B6 Endo/GU Pharmacology Final Exam
Definition & General Causes of Infertility - fail conceive after specif time w/ reg interc
w/o contrac (ie. 12 mts if <35y/o & 6mts if >35 or PCOS)
- 1/3 causes each fem orig, male orig, unk/combo of both partners
- conceiv prob decr 3-5%/yr after 30-32, faster after 37-40y/o by dim oocyte qual+quant
Pathophysiology, Sx, Labs, Causes, Solution for WHO Group I Infertility - - Pathophys =
hypogonadotr hypogon by hypoth-pit fail
- Sx/labs = amen, low FSH/LH, low estrad, +/- elev prolactin
- Causes = eating disords, wt/exerc extremes, hyperprol
- Soln = correct cause (ie. gain wt, thyr med, dopa ag); reg Gn & ind ovul
Pathophysiology, Sx, Labs, Causes, Solution for WHO Group II Infertility - - Pathophys
= normogonadotr anov by hypoth-pit-ovar fail **MOST COMMON**
- Sx/labs = nl FSH, nl-elev LH, nl estrad, elev PRL, galactorr
- Causes = PCOS, ovul-rel dysfunc, hyperPRL
- Soln = meds ind ovul, Gn to reg ovul, decr PRL by Dopa ag
Pathophysiology, Sx, Labs, Causes, Solution for WHO Group III Infertility - - Pathophys
= hypergonadotr hypogon by ovar fail
- Sx/labs = elev FSH, low estrad
- Causes = adv age
- Soln = oocyte don, IVF
Other causes of Infertility - ut/outfl tract abnorms, tub dis by PID
- Treat w/ meds/IVF
Pathophysiology, Sx, Labs, Causes, Solution for Male Factor Infertility - - Pathophys =
anat vars, chrom abnorms, erec/ejac dysf
- Sx/labs = abnl FSH/LH, testost, semen analysis
- Causes = inf, inj, tox expos, syst dis, sperm ABs, hypogon, testic dis, sperm transp
defs
- Soln = IVF, intraut insem, don sperm
**MOST COMMON CAUSE is cryptorch**
Overview of Repro Endocrinology - hypoth secr GnRH stim ant pit gonadotropins
LH+FSH stim ovars+testes
- -reg by inhibin (-FSH) & elev estrog/progest/testost (-GnRH+LH/FSH)
- +reg by activin (+FSH) & estrog (+LH/FSH mid-cyc)
Role of Gonadotropins in Menstrual Cycle - - Follic ph (prolif ph) = low estrog/inhib -->
elev LH/FSH stim follic dev for dom foll form; high sust estrog, mid-cyc LH/FSH surge
for ovul
- Luteal ph (secr ph) = corp lut secr estrog+progest, endom prep for implant by progest
incr blood supp spir arts
**ovar dysf accounts for most infert cases**
,B6 Endo/GU Pharmacology Final Exam
Gonadotropin Function in Women - - FSH = germ c mat by dir stim follic gr+mat, enh
granul c LH responsiveness; steroidogen by follic ph estrog prod in foll
- LH = steroidogen by ovar estrog & lut ph estrog+progest for follic w breakd for ovul &
subseq resuming oocyte meiosis
- hCG = LH analog for steroidogen, plac estrog+progest dur preg
Gonadotropin Function in Men - - FSH = testost bind in Sertoli c mediating cell
mat+spermatid diff (spermatogen)
- LH = steroidogen by test Leydig c prod testost
Role of Gonadotropins in Fertility & Pregnancy - - LH surge = impend ovul prediction det
by ur ovul pred kits --> should engage in interc if LH elev
- implant --> emb hCG prod working @ LH-R, meas in preg tests prev CL loss --> CL
maint cont prod progest+estrad until placenta takes over
Description & Treatment of PCOS - most comm anov infert cause w/ menstr irreg, infert,
obes, hyperandrog, insul resis
- Treat = wt red, low-d OCP/progestin decr LH+androg synth, Spirono for acne+hirsut
b/c anti-androg, Clomiphene if desire preg, MEtformin if diab/metab synd feats or ocul
