juvenile pause
18 months to 4 yyears
when GABA, melatonin, DA, and 5HT inhibit hypothalamus
what is true in constitutional pubertal delay
pubertal age aligns with bone age
kallman syndrome
doesnt make GnRH
cant smell
PROP 1 defect only ___ is conserved
ACTH
four types of inherited hypogonadotropic hypergonadism
Prop 1 defect
CAH
leptin R def
kallman syndrome
main issue with klinefelters
leydig cells dont respond to LH to make testosterone
what is the most potent estrogen
estradiol (e2)
what is primarily secreted from the ovary
estradiol
definition of precocious puberty
females before age 8 and males before age 9
causes of complete precocious puberty
idiopathic
central-glioma, hamartoma (secreting GNRH)
primary severe hypothyroidism (excess TSH mimics FSH)
MC of incomplete precocious puberty in females
autonomous small ovarian c ysts with estrogen secretion by granulosa cells
tx-progestin
four causes of incomplete precocious puberty
McCune Albrihgt
auto E producing follicular cysts
ovarian neoplasm
peutz jeghers
4 stages of sexual differentiation
genetic sex
formation fo gonad
formation of ductal system
differentiatin of eternal genetalia
indifferent gonads
at six weeks
mesenchymal- theca/leydig
epithelial-granulosa/sertoili
wolfian goes with
mesonephric
mullerian goes with
paramesonephric
what produces MIF
sertoli cells
what 2 things does fetal testosterone cause
wolfian completion
DHT–>masculinization
four requirements of masculinization
testicular determining gene action
bilateral gonadal elaboration mIF
5 alpha reductase
androgen R at target organ
what does wolfian duct become
vas deferns
epidiymis
seminal vesicle
gardner’s duct
between ovary and human which can have cysts –if wolfian doesnt regress all the way
what does mullerian duct become
fallopain tube
upper 1/3 vag
uterus
genital tubecle in men and women
men- penis
wo-glans–>clit
urogenital slit
bpy-prostate
girl- lower 2/3 vagina and anterior uretra
labioscotcal sweelings
boy scrotum
girl- labia majora
urethral folds
labia mino
undifferentiated primordial germ cell arises from
endodermal lining of yolk sac
androgen insensitivity aka
pseudohemathro
four most necessary things for graffian follicle
highest mitotic index
most optimal FSH response
high E and inhibin B synthesis
optimal aromatase activity to convert androgens–>E
what prevents E from stimulating another LH surge
progesterone
what is fixed at 14 days
luteal phase
clomiphene
E antagonist; given in luteal phase to increase circulating FSH levels–> follicular recruitment for next cycle
what three things does the menstraul phase involve
hormonlly-regulated matrix degrading proteases
lysosomes
endothelians
pathway of menstrural phase
decrease P–>decrease hydroxyP dehydrogenase–>increase PGF2a–> myometrial and vascular contractions (along with txa2) –>endotheial ischemia and sloughing
mennorhagia
blood loss greater than 80 ml and regular cycles
metrorrhagia
irregular frequent bleeding
menorrhagia
irregular menses with prolonged or excessive blood loss; break through bleeding: unexpected bleeding that occurs while a women is on exogenous hormone mes
definition of delayed puverty
after 16 in boys
or after 13 in girls
main s/sx polycystic ovarian syndrome
insuin resistance
hyperandrogenism
chronic anovulation
athway PCOS
insulin R–>hhyperinsulinemia–>decrease sHBG–>increased androgens
–>ovarian and adrenal hyperandrogenism
–>hypeothalamic effect-increase pulse GnRH
ultrasound criteria of PCOS
12 or more follicles in one or both ovaries, 2-9mm
ovarian volume >10cm
major cx PCOS
endometrial hyperpalsia–>endometrial carcinoma
tx for PCOS not try to get pregs
lifestyle mod
combination hormonal contraceptives or progestin
anti-androgen (spirnolactone) if desired
insulin-sens agents
tx if trying to get preg
clomiphene
but if clomiphene fails, gonadotropin tx but much higher likelihood of multifetal pregn
4 reasons for chronic anov
1) hypothalalmus fails to secrete GnRH
2) pit fails to respond to GnRH
