SBM Reproduction Notes

Review of Basic Principles of Reproduction

1. Contrast the processes of spermatogenesis and oogenesis throughout the life cycles.

Oocytes
Spermatocytes

Genesis
Fetal life
Begins at puberty

Population
Max at birth, number drops with time
Production continues throughout life

2. Describe negative and positive feedback. (VERY IMPORTANT!)

a. The arcuate nucleus and its production of GnRH is the driver of the hypothalamic-pituitary-gonadal axis.
b. Pulsatile secretion of GnRH is required for normal reproductive function.
c. GnRH was initially called LHRH because, when given in the adult (or secreted endogenously), it releases
usually more LH than FSH.
d. When GnRH (LHRH) is suppressed, the pituitary releases primarily small amounts of FSH and no LH.
e. The H-P-G axis is under the primary control of negative feedback.
f. Positive feedback is required for the LH surge and ovulation. High estrogen levels stimulate the
hypothalamus to release more GnRH, which stimulates a surge of LH that helps the follicle break open.
3. Contrast estrogen production in the ovary with androgen production in the testis.
a. In the ovary, hormone production and ovulation are connected in one compartment. When all of the
oocytes are depleted, estrogen production stops. Estrogen production in the ovary is through the twocell mechanism: LH stimulates theca cells to produce androgenic precursors (androstenedione and
testosterone, through cholesterol). These androgenic precursors then move over into the granulosa cell,
which is stimulated by FSH to produce estradiol.
1. BOTH LH and FSH are required for estrogen production and oocyte production
b. The processes of spermatogenesis and androgen production in the testes are separate. Men may
continue to have normal androgen levels with significant abnormalities of spermatogenesis.
1. FSH stimulation of seminiferous tubules (with initiation of spermatogenesis) causes the initial
increase of testicular size at puberty (first sign of puberty in males).
2. LH Stimulation of Leydig Cells causes 10 fold increase in testicular testosterone production
(later in puberty).
i.
Leydig cells constitute < 10% of adult testicular mass.

Female
Target
Female
Product
Male
Target
Male
Product

LH
Theca Cells

FSH
Granulosa Cells

Androgenic precursors
(from cholesterol)
Leydig cells

Estradiol (from androgenic precursors

from theca cells)
Seminiferous tubules

Testosterone

Spermatogenesis + testicular size

4. Describe the different phases of the menstrual cycle.

a. The normal menstrual cycle averages 29 days and is comprised of two phases: (1) follicular or proliferative
phase; and, (2) luteal or secretory phase. The follicular phase may vary in length. The luteal phase is
invariant at an average of 14 days.
5. Teach
a.
b.
c.

the hormonal changes of the ovulatory menstrual cycle.

The LH surge and FSH peak indicate ovulation, which also marks the start of the luteal phase.
Estrogen, which is most prominent during the follicular phase, causes endometrial proliferation.
Progesterone, which is most prominent during the luteal phase, causes the endometrium to become
secretory in nature.
d. The withdrawal of progesterone at the end of the luteal phase is what leads to shedding of the
endometrium, or menses.

Phase
Follicular Phase
Ovulation
Luteal Phase

Prominent Hormones
Estrogen
LH surge + FSH peak
Progesterone

Result
Endometrial proliferation
Follicle ruptures
Secretory endometrium

Menses

Withdrawal of progesterone

Shedding of endometrium

H-P Gonadal Circuit Normal & Accelerated - Male and Female

1.

Apply an understanding of the developmental changes of the hypothalamic-pituitary-adrenal and -gonadal

circuits to disorders of reproduction.
HPG
HPA
Negative Feedback
Positive Feedback
Negative Feedback
Axes
HPO and HPT
HPO only (females)
HPA
Feedback
Estrogen
Estrogen
Cortisol
Hormone
Level
Hypothalamus and pituitary
Arcuate nucleus
Hypothalamus
Result
LH and FSH
LH -> ovulation
CRH -> POMC + ACTH
Development
Midtrimester in utero
Later in pubertal
Maturation of zona reticularis
development
Very first endocrine change of
( E -> FSH in utero and as
Requires very high E and
puberty
neonate)
pulsatile GnRH
First to mature at puberty
Overview
E -> FSH and E -> FSH
E -> LH
Cycles 21-45 days
a.
b.

Feedback shut down during childhood because higher level NTs shut down GnRH (FSH > LH)
Prepubertal DESUPPRESSION of GnRH occurs gradually and first occurs during sleep (result = LH > FSH)

2.

Compare/contrast standards regarding timing of pubertal onset for girls and definition of precocious
puberty. (dont need to know numbers, just general)
Females
Males
First sign of
Thelarche (or adrenarche)
Testicular enlargement
puberty
Age
9-11
10-13.5
Subsequent
Growth spurt
Adrenarche (>10yrs)
events
Menarche (12.8 yrs)
Penile and prostatic enlargement (11-14 yrs)
Ovulation (<50% 1st yr,
Growth spurt
95% after 7 yrs; earlier if menarche is earlier)
Spermarche (EARLY 13.4 yrs)
Skeletal maturation (10.5-16 yrs)
Early puberty
Breast and/or pubic hair development
Very rare
Before age 6 (Af. American) or 7 (Caucasians)
Usually truly pathologic
10x more common than males, usually idiopathic
3.

Recite the differences between central (true) precocious puberty and peripheral (incomplete) precocious
puberty.
4. Give examples of causes of central and peripheral causes of precocious puberty in males and females and
their mechanisms.
Central (True)
Peripheral (Incomplete)
Definition
Acting through or at CNS -> complete pubertal
Appearance of one phase of puberty only
development
Gonadotro
Gonadotropin dependent
Gonadotropin Independent
pins
Cause
Early activation of arcuate nucleus with GnRH
Varies
secretion
LH/FSH
LH > FSH
Gender
Females > males
Males = isolated sexual development (androgens)
Females = isolated thelarche, adrenarche, or
menarche
GnRH?
Responsive (-> downregulation)
Unresponsive
Causes
Idiopathic (50-75%)
Thelarche:
Identified central causes: CNS lesions
Isolated precocious thelarche: after birth from
(hamartoma, neurofibroma, glioma, astrocytoma),
GnRH, will go away with childhood GnRH
hydrocephalus, encephalitis, vascular
suppression
malformation
McCune-Albright Syndrome: caf-au-lait spots,
Primary severe hypothyroidism (rare)
polyostic fibrous dysplasia; progressive, GnRH
independent; from GPCR G mt
Autonomous estrogen producing follicular cyst:
also GnRH independent
Adrenarche:
Isolated precocious adrenarche: likely normal,
adrenal origin
CAH: most commonly 21-OHase deficiency
Insulin resistance: harbinger of PCOS
Isolated Sexual Development:
Exogenous hormones: rare
Serious tumors: worry about these!

Thelarche

Tanner
I
Tanner
II
Tanner
III
Tanner
IV

Nothing

Adrenarche (ADRENAL glands)

Pubic and axillary hair, adult body
odor,
sebaceous gland activity
No pubic hair

Breast budding

Scant pubic hair (can count)

Growth beyond areola

Diffuse pubic hair (difficult to

count)
Abundant hair on mons and labia

Tanner
V

Adult (smoothing of secondary

mound)

Feature
s

Areolar development with

secondary mound of areola

Adult pattern (extends to thigh)

Male genitalia
Enlargement of testes, penis, and
prostate

Enlargement of testes and scrotum

Thinning and reddening of scrotum
Enlargement of penis, mainly in
length
Enlargement of penis in length and
breadth
Development of glands
Adult size and shape

Preadolescent

Normal Development and Disorders of Sexual Development (TBL)

1. Describe the basic principles and 4 basic steps involved in normal sexual differentiation for both male
and female fetuses.

1
Genetic
Sex
2
Formati
on
of Gonad
3
Formati
on of
Ductal
System

4
Differen
tiation
of
External
Genitali
a

Male
Female
Overview SRY (Sex-determining
After germ cell migration, only
region of Y) on short arm
requirement is later ovarian gene
of Y chromosome
action
th
Timeline 5 week begin as protuberances over the mesonephric ducts
4-6 weeks primordial germ cells move to these protuberances
6 weeks germ cells + mesenchymal cells (theca/leydig) +
epithelial cells (granulosa/sertoli)
Determin SRY
Lack of SRY + later ovarian gene
ant
action
Determin **Gonads** direct whether ductal system is male or
ant
female
Adult
Epididymis, vas deferens,
Fallopian tube, uterus, vagina
structur
seminal vesicle
es
Mullerian Sertoli cells -> Mullerian
No MIF (AMH) -> Mullerian system
system
inhibiting factor (AMH)
development
-> regression
Wolffian
Testosterone ->
Regression of Wolffian system
system
completion of Wolffian
system
Develop
Paramesonephric bulbs ->
ment
elongation, lateral fusion,
canalization, and septal
resorption
Hormone 5-alpha reductase: T ->
Lack of androgens -> feminization
s
DHT -> masculinization
of external genitalia
of external genitalia
Genital
-> Glans -> Penis
-> Glans -> Clitoris
Tubercl
e
Urogenit -> Urethral meatus
-> Vagina and urethra
al Slit
Labioscr -> Scrotum
-> Labia majora and minora
otal
folds

2. Given a defect in one of the basic steps for sexual differentiation, predict the end result for gonads,
the internal ductal system, and the external genitalia.
3. Describe one example of a disorder of sexual differentiation of each of the major categories of
abnormalities: genetic, gonadal, ductal, and external genitalia.

Step

Defect

Gonads

Genetic Sex

Turners (45X)
(lack of second X = cant
fully develop
ovary-> loss of oocytes)

Ovarian
streak

Formation of

Internal
Ductal
System
Uterus/vagina

External
Genitalia
Clitoris

Gonad
Formation of
Ductal
System
Differentiati
on of
External
Genitalia

Vaginal Agenesis
Ovary
(paramesonephric bulb
fusion defect)
CAH (21-OHase deficiency Ovary
in 46XX)

Absent

Clitoris

Uterus/vagina

Masculinized

**Concominant renal malformations go along with Mullerian problems

**Can rule out 21-OHase if ambiguous genitalia + palpable testes
**High concentration focal androgens -> descent of testes
4. Recite the genetic inheritance patterns of CAH, 5-alpha reductase deficiency, and androgen
insensitivity.

DSD
CAH
5-alpha reductase deficiency
Androgen insensitivity

Inheritance
Autosomal recessive
Autosomal recessive
X-linked recessive

Delayed Puberty
1. Discuss common causes of delayed puberty in males and females.

Gender
Girls

Element
Breast Development
Menarche
Testicular enlargement

Boys

Delayed if after
13 years
15.5 years
13.5 years

Category

M F
Description
% %
Constitutio 60 30 Normal puberty 2.5 SD
nal Delay
% % delayed from mean
Hypogonad 30 40 Hypothalamus or pituitary
otropic
% % defects -> lack of normal
hypogonadi
GnRH and/or
sm
gonadotropin secretion

Hypergona 10 25 Premature loss of germ

dotropic
% % cells -> lack of ovarian
hypogonadi
hormone production
sm
(females) or androgen
production (males)

Etiology
None identifiable
Permanent: tumors/disease of
CNS, hypopituitarism,
chemo/radiation, idiopathic
Functional: systemic illness (IBD,
celiac), endocrine disorders
(hypothyroidism), stressors
(excessive exercise)
Defects causing failure of
ovarian/testicular function Turners syndrome, gonadal
dysgenesis, chemo/radiation,
synthetic defect, autoimmune
destruction, torsion

2. Discuss the significance of presence or absence of breast development and/or pubic hair in a female
patient presenting with a pubertal abnormality.

Breast Development
Pubic Hair
Developme
nt

Presen
t
Absent

Present
Normal

Absent
HPG axis aberrant

HPA axis aberrant

Suspect androgen
insensitivity

HPA + HPG axes aberrant

Suggests more significant
problem

3. Compare and contrast the etiology of germ cell loss and associated findings of Turner syndrome in
females with Klinefelter syndrome in males.

Karyoty
pe
Epidem
iology
Stature
Second
ary
Sex
Charact
eristic
s

Klinefelter
Syndrome

Turner Syndrome

47, XXY

45, X (paternal error)

1/500 to
1/1,000
Tall,
eunuchoid
Gynecomast
ia

1/5,000
Short
Breast development with
normal pubic hair

46,XY
Gonadal
Dysgenesis
46,XY SRY
defect

Androgen
Insensitivi
ty
46,XY
mutant AR

Tall
Mullerian
internal
ducts, normal
female
external

Short
vagina,
ends in
blind pouch
Female
external

Gonads

Somati
c
Abnorm
alities

Gonadal
failure
(variable
severity)

Ovarian streak, 5% have

menses

Ovarian streak
NO puberty

Cardiovascular (aorta
problems)
Horseshoe kidney
Endocrine thyroiditis and
autoimmune diseases
Turner stigmata: webbed
neck, high palate, nail
hypoplasia, short 4th
metacarpal, multiple
pigmented nevi, other

Germ cell
tumors
Treat with
hormone
therapy

genitalia,
large
breasts
Testes
(internal)
Germ cell
tumors

4. Use the condition of idiopathic hypogonadotropic hypogonadism to discuss the signals for onset of
normal puberty.

Mutation/
Syndrome
GnRH
Receptor
FGFR1
Kallmans
Syndrome

Description

Receptor for gonadotropin releasing hormone, in pituitary, -> FSH/LH

secretion
Involved in growth hormone release GnRH neuronal development
Anosmia + hypogonadotropism; XL-R mutation in KAL gene that
encodes cell adhesion molecule that facilitates migration of neurons
(involved in GnRH neuronal development) most common
GPR54
Receptor for kisspeptin, results in GnRH secretion
Adrenal
Mutation in DAX-1, which is involved in gonadotropin secretion at
hypoplasia
pituitary and hypothalamus
congenital
Leptin
Deficiency -> severe obesity, hypogonadotropism
PROP1
Involved in pituitary development. Mutation = GH, PRL, TSH, LH, FSH
deficiency

Normal and Abnormal Menstrual Cycle

1. Define a normal and abnormal menstrual cycle in terms of cycle length and expected menstrual flow.

Phase
Day
Follicles

Follicular
1
Cohort of 2030 follicles

Hormone
s

Gonadot
ropins
Endomet
rium
Cycle
Length
Amount of
Flow

Withdrawal
of
E and P

Dominant
follicle
(arrested in
prophase)
Others die off
Estrogen

Shedding

14
Dominant
follicle ->
ovulation

VERY high
estrogen

LH Surge +
FSH
Proliferation, growth

Normal
22-45 days; median 27,
mean 29
20-45 mLs, 92% in first
2-3 days

Luteal
Corpus
luteum
(driver of
luteal
phase, VERY
high blood
flow)
Progestero
ne (from
CL)
Estrogen also
high

28
Corpus
luteum
withers with
no hCG

Secretion; compaction,
stabilization

Abnormal
Consistent loss of >80mLs, correlated with
passing large clots

2. Identify abnormal menstrual cycles.

3. Contrast the menstrual cycle in a woman who has polycystic ovarian disease with a normal ovulatory
menstrual cycle (see PCOS presentation). Contrast the normal early anovulatory adolescent
menstrual cycles to the cycles of patients with polycystic ovarian disease.

Ovulat
ion
Endom
etrial
growt
h
Vascul
ar
chang
es
Endom
etrial
shedd
ing
Hormo
nes
Mense
s

Normal Cycle
Ovulatory
LIMITED growth, structurally
stabilized by hormones

PCOS Cycle
Adolescent Cycle
Anovulatory/Oligoovulator Anovulatory but
y
normal
Thickened, unstable,
Limited growth from
large quantity
unopposed
estrogen

Progressive vasoconstriction
and final hemostasis of
coiled arteries

Lack of orderly vascular

changes

Universal, limited

Erratic, non-universal
(potentially prolonged
and heavy), and
incomplete
Long term unopposed E
No feedback

Rapid withdrawal of E & P

Return of hormonal support
promotes healing
Regular (21-45 days)

Irregular (outside 21-45

days)

Relatively limited
menses, universal
Intact negative
feedback between
FSH and estrogen
->
Regular (21-45
days), but variable

Irregular if regular
periods become
irregular or if
outside 21-45 days
4. Describe and explain the changes in gonadotropins that occur in the menopausal transition.
5. Contrast the differences in the differential diagnosis of abnormal uterine bleeding in teens compared
to older reproductive women.
6. Discuss the major categories of menstrual irregularity in reproductive aged women.

Ovulatory (typically OLDER)

Defin Normal HPO axis with
ition
superimposed abnormal
bleeding
Preg
Most common
nan
cy
Infec Cervicitis, PID
tiou
s
Blood vWF, ITP
dyscr
asia
Anat Polyps, hemangiomas, congenital
omi
malformations, myomas
c
Othe Endometriosis, midcycle ovulatory
r
spotting

Anovulation/Oligo-ovulation (typically
YOUNGER)

Hypothal
amics

Psychogenic/stress/diet/exerci
se/body fat (MOST
COMMON), CNS tumors,
systemic disease

Endocrin
opathie
s

PCOS (if menses never

regular), thyroid,
prolactinoma, CAH, cushings,
POF

Other

Ovarian steroid producing

tumors, endometrial
cancer/hyperplasia,
menopause/anovulation

7. Contrast the following terms and explain which ones would be expected to be associated with
anovulation or oligo-ovulation:

Dysfunctional
uterine
bleeding
Breakthrough
bleeding
Metrorrhagia
Menorrhagia
Menometrorrhag
ia
Primary
Dysmenorrhea

Anovulatory bleeding, or bleeding that is not from an anatomical

etiology
Unexpected bleeding that occurs while a woman is on exogenous
hormonal medications
Irregular, frequent bleeding
Prolonged or excessive menstrual blood loss with regular cycles
(implies ovulation is occurring)
Irregular menses with prolonged or excessive blood loss
PGF2: stimulates uterine contractions; produced in ovulatory
cycles, mostly during the first 48 hours; 3x follicular to luteal

1.
2.
3.
4.

