  111. ^ Iversen P, Melezinek I, Shmidt A (Yanvar 2001). "Nonsteroid antiandrogenlar: prostata saratoni rivojlangan, jinsiy qiziqish va funktsiyasini saqlab qolishni istagan bemorlar uchun terapevtik variant" BJU xalqaro. 87 (1): 47–56. doi:10.1046 / j.1464-410x.2001.00988.x. PMID  11121992. S2CID  28215804.
  112. ^ Morgante, E; Gradini, R; Realacci, M; Sotish, P; D'eramo, G; Perrone, G A; Kardillo, M R; Petrangeli, E; Russo, Ma; Di Silverio, F (2001). "Anti-androgen bikalutamid bilan uzoq muddatli davolanishning inson moyagiga ta'siri: ultrastrukturaviy va morfometrik tadqiqot". Gistopatologiya. 38 (3): 195–201. doi:10.1046 / j.1365-2559.2001.01077.x. ISSN  0309-0167. PMID  11260298. S2CID  36892099.
  113. ^ "Search query: "bicalutamide" OR "bicalutamid" OR "bikalutamid" OR "bicalutamida" OR "casodex" "transgender" OR "transsexual" OR "transsexuals" OR "trans girls" OR "transgirls" OR "trans women" OR "transwomen" OR "male-to-female" - Google Scholar". Olingan 2019-03-28.
  114. ^ a b Kliegman RM, Stanton B, St Geme J, Schor NF (2015 yil 17 aprel). Pediatriya bo'yicha Nelson darsligi. Elsevier sog'liqni saqlash fanlari. 2661– betlar. ISBN  978-0-323-26352-8.
  115. ^ a b v Kreher, Nerissa C.; Pescovitz, Ora Hirsch; Delameter, Paul; Tiulpakov, Anatoly; Hochberg, Ze’ev (2006). "Oilaviy erkaklar bilan cheklangan erta balog'at yoshini bikalutamid va anastrozol bilan davolash". Pediatriya jurnali. 149 (3): 416–420. doi:10.1016 / j.jpeds.2006.04.027. ISSN  0022-3476. PMID  16939760.
  116. ^ a b v d e f g h men j k l m n Reiter, Edward O.; Mauras, Nelly; McCormick, Ken; Kulshreshtha, Bindu; Amrhein, James; De Luca, Francesco; O'Brien, Sandra; Armstrong, Jon; Melezinkova, Helena (2010). "Bicalutamide plus Anastrozole for the Treatment of Gonadotropin-Independent Precocious Puberty in Boys with Testotoxicosis: A Phase II, Open-Label Pilot Study (BATT)". Journal of Pediatric Endocrinology and Metabolism. 23 (10): 999–1009. doi:10.1515/jpem.2010.161. ISSN  0334-018X. PMID  21158211. S2CID  110630.
  117. ^ Elliott S, Latini DM, Walker LM, Wassersug R, Robinson JW (2010). "Prostata saratoni uchun androgenlarni yo'q qilish terapiyasi: bemor va sheriklarning hayot sifatini yaxshilash bo'yicha tavsiyalar". Jinsiy tibbiyot jurnali. 7 (9): 2996–3010. doi:10.1111 / j.1743-6109.2010.01902.x. PMID  20626600.
  118. ^ Higano CS (2012). "Prostata bezi saratoni uchun aniq davolash va undan keyin androgenni yo'q qilish terapiyasidan keyin jinsiylik va yaqinlik". Klinik onkologiya jurnali. 30 (30): 3720–5. doi:10.1200 / JCO.2012.41.8509. PMID  23008326.
  119. ^ a b v d e van Kemenade JF, Cohen-Kettenis PT, Cohen L, Gooren LJ (1989). "Sof antiandrogen RU 23.903 (anandron) ning jinsiy aloqaga, tajovuzkorlikka va erkak-ayol transseksuallaridagi kayfiyatiga ta'siri". Jinsiy xatti-harakatlar arxivi. 18 (3): 217–28. doi:10.1007 / BF01543196. PMID  2751416. S2CID  44664956.