issues, Aromatase inhibs off-lab for ovul
Non-pharmacologic therapy for Infertility - - smok cess
- wt modul BMI<30 (ideal 18-30)
- red excess caffeine
- EtOH cess
- folic ac suppl decr NTD w/ 400mcg/d, 5mg/d for high risk NTD incl obes, DM, epilep,
hemat disords, prev NTD kids
- approp coitus freq Q1-2d around expec ovul
Description of Ovulation Induction (OI) for Infertility Management - used in anov pts to
achieve preg w/ interc/IUI (just trying to control time of ovul)
- most for PCOS, hyperPLN, hypogonatr hypogon (uncomm)
Description of Controlled Ovarian Stimulation (COS) for Infertility Management - pts
already having ovul cyc w/ unexpl infert, struc abnorms+dis
- ova coll+fert ex vivo then reimplant (IVF)
Pharmacological Management of Infertility - incl ovul induction & controlled ovar stim
**mult pregs can occur**
Drug Classes & Examples for Infertility Treatment - - SERMs = Clomiphene
- Arom inhibs = Letrozole, Anastrozole
- Gonadotropins = FSH, hMG (hum menop gonadotr), hCG
- Dopa ags = Bromocriptine, Cabergoline
- GnRH ags = Leuprolide, Goserelin
- GnRH antags = Cetrorelix, Ganirelix
,B6 Endo/GU Pharmacology Final Exam
- Progesterone
Procedures nfor nTreatment nof nInfertility n- n- nIntraut ninsem n(IUI) n= nprep nsperm ninsert
ninto nut njust nbefore nantic novul ntime noften nw/ nClomiphene nand/or ngonadotr nfor
novul nind
- IVF n& nemb ntx n= nova ncoll, nfert nex nvivo, nreins ninto nut; nused nw/ ncontr novul nstim
n(ie. ngonadotr, nGnRH nag/antag)
Drug nClasses nused nfor nOvulation nInduction n(OI) n- n- nClomiphene
- Aromatase nInhibitors
- Gonadotropins
- Dopamine nagonists
MOA, nIndications, nAEs, nCIs nof nClomiphene nCitrate n(clomid) nfor nOI n- n- nMOA n= nPO
nSERM- nlike naction, npart nag n@ nER ninhib nestrog n-FB n--> nhypoestrog nstate nperceived
nby nbod nfor nincr nGnRH nrel nincr nFSH/LH+ovul nind; nNO nprogest n(ie. npreg-prom),
nandrog, nanti-androg neffs
- most nwidely nused nagent nfor nWHO nGrII ninfert n(normogonadotr nanov)
- Indics n= ninfert nby nPCOS, nanov, nunexpl ninfert nconcom nw/ nIUI
- AEs n= ncommon nflush, nVM nsx, nvis ndisturb; nserious nvis nloss, n**ovar
nhyperstim/HT n(OHSS), nmult npregs**
- CIs n= nabnl nut nbl, nendom ncarc, nliv ndis, novar ncysts, npreg, nuncontr nthyr/adr ndysf
Clinical nNotes nfor nClomiphene nCitrate n- n- nbeg nmenstr ncyc nD3-5 nx5d, nmax n6cyc
nuse nw/ novul nmost n@6-12d nafter nther nso ntime nsex ninterc/IUI naccordingly
- simple, neffic, ncost-effec, nsafe nw/ n75% nwomen novul n& n30-40% nbec npreg
- DOES nNOT ncorr nunderl nPCOS nabnorms n(ie. nhyperinsul, nhyperandrog)
MOA, nIndications, nAEs, nDIs, nCIs nof nAnastrozole nfor nOI n- n- nMOA n= narom ninhib
nblock naromatase nconv nandrog nto nestrog n--> n+LH/FSH nfor novul nind n(real nhypoestrog
nstate)
- Indics n= nFDA napprov nfor nbreast nca, nunder ninvestig nfor nfail nconceive nw/
nclomiphene nby nmenstr ncyc nD3-7 nadmin nx5d
- AEs n= ncommon ned, nhot nflash nby nvasodil, nrash n(menop nsx); nserious n**decr nBMD**
- DIs n= nTamoxif nred nanastroz nlevels
- CIs n= npreg, ncaution nin nIHD nhx
MOA, nIndications, nAEs, nDIs, nCIs, nNotes nof nLetrozole nfor nOI n- n- nMOA n= narom ninhib
- Indics n= nFDA napprov nfor nbr nca n& nOI nin nendometriosis+PCOS