Polycystic Ovarian Syndrome

Describe the usual physical and laboratory features of polycystic ovarian syndrome (PCOS)
Propose a potential etiology for this syndrome and correlate the physical findings to this etiology
Discuss the risks of untreated PCOS
Explain the rationale for treatment protocols.

Physical
Features

Ovary

Chronic
anovulation
Androgen
excess
Obesity
Acanthosis
nigricans
Endocrine Normal GnRH
Changes
axis
FSH/E2
Negative
Feedback
System
PCOS

VICIOUS
CYCLE

Etiology

Insulin
resistance
Hypotheses

Ring of pearls of many follicles on periphery of ovary

Very dense theca and granulosa cells in core of ovary
Irregular menses, dysfunctional uterine bleeding, and/or
amenorrhea
Hirsuitism (male hair patterns), acne, male pattern hair
loss
Up to 75% (significant portion is lean)
Physical feature of insulin resistance, variably seen in
PCOS
GnRH axis active in neonatal life, then suppressed
throughout childhood, de-suppressed in puberty
Present from intrauterine life, first to mature at puberty
Operates spontaneously to create regular bleeding in a
cycle <45 days in adolescents (E2 falls off => E2
withdrawal bleed)
pulses of GnRH -> Increased LH and decreased FSH.
Tonic high LH suppresses everything else
Polycystic ovaries: NO little blip of FSH on day 0 of
cycle (normally stimulates dominant follicle to form), so
ALL follicles grow
Irregular bleeding: Long term unopposed estrogen
+ nonfunctional feedback -> thick, unstable
endometrium -> erratic, nonuniversal endometrial
shedding (will be incomplete)
Chronic anovulation: have NEITHER spontaneously
operative negative or positive feedback
Menstrual cycles irregular, often 3mo to 1 year
Excess androgen production: LH -> androgen
production by theca cells (normally just precursors for
granulosa cell, but here get liberated; + SHBG ->
free androgens
GnRH pulsatility ->
1. FSH -> multiple follicles unable to mature and
ovulate
2. LH -> ovarian androgens ->
a. Follicular atresia
b. SHBG -> free androgens -> hirsuitism
c. Peripheral aromatization -> GnRH
pulsatility
3. Both 1 and 2 -> anovulation + unopposed
estrogen
GnRH pulsatility, ovarian and adrenal androgen
production, SHBG levels, appetite
Hypothalamus or pituitary defect?

Risks of PCOS
Diagnosis
(Need
2/3,
hyperand
rogenis
m
most
importa
nt)

Hyperandrog
enism
Oligoamenorr
hea or
amenorrhea
Polycystic
ovaries by
US
EXCLUDE

Treatmen
t

Estrogen
Progesterone
Combined
hormonal
contraceptiv
es
Weight loss
Insulin
sensitizing
agent
Anti-androgens
Eflornithine
hydrochloride
Physical
removal of
hair
Ovulation
induction
treatments
(for
conception)

Defect of steroidogenesis?
Metabolic disorder?
Endometrial hyperplasia, T2DM, cardiovascular disease,
sleep apnea, dysphoria, depression, unwanted
pregnancy
Elevated blood androgen levels or physical signs
(hirsuitism, acne, etc)
Cycles less frequent than 35 days
12 or more follicles 2-9mm in size in one or both ovaries
CAH, Cushings syndrome, hyperprolactinemia, primary
hypothyroidism, acromegaly, premature ovarian failure,
simple obesity
Used high-dose short period of time in hospital, NOT by
itself long term
For abnormal uterine bleeding and amenorrhea
Suppress androgen production, SHBG, protects
endometrium
Good long-term conservative treatment
Treat glucose intolerance
Cyproterone acetate, spironolactone, flutamide (all are
teratogenic)
Topical inhibitor of hair growth
Treat hirsutism
Clomiphene citrate: acts as anti-estrogen
Letrozole: aromatase inhibitor
Gonadotropin therapy
Insulin sensitizing agents
Ovarian wedge biopsy/ovarian drilling damage theca

Female Infertility
1. Discuss normal fertility including the expected chance for pregnancy over 1 year and how that chance
for pregnancy changes as women age.

Probability of Conception
25%/cycle
10-15%/cycle
85%

First three cycles

After first 3 cycles
First year
Age
<20
20-24
25-29
30-34
35-39
40-44
>44

% Infertile

11%
33%
87%

Percent Loss
12.2
14.3
13.7
15.5
18.7
33.8
53.2

2. Recite the common causes of infertility

Infert Definition
ility

Caus
es

Primary
infertility
Secondary
infertility
Male Factor
Disorders
Ovulatory
Disorders

Tubal,
pelvic,
endometri
osis

Testi
ng
Treat
men

Decreased
Ovarian
Reserve
Unexplaine
d
Overview
Overview

Failure to conceive after one year of unprotected intercourse <

35 years
Failure to conceive after six months if > 35 years
Inability to maintain a pregnancy past the first trimester
No prior pregnancies
Prior pregnancies
Based on semen analysis volume, concentration of sperm,
motility, morphology
Signs of ovulation: breast tenderness, bloating, menstrual
cramps
Causes: PCOS, hypothalamic suppression (stress, diet, exercise),
hyperprolactinemia, lactational amenorrhea, hypothyroidism,
genetic (early ovarian decline), medications, extremes of BMI
Tubal blockage, mucosal disease, or adhesions: prevent
normal transport of oocyte and sperm; most common = PID
(caused by chlamydia or gonorrhea), can also be caused by
pelvic surgery or appendicitis/IBD
Endometriosis: presence of endometrial glands and stroma in
locations outside the endometrium, associated with
dysmenorrhea; -> tubal transport, pelvic adhesion
Test with hysterosalpingogram
Women who have a reduced amount of follicles in each cohort
After evaluation of couple, no cause is identified; may be due to
subtle causes
Confirmation of ovulation, hysterosalpingogram (tubal patency),
semen analysis
Ovulation induction, intrauterine insemination, assisted
reproductive technologies (IVF)

t
3. Describe factors that impact the chance to become pregnant.
a. Extremes of body weight
b. PCOS
4. Discuss the reproductive implications of increasing oocyte aneuploidy with age
a. Increasing rate of aneuploidy with aging due to impaired meiotic spindle formation -> rates of
chromosomally abnormal oocytes ovulated -> more spontaneous abortions
5. Discuss infertility care as an example of health care delivery issues

Emotional
Aspects
HCDS
Issues

Depression, anger, anxiety common; treatment causes physical

stressors, involves high cost, lots of time off work
Cost often prohibitive, insurance coverage variable

(PHARM: Gonadal Hormones and Inhibitors)

Gonad
Internal
Ductal
Skin
Bone
Metabolic
Other

Estrogen
follicular growth
Endometrial growth, maturation of vagina, cervical mucus

Androgens

vascularization, -> soft skin

osteoblasts
Retention of Na/Cl/H2O, cholesterol
Promotes ductal outgrowth of mammary glands

Thickening, sebaceous glands

skeletal growth, closure of epiphysis
lean body mass (anabolic)
Thickening of vocal cords

Maturation of prostate and seminal vesicles

PHARM: Gonadal Hormones and Inhibitors

1.

Describe the synthesis and metabolism of androgens, the physiologic effects of androgens, age-associated
androgen deficiency, mechanisms of action of Androgens. Describe the clinical uses of androgens, including their
pharmacology, mechanism of action, clinical uses, adverse effects and contraindications.
2. Describe agents used for androgen suppression, including steroid synthesis inhibitors, 5-alpha reductase
inhibitors, anti-androgens, receptor inhibitors and selective modulators of androgen activity (SARMS).
3. Review the physiologic role of estrogen and progesterone in the female reproductive cycle. Describe the action of
synthetic hormones in oral contraceptives.
4. Describe the basics of the biosynthesis of estrogen and progesterone.
5. Recognize the pharmacologic uses of agents that affect the gonadal axis.
6. Discuss the effect of tamoxifen on estrogen receptors, the action of clomiphene on release of LH and FSH, the
action of mifepristone in blocking progesterone in pregnancy
Analog
Mechanism of Action
Use
ADRs/CIs
GnRH
Gonadorelin
Suppression of E/T production in
C/I in pregnancy
Disrupts GnRH pulsatility to
(Factrel,
hormone dependent
Males: diabetes, MI,
LH/FSH
Cystorelin)
breast/prostate cancer
IV
sudden cardiac death,
(respectively)
stroke
Goserelin
Highly bioavailable, more
Delay onset of precocious
(Zoladex)
stable than native peptide
Females: risk for bone
puberty
Naferelin
IN, SC, IM
mineral density, use nonDelay puberty in transgendered
(Synerel)
hormonal contraception,
youth
Leuprolide
not for nursing mothers
Hypergonadism
(Eligard)
LH
hCG
FSH

Pregnyl, follutein,
novarel
Menopur

Estrogen

Progester
one

Androgen
s

AntiEstroge
ns

Shares common subunit

with FSH, hCG, and TSH
Natural product from mare
urine
Natural product from mare
urine
For E, P, and T:
Absence of agonist receptor
complexed with heat shock
protein complex + corepressors
Action: binds to AR in nucleus
-> dissociation of corepressor, recruitment of coactivator

T esters: Tproprionate,
-enanthanate,
cypionate

More gradual absorption,

activity
Given parenterally

Alkylated T:
methyland
fluoxymesteron
e
Transdermal T:
Testoderm,
Androderm,
Androgel, Axiron
Tamoxifen

Orally active

Arimidex
AntiProgesti
ns

Mifeprostone

AntiAndroge
ns

Flutamide
Bicalutamide
Nilutamide

Stimulate ovulation
Contraception (mimics negative
feedback -> LH/FSH)
HRT
Male-to-female transgender
Support pregnancy with high risk
of miscarriage
thickening of uterine lining
caused by post-menopausal
estrogen
Androgen deficiency in aging
men, FTM transgender
Gynecologic disorders: postpartum breast engorgement,
endometriosis, chemo
Anabolic agent following trauma
or surgery
Osteoporosis
Growth stimulation (delayed
puberty in males)
Abuse in sports

SERM: Selective inhibitor of

hormone-binding domain of
E receptor anti-E in
mammary gland and E in
uterus
Blocks aromatase conversion
of T to E -> E, T
Interferes with progesterone
thickening

Oncology breast cancer

Arimidex has efficacy because
E and T

Androgen receptor
modulators: block
activation of androgen
target genes
Orally active, rapidly
absorbed

Blocks uptake and binding of T

and DHT used with LHRH
agonists for prostate cancer
Competitive AR antagonist, long
T1/2 used with LHRH agonists
for prostate cancer
Irreversible AR antagonist, long
T1/2 causes T, so NOT good
for prostate cancer

Post-coital contraceptive
Abortifacient (1st trimester)

C/I in pregnancy, lactation,

breast cancer (hx/FHx)
HRT risk of ovarian cancer,
breast cancer, stroke,
dementia, blood clots
Depression, migraines,
tobacco use, clotting
disorders, seizures, SLE
Breast cancer, ovarian cancer
C/I in kids, pregnancy, breast
feeding, CV disease,
prostate problems,
renal/hepatic disease
Masculinization of women
and kids
Disrupts CNS in early life
H2O retention and edema
CYP enzymes
prostatic hyperplasia,
cancer
liver toxicity with alkylated
T
risk of uterine cancer

Pregnancy, lactation, uterine

cancer
IUD, ectopic pregnancy,
adrenal failure,
hemorrhagic disorders,
porphyria, prolonged anticoagulant or corticosteroid
use
libido
Disruption of male pubertal
development
hepatic enzymes, hepatic
failure
Hyperplasia of mammary
epithelia

Finasteride
Dutasteride
Ketoconazole
Spironolactone

5- reductase inhibitors:
competitive inhibitor,
conversion of T to DHT
Steroid synthesis
inhibitors: non-specific,
will synthesis of other
steroid hormones

BPH, male pattern baldness

Takes 3-6mo to work

Endocrinology of Pregnancy
1.
2.
3.
4.

Describe the hormone interactions that maintain pregnancy in the early postimplantation stage.
Discuss fetal-placental-maternal interactions involved in steroidogenesis during pregnancy.
Describe placental protein hormones and PGs produced during pregnancy.
Recite examples of the clinical effects or uses of placental/pregnancy hormones.

Moth
er
Place
nta

Fetus
Pregn
ancy
Horm
ones

Maternal
endocrine
glands
Syncytiotroph
oblast
Cytotrophobla
st
Hypothalamic
pituitary axis
Measurement
Testing
hCG

Estrogen

Progesterone

Prostaglandins

Aneu
Overview
ploid
y
Scree
ning
AFP
hCG, Estriol
(E3), Inhibin
A

TSH will be LOW because hCG is similar to TSH

ACTH will also be low because of placental ACTH
Pituitary-like: steroids, protein hormones, releasing factors,
endorphins, pregnancy-specific proteins, early pregnancy
factors
Hypothalamus-like: Releasing factors, endorphins,
pregnancy specific proteins, early pregnancy factors
Develops as fetus grows, influences fetal adrenals and fetal
testes, produces steroids essential for normal pregnancy
Measured from first day of last menstrual cycle
hCG serum or urine. Detectable after 2 days; in serum 8-10
days post-conception
Should increase by at least 66% every 48 hours in first
7-8 weeks of pregnancy; wide range of normal
Should be 420-4,480 at 4 weeks, max of 61,200-152,000 at 9
weeks
uterine blood flow; -> changes in blood, skin, breast
development, respiration, GI, carb metabolism
Mostly estriol is produced, but it is rapidly cleared. Produced
by interdependence between fetus, placenta, and mother
Decidual reaction, myometrial contractility, stretchiness of
uterine muscle, breast development
Corpus luteum 6-10 weeks; transient 8-10 weeks due to
transition of CL to placenta
Synthesis: amnion/chorionic membranes
Myometrium: stimulate contractility; has sensitivity to
PGE2 and PGF2 with progresterone, at term, cyclic
uterine contractions
Cervical ripening: PGE2 -> remodeling of collagen matrix
Fetus: prevent premature closure of the ductus arteriosus
Clinical uses: mid-trimester termination of pregnancy,
cervical ripening/induction of labor
Offered during second trimester (15-21 weeks). Detects 75%
of neural tube defects, 80% T21, 60% T18
False positives 5%. Cutoff for elevation = 2 multiples of the
median or more
All different markers get fed into regression formula
Biggest risk factor for neural tube defect. Also in T21 and
T18
T18 everything will be
T21 Estriol will be , hCG and inhibin will be

Partu
ritio
n

Steps

CRH

1.
progesterone, prostaglandins, distension,
estrogen, oxytocin
2.
Smooth muscle without gap junctions -> smooth
muscle with gap junctions
3.
Labor: coordinated contractions across uterus,
accompanied by cervical ripening and softening
Produced by placenta, can predict (in research studies) when
labor will begin
Leads to production of fetal cortisol, which placental CRH
production
Along with ACTH, -> fetal adrenal production of DHEA-S,
which is then converted to estrogen by placenta
estrogen levels mean ratio of E:P is shifted, also uterine
contractile response to oxytocin and fetal lung maturation,
cervical ripening

1.
2.
3.
4.
5.

Describe
Describe
Describe
Describe
Describe

adaptation
adaptation
adaptation
adaptation
adaptation

Plasma

Hematologic

RBCs

Dilutional
anemia
Total
blood
volume
Hypercoa
gulation

Immune
function

Overview

Cardiovascular

Heart
sounds

Cardiac
output

Vasculat
ure
Blood
pressur
e
Mucosa
Diaphrag
m
Ventilati
on

to
to
to
to
to

pregnancy:
pregnancy:
pregnancy:
pregnancy:
pregnancy:

Maternal Adaptations to Pregnancy

Hematologic.
Cardiovascular.
Respiratory.
Renal.
Gastrointestinal.