  120. ^ a b v Gooren L, Spinder T, Spijkstra JJ, van Kessel H, Smals A, Rao BR, Hoogslag M (1987). "Sex steroids and pulsatile luteinizing hormone release in men. Studies in estrogen-treated agonadal subjects and eugonadal subjects treated with a novel nonsteroidal antiandrogen". Klinik endokrinologiya va metabolizm jurnali. 64 (4): 763–70. doi:10.1210 / jcem-64-4-763. PMID  3102546.
  121. ^ a b v de Voogt HJ, Rao BR, Geldof AA, Gooren LJ, Bouman FG (1987). "Androgen ta'sirini blokirovkalash hajmi kamayishiga olib kelmaydi, ammo oddiy prostata prostata gistologiyasini o'zgartiradi". Prostata. 11 (4): 305–11. doi:10.1002 / pros.2990110403. PMID  2960959. S2CID  84632739.
  122. ^ a b Dahl, M; Feldman, JL; Goldberg, J; Jaberi, A (2015). "Britaniya Kolumbiyasidagi transgender kattalar uchun endokrin terapiya: tavsiya etilgan ko'rsatmalar" (PDF). Vankuver qirg'oq sog'lig'i. Olingan 15 avgust 2018.
  123. ^ Cohen-Kettenis PT, Gooren LJ (1993). "Transseksuallarning psixologik faoliyatiga gormonlarni davolashning ta'siri". Psixologiya jurnali va inson jinsiy hayoti. 5 (4): 55–67. doi:10.1300 / J056v05n04_04. ISSN  0890-7064.
  124. ^ Chang C (22 March 2005). Prostata saratoni: asosiy mexanizmlar va terapevtik usullar. Jahon ilmiy. 10-11 betlar. ISBN  978-981-4481-61-8. Arxivlandi asl nusxasidan 2017 yil 8 sentyabrda.
  125. ^ DeVita VT, Lawrence TS, Rosenberg SA (18 March 2016). Prostata va boshqa genitoüriner saraton: saraton: onkologiya tamoyillari va amaliyoti. Wolters Kluwer Health. pp. 1006–. ISBN  978-1-4963-5421-1.
  126. ^ Bennett CL, Raisch DW, Sartor O (October 2002). "Pneumonitis associated with nonsteroidal antiandrogens: presumptive evidence of a class effect". Ichki tibbiyot yilnomalari. 137 (7): 625. doi:10.7326/0003-4819-137-7-200210010-00029. PMID  12353966. An estimated 0.77% of the 6,480 nilutamide-treated patients, 0.04% of the 41,700 flutamide-treated patients, and 0.01% of the 86,800 bicalutamide-treated patients developed pneumonitis during the study period.
  127. ^ Ramon J, Denis L (5 June 2007). Prostata saratoni. Springer Science & Business Media. 256– betlar. ISBN  978-3-540-40901-4.
  128. ^ Dahl, Marshall; Feldman, Jeymi L.; Goldberg, Joshua M.; Jaberi, Afshin (2006). "Transgender endokrin terapiyasining jismoniy jihatlari". Xalqaro transgenderizm jurnali. 9 (3–4): 111–134. doi:10.1300 / J485v09n03_06. ISSN  1553-2739. S2CID  146232471. Flutamide use (750 mg po qd) has been reported by some clinicians (Israel & Tarver, 1997; Levy et al., 2003). Hepatotoxicity has been reported in men receiving comparable doses of flutamide for treatment of prostate cancer (Wysowski, Freiman, Tourtelot, & Horton, 1993), and for this reason we do not recommend flutamide as part of MTF feminization.
  129. ^ Kolvenbag GJ, Furr BJ, Blackledge GR (December 1998). "Receptor affinity and potency of non-steroidal antiandrogens: translation of preclinical findings into clinical activity". Prostata saratoni prostata bezlari. 1 (6): 307–314. doi:10.1038/sj.pcan.4500262. PMID  12496872. S2CID  33497597.
