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 for Treatment of Infertility - - Intraut insem (IUI) = prep sperm
insert into ut just before antic ovul time often w/ Clomiphene and/or
gonadotr for ovul ind
- IVF & emb tx = ova coll, fert ex vivo, reins into ut; used w/ contr ovul stim
(ie. gonadotr, GnRH ag/antag)
Drug Classes used for Ovulation Induction (OI) - - Clomiphene
- Aromatase Inhibitors
- Gonadotropins
- Dopamine agonists
MOA, Indications, AEs, CIs of Clomiphene Citrate (clomid) for OI - - MOA = PO
SERM- like action, part ag @ ER inhib estrog -FB --> hypoestrog state
perceived by bod for incr GnRH rel incr FSH/LH+ovul ind; NO progest (ie.
preg-prom), androg, anti-androg effs
- most widely used agent for WHO GrII infert (normogonadotr anov)
- Indics = infert by PCOS, anov, unexpl infert concom w/ IUI
- AEs = common flush, VM sx, vis disturb; serious vis loss, **ovar
hyperstim/HT (OHSS), mult pregs**
- CIs = abnl ut bl, endom carc, liv dis, ovar cysts, preg, uncontr thyr/adr dysf
Clinical Notes for Clomiphene Citrate - - beg menstr cyc D3-5 x5d, max 6cyc
use w/ ovul most @6-12d after ther so time sex interc/IUI accordingly
- simple, effic, cost-effec, safe w/ 75% women ovul & 30-40% bec preg
- DOES NOT corr underl PCOS abnorms (ie. hyperinsul, hyperandrog)
MOA, Indications, AEs, DIs, CIs of Anastrozole for OI - - MOA = arom inhib
block aromatase conv androg to estrog --> +LH/FSH for ovul ind (real
hypoestrog state)
- Indics = FDA approv for breast ca, under investig for fail conceive w/
clomiphene by menstr cyc D3-7 admin x5d
- AEs = common ed, hot flash by vasodil, rash (menop sx); serious **decr
BMD**
- DIs = Tamoxif red anastroz levels
- CIs = preg, caution in IHD hx
MOA, Indications, AEs, DIs, CIs, Notes of Letrozole for OI - - MOA = arom inhib
- Indics = FDA approv for br ca & OI in endometriosis+PCOS
- AEs = common ed, hot sw, appet loss, **decr BMD/fx**
- DIs = 5-FU, Cilostazol, clarithro, tamox, propranolol; CYP3A4 subs, 2A6
inhib, 2C19 inhib --> use anastroz instead in these pts
- CIs = hypersens, preg
- Notes = more live births than Clomiph & no incr risk
Examples, MOA, Indications, AEs, CIs, Notes of Gonadotropins for OI - incl hCG
(LH analog to mimic LH surge), hMG (1:1 FSH:LH), FSH
- MOA = nl ovar foll dev+mat in women, gon ster prod in wom+men,
spermatog in men by cont elev levels desensit ant pit GnRH rel & pulsat
, B6 Endo/GU Pharmacology Final Exam
expos to physio levels stim GnRH
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 for Treatment of Infertility - - Intraut insem (IUI) = prep sperm
insert into ut just before antic ovul time often w/ Clomiphene and/or
gonadotr for ovul ind
- IVF & emb tx = ova coll, fert ex vivo, reins into ut; used w/ contr ovul stim
(ie. gonadotr, GnRH ag/antag)
Drug Classes used for Ovulation Induction (OI) - - Clomiphene
- Aromatase Inhibitors
- Gonadotropins
- Dopamine agonists
MOA, Indications, AEs, CIs of Clomiphene Citrate (clomid) for OI - - MOA = PO
SERM- like action, part ag @ ER inhib estrog -FB --> hypoestrog state
perceived by bod for incr GnRH rel incr FSH/LH+ovul ind; NO progest (ie.
preg-prom), androg, anti-androg effs
- most widely used agent for WHO GrII infert (normogonadotr anov)
- Indics = infert by PCOS, anov, unexpl infert concom w/ IUI
- AEs = common flush, VM sx, vis disturb; serious vis loss, **ovar
hyperstim/HT (OHSS), mult pregs**
- CIs = abnl ut bl, endom carc, liv dis, ovar cysts, preg, uncontr thyr/adr dysf
Clinical Notes for Clomiphene Citrate - - beg menstr cyc D3-5 x5d, max 6cyc
use w/ ovul most @6-12d after ther so time sex interc/IUI accordingly
- simple, effic, cost-effec, safe w/ 75% women ovul & 30-40% bec preg
- DOES NOT corr underl PCOS abnorms (ie. hyperinsul, hyperandrog)
MOA, Indications, AEs, DIs, CIs of Anastrozole for OI - - MOA = arom inhib
block aromatase conv androg to estrog --> +LH/FSH for ovul ind (real
hypoestrog state)
- Indics = FDA approv for breast ca, under investig for fail conceive w/
clomiphene by menstr cyc D3-7 admin x5d
- AEs = common ed, hot flash by vasodil, rash (menop sx); serious **decr
BMD**
- DIs = Tamoxif red anastroz levels
- CIs = preg, caution in IHD hx
MOA, Indications, AEs, DIs, CIs, Notes of Letrozole for OI - - MOA = arom inhib
- Indics = FDA approv for br ca & OI in endometriosis+PCOS
- AEs = common ed, hot sw, appet loss, **decr BMD/fx**
- DIs = 5-FU, Cilostazol, clarithro, tamox, propranolol; CYP3A4 subs, 2A6
inhib, 2C19 inhib --> use anastroz instead in these pts
- CIs = hypersens, preg
- Notes = more live births than Clomiph & no incr risk
Examples, MOA, Indications, AEs, CIs, Notes of Gonadotropins for OI - incl hCG
(LH analog to mimic LH surge), hMG (1:1 FSH:LH), FSH
- MOA = nl ovar foll dev+mat in women, gon ster prod in wom+men,
spermatog in men by cont elev levels desensit ant pit GnRH rel & pulsat
, B6 Endo/GU Pharmacology Final Exam
expos to physio levels stim GnRH