plasma volume by 45-50% ---- early vasodilation -> RAAS ->

aldosterone -> Na and water retention leads to TBW of 6-8L
RBC volume 25-35% - carries O2 for placenta and fetus, maternal
hemoglobin O2 affinity
iron absorption in gut need an additional gm during pregnancy;
iron deficiency anemia very common in pregnancy
Because plasma volume expands more than RBC volume, Hct and Hgb
appear to fall -> physiological dilution anemia
Still abnormal to have Hgb < 10.5 g/dL
by 40% -> hypervolemia - facilitates maternal and fetal exchange
of respiratory gases, nutrients, and metabolites; supports amniotic
fluid production, buffers postpartum blood loss
factors I, VII, VIII, IX, X -> hypercoagulable state to prevent
excessive bleeding from delivery
-> 10x in rate of venous thromboembolism (all of Virchows triad is
fulfilled)
Placenta does not express MHC I or II. Allows implantation and growth
of foreign embryo
Systemic -> immune function -> risk of severe complications from
some pathogens (influenza, varicella, listeria, malaria)
Dyspnea, fatigue, exercise tolerance, peripheral edema,
cardiomegaly
Systolic murmur in 95%
S1 louder, more widely split; S2 persistently split
S3 heard in 90%
S4 uncommon, pathologic
Mammary souffl in late pregnancy from blood flow in breasts
by 30-50%, functional capacity of heart -> hyperdynamic state
Resting HR is increased
Additionally affected by exertion, labor
Supine hypotension syndrome: when lying supine near term, gravid
uterus compresses IVC, venous return and CO; also compresses
aorta to blood flow to uterus
Progesterone + blocked angiotensin II -> vasodilation -> PVR,
venous elasticity and capacity; stasis, venous pooling
BP early, nadirs mid-pregnancy from SVR; returns to normal BP by
term (shallow U shape)
BP 140/90 mmHg is never normal in pregnancy
vascularity, edema, hyperplasia, friability -> congestion
Resting level rises above non-pregnant position, but no change in
function
tidal volume, alveolar ventilation, and minute ventilation due to
progesterone effects on CO2 chemoreceptors ->

hyperventilation -> PaCO2; facilitates diffusion of CO2 from fetus

Mild compensated respiratory alkalosis = normal
PaO2 normal to slightly , PaCO2 due to hyperventilation, HCO3-
due to compensation by kidneys
Arterial pH in non-pregnant range with mild hypoxia and
hypercapnea may signify impending respiratory failure in
pregnancy
Dyspnea Affects 60-70% of pregnant women; may be progesterone ->
sensitivity of central CO2 chemoreceptors
Kidneys
Dilation of renal calices and ureters (hydronephrosis) begins early,
and
persists 3-4 mos post-partum
ureters
Due to smooth muscle relaxing effects of progesterone, enlarged
uterus and right ovarian vein block right ureter
risk of ascending UTIs due to stasis
GFR
GFR by 50% early in pregnancy - creatinine, BUN, slight in
proteinuria but always <300 mg/day, drug clearance
Hyperfiltr
excretion of Na, K, Ca, and glucose; renal excretion of HCO3
ation
(compensation for respiratory alkalosis)
GI
Nausea, vomiting, ptyalism (excessive salivation), cravings, and
symptom
aversions common
s
heartburn from LES tone
Prolonged transit time (affected by progesterone) -> absorption,
constipation, hemorrhoids
Liver
Estrogen -> liver protein synthesis, coagulation factors, CYP450
( toxin clearance)
total, direct, indirect bilirubin (jaundice) is not normal during
pregnancy
liver transaminases are not normal in pregnancy
Ca
maternal PTH -> synthesis of 25OHD3. Placenta produces
Metaboli
1hydrolase, converts 25-OHD3 -> 1,25OH2D3 -> intestinal
sm
absorption of Ca -> mineralization of developing fetal skeleton,
lactation
Will sacrifice maternal bone stores if calcium intake inadequate
Energy
Relative diabetogenic state due to E, P, and human placental
Metabolis
lactogen -> activity/growth of pancreatic cells
m
-> lower fasting glucose levels, peripheral insulin resistance, lipolysis
Maternal utilization of fat stores preserves glucose and amino
acids for fetal needs

GI

Renal

Respiratory

Arterial
blood
gas

Pathophysiology of Pregnancy with Patient Presentation

1. List etiologies and describe: Maternal Hemorrhage.
2. List and describe: Hypertensive disorders of pregnancy.
3. List and describe common Infections in pregnancy
Overview

Maternal
Hemorrha
ge
Antepartu
m

Maternal
Mortality Ratio
(MMR)
Main Causes
Overview
Placenta Previa

Placental
Abruption

Maternal
Hemorrha
ge
Postpartu
m

Overview

Main Causes
Risk Factors
Uterine Atony

Hypertensiv
e
Disorders
Preeclamp
sia
and
Eclampsia

Overview
Main Causes
Mild Preeclampsia
Severe
Preeclampsia
HELLP syndrome
Eclampsia
Pathophysiology

Systemic Effects
Of Preeclampsia

Infections
- Puerperal
Sepsis

Epidemiology
Definition
Cause

The number of maternal deaths within 42 days of a pregnancy per 100,000 live births
Hemorrhage, VTE, hypertensive disorders (CNS hemorrhage), indirect causes (CV disease,
non-obstetric injuries), infection
Antepartum hemorrhage: bleeding during an ongoing pregnancy that threatens the
wellbeing of the mother or the fetus
Definition: Placenta over cervix. Incidence 0.5%
Presentation: 70% present with painless vaginal bleeding, 20% with contractions +
bleeding
Risk factors: multiparity, AMA, prior placenta previa, multiple gestation, prior cesarean,
tobacco use
Diagnosis: ultrasound (transabdominal or transvaginal)
Definition: premature separation of normally implanted placenta, 0.5-1.5%
Presentation: complete abruption can result in fetal death; painful vaginal bleeding
in 80% (amount not correlated with amount of abruption), fetal HR usually non-reassuring
Concealed hemorrhage = blood dissects upward toward fundus without vaginal bleeding
External/revealed hemorrhage = blood dissects toward cervix
Diagnosis: ultrasound only 50% accurate, but used to exclude previa
Cause: hemorrhage into decidua basalis, which -> further separation, bleeding,
compression, and destruction; inciting cause unknown, but may be due to trauma
Risk factors: maternal hypertension, prior placental abruption, trauma, polyhydramnios,
premature rupture of membranes, tobacco use
Occurs in 4% of deliveries (immediately after), contributes to 20% of in-hospital maternal
deaths
Average blood loss <500cc vaginal, <1000cc with cesarean
Criteria: 10% drop in Hct, need for transfusion, or signs and symptoms
Uterine atony (80%), genital tract trauma, retained placental tissue, low placental
implantation, uterine inversion, coagulation disorders
Prolonged/augmented/rapid labor, h/o postpartum hemorrhage, overdistended uterus,
operative delivery, MgSO4, chorioamnionitis
Definition: failure of uterus to contract after placental separation and close blood vessels,
-> blood loss from myometrial spiral arterioles and decidual veins of intervillous spaces
Occur in 10-20% of pregnancies, with pre-eclampsia in 5-8%
Lead to 8% of maternal deaths in US, associated with CNS hemorrhage and stroke + fetal
and neonatal complications
Preeclampsia or eclampsia, chronic hypertension, gestational hypertension
New-onset hypertension (140/90) after 20 weeks in a woman with previously
normal BP, or new onset proteinuria 300mg/24 hrs after 20 weeks
BP 160/110 on 2 occasions at least 6 hours apart, or proteinuria 5g/24hr, or renal
insufficiency (Cr >1.1mg/dl), pulmonary edema, new onset cerebral disturbances,
epigastric/RUQ pain, liver function, thrombocytopenia
Hemolysis, Elevated Liver enzymes, Low Platelets a high morbidity variant of
preeclampsia
Tonic-clonic seizures in a woman with pre-eclampsia not attributable to other causes,
generally <24 hours post-delivery
Abnormal cytotrophoblast invasion + remodeling of uterine spiral arterioles at implanation
-> placental hypoxia/ischemia
--Current theory: imbalance in angiogenic and antiangiogenic proteins -> VEGF and PIGF +
sFlt1 -> endothelial cell dysfunction -> vasoconstriction + PGE2/NO,
PGF/TXA2/endothelin-1
CV: SVR, HTN
Renal: afferent arteriolar constriction, GFR, glomerular injury, proteinuria, ARF, oliguria
GI: hepatic necrosis/hemorrhage, liver enzymes, RUQ pain, hepatic hematoma
CNS: resistance of cerebral vascular blood flow, cerebral O2 consumption, h/a, vision
disturbances, seizures, encephalopathy, stroke
Hematologic: endothelial cell injury with capillary permeability, edema, IV volume
depletion, hemoconcentration, coagulation abnormalities
Respiratory: capillary permeability, pulmonary edema
Reproductive: uterine artery vascular resistance, pulmonary blood flow, nutrient/O2
delivery, abruption placentae
Occurs in 6-7% of vaginal deliveries, 10-15% of cesarians
A temperature of 100.4F or higher that occurs for more than 2 consecutive days during
first 10 postpartum days
Most common = endometritis (mixed anaerobe infection, caused by necrotic
endometrium/placental fragments -> favorable growth conditions), also from perineal and
cesarean wounds; 70% mixed anaerobic

Consequences
Risk Factors

Septic shock, pelvic thrombophlebitis, pelvic abscess

Poor nutrition/hygiene, premature rupture of membranes, chorioamnionitis, prolonged labor,
numerous vaginal examinations, manual removal of placenta, Cesarean delivery, retained
placental fragments

Endocrinology / Physiology of Pregnancy and Delivery with Childbirth Movie

1. Be able to discuss the events surrounding the onset of labor.
2. Define and use appropriate terminology regarding labor and delivery.
Lab
or

Definition
Synonyms
Clinical
Diagnosis
Initiation
Power

Passage

Phas
es

Phase 0
Phase 1
Phase 2

The physiologic process by which the uterus expels, or attempts to expel, the fetus and placenta at 20
weeks or more of gestation
Parturition, childbirth, accouchement
Painful uterine contractions causing cervical effacement and dilatation
Unknown! Progesterone withdrawal, oxytocin, uterine stretch, prostaglandins
Fetal endocrine control (placental CRH and estrogen seem to be triggers, shift ratio of E to P)
Myometrium = interwoven bundles of smooth muscle cells in a spiral arrangement, matrix of collagen and
GAGs, gap junctions that allow rapid transmission of signals, marked in late pregnancy
Contractions pull up on muscles and out on cervix
Measured in intensity, frequency, and duration via palpation, IUPC, tocodynamometry
At height of contraction, uterus cannot be indented
External monitoring: tocodynamometer (measures contractions) + transducer (fetal heart rate)
Internal monitoring: use intrauterine pressure catheter + scalp electrode
GOOD CONTRACTION: covers entire uterus, gradient so all parts reach peak at same time, IUP 5060mmHg, frequency q2-4min, complete relaxation between contractions
Have different shapes and planes of pelvis as you move through. Ischial spines are typically rate limiting
factor
Fetal head: bones arent fused together so baby can fit through; flexion of head produces lowest
diameter
Lie: long axis of fetus to long axis of mom (longitudinal, oblique, transverse); typically settle by 36 weeks
Presenting part/presentation: what can be felt on vaginal exam, a point of reference (cephalic, breech,
shoulder)
Position: relationship of baby part to four quadrants of maternal pelvis (OA, ROT, OP, LOT [O=occiput])
Attitude: relationship of fetal parts to itself (flexed, military, extended)
Station: how far babys head is engaged in pelvis
Leopold maneuvers: can tell multiple aspects of babies lie, presentation, position, attitude
Cardinal movements: engagement, flexion, descent, internal rotation, extension, external
rotation, expulsion
Pregnancy: Functional quiescence; inhibitors include progesterone, prostacyclin, relaxin, NO
Uterine priming: Release of inhibition as well as estrogen (a uterotropin) -> ion channels, gap junctions
Stimulation: uterine irritability PGE2, PGF2, oxytocin

3. Describe the pattern of normal labor, including its stages, mechanism, duration, and management.

Stag
e
Prod
rom
e

Stag
e1

Stag
e2
Stag
e3

Tim
e
Day
s

Prelabor changes
Cervical ripening: collagen chains fracture, more hydrophilic GAGs,
H2O -> softer, thinned out
Lightening: dropping, babys head engages with pelvis, -> room
to eat/breathe, urination
Passing the mucus plug (may be bloody)
Braxton-Hicks contractions: from 10 weeks on, non-propagated,
may not be felt
10
From beginning of labor until full cervical dilation (10cm)
hrs Initial phase: when cervix isnt doing much; Active phase: effaced
cervix
Cervical effacement: obliteration of canal/thinning of cervix
Cervical dilatation: enlargement of cervical opening
Fetal descent: to lower station (i.e. through pelvis)
Pain: contractions -> cervical dilatation (hypoxia, nerve compression,
peritoneal stretch) -> visceral afferents (sympathetic) to T10, 11, 12
30
From full dilation to delivery of fetus; the pushing stage
mi Pain: distention of pelvic, floor, vagina, perineum -> sensory branches
n
of pudendal nerve (S2, 3, 4); treat with pudendal block or local
anesthetic
5
From delivery of fetus to delivery of placenta and membranes
mi

n
4. Recognize the existence of abnormal labor patterns and abnormal fetal presentations, possible
causes of these abnormalities, and possible management options.

Contractions
Interval
Walking
Pain
Sedation

True Labor
Regular
Decreases
Makes worse
Abdomen AND back
Has no effect

Power

Causes
Uterine dysfunction

Passeng
er
Passage

Abnormal size, presentation,

development
Abnormal pelvic size or architecture

False Labor
Irregular
May stay the same
Make make better
Abdominal
Subsides
Solutions
Augmentation, pain relief,
amniotomy
Change maternal or fetal position
Change maternal position to open
pelvis

Disorders of Implantation, SAB Ectopic; Trophoblastic Disease; Placenta and Trophoblastic

1. Describe the general functions of the placenta.
Fetal surface has lots of vessels, maternal surface has blood on it
Gets blood from maternal circulation through endometrial arteries moms blood exchanges with chorionic villi
Function
Gas transfer
Immunology
Hematopoiesis
Metabolism and secretion
Synthesis and secretion
Heat transfer
Catabolic and resorbtive functions
Excretion, water balance, pH regulation

Normally performed by
Lung
RES
Bone marrow
Liver
Endocrine
Temperature homeostasis
GI tract
Kidney

2. Discuss the common disorders of early and late pregnancy.

Ectopic pregnancy

Spontaneous abortion

Definitio
n
Prevalen
ce
Types

Fetal
Cause
s
Matern
al
Cause
s
Definitio
n
Incidenc
e
Sites
Causes

Histolog
y

Disorders of Early Pregnancy

Spontaneous pregnancy loss before 20 weeks gestation
15-20% of all recognized pregnancies, but 50-60% of all conceptions
Complete: spontaneous expulsion of all fetal and placental tissue from
the uterine cavity
Incomplete: passage of some but not all fetal or placental tissue
through the cervix
Threatened: uterine bleeding from a gestation without cervical dilation
or effacement; occurs in 20-50% of all pregnancies, only half abort,
usually light bleeding
Inevitable: uterine bleeding from a gestation accompanied by cervical
dilation but without expulsion of any placental or fetal tissue through
the cervix
Missed: fetal death without expulsion of any fetal or maternal tissue for
at least 8 weeks
Septic: any type of abortion that is accompanied by uterine infection
Defective implantation: inadequate to support fetal development
Genetic: aneuploidy, polyploidy, and translocation account for 60% of
early abortions
Inflammatory/infectious: toxoplasma, mycoplasma, listeria, viruses
Uterine abnormalities: leiomyoma, polyps, anatomical defects
Hormonal/metabolic abnormalities:
Implantation of trophoblast at any site other than the normal
uterine location
Increasing since the 1970s, but fatality has decreased
Most common = fallopian tube (97%) [ampullary portion 80%, isthmic
portion 6-12%]
Can also be cervical, corneal, ovarian, combined
PID with chronic salpingitis is the most important predisposing condition
(35-50% of patients)
Other = peritubal adhesions from appendicitis, endometriosis, failed
tubal ligation, previous abdominal/pelvic surgery, assisted reproductive
technologies
Hemorrhage and distention of lumen of fallopian tube, with chorionic villi
floating around

Pre-Eclampsia

Presenta Typically in first trimester; abdominal pain (none, mild, or severe)

tion
Spotting/light vaginal bleeding NOT a marker of how severe the
hemorrhage is
Variable intraperitoneal bleeding can be life-threatening!
Diagnosi Ultrasound: valuable, but doesnt always give the answer, need -hCG
s
< 1,500
Quantitative -hCG: first detectable at implantation, typically doubles
q2days
Can use single value to interpret US findings (if hCG<1,500, will not be
able to see anything), and serial values to establish viability of
pregnancy too early for sonographic detection
Serum progesterone: level helps determine if pregnancy is viable
Culdocentesis: another method
Treatme Medical: methotrexate; Surgical: removal
nt
Disorders of Late Pregnancy
Descript Abnormal trophoblast -> ankle edema, hallucinations, and proteinuria.
ion
Need to deliver placenta!
Prevalen 7-10% of pregnancies, usually in 3rd trimester
ce
Risk
G1P0, hypertension before pregnancy, glucose intolerance of pregnancy,
factors
thrombophilia, multifetal
Pathoge Diffuse endothelial dysfunction, vasoconstriction (HTN), vascular
nesis
permeability (edema, proteinuria)
Faulty placenta: see failed remodeling of spiral arteries (the ones
that constrict with menstruation). Normally cytotrophoblast invades
spiral arteries -> lots of blood flow. In preeclampsia, have tiny spiral
arteries not suited to demand of blood flow
Histolog Small, infarcted placenta; thickened wall (atherosis) of spiral artery
y
clogged with foam cells; extension, depth, and #
Presenta CNS: headache, hallucination, visual changes, seizure (with eclampsia),
tion
hyperreflexia
Renal: hypertension, proteinuria, oliguria
Heme: thrombocytopenia, hemoconcentration, intravascular hemolysis
Cardiac: edema (heart failure)
Hepatic: elevated LFTs, liver capsule rupture
Treatme Support + delivery of placenta
nt

3. Describe the proliferative diseases of gestational trophoblast.

Complete
hydatidifor
m mole

Preval
ence
Pathol
ogy

Partial
hydatidifor

Preval
ence

Gestational Trophoblastic Disease

1/1000-1/1500 pregnancies; always 2n, paternal
chromosomes, mostly from single 23X sperm fertilizing
an enucleate egg -> 46XX embryo; 20% metastatic
complications
Villi are edematous (big cisterns of edema), diffuse
trophoblastic proliferation, villi look like grapes
Enlarged to the point where you can see chorionic villi with the
naked eye
1/750 pregnancies; triploid one maternal set + dispermy
fertilization -> trophoblastic overgrowth and abnormal fetal

m mole
Choriocarcin
oma

Managemen
t

Pathol
ogy
Preval
ence
Outco
mes
Other
Overv
iew

development; fewer metastatic complications

Placental tissue with partial villous dilatation; some villi are
edematous, focal trophoblastic proliferation
1/20-30,000 pregnancies; malignant tumor arising from
gestational trophoblast secretes hCG
Metastasizes to lung, brain, and liver, treat with
chemotherapy (do NOT wait/follow)
Non-gestational: gonadal origin, may be part of a mixed germ
cell tumor
Evacuate molar tissue, perform serial hCG testing weekly until
hCG = 0
Avoid pregnancy x 6 months. One of the first curable cancers!
**Pay attention to women who have abnormal bleeding after
their pregnancy!!