  130. ^ Gretarsdottir, Xelga M.; Byornsdottir, Elin; Byornsson, Einar S. (2018). "Bikalutamid bilan bog'liq bo'lgan o'tkir jigar shikastlanishi va migratsion artralgiya: noyob, ammo klinik jihatdan muhim bo'lgan salbiy ta'sir". Gastroenterologiyada amaliy hisobotlar. 12 (2): 266–270. doi:10.1159/000485175. ISSN  1662-0631. S2CID  81661015.
  131. ^ a b TransLine (5 April 2019). "Gender Affirming Hormone Therapy Guidelines" (PDF). Arxivlandi asl nusxasi (PDF) on 2020-01-11. Olingan 11 yanvar 2019.
  132. ^ Ettner R, Monstrey S, Coleman E (27 May 2016). Transgender tibbiyoti va jarrohlik printsiplari. Yo'nalish. 169– betlar. ISBN  978-1-317-51460-2. In Europe, the most widely used drug [in the treatment of male-to-female patients] is cyproterone acetate [...]
  133. ^ Erickson-Schroth L (12 May 2014). Trans organlari, Trans Selves: Transgender hamjamiyati uchun manba. Oksford universiteti matbuoti. 258– betlar. ISBN  978-0-19-932536-8. Arxivlandi asl nusxasidan 2016 yil 24 iyunda. Cyproterone [asetate] transgender ayollarda asosiy testosteron bloker sifatida AQShdan tashqarida keng qo'llaniladi. Cyproterone, ammo Qo'shma Shtatlarda har qanday kasallik uchun sotishga ruxsat berilmagan va jigar muammolari bilan bog'liq.
  134. ^ F. Uilyam Danbi (2015 yil 27 yanvar). Akne: sabablari va amaliy boshqaruvi. John Wiley & Sons. 142– betlar. ISBN  978-1-118-23277-4.
  135. ^ Loren S Schechter (2016 yil 22-sentyabr). Transgender bemorni jarrohlik yo'li bilan boshqarish. Elsevier sog'liqni saqlash fanlari. 26–23 betlar. ISBN  978-0-323-48408-4.
  136. ^ H.J.T. Coelingh Benni; H.M. Vemer (1990 yil 15-dekabr). Surunkali giperandrogenik anovulyatsiya. CRC Press. 152– betlar. ISBN  978-1-85070-322-8. CPA Qo'shma Shtatlarda mavjud emas. Shunday qilib, spironolakton hozirda qo'llanilmoqda. [...] Bizningcha, [spironolakton] zaif antiandrogen ta'siriga ega.
  137. ^ Tommaso Falcone; Uilyam Xird (2007 yil 26 aprel). Klinik reproduktiv tibbiyot va jarrohlik bo'yicha elektron kitob. Elsevier sog'liqni saqlash fanlari. 285– betlar. ISBN  978-0-323-07659-3. [Flutamid] shuningdek, spironolaktonga qaraganda hirsutizmni davolashda samaraliroq bo'lib, 6 oylik flutamid bilan davolashdan so'ng hirsutizm ko'rsatkichlari deyarli normal darajaga kamayadi, spironolakton bilan davolangan ayollarning atigi 30% kamayishi bilan.
  138. ^ Rowland DL, Incrocci L (2008 yil 2-may). Jinsiy va jinsiy identifikatsiyani buzish bo'yicha qo'llanma. John Wiley & Sons. 444– betlar. ISBN  978-0-470-25721-0. Spironolakton - bu Qo'shma Shtatlarda eng ko'p buyurilgan antiandrogen [feminizan gormon terapiyasi uchun].
  139. ^ Snayder BW, Winneker RC, Batzold FH (1989 yil dekabr). "Win 49596 ning kalamushdagi endokrin profili: yangi androgen retseptorlari antagonisti". J. Steroid biokimyosi. 33 (6): 1127–32. doi:10.1016/0022-4731(89)90419-6. PMID  2615357.