3) failure of HPO axis + feedback needed for LH surge
4) inteference with gonadal steroid feedback by other endocrine systems
end organ abnormalities in primary amen
inability of organs to respond to normal cyclic ovarian steroid production adn produce bleed
explanations for primary amen
kallman
transverse vaginal septa
definition of primary amenorrhea
failure to menstruate by age 16 with normal secondary sex chracteristics OR
age 14 without signs of normal sex maturatin
secondary amen
absence of three menstraul cycles or absence of menstraul bkleeding for 6 months
first step-check hcg
reasons for secondary amenorrhea
PCOS premature ovarian failure asherman syndrome hyperprolactinemia hypothyroidism CAH, cushing, obseity pituitray disorder
asherman syndrome
occlusion of uterine cavity by adhesions secondayr to postpartum cutterage or some bad uterine procedure (D&C)
biggest decline in fertility between ages
25-29
fecundability
probability of conception in a single menstraul cycle
aneuploid comes from
errors in meiosis 2
definitions of abnormal fetility
under 35: failure to conceive after 1 year unprotected six
>35: after 6 months
blastocyst hatches into
trophoectodermal cells–>trophoblast cells–>anchor to endometrium
endometrium–>decidualization
on implantation..
embryo invades maternal tissue and trophoblast cells differentiate into cytotrophonlast and syncutitrophoblst
3 processes implantation
apposition- blasto sits next to endo metrium (LIF, PGs)
adhesiob- ligands on surface of trophoblast bind R on endometrial site of implantation (hep & hep sulfate proteoglycans)
invasion- regional change expressed surface molecules and secretion of proteases by embryo to digest cells of decidua
job of cytotrophoblast
invade endometrium and connect to spiral arterioles
syncytiotrophoblast secretes
hcg
TGFB
tgfB–>increase in syncytioblast formation, block trophoblast invasiofa
factors that help with implantation
Leukemia inhib factor integrins TGF B EPGF ILIB
when does placenta take over producing progesterone
9 weeks
hcg serum level correlates with
cytotrophoblast cell mass
three jobs hcg
rescue CL
gonadal and adrenal hormone production
immune sup so can tolerate fetus
variation in hcg level
higher than normal- multiple gestations
failure to rise on subsequent hcg levels- nonviable or ectopic
HPL
keeps mothers blood glucose stable, similar to GH
product of placenta
CRH, POMC (ACTH PRECURSOR)
preduced in last month, timing partuition
2 sides of placenta
uterine side: millions of villi
fetal side: smooth membrane (amnion)–umbilival cord inserts here
increased placental E leads to
increased hepatic production TBG–>decrease free thyroid hormone so increase trh and tsh, increase in total t3 t4
also increase in pit to double its lacototrophs and therefore prolactin secretion–>puts placenta at risk for ischemic damage
four jobs of prostaglandins
myometrium contraction
cervical ripening (PGE2)
inhibit PDA closure in ductus
induce labor or term preg
alpha fetoprotein is high and low in
high in spina bifida (decreased by taking folate but doesnt decrease already elevated levels of alpha FP)
derease in trisomy 21
where does afp come from
fetal liver
estrogen fx in preg
increase uterine flow
comes from E3 in preg
progesterone jobs
increase decidual rxn to allow implantation
decrease myometrial contract
increased stretchiness of uterine muscle
breast dev
main cause of ectopic pregnancy
PID with chronic salpingitis
dx ectopic preg
US or bcg (either serial or one over 1500)
if unclear whether ectopic yet (empty uterus, Bhcg
wait
tx of ectopic
surgery and mtx
hcg indications of getstaional trophoblastic disease
plateau of hcg x 3 weks or hcg inc x 2 weeks
what do moles look liek
edematous tissue with highly edematous villi
complete hydafiform mole
always 2n
only trophoblastic tissue
mets 20% of time
tx of complete hydatiform mole
evac of molar tissue, serial hcg, avoid preg for 6 months and take hcg for six months
partial hydaliform mole