Clinical Contraception
1. Describe the component/s of a combination birth control pill, contraceptive patch, contraceptive ring,
birth control shot (medroxyprogesterone acetate contraception), IUDs, implants, and emergency
contraception.
2. Identify the mechanism of action of combination birth control pills, rings and patches, IUDs, and
emergency contraception in preventing a pregnancy.
3. Recognize the absolute contraindications to estrogen containing hormonal contraceptives in
clinical patient cases.
4. Discuss the difference in clotting risk between progestin only contraception and estrogen containing
contraception.
5. Apply knowledge regarding side effects, pathophysiology, and efficacy (e.g. menstrual pattern
changes), duration of action (e.g. Depo-Provera), special considerations( e.g. BMI in patients using
patch, active cervicitis in IUDs) in counseling patients regarding their potential appropriate and
optimal contraceptive choices.

Hormones
Combin
ation
OCP

Ethinyl
estradiol +
MANY different
progesterins
Low dose if
<35g EE (ALL
should be low
dose unless
specialized)
Continuous: ->
inhibited Gn
secretion

Contra

150 mcg

Mechanism of
Action
Progestin = main
component, LH
surge ->
ovulation; also
mucus; ->
endometrial and
ovarian cancer
Estrogen =
potentiates
progestin action ->
dose, better cycle
control by friability
of vessels, inhibits
follicular
maturation by
FSH
28 pills > 21 pills
forgotten doses
Less effective

Adverse Effects
P = androgenic (modern
generations = less androgenic)
Absolute contraindications:
1. Thromboembolic
disorders
2. liver function
3. Abnormal vaginal
bleeding
4. Pregnancy
5. Smokers >35
6. Known/suspected
breast cancer
Thrombosis = estrogen
dependent (NO risk with
progesterone), MUST ask
about clotting history!
Relative contraindications:
often not as relevant; surgery,
DM, Gb disease, migraines (if

ceptiv
e
Patch
Contra
ceptiv
e
Ring
Birth
Contr
ol
Shot
IUD

Norelgestromin
20mcg EE

>90kg women

Ethinyl Estradiol
Etonogestrel

Risk of pregnancy if
out >3hrs

Medroxyprogester
one acetate

Injections q3months

Copper (non
hormone)

Inflammatory reaction
prevents
fertilization
Makes cervix
inhospitable to
sperm
Lasts 3 years

Levonorgestrel
Implan Etonogestrel
ts
Emerge Levonorgestrel
ncy
(~4x higher
Contra
dose than OCP)
ceptio
n

Delay/stop follicular
maturation
Does NOT block
fertilization or
interrupt after
implantation
85% effective if taken
within 72hrs

>35), HTN; look these up on

CDC site if you have questions

bone mineral density

May last up to 1yr
Weight gain in heavy patients,
esp. teens
Contraindicated in malshaped
uterus, fibroids, active
presence of chlamydia or
gonorrhea
Very irregular bleeding
C/I in breast cancer
Indications: no contraception,
broken condom, >2 missed OC
pills, missed injection
(>13wk)/patch (>2 days)/ring
(>3hrs)

6. Formulate a counseling conversation to accomplish the following: You are a clinician and advising a
21 year old regarding contraception. She is set on using an oral contraceptive pill. She has no
contraindications. How will you conduct an interactive counseling session rather than a lecture on
oral contraceptives? What anticipatory guidance will you give her? How will you attempt to decrease
the chance she will discontinue the oral contraceptive? How would you maximize the chance she will
remember to take her pills daily?

Population Health Implications

1. Discuss the high US unintended pregnancy rate.
a. Why? High rate of sexuality (50% by 17) + Poor contraceptors
i. Teens are not abstract thinkers!!!
b. NOT JUST A TEEN PROBLEM! Rates of unintended pregnancy are high in all reproductive groups
2. Compare and contrast pregnancy rates and efficacy of contraception between unprotected coital
activity, estrogen containing combination contraceptives, IUDs, medroxyprogesterone acetate
contraception, withdrawal, and condoms.
a. 40% of unintended pregnancies in 5-7% of sexually active couples who use no contraceptive method
i. 60% in women using some form of birth control!
b. LARCs (IUDs and rods) are the best!

Method
Tubal sterilization
Male condom
Vasectomy
Three-month injectable
Pill (combined)
IUD Copper
IUD Mirena
Periodic abstinence
One-month injectable
Implant
Patch
Emergency
Contraception
Diaphragm
Withdrawal
No method

Perfect
Use
(%/yr)
0.5
2
0.1
0.3
0.3
0.6
0.1
1-9
0.05
0.05
0.3

Typical
Use
(%/yr)
0.5
15
0.15
3
8
0.8
0.1
25
3
0.05
8
15

6
4
85

16
27
85

Continuation
Rates
(age 15-24)

% Use
17%
11%

16%
30%

19%

85%

11%

3. Cite an example of a health care disparity related to unintended pregnancy rates or contraception in
the US.
a. Highest in women age 18-24, unmarried women, low income women, women who had not completed high
school, and minorities
4. Recognize/apply strategies that would increase utilization of contraception to meet the goal of
decreasing the unintended pregnancy rate.
a. Education about contraception
b. Sexual education in schools
i. Abstinence only education in use does not work no delay in activity + no increased contraceptive
use
ii. Educating skills (ways to say no to sex) works
iii. Making contraception a societal normative responsibility for both teen male and female
c. Providing free condoms @
d. Increase IUD or other LARCs @
e. Parents who talk about sex are more likely to have abstinent kids discuss values, latchkey coitus,
spend time, understand normal adolescence
f. Improve utilization of OCPs memory cue to take OCP
i. Also discuss what problems they had remembering, concerns, finances, BTB/amenorrhea; call if
decide to quit
5. Discuss the issue and give an example that may be interpreted as gender bias as it applies to
contraception.
a. Legislation allows employers to opt out of coverage if they are opposed to contraception
b. Gender bias more marked in low SES women in poverty 6x rate of failure of contraceptives than women
at 200% of poverty level
c. Viagra vs. contraception coverage inconsistencies both are lifestyle drugs

Breast Development / Lactation

1. Appreciate the interplay of a variety of hormones in the complete development of the mammary
gland.
2. Discuss how lactation is initiated and maintained.
3. List the advantages of breastfeeding, and be familiar with the content of human milk.
4. Be aware of public health aspects of lactation.

Anatom
y

Embryol
ogy

Location

Arterial
supply
Venous
drainage
Lymphatic
drainage
Overview

Mammo Childhood
genesis
Puberty

Menstrual
cycle

Adult
Pregnancy
Menopause
Lactoge
nesis

Prerequisites
Hormones
Milk factory

Stage 1
Stage 2

Superficial fascia over pectoralis fascia, between 2nd and 6th

intercostal spaces
Tail of Spence extends into axilla
Ligaments of Cooper = connective tissue in breast
Internal mammary artery + intercostal arteries + axillary,
lateral thoracic
Internal thoracic + axillary + intercostal veins
Extensive, to axillary, parasternal, + clavicular nodes
Ectoderm: mammary ridge/crest at 4-5 weeks, epithelial
nodules and cords at 5-7mos
Mesoderm: smooth muscle, CT, blood vessels; elevates
nipple and areola
Male and female identical at birth
No sex differences, rudimentary ducts, not much stroma,
somatic growth only
Ages 8-14, size, E -> growth/branching of lactiferous
ducts, with fat accumulating btw lobes, enlargement +
pigmentation of nipples and aerola
Luteal phase: proliferation of ductal system, slight lobularalveolar development, vascularity, some edema and
tenderness; variation in size related to water retention
Proliferative phase: regression of edema postmenstrually
Resting phase until pregnancy
1st Tm to early 2nd Tm: extension of luteal phase; after this
= Lactogenesis
Slow atrophy of lobulo-alveolar tissues + lobuloalveolar
multiplication, hyperplasia, and hypertrophy
Fully developed mammary gland + withdrawal of E and P ->
inhibition of lactose synthesis in alveolar cells
Need pituitary, gonads, adrenal, placenta, and pancreas
Estrogen -> development of pituitary lactotropes and PRL
secretion
After pregnancy, transcellular pathways -> lactose, Ca,
PO4, citrate, milk protein, lipids, H2O, Na/K/Cl, IgA
--Breast milk = a total food (except vitamin K, also has little
iron)
During pregnancy, paracellular pathways -> cells, NaCl,
plasma proteins -> colostrum. Very important!
Differentiation of alveolar cells, beginning secretion into
alveoli, leukocyte infiltration
Post-partum; mammary blood flow, glucose/O2 uptake,
rapid in cell size and number of secretory organelles,

Stage 3

Advanta
ges
Of
Breastf
eeding

Immune
function
Customizatio
n
Improved
health
outcomes
Mother

Issues
with
Breastfe
eding

Contraindic
ations
Rates
Obstacles

Nursing
difficulties

distension of alveoli with milk

Lactopoiesis: maintenance of established milk secretion
Prerequisite = emptying of alveoli
Suckling -> hypothalamus -> DA secretion -> anterior
pituitary -> Prolactin -> casein mRNA
Suckling -> PVN in hypothalamus -> Oxytocin ->
contraction of myoepithelial cells -> milk ejection (let
down) -> milk to babe, pressure on alveoli
Includes cellular components (Ms, other leukocytes),
secretory IgA + IgG, lactoferrin
Preterm milk different than term and infant age; variation
in fat content during feeds and between feeds
unsaturated FAs, high bioavailability
Infants: acute otitis media, atopic dermatitis, asthma,
childhood leukemia, DM, gastroenteritis, NEC, obesity,
severe LRIs, SIDS
Mothers: breast cancer, T2DM, ovarian cancer, postpartum
depression
Involution of uterus postpartum ( blood loss), bonding,
lactational amenorrhea, retained postpartum weight
AIDS, active TB (respiratory contact), taking street drugs,
uncontrolled EtOH, treatment for breast cancer, certain
medications (chemo, thyrotoxic, immunosuppressive),
infant with galactosemia
Would like at least 75% to initiate BF, 40% exclusive BF
through 3mo, 50% any BF at 6mo
Not currently meeting these goals
Poor latch baby issues or moms anatomy
History of breast augmentation or reduction surgery
Lack of supportive family (the mother in law effect)
Lack of knowledgeable medical providers/hospital practices
that may adversely effect lactation
Societys view of the breast as a sex object
Inverted nipples -> poor latch; fissures in nipple -> pain,
possible infection, breast engorgement -> possible
abscess, emotional stress -> poor letdown, h/o breast
surgery, Sheehans syndrome

Benign Mammary Gland; Benign Breast Disease, Fibroadenoma, Mastalgia, Mastitis

1. Identify the signs, symptoms and main diagnostic techniques of benign non-neoplastic and neoplastic
breast diseases.
2. Apply the relative frequency of all types of breast disease to a discussion of this subject.
3. Differentiate the histological changes encompassing non-proliferative (fibrocystic) and proliferative
breast disease, distinguishing those patterns that correlate with an increased risk of developing
carcinoma.
4. Understand risk factors for the development of breast cancer and strategies for management of high risk
patients.

Cyclic
Breast
Pain

NonCyclic
Breas
t Pain
ExtraMam
mary
Breas
t Pain

Epidemiology
11% of
premenopausal
women
Age 30-40s
Requires no
additional w/u
Age 40-50s
Focal pain or PE
finding ->
diagnostic
evaluation,
mammogram, US

Diagnostic
Technique
Physical
Exam

Mammogra
phy
Ultrasound
MRI
Biopsy

40%

Etiology
Unclear

Presentation
Most have spontaneous
resolution
Starts in luteal phase,
dissipates with menses
Diffuse, bilateral pain, can
radiate to axilla
Unilateral, localized to one
quadrant

Trauma, thrombophlebitis,
mastitis, medications,
benign tumors, cancer,
often idiopathic
Musculoskeletal: costochondritis, chest wall pain,
fibromyalgia, cervical radiculopathy, shoulder pain, VZV,
pulmonary embolism, pleurisy

Details
Ask about pain, character, periodicity, relation to menses
Palpate breasts for dominant mass, include neck, chest, regional lymph
nodes
Pay attention to growth asymmetry. Look for dominant masses!
hardness, definition, mobility, size
Also look for nipple discharge, skin changes
DO NOT IGNORE CLINICAL FINDINGS EVEN IF EXAM IS
NEGATIVE!!! MUST GET BIOPSY
NOT perfect; 20% FNR (40% in young women with dense breasts)
neg. mammogram + palpable mass = uninformative
Look for microcalcifications, new densities, asymmetry
Differentiate solid vs. cystic; adjunct to mammogram
For women at highest levels of risk. Also before surgery
Indicated in patients with suspicious physical exam and normal
imaging
Recommend core biopsy rather than FNA for all breast pathology
Guidance: US, stereotactic (mammography), or MRI; surgical (if
imaging normal); blind (if huge tumor)
Path report: correlates with imaging findings, includes risk of
developing cancer, additional imaging, surgical needs

Non-Proliferative (fibrocystic) and Proliferative Breast Disease

25%

25%

9%

1%

Malignant Neoplasms
Carcinoma
Ductal Carcinoma (non-special)
Ductal Carcinoma (special)
Tubular
Medullary
Papillary
Mucinous
Lobular Carcinoma
Pagets disease
Inflammatory Carcinoma
Sarcoma
Benign neoplasms
Fibroadenoma
Intraductal papilloma
Lipoma, granular cell tumor
Inflammatory Disorders
Acute mastitis
Periductal mastitis
Duct ectasia
Fat necrosis
Lymphocytic mastopathy
Granulomatous mastitis
Mondors Disease
Developmental, Hypertrophy Disorders

Benign
Lesions
Fibrocysti
c Disease

99%
75%
11%
6%
2%
1%
2%
10%
2%
2%
1%
62%
25%
13%

Risk

Presentation

Management

Histology/Imaging

Understanding
and support
Non-narcotic
analgesics,
diuretics,
hormones
Subcutaneous
mastectomy

Proliferati
ve with
atypia

RR of
BC
4-5x

Lumpy bumpy breasts

Additive cyclic
changes related to
menses
Most intensive
mid/late childbearing
years
Swelling, lumps, pain,
tenderness, nipple
discharge

Cysts and fibrosis

Adenosis

Proliferati
ve
without
atypia

No
risk
of BC
RR of
BC
1.52x

Acute
Mastitis

Periductal
Mastitis

Surgery to
exclude
malignancy,
then watch
Inflammatory Disorders
Lactational staph/strep
Abx, continued
milk
expression
Rarely surgical
drainage
Recurrent subareolar abscess
Drainage +
Abx, smoking
cessation

Epithelial hyperplasia
Sclerosing adenosis
Complex sclerosing
lesion (radial scar)
Papilloma (80% w/
nipple discharge)
Atypical ductal or
lobular hyperplasia
Flat epithelial atypia

Keratinizing
squamous
metaplasia

Duct
Ectasia

Mimics cancer on
mammography
calcifications, architectural
distortion, nipple retraction

Fat
Necrosis

Clear history of trauma in 50%

Mimics cancer on
mammography

Lymphocy
tic
Mastopat
hy
Granulom
atous
mastitis
Mondors
Disease

A/w T1DM, autoimmune thyroid

dz
A/w sarcoidosis, Wegeners, TB,
foreign objects in breast
Heavy pendulous breasts +
underwire bra; often posttraumatic

Total duct
excision if
recurrent
None

Duct dilation,
inspissated
secretions,
periductal
inflammation

Self-limiting
Only
symptomatic
tx prn
Lymphocytic infiltrate
surrounding ducts
and blood vessels
Non surgical
Steroids if
refractory
Warm packs
Ibuprofen

Superficial
thrombophlebitis of
the veins of the
anterior chest wall

Developmental Hypertrophy Disorders

Polythelia, Accessory breast tissue/nipples
Polymast
along milk line
ia
Gynecoma Idiopathic = unilateral
stia
Due to in E or in E/T ratio
opiates, digitalis, hormonesecreting tumors,
paraneoplastic, metabolic
Benign Tumors
Fibroaden Classic
Pt < 30, has firm,
Dx = tissue or
Presence of fibrous
oma
mobile lump
excisional
and glandular tissue
= no
(breast mouse);
biopsy
overgrowth
risk
often
painful
Recommend
Compressed
ductal
Comple
excision for
structures
x = 2x
large,
surrounded by
risk
symptomatic
periductal fibrosis
If no excision,
surveillance
Intraducta
Mid to late
Consider
In terminal ducts
l
reproductive years
breast MRI for
beneath areola
Papillom
Most common cause
discharge
a
of bloody discharge
Excise (some
in premenopausal
premalignant)
women

1.
2.

3.
4.

Early Detection of Breast Cancer

Describe potential harms of screening tests, such as for breast cancer.
a. Overdiagnosis: diagnosing disease that would never have been symptomatic
Discuss the potential for overdiagnosis in relationship to mammography.
a. Only 25% of lesions would ever cause a problem
b. Per 1000/10 yrs over age 50, 490-670 will have at least one false alarm, 70-100 of whom will undergo
a biopsy
c. Per 1000/10 yrs over age 50, 3-14 women will be overdiagnosed and treaded needlessly with surgery,
radiation, and/or chemotherapy
Describe the benefits of mammography.
a. Per 1000/10 yrs over age 50, 0.3-3.2 women will avoid a breast cancer death
Discuss the politics of mammography.

Breast Malignancy
1. Identify the most important epidemiology / risk factors for breast cancer.

Age
Estrogen
exposure
Family history
Prior cancer
Prior radiation
Biopsy
Obesity
Alcohol

**60-70% have NO risk factors**

with age
Endogenous estrogens early menarche, late menopause
Exogenous estrogens HRT for 10 years is no good!
Full-term pregnancy better to have a child!
Inherited mutations = premenopausal and bilateral (or
postmenopausal)
Syndrome - risk
Especially of chest wall in early years
Atypical hyperplasia or CIS
exercise (minor)
(NOT tobacco) 2x risk

2. Apply the different breast imaging techniques depending on the clinical circumstances. (see previous
lecture)
3. Differentiate the varying types of breast carcinoma and their prognostic implications based on the
different pathology sub-classifications.