  140. ^ Neyman, Fridmund (1996). "Siproteron asetat farmakologiyasi - qisqacha sharh". Prostata saratoni antiandrogenlari. 31-44 betlar. doi:10.1007/978-3-642-45745-6_3. ISBN  978-3-642-45747-0.
  141. ^ Shreder, Fritz X.; Radlmayer, Albert (2009). "Steroidal antiandrogenlar". V. Kreyg Iordaniyada; Barrington J. A. Furr (tahr.). Ko'krak va prostata saratonida gormonlarni davolash. Humana Press. 325-346 betlar. doi:10.1007/978-1-59259-152-7_15. ISBN  978-1-60761-471-5.
  142. ^ a b v d e f g h men j k "Casodex® (bicalutamide) planshetlari" (PDF). FDA. Arxivlandi (PDF) asl nusxasidan 2019 yil 30-iyulda.
  143. ^ a b v d e f g h men j k l m n o p Shoulver, Melissa; Eugster, Erika A. (2015). "Periferik erta yoshdagi balog'at yoshini davolash". Stenddan klinikaga qadar balog'at yoshi. Endokrin rivojlanish. 29. 230-239 betlar. doi:10.1159/000438895. ISBN  978-3-318-02788-4. ISSN  1421-7082. PMC  5345994. PMID  26680582.
  144. ^ a b v d e Zaxarin, Margaret (2019). "Balog'at yoshidagi buzilishlar: menejmentning farmakoterapevtik strategiyalari". Bolalar farmakoterapiyasi. Eksperimental farmakologiya bo'yicha qo'llanma. 261. 507-538 betlar. doi:10.1007/164_2019_208. ISBN  978-3-030-50493-9. ISSN  0171-2004. PMID  31144045.
  145. ^ Neyman A, Eugster EA (dekabr 2017). "Qizlarni va o'g'il bolalarni Maqtab-Olbrayt sindromi bilan voyaga etmagan balog'atga etish davosi - Yangilanish 2017". Pediatr endokrinol rev. 15 (2): 136–141. doi:10.17458 / per.vol15.2017.nau.treatmentgirlsboys. PMC  5808444. PMID  29292624.
  146. ^ a b v d e f g h men j k l m n o p AstraZeneca farmatsevtika (2008-12-15). "Testotoksikoz uchun NDA 22-310 / S-001 Casodex (bicalutamide) klinik tekshiruvi". Arxivlandi asl nusxasi (PDF) 2019-07-30. Olingan 2019-07-29.
  147. ^ a b v d e Haddad, Nadin G.; Eugster, Erika A. (2012). "Periferik erta balog'at yoshi: o'sishni yaxshilashga qaratilgan tadbirlar". Sog'liqni saqlash va kasalliklarda o'sish va o'sishni kuzatish bo'yicha qo'llanma. 1199-1212 betlar. doi:10.1007/978-1-4419-1795-9_71. ISBN  978-1-4419-1794-2.
  148. ^ Diaz-Tomas, Alisiya; Shulman, Doroti (2010). "Bolalar va o'spirinlarda aromataza inhibitorlaridan foydalanish: nima yangi?". Pediatriyadagi dolzarb fikrlar. 22 (4): 501–507. doi:10.1097 / MOP.0b013e32833ab888. ISSN  1040-8703. PMID  20489637. S2CID  23933791.
  149. ^ a b v Fuqua, Jon S. (2013). "Barkamol balog'at yoshini davolash va natijalari: yangilanish". Klinik endokrinologiya va metabolizm jurnali. 98 (6): 2198–2207. doi:10.1210 / jc.2013-1024. ISSN  0021-972X. PMID  23515450.
  150. ^ a b Mauras, Nelly (2011). "Qisqa bo'yli bolalarda balog'at yoshidagi o'sishni maksimal darajada oshirish strategiyasi". Shimoliy Amerikaning pediatriya klinikalari. 58 (5): 1167–1179. doi:10.1016 / j.pcl.2011.07.007. ISSN  0031-3955. PMID  21981954.