fetal + trophoblast tissue
persists or mets less ffre
placentazl site trophoblastic tumor
rare intermediate trophoblast cells
deeply microinvASIVE and non respon to chemo
hpl and hcg lo
MC maternal death in US
HTNisve disorder due to CNS hem
placenta previa increases risk for
placenta acretia
pain in placneta previa
painless
CAUSE OF ABRUPT PLACENTA
dissecting hematoma into decidus basalis due to trauma, inherent weakness of spiral aa (pre-eclampsia)
pre-eclamp/eclamp is an imbalance between
angiogenic factors (decrease VEGF, PIGF) antangiogenic (inccreased SFLT1)
endometriosis is common after preg because
normally protective vaginal acidity neutralized by alkaline amniotic fluid–>overgrowth of bacteria
what does the mother/fetus need in preg
volume support/perfusion
nutrition/oxygenation
waste/toxin clearance
mother surviving potential hemorrhage (increase coag)
factors that increase CO
increased exertion
labor (pain, catec)
arterials and venous
arterial- decrease PVR
venous- increase elasticity adn capacity
supine hypotensionsyndrome
aka inferior vena cava syndrome
compression of inf vena canva–>diminished venous certurn–>decrease CO
aorta compression–>decreased blood flow to uterus, bradycardia, hypotension, syncope, fetal heart changes
physiological anemia of preg
plasma expands more than RBC making hematocrit and hemoglobin appear to fall
hematological changse
incressed Fe absorption in gut
increased bolume
increase RBC volume
placenta does not express
MHC I or MHC II
liver chemistry in rpeg
generally unchanged, except increased alk phos due to placental isoenzyme
progesterone and physiological dyspnea
progesterone induces increase sensitivity of central Co2 chemo R
start of labor
placental CRH+ Acth increase–>increase fetal adrenal rpoduction–> fetal DHEAs converted to E by placenta–>develop gap jx in myometrium so contract
–>fetal cortisol (pos FB on CRH)–> develops surfactant and phospholipids–>increase fetal lung maturation –>increase Pgs–>cervical ripening
3 phases of parturition casade
phase 0= pregnancy- functional quiescence
phase 2= primring- relase of inhib–>gap jx
phase 3- stimulation–>pushing, increase pge2, p2a, oxytocin
walking in labor
true labor- makes worse
false labor- makes less
effects of contraction (4)
cervical effacement-obliteration of cancal
cervical dilation-enlarge cervical opening
fetal descent
pain
3 ps labor
power
passage passenger
4 passage components
lie
presenting part/presentation
position
attitude (flexed, military, extended)
4 stages labor
prodrome- prelabor changes
stage 1- 10 hrs; begin labor->full cervical dilation (10cm)
stge 2- 30 mins: full dilation–>delivery of fetus
stage 3-5 mins: delivery of fetus–> delivery of placenta
pain is due to
cervical idlation (visceral aff to t10, 11,12)
hypoxia
nerve compression
peritoneal stretch
stage 2 pain
distention of plevic floor, vagina, perineum
sensory branch purdenal (s2,3,4)
4 changes hwen going into labor
cervical ripening
lightening (dropping - mom feels like she can breathe better, but increase urination)
passing out mucus plug
braxton-hicks contraction
what happens in cervical ripening
collagen chains fracture
more hydrophilic glycosaminoglycans
increase h20–softer, thnned out
monozygotic pregnancies occur
72 hours post fertilization
monoamniotic monochronic
13-16 days
same streak, yolk sac
conjoined twins
damc
mc monozygotic twins
3-8 days
diamniotic dichornoc
fused placenta–divison before inner mas forms
dizygotic pregnancy is the main cause of
spontaenous mutlifetal pregnancies
main cause of multifetal pregnancy
increase in GNrh–>more follicles mature
manual vaccum aspiration
5-10 weeks
simplest, safetst
no need cervical dilation
D&C
upper limit 12-13 weeks
vacuum/mechanical means-requires cervical dilation
medical
mifepristone-progestin R antagon
5 weeks or less 85% success rate
given day 1, misoprostol on day 3 and deliver within 3 hrs
how does progestin work in OC
increase cervical mucosa–>block LH surge–>decrease estrogen Receptors