Lobular

Ductal

Ductal
Carcinoma
in Situ
(74%)

Ductal
Carcinoma
(74%)

Lobular
Carcinoma
in Situ

Prognosis
50% chance of invasion with
recurrence
Treat as cancer

Mucinous, tubular types (special,

11%) have good prognosis
Ranges from 10-85% 10-yr survival
based on stage, angiolymphatic
invasion, and margins on resection
Most important factors = size,
nodal status
Treat as risk factor to cancer or
indicator of unstable breast. Even
with removal, equal risk of disease
in BOTH breasts

Findings/Histology
Most common finding on
screening mammogram
(non-palpable)
Non-invasive
Linear, pleomorphic
calcifications in one
breast on mammography
Diffuse malignant
calcifications
Nipple inversion
Blockage of lymphatics ->
peau dorange

Treatment
Excision! local radiation
Local control: eradication of all known
tumors within breast and regional nodes
(surgery, radiation therapy, neoadjuvant
chemo)
Systemic control: aka systemic adjuvant
therapy; tamoxifen
Targeted therapy: use of anti-tumor
treatments that interfere with specific
targeted molecules/pathways needed for
tumor growth
Also use radiation + chemo + systemic
adjuvant therapy + excision
Surgery to exclude malignancy, then close
surveillance

L. Carcinoma

Prognostic factor: factor which imparts an equivalent relative benefit (or risk) regardless of whether the patient
receives treatment or not
Predictive factor: factor which imparts a relative benefit in terms of improved response to a specific treatment
(Her2+ = Herceptin susceptible)

Type
Luminal A
Luminal B
Basal-Like
Her2/Neu
Positive

% of
DCs
40-55%
15-20%
13-25%

E
R
+
+
-

P
R
+
+
-

Her2/Ne
u+
-

7-12%

Details
Responds to hormonal treatments
Higher grade and proliferative activity
Expresses myoepithelial markers; a/w
BRCA1
Higher grade and proliferative activity

4. Identify the treatment choices for non-invasive breast cancer, localized (non-metastatic) invasive
breast cancer, and metastatic breast cancer.

Non-

Local Therapy

Starts with lumpectomy + removal of sentinel node + XRT

Invas
ive
Systemic
Adjuvant
Therapy

Follow Up
Localized (NonMetastatic) Invasive
Metas
tatic

(to breast alone)

Radical mastectomy If local recurrence, huge tumor,
extensive multifocal disease, or C/I to CRT
Systemic chemotherapy or hormonal therapy to
micrometastases
Tamoxifen: mixed ER antagonist/agonist functions as
antagonist in breast, agonist in endometrium and bone
---ADRs: premature menopause, carcinogenesis,
thromboembolism, weight gain, fatigue, chemo brain
Herceptin (trastuzumab): humanized anti HER2 mAb for
Her2+ tumors
---Must tailor use to risk of recurrence: risk =
benefit of chemotherapy
Annual mammography + clinical exam; watch for late
complications
See above
Incurable, but still often treated aggressively.

Childhood Sexual Abuse

1. Describe the epidemiology of child sexual abuse. Contrast child sexual abuse prevalence with that of
other common conditions.
2. Identify common victim-perpetrator relationships.
3. List 3 frequent co-morbid social findings.
4. Discuss child sexual abuse as a determinant of health over the lifespan.
5. Identify obligations for child protection reporting.
6. Discuss the multidisciplinary response to child sexual abuse; identify clinician resources.
7. Identify basic principles for safe assessments and discharges of potential child abuse victims.
8. Identify 7 specified anatomical landmarks in normal prepubertal female external genitalia.
9. Predict the most common exam finding in a prepubertal child following penetrating vaginal or anal
sexual abuse.
10. Recognize common presenting symptoms of child sexual abuse and possibility of delayed or partial
disclosure.

Overview Definition

Epidemio
logy

Overview

VictimPerpetrator
Relationship
s
Co-morbid
Findings
Determinant
of health
Professio Reporting
nal
Obligations
Respon Clinician
se
Resources
Principles for
Safety and
Discharge
Clinical
Skills

Normal
Prepubertal
Female
Genitalia
Exam
Findings
Symptoms
(red flags)

Disclosure

Child Sexual Abuse

Child engaged in sexual activities that he or she cannot
comprehend, for which he or she is developmentally
unprepared and cannot give consent; and/or that
violates the law or social taboos of society
By 18, 25% females, 17% males. 1% each year. Most not
reported
60% known but not related. 30% family members. 10% not
known to child. 23% adolescents or other children.
Women responsible for only 14% of known boys and 6%
of girls
Physical abuse, battered mother, substance abuse in home
-> ischemic heart dz, cancer, stroke, chronic lung dz,
diabetes
Required to report REASONABLE SUSPICIONS (not
certainty of diagnosis)
Child abuse pediatricians, Child Protective Services,
law enforcement, WISE
Safety comes first: needs to be private and alone, need
safety plan. Never ask child leading questions. Leave
formal interview to experts dont repeatedly ask
children questions
Labia majora, labia minora, urethra, clitoris, vagina,
hymen, posterior fourchette (know this)
Vast majority of kids abused will have normal
genital exam (77% girls, 100% boys) mucus
membranes heal very quickly and without a scar. More
likely positive findings if blood/pain at time of assault
Behaviors: young kids putting mouth on genitals, ask to
engage in sex acts, intimate intercourse, insert objects
into vagina or anus, touch animal genitals
Non-specific: recurrent UTI, non-specific genital
complaints, somatic complains, aggression
Disclosure is a process, not an event

Interpersonal Violence + Sexual Assault

1. Describe the professional's role in treating sexual assault (SA) and domestic (intimate partner)
violence and discuss the importance of teamwork in response to intimate partner violence (IPV).

2. Identify acute injuries associated with IPV and SA and discuss the required documentation, testing
and treatment (prophylaxis) associated with the acute evaluation.
3. List long-term consequences (physical, emotional, and overall health status) of IPV and SA.
4. Discuss the prevalence and social context of IPV and SA.
5. Describe the overlap of IPV and SA with other major problems, including child abuse and substance
abuse.

Definitions

Demograph
y&
Prevalenc
e
Crimes
Health
Conseque
nces
Evaluation
&
Document
ation
Treatment
Response
Perpetrator
s
Signs/Symp
toms
Victim
Blaming
Responding
with
Empathy

Sexual Violence
Non-consensual sexual contact by coercion, physical force, threat of
bodily harm, or when consent is not possible
A range of cultural messages and personal behaviors, which includes
coercion, manipulation, pressure, and violence that violates personal
boundaries and/or persons right to choose, with the intent of gaining
power and control over another person
Majority associated with use of EtOH/drugs. <50% reported. 6%
offenders ever spend time in jail.
Focus = power and violence. Progression of offenses (voyeurs ->
rapists). Incestuous families
Acute distress -> depression, exhaustion, restlessness -> PTSD.
Disruption of relationships -> sexual dysfunction. Chronic pain,
hypersexuality, revictimization. use of medical services. health
status.
Need careful, accurate history. Privacy + Consent + Chain of evidence
+ Encourage reporting.
Complete physical exam as per rape exam kit
Treat acute injuries. Test for STDs, pregnancy. Involve support agencies
(WISE), police. Follow up.
Interpersonal Violence
Controlling, possessive, entitled, manipulative. Disrespect partner.
Confuse abuse and low. Strive to have good public image.
Deny/minimize abuse
Bruising/burns, malnutrition, frequent illness, isolation, extreme anxiety,
depression, neglect, STDs
Victims face barriers to reporting must support them! Why does he
do this? vs. Why doesnt she leave? (<- victim blaming)
Victim is the best expert on her safety. Do believe, listen, respect,
and refer.

Adolescent Sexuality
1.
2.
3.
4.
5.

Describe adolescent sexuality in terms of standard adolescent developmental tasks.

Discuss the epidemiology of sexual behaviors in adolescents.
Describe basic concepts of confidentiality in adolescent healthcare.
Discuss sexually transmitted infections in adolescents including basic epidemiology and prevention.
Recite ways to strengthen sexual health choices in adolescents.

Develop Overview
mental Preadolesc
Change
ent
s
Early
Adolescen
t (10-13)

Epidemi
ology

Middle
Adolescen
t (14-16)
Late
Adolescen
t (17+)
Added
Risks
LGBTQ
Key Points

Issues
Confide Laws
ntiality Age of
Majority
Emancipate
d minor
Mature
minor
doctrine
Age of
Consent
Exceptions
STIs

Risk factors

Screening
Strengt
hening

Overview

Biologic sex -> gender identity -> gender role

Gender identity: usually (not always) based on biologic sex
Gender roles: toddlers and young kids aware
Early pubertal changes
Sexual orientation: attraction to same/different/both/neither
sex
Sexual fantasy + masturbation
Physical maturity
Early sexual exploration/behavior: the way one chooses to
express sexual feelings
Adult, intimate sharing relationships
4x suicide. 42% of homeless youth. substance abuse,
violence/victimization, STI
50% of high schoolers active at least once. 33% currently
active. 33-40% have had oral sex
Median age of sexual debut 17yo. 1/3 report pressure. Mixed
w/ high risk behavior
MANY unplanned pregnancies. Many STIs (50% of all STIs).
Very little safe sex. Lots of EtOH and drug use. Virginity
pledges not effective.
State dependent
18 full decision making capacity
Achieved adult milestones military service, marriage,
parenthood, independent financial status
Adolescent who is mature can give consent for medical care;
common-law rule
16
Emergency care, Reproductive care (12-14yrs - pregnancy, STI
testing, contraception), Mental healthcare
Biological: Immature cervix with ectopy. Nave immunity.
risk for forced sexual activity
Developmental: no concrete thinking, difficulty assessing
risk, # of sexual partners, risk of coerced sex, concomitant
substance use
Should have YEARLY screening for GC/CT/HIV. Pap smear at
age 21
Thats a really great decision for you and Im so glad that
youve made that decision. How can I support you in case

Sexual
Health
Choices

Prevention
Techniques

you change your mind and decide to have sex? Condoms

condoms condoms!
Delay sexual debut! Condoms. Vaccination (HepB).
Contraception especially LARC
Listen, timing, education, respect privacy. Focus on strength of
family and community. Avoid jokes.
Ask open ended/nonjudgmental questions. Make no
assumptions. Encourage positive behaviors

Abortion
1. Describe the different types of abortions.

Abortion

Viability
Induced
abortion
Safety

Benefits
of Legal
Abortion

Rights of
a Patient
Rh
Prophyla
xis
Aftercare

Termination of pregnancy before 20 weeks gestation, calculated from

date of onset of last menses, OR
Conclusion of a pregnancy by any means before the fetus is sufficiently
developed to survive (viability)
Early: before 12 weeks
Late: from 12-20 weeks
Generally accepted age = 23 weeks (25% survival at DHMC) - 0%
chance at 23 weeks, 92% chance at 28 weeks
Intentional medical or surgical termination of a pregnancy
Elective if performed for a womans desires, therapeutic if performed
for reasons of maintaining health of the mother
Risk of death from legal abortion = 0.67/100,000. Risk of death from term
pregnancy 9/100,000
The more restrictive a countrys abortion law, the higher the rates of
unsafe abortion and related mortality
Deaths from illegal abortion used to be major cause of maternal mortality
lots of septic spontaneous abortions
1940s - >1,000 women/yr dead from abortion complications. 2009 8
deaths from legally induced abortions
Restricting access to safe abortion does not save fetuses, but often kills
mothers
1.
Continuing pregnancy and keeping the child
2.
Continuing pregnancy and placing the child for adoption
3.
Induced abortion of a non-viable gestation
Needed for ALL Rh negative patients after abortions!, o/w 5% risk of Rh
sensitization
Pelvic rest for 2 weeks, take temperature 2x/day. No standard bleeding
pattern worry if more than normal period
Pain and cramping very common, as is mild depression from drop in
hormones
Menstruation returns after 4-8 weeks. Pregnancy symptoms subside in 12 days
Procedure is not complete until adequate contraception is
provided.

2. Compare the different methods for performing first and second trimester elective pregnancy
termination.

Type

Description

Requirements
First Trimester Abortion
Manual Uses modified syringe
Early recognition of
Vacuu
that creates a vacuum,
pregnancy 5-10
m
hooked up to a cannula,
weeks from LMP
Aspirat
suction -> termination of Cervical dilation if
ion
pregnancy
>6mm cannula used
Simplest, safest, least
Rh prophylaxis!!!
expensive
Examination of aspirated
tissue is essential

Complications
0.7% pelvic infections
0.5% retained
products of
conception
Need for repeat
aspiration
V. rare uterine
perforation

Dilatio
n and
Curett
age

Removal of pregnancy
contents by mechanical
means (vacuum most
common)
Usually performed in
freestanding clinics

Medica
l
Aborti
on

<12-13 weeks
gestational age
Dilation of the cervix
Premedication with
NSAID
Local, spinal, or
conscious sedation
<9 weeks gestational
age

Mifepristone
progesterone antagonist,
600mg single oral dose
Misoprostol on day 3,
400mcg PO/intravaginal
Patient then remains in
clinic for 4 hours
expulsion of pregnancy
Second Trimester Termination
Dilatati Mechanical and suction
Laminaria: take up
on
removal of formed
water from cervix +
and
pregnancy after cervical
exert gentle pressure
Evacua
dilation
-> dilation
tion
Can pre-inject IU
abortifacients to
terminate fetus
Prosta Typically misoprostol
glandi
n
Suppos
itorie
s
IV
Also effective
HighDose
Oxytoc
in
Hyster Surgical method remove (Not done)
otomy
pregnancy abdominally

Infection (10x more

common than
surgical abortion, but
still rare)

complications vs. 1st

trimester abortion

Higher complication
rates

Risk of water
intoxication

3. Discuss the common complications that can arise as a result of having an abortion.

Complication
Cervical Shock
Cervical
Lacerations
Uterine
perforation
Hemorrhage
Post-Abortal
Syndrome

Description
Vagal response to dilation of cervix patient passes out
Occur when dilating cervix too quickly
Blind procedure, so can puncture uterus
From uterine perforation or uterine atony
Uterus doesnt sufficiently contract, fills up with clots -> swollen
abdomen

Urinary Incontinence
1.
2.
3.
4.
5.
6.
7.
8.
9.

Identify and name the major anatomic and histologic features of the bladder and urethra in the male and female.
Define incontinence.
Describe the epidemiological features of incontinence.
Describe the natural history and progression of incontinence.
List the risk factors for incontinence.
Recite the important components of the history when interviewing a patient with incontinence and the physical exam of a patient
with incontinence.
Discuss the laboratory, radiologic, or urodynamic tests, if any, that should be ordered in a patient with incontinence.
Identify the indications for treatment of incontinence.
Discuss the nonsurgical treatment options for stress and urge incontinence, describe their side effects, and outline the
mechanisms by which they work.

Incontin
ence
Innervati
on

Symptom
Sign
Parasympathe
tic
Sympathetic
Somatic
Overview

Risk
Factors
Reversib
DIAPPERS
le
causes
Constant Incontinence
Mixed incontinence
Evaluati
History
on
Physical

Urinalysis

Treatme
nt

Voiding
Diaries
Pad test
Post-void
Residual
Urodynamics
Presumptive
First Line
Behavioral
Devices
Drugs

FollowUp

Overview

Leakage of urine that interferes with ones quality of life or health

Demonstration of urine loss
Pelvic nerves -> contraction of bladder -> pee
Fight or flight you dont wet
Contraction of pelvic floor maintain continence
See reversible causes, plus smoking, low intake, high impact sports, DM, stroke, estrogen depletion,
pelvic muscle weakness, pregnancy, delivery, episiotomy, weight
Delirium, Infection, Atrophic vaginitis, Pharmacologic, Psychological, Excessive urine production,
Restricted mobility, Stool impaction
Congenital ectopic fistula, Iatrogenic vesicovaginal fistula
Many cases are mixed stress/urge, stress/overflow, urge/overflow
Onset, frequency, severity, pattern; pad use (?); drinking/voiding habits; medications
Neurological problems, past surgical/medical history; social history work, smoking history
Also want to know response to previous treatment, assessment of bother, expectations of treatment
Abdominal: scars, distended bladder
Pelvic: atrophic, prolapse, Kegel
Provocative stress test: positive if leakage seen with abd. p. at reasonable volume
Rectal: tone, prostate size
Neurologic assessment: overall coordination; if concerns, MMS, sensation, reflexes
+ RBC (microscopic) w/u for hematuria
+ WBC culture, r/o infection
Intake (time, volume, type); output (time, volume), incontinence episodes/pads
Use pre-weighed pads, then weigh to see how much leakage occurred
Through ultrasound or catheter; very important!!!
RARE as part of initial workup assess storage, outlet, and emptying
Assess bother, expectations, and transient causes
Absorbent products, external collection devices, clamps (males), indwelling catheters
Timed voiding. Modify fluid intake. Bladder retraining. Pelvic floor exercises. Electrical stimulation.
Weight loss
Pessaries hold bladder neck in place
Antimuscarinics - Side effects: dry mouth, flushing, constipation, urinary retention, cognitive
dysfunction, c/I in narrow angle glaucoma
Mirabegron (3-agonist) fewer side effects, no cognitive dysfunction, very effective, but $$$
Determine response to treatment. Check post-void residual

Stress
Overflow
Urge
incontinenc
incontinenc
Incontinenc

10. List the symptoms and signs of the various types of incontinence: stress, urge, overflow, and mixed.

Cause
Bladder dysfunction
detrusor
overactivity of
neurogenic or nonneurogenic origin;
poor compliance of
bladder
Bladder
hasnt
emptied, is always
somewhat full

Anatomic (mobility of
bladder neck) or
intrinsic sphincter
deficiency (bladder
neck dysfunction)
Particularly with
hormonal changes,