  151. ^ a b v Xaddad, Nadin G.; Eugster, Erika A. (2019). "Tug'ma buyrak usti bezining giperplaziyasi, shu jumladan sabablari, oqibatlari, boshqaruvi va natijalari". Eng yaxshi amaliyot va tadqiqotlar Klinik endokrinologiya va metabolizm. 33 (3): 101273. doi:10.1016 / j.beem.2019.04.007. hdl:1805/19111. ISSN  1521-690X. PMID  31027974.
  152. ^ a b Misra, Madhusmita; Radovik, Salli (2018). "Barkamol balog'at yoshi". Bolalar endokrinologiyasi. 589-615 betlar. doi:10.1007/978-3-319-73782-9_26. ISBN  978-3-319-73781-2.
  153. ^ DM Stayn; MM Grumbax (2015 yil 11-noyabr). "Fiziologiya va balog'at yoshining buzilishi". Shlomo Melmedda; Kennet S. Polonskiy; P. Rid Larsen; Genri M. Kronenberg (tahr.). Uilyams Endokrinologiya bo'yicha elektron kitob. Elsevier sog'liqni saqlash fanlari. 1074-1218 betlar. ISBN  978-0-323-34157-8.
  154. ^ Frank, Grem R. (2003). "Pubertal skelet fiziologiyasida estrogen va androgenning o'rni". Tibbiy va bolalar onkologiyasi. 41 (3): 217–221. doi:10.1002 / mpo.10340. ISSN  0098-1532. PMID  12868122.
  155. ^ a b Momper, JD; Mulugeta, Y; Burckart, GJ (2015). "Bolalarda giyohvand moddalarni ishlab chiqarish bo'yicha muvaffaqiyatsiz sinovlar" Klinik farmakologiya va terapiya. 98 (3): 245–251. doi:10.1002 / cpt.142. ISSN  0009-9236. PMID  25963725. S2CID  23377152.
  156. ^ a b v d e f Lenz, A. M.; Shulman, D .; Eugster, E. A .; Rahhal, S .; Fuqua, J. S .; Peskovits, O. H .; Lyuis, K. A. (2010). "Testotoksikozda bikalutamid va uchinchi avlod aromataz ingibitorlari". Pediatriya. 126 (3): e728-e733. doi:10.1542 / peds.2010-0596. ISSN  0031-4005. PMC  4096839. PMID  20713483.
  157. ^ Lyuis, K. A., Lenz, A., Eugster, E. A., Fuqua, J. S., Pescovitz, O. H., Rahhal, S., & Shulman, D. (2009, yanvar). Testotoksikozli ikki o'g'il bolada uzoq muddatli bikalutamid va 3 (rd) avlod aromataza inhibitori terapiyasi. Gormonlar tadqiqotida (72-jild, 266-267-betlar).
  158. ^ Mitre, N .; Lteif, A. (2009). "Luteinizan gormon retseptorida yangi mutatsiyaga uchragan bolada anastrozol va bikalutamid bilan oilaviy erkak tomonidan cheklangan erta jinsiy balog'at yoshini davolash (testotoksikoz)". Pediatrik endokrinologiya va metabolizm jurnali. 22 (12): 1163–7. doi:10.1515 / JPEM.2009.22.12.1163. ISSN  2191-0251. PMID  20333877. S2CID  297301.
  159. ^ Tessaris, Daniele; Matarazzo, Patriziya; Mussa, Alessandro; Tuli, Gerdi; Verna, Francheska; Fiore, Lyudovitsa; Lala, Roberto (2012). "Makkun-Olbrayt sindromi tufayli periferik balog'at yoshiga etgan yosh bolada bikalutamid va anastrozol bilan birgalikda davolash". Endokrin jurnal. 59 (2): 111–117. doi:10.1507 / endocrj.EJ11-0214. ISSN  0918-8959. PMID  22068112.