- AEs n= ncommon ned, nhot nsw, nappet nloss, n**decr nBMD/fx**
- DIs n= n5-FU, nCilostazol, nclarithro, ntamox, npropranolol; nCYP3A4 nsubs, n2A6 ninhib,
n2C19 ninhib n--> nuse nanastroz ninstead nin nthese npts
- CIs n= nhypersens, npreg
- Notes n= nmore nlive nbirths nthan nClomiph n& nno nincr nrisk
Examples, nMOA, nIndications, nAEs, nCIs, nNotes nof nGonadotropins nfor nOI n- nincl nhCG
n(LH nanalog nto nmimic nLH nsurge), nhMG n(1:1 nFSH:LH), nFSH
- MOA n= nnl novar nfoll ndev+mat nin nwomen, ngon nster nprod nin nwom+men, nspermatog
nin nmen nby ncont nelev nlevels ndesensit nant npit nGnRH nrel n& npulsat nexpos nto nphysio
nlevels nstim nGnRH
, B6 Endo/GU Pharmacology Final Exam
- Indics n= nanov/oligoov nto nstim nsing nfoll ndev+sing negg novul
- AEs n= nmult ngest n(higher nrate nthan nclomiph+AIs), novar nhyperstim n(OHSS), ninjec-site
nrxns
- CIs n= nuncontr nnon-gon nendocrinops, ntum/ca, npreg, nprim novar nfail, nabnl nidiop nut nbl
- Notes n= nimprov npreg nrates nin nnl novul nby nstim novar nprod n1+ nfolls nif ngiven
nw/ nIVF/IUI; nSQ/IM nbut nno nPO nform
Example nof nGonadotropin nProtocol n- n- nD3-5 n= nmeas nhorm nlevs+US nensur nno npre-
ex novar ncysts; ngonadotr ninjecs nFSH/LH nstart ndep non nhorm nlevs, ndosing, ntiming nw/
nvarying nresp; nlarger ndose n--> ngreater nrisk nmult ngest
- D6-10 n= nanother nUS nmeas nfollic ngr, nmaybe nchange ndose nmimic nnat nhorm nflucs
nw/ ngoal n1-2 n>18mm ndiam nfolls; n3+ n>15mm nfolls nthen ncyc ncancelled nb/c nrisk nof
nmultiples+OHSS
- D10-16 n= nfoll nready nshown non nbl ntests+US nmeas nso nhCG n(LH) ninjec ntrig novul;
nfollow nw/ ninterc/IUI
Prolactin nPhysiology n- nhypoth nsecr nDopa+TRH, npit nsecr nPRL nstim nby nTRH n&
ninhib nby nDopa
- lact nind+maint
- prod nstim nby nestrog+br-feed
- elev nPRL ninhib novul nin nfems+spermatog nin nmales
Prolactin nPathophysiology n- nelev nant npit nPRL nfrom nprolactinoma n--> n-hypoth
nGnRH ndecr ngonadotr nsensit nto nGnRH n--> n-ant npit nLH/FSH n--> n-ovar/test
nestrog/androg, nhypogon/infert
Sx n& nCauses nof nHyperprolactinemia n- n- nSx n= namen, noligomen n("spotty" nperiods),
ngalactorr, ninfert nfrom n-GnRH
- Causes n= npit ntum, ndrugs nincl ndopa nantags, nPRL nstims, nVerapamil
Drugs npotentially ncausing nHyperprolactinemia n- n- nDopa nantags n= nantipsychs,
nPhenothiazines, nmetoclopramide, ndomperidone
- PRL nstims n= nmethyldopa, nreserpine, nSSRIs, ndexfenfluramine, nestrogs,
nprogestins, nprotease ninhibs, nGnRH nnaalogs, nbenzos, nTCAs, nMAOIs, nH2RAs,
nopioids
- Verapamil
Examples, nMOA, nIndications, nPK, nAEs, nCIs nof nDopamine nAgonists nfor
nHyperprolactinemia n- nincl nBromocriptine n& nCabergoline
- MOA n= ndopa nD2-R nags ninhib npit nPLN nsecr
- Indics n= ninfert nfrom nhyperprol, nPark nDis, nT2DM
- PK n= nBromo nw/ n7hr ndur ntaken ndaily, nCabergoline nw/ n65hr ndur ntaken
nweekly/biweekly
- AEs n= ncommon nCNS ndizz, nfatigue, nHA, nGI; nserious n**psych+hallucs**, nhypoTN,
nsync, npulm nfibr n--> ntake npsych nhx nbefore nstarting
- CIs n= nbreastfeed, npostpart nesp nCVD/seiz nhx, nsync nmigr, nuncontr nHTN;
nCAUTION nw/ npre-ex npsych ndisords
- DIs n= nw/ ntriptans, nergot nalkaloids, nmetoclopramide, nstrong nCYP3A4 ninhibs n(ie.
nketocon, nclarithro, nHIV nprot ninhibs, nergot nalks)