Occurs when
Urgency! Without
warning, on the
way to to the
toilet, around
water, when full,
bedwetting
Extremes of
bladder fullness
dribbling,
frequency,
nocturia,
urgency; stress
maneuvers
Coughing,
laughing,
sneezing,
walking, bending
over, getting out
of a chair

Pathophysiology
Detrusor overactivity: bladder
pressure > sphincter ability;
idiopathic (elderly/obstructed)
or neurogenic (suprasacral
lesions)
Poor compliance: incremental
Obstruction:
women

rise in pressure
with (RARE
volume,
prolapse, post-suspension);
men (prostate disease, urethral
structure)
Poor contractility: DM,
longstanding obstruction, spinal
injuries, radical
pelvic
surgery,
Anatomic:
Descent
of bladder
from weak pelvic floor ->
increase in pressure from
intra-abdominal pressure + NO
increase in pressure on urethra
-> leakage

Conservative Tx
Complete bladder
emptying (clean
intermittent
catheterization
Anticholinergics
Alpha-antagonists
Complete bladder
emptying (clean
intermittent
catheterization)
Timed voiding
Indwelling
catheter
Pelvic
floor
exercises
Weight loss
Pessary
Alpha-agonists,
estrogen,
antidepressants

Surgical Tx
Tx obstruction
Botox
Nerve stimulation
turn it up turns
it off
Augmentation
cystoplasty
Relieve
obstruction

Mesh or fascial
slings not a
problem if done
and followed
correctly
Submucosal
injection to

Perinatal Psychiatric Illness

1. Describe the epidemiology and consequences of perinatal psychiatric illness.

Epidem
iology
Conseq
uence
s

Perinatal Psychiatric Illness

Mood/anxiety disorders 2x as common in women as in men; affect up to
20% of women during/after pregnancy
Many are untreated lack of treatment resources, concern about safety of
treatment
substance use, weight gain, prenatal care, poor QoL, interpersonal
conflict, risk of suicide/self-harm, adverse outcomes

2. Recognize risk factors and symptoms of perinatal psychiatric illness.

Baby Blues
Prevale
85%
nce
Risk
Childbirth
Factor
s
Sympto Mild postms
partum mood
disturbance,
lasting <2
weeks

Conseq
uence
s
Treatm
ent

Postpartum Depression/Anxiety
10-20%

Postpartum
Psychosis
1-2/1000

Personal h/o depression, PMS, or

BPD (can be first
PPD, depression during current
presentation)
pregnancy, FHx of PPD, current life
stressors, lack of social support,
unwanted pregnancy
Same as episode of MDD in postDevelops in first
partum period: SIGECAPS
few days to
Anxiety often predominates, can
weeks
have OCD-like intrusive thoughts
Agitation,
disorientation,
confusion, auditory
hallucinations
(often about infant)
Psychiatric
bonding, QoL, marital discord,
emergency! Risk
possible developmental delays,
of suicide or
~risk of suicide or infanticide
infanticide
Exclude medical causes (thyroid,
Hospitalization
anemia), social supports
Therapy SSRIs

3. Identify principles of treatment of psychiatric illness during pregnancy and breastfeeding.

4. Recognize the limitations of the body of evidence regarding safety of psychiatric medications during
pregnancy and lactation and explain the need to balance risks and benefits of treatment with risks of
untreated psychiatric illness.

Weight risks
vs. benefits

a.
b.
c.

Pregnancy
Untreated illness vs.
Treatment
Untreated illness =
adverse exposure

Breastfeeding
Treatment vs. Not breastfeeding
No clozapine (-> agranulocytosis), lithium
needs extra monitoring

No RCTs most data retrospective and observational, with lots of confounders (but more data on SSRIs
than many other commonly used meds in pregnancy); few studies control for degree of psych symptoms
No decision is risk free going without meds carries its own risk, but absolute quantification of risk is
impossible
Safest medication often the one that results in full remission of symptoms if you take a med, might
as well have it work!

d.
e.
f.
g.
h.
i.
j.

Use older medications with more data (fluoxetine, sertraline, citalopram), but base choice on past
response
Use lowest effective dose of single medication if possible
Do not taper prior to delivery
Consider non-medication somatic treatments
Therapy almost always first line, but hard to come by
High relapse rates for MDD, BPD if meds discontinued during pregnancy
Must consider individual illness history (how bad is illness?), response to meds (little benefit probably
not worthwhile), beliefs and preferences about meds during pregnancy, and obstetric risk factors

Cervical and Vulvar Disease

Know when to screen patients for cervical cancer and to know how to interpret the results
Be able to discuss describe the appearance of lichen sclerosis, distinguish it from other vulvar dermatosis, and
initiate treatment.
Cervical Disease
Cervical Risk
Same RFs as for STDs multiple sexual partners, early sexual intercourse, partners who have had
Cancer
factors
partners with cervical cancer, current/prior HSV infections, HIV, h/o STDs, immunocompromised,
+
smokers, substance abuse
Screeni
When
Age < 21
No screening
ng
Age 21-29
Cytology alone, every 3 years
Age 30-65
HPV and cytology co-testing q5yrs
Age >65
No screening following adequate negative prior screening
After hysterectomy
No screening
HPV vaccinated
Follow age-specific recommendations (likely will change)
Conventio
Smear brush on slide, discard remainder. Problem = 90% of cells -> trash; smear looks bloody and
nal
mucusy
Pap Slide
LiquidBrush placed into vial of liquid, which dislodges cells. Vial -> lab -> slide. Easier to interpret clean,
Based
thin layer of cells. Residual material (in vial) used to perform additional tests on same specimen.
Pap
Method
Pap
Infections
Actinomyces (fluffy pink/purple blobs). Candida albicans (purple branching hyphae). HSV (Cowdry
Smear
inclusions). HPV (enlarged, hyperchromatic nuclei, clear cytoplasm [coilocytosis])
Finding
ASCUS
Atypical Squamous Cell of Undetermined Significance. Reflex testing for HPV upon finding ASCUS
s
If no high risk HPV, -> routine screening (99% NPV). If high risk HPV, -> colposcopy & biopsy
ASC-H
ASCUS, cannot exclude high-grade lesion. Automatically do colposcopy and biopsy
Dysplasia Epithelial cells have undergone abnormal maturation and atypical cytologic alterations (cell size,
shape, organization) see below
Low grade (LGSIL) [i.e. squamous intraepithelial lesion]: condyloma or CIN I (mild dysplasia)
High grade (HGSIL) [i.e. cervical intraepithelial neoplasia]: CIN II (moderate) or CIN III (severe
dysplasia or CIS)
(VAIN instead of CIN for vaginal dysplasia)
Oncogenic
Low risk types: HPV 6, 11; -> low grade SIL
ity
High risk types: HPV 16, 18; -> low OR high grade SIL, invasive carcinoma
Colposc
Mosaic
opy
change
1.
2.

Punctatio
n

Acetowhi
te

Treatm
ent

3.

CIN I
CIN II/III

Repeat pap smears at 6 and 12 months, OR HPV testing 12 months

Cryotherapy: freeze and kill abnormal cells
Loop electrode excision procedure (LEEP): excise all abnormal cells; done in office, more
conservative, fertility
Cone biopsy: cut around lesion in sort of a cone shape

Learn the common presentation of a bartholins gland cyst/abscess, and provide proper management. (no questions
on this)
Bartholins Gland Problems
Norm
Function
Secrete mucus, moisture to vulva; located at 4 and 8 oclock positions of vaginal orifice; 0.5 cm in size

al
Absce
ss

Pathophysiolo
gy
Treatment
Long-Term

Cyst

Pathophysiolo
gy
Findings
Treatment

Duct blockage -> cyst formation -> infection (polymicrobial)

Incision and drainage -> immediate relief
Use broad spectrum Abx if surrounding cellulitis
Ensure long-term drainage Word catheter for 2-4 weeks (from abscess to vagina), formation of
epithelialized tract
Chronic inflammation -> obstruction of orifice -> cystic dilatation of duct
1-3cm cyst, usually asymptomatic
None needed, unless >40 (then worry about very small chance of bartholin gland carcinoma

Uterus & Fallopian Tube

1. Discuss the symptoms, diagnosis, and treatment of uterine leiomyoma.

Epidemi
ology
Sympto
ms
Physical
exam
Radiogr
aphic
Treatme
nt

Leiomyoma
Caucasian women; black women, highest in 5th decade of life
Abnormal uterine bleeding (size + position in wall), pain, pelvic pressure,
lower urinary complaints ( frequency)
Reproductive complications: implantation, pregnancy; miscarriage
Enlarged, firm, non-tender uterus, irregular contour; if >12 weeks gestation
size, can palpate in abdomen
US: most common, least expensive
MRI: more expensive, excellent accuracy; useful in some circumstances
Expectant management
Medical management: hormonal (OCPs, Mirena - bleeding), NSAIDs (
pain with menses)
GnRH analogues: fibroid size by chemically inducing menopause;
very expensive, only approved for 6mo
--Used to reduce fibroid volume preoperatively, or as a bridge to
menopause in perimenopausal patient
Surgery: myomectomy or hysterectomy
--Can also do uterine artery embolization selectively occlude the arterial
blood supply to the fibroid

2. Differentiate the different types of endometrial hyperplasia.

3. Determine clinical risk factors for unopposed estrogens leading to endometrial hyperplasia and
cancer.

Endometrial Hyperplasia
Simple
Hyperpla
sia

Aden
oCa
?
1%

Withou Proliferation of glands and stroma, irregular dilatation of

t
glands/crowded small glands; 1% -> adenocarcinoma
Atypia
With
Similar to without atypia, but shows cytologic atypia
8%
Atypia
in glandular epithelial cells (loss of polarity, vesicular
nuclei, prominent nucleoli
Complex
Withou number and size of endometrial glands, + crowding
3%
Hyperpla
t
and branching of glands
sia
Atypia Little intervening stroma, abundant mitoses; similar to
proliferative endometrium
With
Looks like endometrioid adenocarcinoma non23Atypia
confluent glands, mitoses, atypia
48%
Loss of PTEN gene expression. Manage with
hysterectomy (trial of progestin in young women)
Endometrial
Closely packed neoplastic glands
Adenocarcinoma
Pathophys Chronic, unopposed exposure to estrogen obesity, PCOS, estrogeniology
secreting tumors, exogenous estrogens, tamoxifen
Symptoms Post-menopausal bleeding, or premenopausal irregular bleeding
Diagnosis Office biopsy D&C hysteroscopy
Treatment Without atypia: progestins
With atypia: hysterectomy

4. Understand the etiology of salpingitis and the significance of hydrosalpinx, an important clinical
sequela.

Salpingitis
Definit Inflammation of the fallopian tube; most commonly from ascending infection
ion
(PID)
Diagno Abdominal tenderness rebound, adnexal or cervical motion tenderness, +
sis
>1 of:
--T > 38, WBC > 100,000, pelvic abscess on imaging, pus on culdocentesis or
laparoscopy
Histol
Acute salpingitis: edema with mixed inflammatory infiltrate
ogy
Organi C. trachomatis and N. gonorrhea most common; less common =
sms
Mycoplasma, Streptococcus, Staphylococcus, Haemophilus, Bacteroides, E.
coli, Peptostreptococcus, Clostridium, Actinomyces
Hydro
Fluid in fallopian tube -> Very dilated lumen, fewer folds, compression of
salpi
muscular layer
nx

Ovarian Neoplasms with Patient Presentation

Describe the most common ovarian neoplasms according to age
Recite the pathogenesis of epithelial ovarian cancer
Discuss familial ovarian cancer syndromes BRCA1, BRCA2, HNPCC
Be able to evaluate an adnexal mass
BENIGN
Functional
Follicle Cyst
Originate in un-ruptured Graafian follicles or ruptured follicles that have sealed immediately.
Structures
Will have physiologic lining! Typically <6cm
Hemorrhagic
Will have physiologic lining! Typically <6cm
luteinized
cyst
Corpus luteum
Body formed following ovulation. Will have physiologic lining!
Neoplasms
Serous
20% bilateral. See single layer of tall, columnar ciliated cells resembling normal tubal
Cystademona
epithelium
No atypia, architectural complexity, or invasion. Looks smooth and glistening grossly.
Mucinous
5% bilateral. Single layer of tall, columnar mucin-producing epithelium.
Cystadenoma
Mature
Can have hair, teeth, sebum, other
teratoma
Fibroma
Secondarily
Endometriotic
Secondary to endometriosis involving the ovary, get cystic cavity filled with blood
Involving
Cyst
Ovary
MALIGNANT
Genes
BRCA1
Lifetime risk of ovarian cancer 45%. Mutation occurs in 1/800 ( in Ashkenazi Jews)
BRCA2
Lifetime risk of ovarian cancer 35%. Also lots of other cancers
HNPCC
Modified Amsterdam criteria: 3 affected individuals in 2 generations with 1 affected <50yrs
Lifetime risk of ovarian cancer 35%. Colon cancer = 50%. Endometrial cancer = 60%
Pathogenes
Metaplastic
Epithelial neoplasms look like tissues seen elsewhere in female GU tract. p53 mutations
is
Transformatio
common
Theories
n
Ovulation
Women with ovarian cancer have more ovulatory cycles than women without more cycles of
theory
damage and repair. Thought is that epithelial inclusion cyst formed at time of ovulation
undergoes malignant transformation.
Prevention? Suppress ovulation hormonal contraceptives
Serous Tubal
Ovarian inclusion cysts might originate from epithelial lining of fallopian tube. Fimbrial cell
Intradamage -> p53 mutation -> migration into ovary
Epithelial
Carcinoma
Carcinomas
Serous
65% bilateral. Good survival. Can be solid, cystic, papillary, necrotic, or hemorrhagic
Adenocarcino
ma
Mucinous
Mucin often more obvious in cystadenoma
Adenocarcino
ma
Clear Cell
Neoplastic cells with cleared cytoplasm
Carcinoma
Germ Cell
Dysgerminoma
Neoplastic cells with cleared cytoplasm, intermingled with lymphocytes. Typically unilateral,
Tumors
solid.
EVALUATION
History
Age, menstrual status (see below), hormone use, presenting symptoms, US appearance, biomarkers
Biomarkers
CA-125
Serous epithelial cancer (or any itis of the abdomen)
CEA
Colon cancer
hCG
Choriocarcinoma
AFP
Endodermal sinus tumor
LDH
Dysgerminoma
Inhibin,
Granulosa cell tumor
Estradiol
Treatment
Cytoreductive
Goal = eliminate the tumor resect urinary, intestinal, and/or hepatic structures -
Surgery
survival
Intraperitoneal
IP/IV Cisplatin/paclitaxel confines chemo to peritoneal space with minimal side effects, high
Chemotherapy
local concentrations
Disadvantages: difficult to access, sometimes contraindicated, not usually available locally;
but survival 21 months!

Benign

1.
2.
3.
4.

Functional Structures
Germ Cell
Stromal
Epithelial

Pre-Pubertal
-Mature teratoma (most
likely)
---

Reproductive Age
Follicle cyst
Corpus luteum
(combined = most common)
Mature teratoma

Post-Menopausal
--

-Serous cystadenoma
Mucinous cystadenoma

Fibroma
Serous cystadenoma
Mucinous cystadenoma

Mature teratoma

Malignant

Secondary
Involvement
Germ Cell

Stromal
Epithelial

Metastatic

--

Endometrioma

--

Dysgerminoma
(most common malignant)
(looks solid on US)

Dysgerminoma
Immature teratoma
Endodermal sinus tumor
Embryonal tumor
Choriocarcinoma
-Serous, mucinous
(low malignant potential)
Endometrioid, clear cell
carcinoma
Serous adenocarcinoma
Non-ovarian malignant tumors

Same as RA, but

more common menopausally

Juvenile granulosa cell tumor

--

2
3
4

Lab: Female Genital Tract

Describe the process of how a Pap smear is read.
a Pap test: cells removed from cervix with brush, which is placed in solution + agitated to dislodge cells.
Cells are dropped via machine guidance onto small circular area of slide, then stained and visualized with
microscope.
b Cytotechnologist searches slide for abnormalities. If found, slide is referred to cytopathologist, who
makes diagnosis.
Recognize the cellular components of a normal (negative) Pap smear.
Recognize cells indicative of a squamous intraepithelial lesion in a Pap test.
Correlate a Pap smear with a corresponding surgical biopsy of the cervix.

Infec Bacte
tion
rial

Chlamydia: non-specific cellular changes, use NAAT

N. gonorrhea: diagnose via culture, not pap
Dorderlein bacilli: rod-shaped normal bacteria present in vagina, help
maintain acid pH and inhibit pathogenic bacterial growth
Bacterial vaginosis: see coccobacilli that may adhere to surface of
squamous cells (clue cells)
Funga Actinomyces: may be colonizer or invasive -> PID; associated with
l
IUDs; look like filamentous blue-purple clumps (big fluffy balls)
Candida: most common pathogen in female genital tract; see yeast
forms and pseudohyphae, with neutrophils in background
--Risk factors = pregnancy, OCPs, Abx, diabetes, tight-fitting clothing
Viral
HSV: see multinucleated cells with Cowdry type A inclusions
(large, distinct, eosinophilic) or Cowdry type B inclusions (glassy,
basophilic, multiple nuclei)
Proto Trichomonas vaginalis: pearl shaped structures with small nucleus
zoal
on background of acute inflammation (neutrophils)
--May coexist with long, filamentous bacterium (leptothrix)
Dysp Norm Maturation begins immediately above basal layer ( cytoplasm,
lasi
al
flattening)
a
Squa Superficial squamous cells: very normal; have abundant cytoplasm
mou
and small round nuclei
s
Intermediate squamous cells: normal or low estrogen; have
Cells
abundant cytoplasm, nucleus roughly size of neutrophil + more open
Parabasal cells: common with low estrogen levels; small amounts of
cytoplasm, nuclei like intermediate cells
Squamous metaplastic cells without atypia: common; more dense
cytoplasm, variable shape and size
Parakeratotic cells without atypia: arise from chronic irritation, but
not atypical; small round orange cells with small round dark nuclei;
appear on outer layer of cervix
HPV
Types 16, 18, 31, and 35 associated with high grade dysplasia. Types 6
and 11 associated with condylomas
Condylomas: characterized by presence of koilocytes (cells with
cleared cytoplasm and 1 nucleus that is enlarged and
hyperchromatic) + thickened squamous epithelium
ASCU Squamous cells with nuclei >3x size of a neutrophil, but lack other
S
features of atypia
CIN I Maturation begins in lower third (mitotic figures end here); still have
abundant cytoplasm on PAP smear, lack cytoplasmic clearing, have
enlarged hyperchromatic nuclei
CIN II Maturation begins halfway up the epithelium; see moderate
amounts of cytoplasm + large nucleus (less time to mature)

CIN
III
Ca IS
Inva
siv
e
SCC

Cytol
ogy

Maturation begins in upper 1/3 of mucosa; have very little

cytoplasm + large nuclei
No maturation occurs at all. Mitotic figures seen everywhere. Very little
cytoplasm.
Tumor cells with phagocytosed inflammatory or epithelial cells. Nuclei
round, hyperchromatic. Prominent nucleoli. Might have keratinization.