  160. ^ O'zcabı, Bahar; Tahmiscioğlu Bucak, Feride; Seylaner, Serdar; O'zcan, Raxshan; Buyukünal, Cenk; Ercan, Oya; Taysus, Beyxan; Evliyaoğlu, Olcay (2015). "Testotoksikoz: LHCGR genida yangi mutatsiyaga uchragan ikkita holat to'g'risida hisobot". Pediatrik endokrinologiyada klinik tadqiqotlar jurnali. 7 (3): 242–248. doi:10.4274 / jcrpe.2067. ISSN  1308-5727. PMC  4677562. PMID  26831561.
  161. ^ Xovinga, I. K., va Styuart, A. V. (2016, yanvar). Oilaviy testotoksikoz: natija va moyak bezlari bilan bog'liqligi. Pediatriyadagi gormonlar tadqiqotida (86-jild, 263-263-betlar). doi: 10.3252 / pso.eu.55ESPE.2016 https://www.postersessiononline.eu/173580348_eu/congresos/55ESPE/aula/-P1_353_55ESPE.pdf
  162. ^ Kor, Yilmaz (2018). "Kechki tashxis qo'yilgan oilaviy testotoksikoz va uzoq muddatli davolanishni kuzatish holatida markaziy balog'at yoshi". Gormonlar. 17 (2): 275–278. doi:10.1007 / s42000-018-0029-1. ISSN  1109-3099. PMID  29858851. S2CID  46923277.
  163. ^ Nabhan, Zeina M.; Eugster, Erika A. (2019). "Epizodik kurs bilan testotoksikoz: seriyadagi noodatiy holat". AACE Klinik holatlar bo'yicha hisobotlar. 5 (1): e50-e53. doi:10.4158 / ACCR-2018-0246. ISSN  2376-0605. PMC  6876971. PMID  31967000.
  164. ^ Arya, Ved Bxushan; Devies, Justin H. (2019). "Idiopatik gonadotropindan mustaqil bo'lgan balog'at yoshi - muntazam ravishda kuzatuv zarurmi?". Pediatrik endokrinologiya va metabolizm jurnali. 32 (4): 403–407. doi:10.1515 / jpem-2018-0419. ISSN  2191-0251. PMID  30849047. S2CID  73480792.
  165. ^ Kreher, Nerissa C. (2007). "Familial Male-Limited Limited Precocious Puberty". Balog'at yoshi etuk bo'lsa. 383-401 betlar. doi:10.1007/978-1-59745-499-5_18. ISBN  978-1-58829-742-6.
  166. ^ Levey HR, Kutlu O, Bivalacqua TJ (2012). "Ishemik kekemelik priapizmini tibbiy boshqarish: adabiyotning zamonaviy sharhi". Osiyo Andrologiya jurnali. 14 (1): 156–63. doi:10.1038 / aja.2011.114. PMC  3753435. PMID  22057380.
  167. ^ Broderik GA, Kadioglu A, Bivalacqua TJ, Ghanem H, Nehra A, Shamloul R (2010). "Priapizm: patogenezi, epidemiologiyasi va boshqaruvi". Jinsiy tibbiyot jurnali. 7 (1 Pt 2): 476-500. doi:10.1111 / j.1743-6109.2009.01625.x. PMID  20092449.
  168. ^ a b v Chow K, Peyn S (2008). "Vaqti-vaqti bilan priapismik holatlarni farmakologik boshqarish". BJU xalqaro. 102 (11): 1515–21. doi:10.1111 / j.1464-410X.2008.07951.x. PMID  18793304. S2CID  35399393.
  169. ^ a b v Dahm P, Rao DS, Donatucci CF (2002). "Priapizmni davolashda antiandrogenlar". Urologiya. 59 (1): 138. doi:10.1016 / S0090-4295 (01) 01492-3. PMID  11796309.
  170. ^ a b v Yuan J, Desouza R, Vestni OL, Vang R (2008). "Priapizm mexanizmining tushunchalari va takroriy priapizmni davolashning mantiqiy asoslari". Osiyo Andrologiya jurnali. 10 (1): 88–101. doi:10.1111 / j.1745-7262.2008.00314.x. PMID  18087648.