how do OCps work
gonadotropin secretion inhibited
LH surge suppressed by progestin
follciular maturaiton and selection of dominant follicle blocked by estrogen
aboslute risks of ocp
thromboembolic disorders impaired LFTs abnroaml vaginal bleed pregnancy smokers >35 with suspect brst cancer migraines with aura focal seizures
injectables patches
depo- weight gain, not good if plannign preg in year
transdermal patches- weekly app, less effective in obese
IUD Cooper does NOT
block ovulation
mechanism of IUD
blocks interaction of oocyte and sperm
conceptive rod
prog only
3 years
irreg bleeding for first few months
CI in breast cancer
vaginal ring
doesnt decrease bleeding
thelarche
estrogen stimulates lactiferous duct growth
fat accumulates between lobes
duct branching and elongating
terminal buds
luteal phase and boobs
increase proliferation of duct system
slight aloveolar lubualr devlepment
increase vascularity
edema and tenderness
1st trimester-early 2nd breasts
hyperplasia/hypertrophy
stromal decreases
increase vascularity
mid prg–>onward
less mitosis as alveolar cells differentiate and begin to secrete–pricen by progesterone
pre-reqs for brast feeding
fully developed mammary glands
withdrawal a and p to show prolactin binding sites
lactopoesis (stage 3)
prolactin (increases casein protein)
oxytocin->contract myoepi cells–>milk let down
preadolescent
gender identity, gender roles
early adolescent
early puberty, sexual fantasys, mast
middle adolescent
physical maturty, sexual exploration
late adoelscent
adult
intimate sharing
oxytocin pathways
nipple stim anterolateral columns brainstem medialf orebrain bundle paraventricular nucleus post-pituitary-->increase oxygen relase
purple boobs on H
glandular lumina
benign microcalc
fat necrosis
benign breast tumors
fibroadenoma
hamartma
apocrine metaplasia in fibrocystic change
does not incerase risk carcinoma
2x risk for carcinoma
ducta hyperplasia and sclerosing adenosis
5x risk of breast cancer
atypical hyperplasia
MC of bloody nipple discharge
intraductal papilloma!–benign but can have cancer in it
not risk factors of braest cancer
smoking
breast size
fibrocystic change
conervative lumpectomy and chemo contraindicated in
large tumors
highly invasive
female where XRT is contraindicated
neoadjuvant therapy given before surgery to
decrease tunor size or effects
estrone in menopause
dominant androgen
does not protect or change bone density except in obese people because increase in aromatase–>increase in estrone
changes in menopause
1) shorter cycles (due to increase fsh)
2) luteal insufficency (decrease progesterone)
3) annovulation
bleeding occurs due to
estrogen withdrawal
what continues after menopause
androgens
hot glash mech
decrease E–>decrease endorphins in hypothal–>increase NE–>inapp heat lsos
5ht involved so ssris help
how does estrogen work on osteoporosis
blocks it by blocking PTH stimulation of Ca mobilation (impedes osteoclast activity)
tx lichen schelrosis
steroids
.leiomyoma
premaeno women, enlarge with estrogen
serous neoplasms often
bilateral
Ca125
serous ovaraian neoplasm
kra mutation
mucinous carcinoma
seminoma chrom
12p
treatment of spermatocytic sepminma
none unless transform- chemo and rad
teratoma and chemo
destroys malignant potential but leaves cartilage can grow and undergo malignant transformation
peyronie’s disease
penis bleeds when erect
HGPIN
high grade prostatic intraepithelial neoplasm
repeat 2-3 years
atypical small acinar proliferation
repeat by 3 months
1st lne tx prostate cnacer
castration
or leuprolide
2nd line prostate cancer
docetazel- apoptosis through blocking of microtubule depol
bispohphates and vitd/ca
mechanism of erection
release NT–>smooth muscle relax in sinusoids–>arterial dilation–>increase BF–>sinusoids expand and compress emissary vein–>trap blood–>increase intracavernosal pressure
three jobs of granulosa cells
1) make inhibin
2) aromatize androgens to estrogen
3) follicular growth