The Menopause Transition

1. Describe the events in the HPO Axis at the menopausal transition and the resultant effect on the
menstrual cycle
2. Describe the common short and long term effects of estrogen deficiency
3. List the risks and benefits of hormone replacement therapy

Definiti
ons

Menopause
Postmenop
ausal
Perimenopa
use

Epidemi
ology

Premature
menopaus
e
Early
menopaus
e
Overview
Earlier with

Menstr
ual
Chang
es

Short
cycles

Interspers
ed
normal
cycles
Luteal
insufficie
ncy

The permanent cessation of menses due to failure of the

ovaries
Woman hasnt had a period for 12 consecutive months (a
retrospective term)
Time between when symptoms start to one year after the last
period, accompanies change from normal ovulatory cycles to
cessation, marked by menstrual irregularity
Menopause before age 40, same as premature ovarian failure
Menopause between age 40-45
Mean 51 (range 40-55). Constant over the yrs. Affected by
genetics, NOT by pariety, menarche
Smoking, vegetarianism, undernourishment, pelvic radiation,
chemotherapy, ovarian surgery
Fewer oocytes recruited -> estradiol -> FSH -> faster
follicle maturation to produce enough estradiol to trigger
LH surge (as much as 1 week early). Luteal phase constant,
but overall cycle shortened. Also more likely to have multiple
follicles maturing -> twinning!
Sporadic ovulatory cycles of normal length

After age 40, ovarian follicles become less response to FSH ->
fewer oocytes available in early follicular phase -> inhibin
and estradiol -> FSH levels -> dysfunction of corpus
luteum -> progesterone secretion -> heavier menses
Anovulatio Accelerated decline in follicles -> anovulation -> cycle
n
length and variability
--Bleeding from fluctuations in E level. Episodes spread out
and then stop.

Sympto
ms

PostMenopau
sal
Hormone
s
Vasomotor
symptom
s

Skin
Changes
Genital
Tract
Psychologic
al
Somatic sxs
Weight gain
Osteoporo
sis

Coronary
heart
disease
Treatme Reassuranc
nt
e
Menorrhagi
a
Comfort

ovarian synthesis of estrogens and inhibin. Ovary

continues to make androgens (testosterone,
androstenedione) -> peripheral conversion to estrone in fat
and muscle. Testosterone production may continue for years
GnRH release -> 4x FSH
Overview: occur during menstrual cycles when estradiol
levels are lowest (e.g. right before period)
Hot flashes: sudden sensation of heat centered in face and
chest that rapidly becomes generalized, lasts 2-4 minutes,
can arouse from sleep -> sleep disturbance. Present in
75% of women
Pathophysiology: skin temperature from peripheral
vasodilators, associated with chills, anxiety, heart
palpitations
Etiology: uncertain; likely related to dysfunction of central
thermoregulatory centers in hypothalamus initiated by
estrogen withdrawal. E -> endorphins in hypothalamus
-> release of NE -> set point in hypothalamic
neuroregulatory nucleus -> inappropriate heat loss. 5-HT
also involved.
Increased with: induced menopause, AfAmerican, smoking,
depression, anxiety, triggers
Decreased with: exercise, Japanese/Chinese ancestry
Hirsuitism + temporal balding (from androgens). Thinning of
skin. Wrinkles. Dry, itchy skin
Vulvar and vaginal atrophy. Vaginal dryness, irritation,
spotting with sex. Dyspareunia. Urinary symptoms and
incontinence. libido.
Depression, irritability, loss of concentration, poor memory
Headache, dizziness, palpitations, breast pain, breast
enlargement or shrinkage, joint aches, back pains
Metabolism slows, unknown connection to estrogen
5%/yr loss in bone for 5 years during menopause, greatest in
trabecular bone -> fractures
Etiology: estrogen regulates bone resorption, so menopause
-> responsiveness to PTH
Risk factors: white, calcium intake, vitamin D, physical
activity, body habitus, medications
Diagnosis: DEXA scan -> bone mineral density -> T score. If
2.5 SDs below mean = osteoporosis
Normally, estrogen vascular resistance, blood flow,
endothelin, HDL, LDL
Menopause = natural process. Some women just need to be
reassured that symptoms will go away
Occasionally need treatment with hormones (Mirena IUD)
Vaginal lubricants and natural products can be helpful

measures
Nonhormone
Vaginal
Estrogen
Hormone
Replacem
ent
Therapy

SSRIs, SNRIs, -adrenergic agonists (clonidine), and

gabapentin can be helpful
Low dose estrogen delivered vaginally as cream, tablet, or
ring to restore sexual function
Principles: reasonable in symptomatic patients. Should use
smallest dose possible to relieve symptoms for shortest
duration of time. If woman has uterus, must give
progesterone to prevent endometrial Ca
Risks: can increase cardiovascular events and breast cancer

Female Sexual Dysfunction

1. Describe models of the female sexual response cycle.

Linear
Model
(Masters
and
Johnson)

Circular
Model

Biopsych
osocial
Model

Excite
ment
Platea
u
Orgas
m
Resolu
tion
Biology
Psychol
ogy
Sociocu
ltural
Interpe
rsonal
Overvie
w

Clitoris
Increases in
length
Retracts under
clitoral hood,
very
sensitive

Labia
Increase in
size, separate
outward

Vagina
Begins to
lubricate,
lengthen, and
distend
Minor lips turn
Entrance
bright red and
contracts,
increase in
barrel
size
expands
Strong
contractions

Other
Uterus and
cervix pull
up and
away

Uterus also
contracts

Physical health, neurobiology, endocrine function

Performance anxiety, depression
Upbringing, cultural norms and expectations
Quality of current and past relationships, intervals of abstinence,
life stressors, finances
Emotional intimacy motivates responsiveness to sexual stimuli,
which governs arousal and desire -> emotional and physical
satisfaction. Spontaneous sexual drive (hunger) can interject
anywhere

2. Know the major categories of female sexual dysfunction.

Overview

Distres
s
Prevale
nce
Risk
Factor
s

Female
Sexual
Interest/Aro
usal
Disorder

Descrip
tion
Etiolog
y
Desire
vs.

Dysfunction NOT necessarily linked with distress distress

is important for diagnosis!
Highest in East and Southeast Asia + Middle East. Low
desire > arousal > pain
Rate of about 10% in US
More common in younger women (likely reporting issues)
Depression, anxiety, sexual abuse, relationship discord,
stress (emotional or environmental)
Other: gyn and breast cancers, non-nerve sparing radical
hysterectomy or cystectomy, premature ovarian failure,
neurologic disease, HTN, DM, partner sexual dysfunction,
perfectionism, negative sexual attitudes
Oral contraceptives: sex hormone binding globulin ->
testosterone
Loss of sexual interest or arousal for at least 6 months or
more that is causing distress
Most prevalent sexual disorder in women! Peaks age 40-60.
Sexual desire results from interplay of sexual response
system and stimuli stimuli only effective in the context of
system that allows for sexual responsiveness
Subjective sexual arousal is multifactorial strongly
modulated by cognition and emotion

Arous
al

Female
Orgasmic
Disorder
Genitopelvic
Pain/Penetr
ation
Disorder

Most women cannot clearly distinguish these. Genital

arousal = reflex. Subjective arousal = slow, strongly
modulated by cognition and emotion. Arousal can
trigger desire, but many women never/infrequently
sense desire. Positive experiences are reinforcing
Treatm Consider the circular cycle. Sensate focus exercises
ent
move back to intimacy and pleasure (vs. sex) via focusing
on feeling pleasure and understanding touch
Descrip Marked delay in, infrequency of, or absence of orgasm, or
tion
markedly reduced intensity or orgasm sensation
Etiologi SSRIs (can occur in up to 70%)
es
Descrip Marked difficulty with vaginal intercourse or penetration
tion
caused by marked vulvovaginal or pelvic pain during
penetration, fear/anxiety regarding pain on penetration, or
tensing/tightening of pelvic floor muscles during
attempted vaginal penetration
Dyspar Treat underlying gyn condition. Important to remove pain
eunia
from sexual experience
Vulvod Vulvar discomfort (burning, dysuria) for minutes or hours
ynia
after penetration attempt
Vaginis Pelvic floor musculature tenses up and can prevent
mus
penetration (fear? Emotions? Arousal?)

3. Describe the approach to assessing sexual function and dysfunction.

Sexu
al
Histo
ry

Treat
men
t

Appro
ach
Difficu
lties
Langu
age
NonPhar
m
Medic
ation
s

Normalize conversation. Dont assume. Be open. (identification,

attraction, and behavior may not match)
Not sure what to do when you get an answer. Fear of offending
patient. Lack of justification. Generational obstacles (especially with
elderly). Fear of sexual misconduct charge.
Dont assume medical terms will be understood. Avoid being overly
superficial. Watch for slang may be alienating.
CBT, mindfulness, sex therapy, physical therapy, psychiatric services,
lifestyle changes, lubricants, devices
Topical estrogen, systemic HRT, ?androgens, ?DHEA

Penis, Benign & Malignant Testis

1. Recite the benign and malignant lesions of the penis.

Conge
nital
Anato
mic/
Struct
ural
Infecti
ous
Inflam
mator
y

Tramat
ic
Vascul
ar
Benign
Neopla
stic
Malign
ant
Neopla
stic

Hypospad
ias
Epispadia
s
Phimosis
Paraphim
osis

Penile Disorders
Proximal urethral meatus + hooded foreskin + chordee
(curvature). DO NOT CIRCUMCISE!
Urethra on dorsal surface of penis. Very rare! Bladder can form
on outside of body.
Narrow contraction of tip of foreskin. 90% can fully retract by
age 3
Entrapment of the uncircumcised prepuce behind glans penis.
Prevent by ALWAYS returning uncircumcised foreskin to
normal position!

STD
Balinitis

Inflammation under foreskin, usually related to poor hygiene.

Treat with hygiene and antifungals
BXO
Balanitis xerotica obliterans. From lichen sclerosis chronic
inflammation -> pathological phimosis, meatal stenosis. Treat
with steroids circumcision
Peyronies
Fibrotic plaque in tunica of penis (probably caused by
Disease
microtrauma) -> curvature of erect penis
Penile
Sudden bending of penis during intercourse -> rupture of
fracture
corpora cavernosa, rapid loss of erection. May injure urethra.
Treat with surgical repair.
Erectile dysfunction
Condylom
a
acuminat
a
Penile
Cancer
Site
Gross
Histology
Staging
Treatment

Aka genital warts, caused by HPV 6 and 11. Treat with

chemical/physical destruction, immunotherapy, surgical
excision
Rare in US. Only found in uncircumcised men, associated
with chronic irritation and HPV 16/18
Begins on glans or inner surface of prepuce
Ulcerated or fungating mass
SCCs with variable keratinization and keratin pearl formation
TNM (like everything else). Mets to Inguinal and ilial lymph
nodes; hematogenous spread is uncommon
Local excision, laser, partial penectomy
Assess and treat inguinal nodes. Dissection can -> bad
lymphadenopathy

2. Recognize that a solid testicular mass is a tumor until proven otherwise. A scrotal ultrasound is a
simple and reliable test to identify masses that are likely to be tumors.
3. Discuss the significance and pathology of cryptorchidism and hydrocele.

Caus
es

Skin
Tunica
Vas
Deferens
/ Cord

Scrotal Mass
Sebaceous cyst, Infections
Hernias. Hydrocoele: tunica vaginalis on surface of testicle swells
up, fluid-filled. Unknown cause
Varicocele. Post-vasectomy granuloma

Evalu
atio
n

Epididymi
s
Testis
History
Exam
**Scrotal
Ultrasou
nd**

Epididymal cyst. Epididymitis. Spermatocele

Tumor. Traumatic hematoma. Epididymo-orchitis
Painful or not painful?
Inspection. Palpation location, can you get above the mass?
Percussion, auscultation
Trans-illumination: can tell you if its fluid filled or not
Should be considered part of the physical exam! Great
test!!! A scrotal ultrasound is a simple and reliable test to
identify masses that are likely to be tumors.
Acute Scrotum

Conge
nital
Infectio
us

Inflam
mator
y
Neopla
stic
Traum
atic
Vascula
r
(Torsion
)

Anato
mic/
Struct
ural

Not many
Epididymitis: kids = congenital, E. coli; young men = STI (chlamydia, GC);
older men: associated UTI, E. coli, Pseudomonas
--Pathogenesis: infection ascends -> vas deferens/lymphatics ->
epididymis/testis
--Pathology: acute = suppurative abscess, chronic = fibrosis/scarring
Orchitis mumps (viral), TB (caseating granulomas), tertiary syphilis
(gummas, diffuse inflammation)
Fouriers gangrene: need significant debridement! Cellulitis, fasciitis,
crepitus -> Rapidly extends
Henoch-Schonlein Purpura: vasculitis in kids, preceded by viral infection,
caused by IgA deposition in vessels; -> associated swelling of testicle
Tumor rupture VERY rare. Cancer typically does NOT present as acute
scrotum
Testicular contusion, rupture, or hematocele
Testicular torsion: surgical emergency! If you dont de-torse, can lose
testicle. Sudden severe pain! Diagnose with ultrasound look for blood
flow (will be absent).
--Occurrence: highest in neonates (in utero, shortly after birth) and
adolescence (commonly a/w bell clapper anomaly, may occur in sleep)
--Pathogenesis: twisting of spermatic cord cuts off venous drainage to
testis -> hemorrhagic infarction
--Pathology:
Other: Torsion of appendices of testis/epididymis. Testicular infarction:
Incarcerated hernia: bowel stuck
Strangulated hernia: bowel twisted and losing blood supply

4. Recognize that cryptorchidism (an undescended testis) is a risk factor for testis cancer
5. List the 2 primary pathological sub-classifications of germ cell tumors: Seminomas and Non
seminomatous germ cell tumors
6. Name the 2 primary tumor markers that germ cell tumors produce and that can be measured in the
serum: Alpha feto protein and Beta human chorionic gonadotropin.
7. Recognize that pure seminomas never produce alpha feto protein.
8. Outline the WHO classification of testicular germ cell cancers. (tumors of one type versus multiple types)
9. Describe the importance of serologic markers for testicular cancer.

Testis Cancer (remember seminoma vs. non-seminoma + staging)

Overv Risk
Cryptorchidism (3-14x). Prior/family history of testis cancer.
iew
Factors
Infertility (underlying undiagnosed genetic issue)
Presentatio Males 18-35. Painless solid mass of body of testis. May have h/o
n
minor trauma (draws attention to testes -> self-exam -> find
mass). Ultrasound demonstrates testis mass
Tumor
Alpha-fetoprotein: from yolk sac elements; half-life 5 days;
Markers
very important in diagnosis and typing. NOT present in
seminomas. Most associated with yolk sac tumors
hCG: produced by syncytiotrophoblast cells; t 24hrs; only
20% of seminomas and <60% of NSGCTs
Lactate dehydrogenase: reflects cellular turnover
Diagnosis
Biopsy = inguinal orchiectomy (98% of the time = take out
the testis [through abdomen] at time of biopsy). Prevent
contamination of scrotal lymphatics
Germ Seminom Most common
Gross: firm,
Histology: sheets of
Cell
a
(50%). Contains
tan, solid,
uniform cells, divided
Tumo
isochromosome
bulging;
by septae, polyhedral
rs
12p.
fleshy,
cells with prominent
(95
Peak in 30s. Never
nodular, and
nuclei, lymphocytes,
%)
make AFP!
homogenous
granulomas
Embryonal 20-30yo
Gross:
Histology: solid and/or
Carcinom Not a true
variegated,
tubular; pleomorphic,
a
carcinoma
often with
primitive cells with illnecrosis and
defined cell borders
hemorrhage
(ugly)
Yolk Sac
Frequent
Gross:
Histology: very variable;
Tumor
component of
homogenous,
contains Schiller-Duval
mixed germ cell
yellow-white,
bodies, hyaline globules
tumor, rarely pure
mucinous
(with AFP)
appearance
AFP (very
specific!)
Most common
testicular
neoplasm in kids
Choriocarci Most
Gross: red,
Histology: syncytio- and
noma
aggressively
hemorrhagic,
cytotrophoblastic cells
behaving early,
necrotic
(hCG factories), lots of
widespread
vascular invasion
dissemination/
metastases
Relatively
uncommon as
pure, but can be in
mixed GCTs
Marked elevation
of hCG
Teratoma
In infancy (usually
Gross:
Histology: mature
mature) or young
Variegated,
and/or immature

Stagi
ng

Treat
men
t

Spermatoc
ytic
Seminom
a
TNMS
Stage I
Disease
Stage II
Disease
Stage III
Disease
Overview

Seminom
a
NSGCT

adulthood (usually
nodular, solid,
elements from all
mixed, has
and cystic
embryonal layers, can
malignant
be functional or ->
potential)
secondary malignancies
Benign, in older
Looks different from usual
men, NO
seminoma!
malignant
transformation
Tumor, nodes, metastases, serum markers
Limited to testis/scrotum
Spread to regional lymph nodes
Visceral or supra-diaphragmatic spread, OR regional node limited
disease with significant tumor marker elevations
Determine seminoma vs. non-seminomatous germ cell
tumor, then stage
**If AFP is elevated, even if histology looks like
seminoma, its a NSGCT!
Extremely sensitive to chemo and radiation! Will kill all of
tumor! Always orchiectomy, then: Stage I = 1 dose of chemo;
Stage II = radiation; Stage III = course of chemo
Non-seminomatous germ cell tumor = sensitive to chemo,
but may have teratomatous elements that remain after
chemo that have to be surgically removed
Stage I orchiectomy + observation. Stage II/III = chemo
surgery to remove residual masses.