  171. ^ Dart RC (2004). Tibbiy toksikologiya. Lippincott Uilyams va Uilkins. 497, 521-betlar. ISBN  978-0-7817-2845-4. Arxivlandi asl nusxasidan 2016 yil 11 mayda.
  172. ^ Skidmore-Roth L (2013 yil 17-aprel). Mosby-ning 2014-yilgi hamshiralar uchun dori-darmonlari to'g'risida ma'lumotnoma - Elsevieron VitalSource. Elsevier sog'liqni saqlash fanlari. 193-194 betlar. ISBN  978-0-323-22267-9.
  173. ^ m Sternberg MH, BGni unuting, Xiggs DR, Weatherall DJ (17 avgust 2009). Gemoglobinning buzilishi: genetika, patofiziologiya va klinik boshqaruv. Kembrij universiteti matbuoti. 476– betlar. ISBN  978-1-139-48080-2. Arxivlandi asl nusxasidan 2017 yil 24 avgustda.
  174. ^ Migliari R, Muscas G, Usai E (avgust 1992). "Casodexning prostata saratoni rivojlangan bemorlarda uyqu bilan bog'liq erektsiyalarga ta'siri". J. Urol. 148 (2 Pt 1): 338-41. doi:10.1016 / S0022-5347 (17) 36588-6. PMID  1378907.
  175. ^ a b v d e f Gooren LJ (2011). "Klinik tekshiruv: Jinsiy huquqbuzarlarni androgen mahrum qilish bilan davolashning axloqiy va tibbiy mulohazalari". Klinik endokrinologiya va metabolizm jurnali. 96 (12): 3628–37. doi:10.1210 / jc.2011-1540. PMID  21956411.
  176. ^ a b v Houts FW, Taller I, Tucker DE, Berlin FS (2011). "Jinsiy xatti-harakatni androgendan mahrum qilish bilan davolash". Psixosomatik tibbiyotning yutuqlari. 31: 149–63. doi:10.1159/000330196. ISBN  978-3-8055-9825-5. PMID  22005210.
  177. ^ a b v Giltay EJ, Gooren LJ (2009). "Jinsiy huquqbuzarlarda androgen etishmovchiligini davolashning potentsial yon ta'siri". Amerika Psixiatriya Akademiyasi jurnali va qonun. 37 (1): 53–8. PMID  19297634.
  178. ^ Xon O, Mashru A (2016). "Jinsiy huquqbuzarlikni boshqarishda testosteronni bostiruvchi vositalardan foydalanish samaradorligi, xavfsizligi va axloq qoidalari". Endokrinologiya, diabet va semirish bo'yicha hozirgi fikr. 23 (3): 271–8. doi:10.1097 / MED.0000000000000257. PMID  27032060. S2CID  43286710.
  179. ^ Xavfli jinsiy jinoyatchilar: Amerika psixiatriya assotsiatsiyasining tezkor guruh hisoboti. Amerika Psixiatriya Pub. 1999. 111-bet. ISBN  978-0-89042-280-9.
  180. ^ Wadhwa VK, Weston R, Parr NJ (2011). "Bikalutamid monoterapiyasi suyak mineral zichligini, mushaklarning kuchini saqlaydi va prostata saratoniga chalingan osteoporotik erkaklar uchun sog'liq bilan bog'liq hayotiy ahamiyatga ega". BJU xalqaro. 107 (12): 1923–9. doi:10.1111 / j.1464-410X.2010.09726.x. PMID  20950306. S2CID  205543615.
  181. ^ Rousseau L, Couture M, Dyupont A, Labrie F, Couture N (1990). "LHRH agonisti va flutamid bilan estrodiol blokadalarning erkak ekspressionizmining og'ir holatlarida ta'siri". Kanada psixiatriya jurnali. 35 (4): 338–41. doi:10.1177/070674379003500412. PMID  2189544. S2CID  28970865.