1.

Prostate: Benign and Malignant

Discuss the pathophysiology of benign prostatic hypertrophy (BPH), and explain differences in nomenclature
between histological and clinical diagnoses.

Terminolog
y

Pathophysi
ology
Evaluation

Manifestati
ons
Pathology

Treatment

Clinical BPH
Microscopic
BPH
Macroscopic
BPH
Lower UT
symptoms
(LUTS)
Overview

Lower urinary tract symptoms (LUTS), bladder dysfunction, hematuria, UTI resulting from
macroscopic BPH
Histologic evidence of cellular proliferation of the prostate
Enlargement of the prostate resulting from microscopic BPH
Complex of voiding symptoms (straining, hesitancy, urgency, frequency) that may be caused
by macroscopic BPH

Proliferative process of stromal and epithelial elements of the prostate -> macroscopically
enlarged prostate gland
Originates in transition zone around urethra; typically in men >40. Unknown etiology. Not
pre-malignant!
History
Identify other causes of voiding dysfunction
Digital Rectal
Check prostate size. Does not correlate precisely with symptom severity, degree of
Exam
obstruction, or treatment outcomes
Urinalysis
R/o UTI, hematuria
Serum PSA
If detection of prostate cancer would alter management (not super old)
Other
Uroflow, postvoid residual, urodynamics, transrectal ultrasound
LUTS, poor bladder emptying, urinary retention, overactive bladder, UTI, hematuria, renal insufficiency
Gross
Microscopic
Behavioral
Medical

Surgery

Enlarged, nodular prostate. Discrete periurethral nodules, may compress prostatic urethra
Both stromal and glandular proliferation. Mixed hyperplasia + hypertrophy. Drive by T->
5R -> DHT
fluid intake, avoid caffeine/EtOH, timed voiding
-blockers (tamulosin): block 1-ARs in prostate -> relax prostatic smooth muscles ->
bladder outlet obstruction; get improvement in sxs and flow rate
5--reductase inhibitors (Finasteride, Dutasteride): block conversion of T -> DHT via
competitive inhibition -> prostate size by up to 50%; sxs and risk of surgical
intervention, urinary retention
--Side effects: libido, ejaculatory disorder, impotence, breast enlargement
Anticholinergic medications: block cholinergic receptors in the bladder that enable bladder
contractility; for men with overactive bladder associated with chronic outlet obstruction
outlet resistance: trans-urethral resection of prostate, laser prostatectomy, simple
prostatectomy

2.

Explain how medical interventions for symptomatic benign prostatic enlargement impact the pathophysiology of
the condition.
3. Discuss benign versus malignant causes of elevated serum PSA.
Prostate Specific Antigen
Description Serine protease responsible for semen liquefaction, specific to prostate. A marker of risk with imperfect sensitivity
and specificity
Elevation
Disruption of cellular architecture - prostate cancer, prostatitis, BPH, prostate massage, prostate biopsy
Normal
with age and prostate size, no normal value, just a range
PSA
4.

Discuss the pathophysiology of prostate cancer, and compare the natural history of low risk and high risk disease.
Prostate Cancer
Epidemiology
Common condition associated with aging; 75% of men >85 years! Most common non-skin cancer in US men.
Lifetime risk of disease = 16.7%, lifetime risk of death = 2.6%. Incidence with screening.
Etiology
Multifactorial androgens, age, race (AfAmerican), family history of early cancer, inflammation,
environmental + genetic influences
Detection
PSA: discussed above
DRE: assess size, nodules, + confounders of elevated PSA (like prostatitis)
Prostate biopsy: transrectal, US guided; take 12 biopsies of peripheral zone
Risk
Low risk: PSA < 10, Gleason 6, cT1c-2a. High cure rate, but most would never have caused problems!
Categories
Takes 15-20yrs to cause issues. Treat very low risk dz with active surveillance
Intermediate risk: PSA 10 but <20, Gleason 7, cT2b
High risk: PSA 20, Gleason 8-10, cT2c+; often metastasize by time of diagnosis
-- risk of progression and mets without treatment, also recurrence and mortality with treatment
Determined by highest of any one score (i.e. if PSA20, always high risk)
Gross
Tough to see (chalky yellow), need to sample entire gland
Pathology
Histology
Cells larger than normal, ampiphilic, prominent nucleoli
Gleason
Based on gland architecture. Cytologic features similar in all grades. Starts at grade 3 (nodule with small
Grading
infiltrating tubules), then up to grade 5 (no gland formation, just solid sheets with necrosis)
System
Gleason Score = primary grade (most prevalent grade recognized) + secondary grade (second most
prevalent grade recognized)
Pathologic
pT1: clinically unapparent tumor, incidental

Stage
Select Biopsy
Findings

Progression +
Symptoms
Treatment of
Metastatic
Disease

pT2: cancer confined to prostate gland

pT3: extraprostatic invasion or seminal vesicle invasion
pT4: invasion of other organs (rectum, bladder, pelvic wall)
High-grade prostatic intraepithelial neoplasia (HG-PIN): architecturally benign prostatic ducts lined by
atypical cells, considered precursor to cancer; repeat biopsy within 2-3 yrs
Atypical small acinar proliferation (ASAP): suggestive but not diagnostic of cancer ( risk 40-50%),
repeat biopsy in 3mo; see small cluster of glands that looks like cancer, but not diagnostic
Local: extraprostatic extension, seminal vesicles, rarely rectum; -> bladder outlet obstruction, hematuria
Metastatically: lymph nodes, bone; -> bone/back pain, pathologic fractures, neuro compromise, anorexia/wt
loss
Androgen deprivation therapy: castration -> atrophy of prostate epithelium; typically via LHRH agonists
(leuprolide); need 2 wks of androgen receptor blocker first to prevent flare
Other hormones: androgen receptor blockers, ketoconazole (works in 4hrs to T), abiraterone (-> extreme
in T)
Chemotherapy: all patients ultimately become hormone-refractory, then use docetaxel (-> apoptosis)
Treatment of bone mets: bisphosphonates inhibit osteoclastic activity -> bone resorption ->
incidence of skeletal events

Early Detection of Prostate Cancer

1. Explain how early detection of prostate cancer can affect incidence.
a. 3% die from prostate cancer
b. 17% are diagnosed with prostate cancer
c. Over 50% have prostate cancer (huge reservoir)
2. Describe the depth of the prostate cancer reservoir.
a. Predominately causes death in older men (vs. middle aged women with breast cancer)
b. Among men dying from accidental death, 80% of those 70-79 have prostate cancer!
3. Discuss how early detection produces misleading survival statistics.
a. Now, 5-yr survival in prostate cancer is over 99.9%, versus 43% in 1950
b. However, mortality rate is still 31.4/100,000 (same as in 1950) deaths over entire population
c. Looking at survival gives you credit for overdiagnosis, as well as lead time bias
4. Relate the real effects of prostate cancer screening.
a. Mortality benefit to overdiagnosis harm ranges from 1:30 to 1:100!
5. Explain what an "abnormal" PSA is.
a. Range is set relatively arbitrarily can find cancer at any PSA level

1.
2.
3.
4.
5.
6.
7.
8.

Imaging: Male and Female Reproductive Systems

List the imaging modalities available for imaging reproductive systems and describe why ultrasound is more
commonly used than CT or MRI.
Discuss the basic principles of how ultrasound and Doppler work and why ultrasound is a good modality for
imaging the reproductive organs.
Correlate the basic anatomy of the reproductive organs with their basic normal imaging appearance on
ultrasound.
List common causes of acute testicular pain and
understand their basic ultrasound appearance
List common causes of female pelvic pain and understand their basic ultrasound appearance
List common causes of abnormal uterine bleeding and understand basic ultrasound appearance
Describe how Doppler ultrasound can help to differentiate orchitis from testicular torsion
Explain why a hemorrhagic ovarian cyst appears different from a simple ovarian cyst on US and how Doppler can
help differentiate a hemorrhagic cyst from an ovarian neoplasm
Hysterosalpingogram
CT
MRI
Ultrasound

Uteru
s

Normal
Polyps
Endometrial
Cancer
Fibroids

Ovari
es

Normal
Simple Cyst
Hemorrhagic
Cyst
Endometrioma
Torsion
Tubo-ovarian
Abscess
Tumors
Ectopic
pregnancy

Teste
s

Prost
ate

Normal
Torsion
Epididymo-Orchitis
Tumors
Varicocele
Normal
Cancer

Distends endometrial cavity. Cervix is cannulated and contrast dye is injected into
Terms are density, attenuation
Terms are signal intensity, brightness
Uses very high frequency sound waves that reflect to form an image. Terms are an/iso/hyper/hypoechoic.
Passes straight through fluid (anechoic), completely reflected by calcium and air. Can use Doppler to
see flow
Sonohysterogram: fluid injected into endometrial cavity, outlines mucosa
Ante- or retroverted, homogeneous myometrium. Echogenic endometrium, varies in appearance with
age and phase of menstrual cycle. Early proliferative = line, secretory = big white gob. Mid-cycle = 3
nice layers (trilaminar phase)
Growths into cavity from mucosal/glandular surface. Echogenic (bright) mass with vascular pedicle
Abnormally thickened endometrium with possible invasion of myometrium. Heterogeneous,
disorganized, very vascular.
Fibrous smooth muscle growths that come from myometrium. Can be submucosal (most problematic),
intramural, or subserosal. Darker than surrounding myometrium. Can be calcified
Attached to broad ligament, anterior to iliac vessels.
Contains small follicles, dominant follicle, or corpus luteum (huge) depending on phase of cycle
Thin walled, purely anechoic structure (filled with serous fluid). Color Doppler is key!
Complex, heterogeneous cyst with blood (less black than serous fluid). Flow only around edge. May
have clot or fibrin stranding.
Homogeneous adnexal cyst filled with old blood products
Enlarged, edematous, abnormal looking ovary w/ /no blood flow (loses venous drainage). Check
for lead point (causes twisting)
Complex mass in adnexa. Usually from ascending infection -> PID
Complex cystic or solid ovarian lesions. May be asymptomatic until large
Usually b/t uterus and ovary in fallopian tube. Complex adnexal mass w/ echogenic vascular ring of
blood flow. Must do pregnancy test! Dont definitively call pregnancy intrauterine until you
see yolk sac!
Homogenous testes + epididymis, with symmetric vascularity
/absent blood flow
blood flow in testes and epididymis due to infection and inflammation
Focal mass. Often hypoechoic.
Enlarged tortuous veins, commonly on left side (left gonadal vein -> left renal vein rather than IVC)
Transitional zone hypoechoic relative to more echogenic peripheral zone
Mass on US

Lab: Male Pathology

Male Reproductive Anatomy, Physiology and Infertility

1. Correlate the normal male reproductive anatomy, physiology, and semen parameters to a basic male
evaluation.
2. List genetic and nongenetic causes of male reproductive dysfunction.

Spermat
ogenesi
s
Evaluati
on of
Infertile
Male

Treatme
nts

Cell
types
History

Spermatogonia -> spermatocytes -> spermatids ->

spermatozoa

Gonadotoxins: smoking density, motility, fertility, natural

conception; offspring risk of pediatric cancer
--Others: marijuana use, excess alcohol, huge excess caffeine,
anabolic steroids
Medications: fewer is better; most are not tested against
sperm count; shouldnt take supplements
Be healthy eat balanced diet, exercise, sleep
Prior illnesses/surgeries, ejaculatory function, meds, allergies,
etc.
Anaboli -> azoospermia. Treat by stopping all anabolics, waiting for
c
pituitary to respond (a few months), wait for sperm to return
Steroi
(may be 6-9 months)
ds
Physical Very important! Have to examine whole genital structure.
Exam
Penis
Hypospadias -> sperm delivery problem. Chordee: curvature
Exam
may prevent vaginal intercourse. Phimosis: inability to retract
foreskin
Testes
Check for presence of testes in scrotum, unilateral or bilateral.
Exam
Check size (small is bad) and consistency (soft is bad)
Duct
Check for blockage of vas or epididymis, congenital absence of
Exam
the vas
Varicoce Common cause of spermatogenic deficiency. Surgical correction
le
-> great improvement
Spermat Spermatocele: may obstruct epididymis. Hydrocele: may
ic
affect spermatogenesis
Cords
Genetic Non-obstructive azoospermia: Y chromosomal
s
microdeletion of azoospermia factor (AZF); find using PCRbased assay; if deleted, means no sperm ever, but needs no
testis biopsy
--With AZFc, have a few sperm, but will have issues with male
offspring (will carry same gene)
Kleinfelter syndrome: 47 XXY, in 1:500 live male births and 510% of azoospermics. No single phenotype - Men are not
necessarily hypogonadal or eunichoid, may present with
infertility. 60% may have sperm in testes. Do testicular sperm
extraction to find sperm!
Congenital bilateral absence of the vas deferens: based on
mild mutations in CF genes. Must do CF mutation analysis in
both partners
Surgery Many different surgeries possible, including testis sperm
extraction, epididymal sperm aspiration, etc.

Fertility
Preserv
ation

Post-pubertal males with malignancy who can ejaculate

should freeze sperm prior to spermatotoxic chemo/radiation,
ablative surgery. If ejaculation not possible or pre-pubertal,
preserve testis tissue

Never forget you are a doctor first, no matter what specialty you practice
For both male and female:
o Be healthy:

Balanced diet

Exercise

Sleep

No smoking, drugs, excessive alcohol

Anabolic steroids (or prescribed testosterone)
o Reduce or completely suppress sperm production
The physical examination can be everything to the diagnosis
The Y chromosome houses genes that are involved in sperm production
o A male can have a microdeletion of the Y chromosome and azoospermia
Klinefelter Syndrome : no single phenotype
Congenital Bilateral Absence of the Vas Deferens
o Cystic Fibrosis mutation analysis is required

Male Sexual Function, Physiology & Disease

1. Describe the mechanism of tumescence.

Anatomy
Physiolog
y

Mechanis
m of
Tumescen
ce

Erectile
Dysfuncti
on

Basic
Workup
of ED
Treatment
Options

Penis

Corpus cavernosum: contains sinusoidal erectile tissue,

surrounded by tunica albuginea
Corpus spongiosum: contains urethra
Neurology Parasympathetic: -> erection via NO, cGMP
Sympathetic: -> detumescence
Somatic: sensation
Types of
Psychogenic: audiovisual and fantasy, cortical output ->
Erection
spinal erection center (S2-4)
Reflexogenic: tactile stimulus via dorsal nerve -> spinal
erection center (S2-4)
Nocturnal: during REM sleep, unknown mechanism -> spinal
erection center (S2-4)
Flaccid
Smooth muscle tonically contracted. Low arterial inflow
State
Stimulate Release of neurotransmitters -> smooth muscle
d State
relaxation in sinusoids
Arterial dilation: blood flow into sinusoidal space
Expansion of sinusoids: -> compression of emissary veins,
trapping of blood as outflow decreased
intracavernosal pressure: rigid erection with contraction
of the ishiocav muscles
Risk
Aging: not solely a risk factor, but all the other things that
factors
go along with aging are
Lifestyle issues: lack of exercise, obesity, heavy drinking,
recreational drugs, smoking
Hypertension: atherosclerosis important contributing factor
to ED
Psychoge Anxiety, fear of failure. Depression. Marital conflict/strained
nic
relationship. Ignorance, misinformation.
Will often present as situational erectile dysfunction
Neurogen Central: Parkinsons, Alzheimers, CVA, tumor, trauma
ic
Other: spinal cord, peripheral
Arterioge Atherosclerotic: part of generalized process, incentive for
nic
lifestyle modification
Traumatic: old bike seats
Drug
-blockers libido. Spironolactone -> ED, gynecomastia.
Induced
Ketoconazole, cimetidine anti-androgen
Endocrine Diabetes, thyroid disease, testosterone deficiency
History
Duration of impotence (?AM erections), libido, partners. CAD,
DM, PVOD, renal function. EtOH, tobacco
Physical
Penis: micropenis, Peyronies. Testicles: size, consistency.
Complete neuro/vascular exam
Labs
Testosterone, LH, TSH, lipid/cholesterol
PDE5
PDE5 normally breaks down cGMP, which is important in the
Inhibito
cascade of tumescence (anti-tumescence)
rs
Sildenafil: t = 4 hrs
Tadalafil: take 1-2hrs before sexual activity. Lasts much,

Priapism

much longer (t = 17.5 hrs)

NOT for those on nitrates
Intracav Papavarine: inhibits PPDE -> blocks Ca influx
ernosal Phenoxybenzamine/Phentolamine: -blockade
Injection PGE1: vasodilation
Others
Vacuum erection device, intraurethral prostaglandin E1
Types
Arterial: painless erection without detumescence
Venous: painful erection without detumescence;
emergency! Can -> ischemia and fibrosis
Treatment Oral meds, irrigation, sympathomimetic agents, shunts

Most ED is vasculogenic
Treatment begins with oral agents
o PDE5 inhibitors
o Increase intracellular cGMP
o Increase in intracavernosal sm. muscle relaxation
Priapism
o High flow
o Low flow

Ischemic: needs treatment immediately