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TABLE OF CONTENTS

1. Fetal Development
Reproduction 2. Pregnancy and Menstruation
3. Pathologies of Pregnancy
4. Female Pathology
5. Male Pathology
6. Pharmacology

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 OUTLINE
1. Fetal Embryology 7. Chromosomal Disorders
©
A. Fertilization A. Klinefelter Syndrome
B. Implantation B. Turner Syndrome

Reproductive C. Bilaminar Disc

D. Gastrulation 8.
C. Double Y Syndrome
Sexual Development Disorders Part 1

System: Fetal 2.
E. Embryonic Period
F. Fetal Period
Germ Layers
A. Sexual Development Overview
B. 5a reductase Deficiency
C. Androgen Insensitivity Syndrome

Development A. Ectoderm
B. Neural Crest Cells
C. Mesoderm
9. Sexual Development Disorders Part 2
A. Placental Aromatase Deficiency
B. Kallmann Syndrome
D. Endoderm 10. Male Anatomy

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3. Teratogens
A. Medications
A. Organs
B. Blood Flow
B. Recreational Drugs C. Lymphatics
4. Pharyngeal Apparatus D. Anterior Urethral Injury
A. Pharyngeal Clefts E. Posterior Urethral Injury
B. Pharyngeal Arches 11. Female Anatomy
C. Pharyngeal Pouches A. Organs
D. Aortic Arches B. Blood Flow
5. Sexual Differentiation C. Lymphatics
A. Female Development D. Nerves
B. Male Development E. Ligaments
C. Homologs
6. Disorders of Genital Embryology
A. Male Disorders of Development
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Morula

Early Development IZygote

Fertilization: (fertilization)

♦ Ampulla of oviduct
♦ Morula: 4 days post-fertilization
Implantation:
♦ Blastocyst implantation on day 6
■ Ectopic pregnancy
■ Placenta previa
♦ Trophoblast penetrates endometrium
♦ Trophoblast divides —> Syncytiotrophoblast + Cytotrophoblast
Bilaminar Disc:
♦ Bilaminar embryonic disc = Epiblast + Hypoblast
♦ Epiblast = Amniotic sac
♦ Hypoblast = Yolk sac
Gastrulation:
♦ Epiblast —► Primitive streak —> Ectoderm, Endoderm, Mesoderm
♦ Notochord and neural plate formation
■ Notochord = Nucleus pulposus
■ Neural plate= Brain and spinal cord
♦ Week 3-8 teratogen exposure —► Embryonic malformations
Embryonic Period:
♦ Major organ development begins
♦ Week 4 —> Neural tube closes, heart beats, limb formation
Fetal Period:
♦ Week 8 —► Fetal movement
♦ Week 10 —► Sex of fetus recognizable
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Early Embryonic Orientation

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Trophoblast Splits: Syncytiotrophoblast

- Syncytiotrophoblast - Embeds in Endometrium

- Cytotrophoblast - Contact with O2 Diminishes invasive nature
- Produces hCG (Human Chorionic
Gonadotropin) around 7 days
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Clinical Correlate: Ectopic Pregnancy

Uterus

Fetus

MlpsJ/commons.wikimeciia.org/wiki/File:Pfegnancy ultrasound .110325143136.1432470 jpg

Normal Sonogram Ectopic Sonogram

- Fetus develops outside of uterine cavity
- Uterine Tubes, Ovary, Abdominal Wall
- Not a viable pregnancy
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Clinical Correlate: Placenta Previa

Placenta Previa:

- Marginal: Placenta is adjacent, but

not covering the cervical opening
- Partial: Placenta partially covers
cervical opening
- Complete*: Placenta completely
covers cervical opening
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Symptoms:
- Vaginal bleeding after 20th
week gestation

Treatment:
- Bed rest, limited activity
- *requires Cesarean delivery

Normal location of placenta Placenta previa

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Germ Lavers
Ectoderm:
♦ Surface ectoderm —► Epidermis, adenohypophysis, hair, nails, salivary glands
♦ Neuroectoderm —► CNS and brain HIGH YIELD
Neural Crest Cells:
♦ Subset of ectoderm
♦ Neurons of the PNS, leptomeninges
♦ Bones, connective tissue of the skull
♦ Endocardial cushions, aorticopulmonary septum
♦ Melanocytes
♦ Chromaffin cells of adrenal medulla
♦ Enterochromaffin cells
Mesoderm:
♦ Axial —► Notochord —► Nucleus pulposus
♦ Paraxial —> Vertebrae, ribs, skeletal muscles
♦ Intermediate —> Kidney, gonads
♦ Lateral plate —► Cardiovascular system, microglia, stems cells of hematopoietic origin, limbs
Endoderm:
♦ Head and neck —► Eustachian tube, thymus, parathyroid gland, tonsils, pharynx
♦ Organs —> Gl tract, respiratory tract, urinary tract

EHBLASr -■» ecppe*"!

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Clinical Correlate: Anencephaly

Characteristics:

- Cranial end of the neural tube (rostral neuropore) fails to close between days 23-26 of development
- Causes major loss of brain, skull, and scalp
- Survival is slim. Only 5% of children live past 7 days.

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https ://corrimons.wikimedia.orgAviki/File:Anencephaly-web.jpg
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Teratogenic Medications
Medications:
ACE inhibitors —► Fetal kidney damage —► Oligohydramnios
Anti-epileptic/ Folate Antagonists —► Neural tube defects HIGH YIELD
Fluoroquinolone —> Cartilage damage
Tetracycline —► Discolored teeth, decreased bone growth
Chloramphenicol —> Gray baby syndrome
NSAIDs —► Premature closure of the ductus arteriosus
Methimazole —► Aplasia cutis
Lithium —► Ebstein anomaly
Thalidomide —► Limb defects
Tretinoin/Vitamin A toxicity —► Risk of spontaneous abortion
Recreational Drugs:
♦ Alcohol —> Fetal Alcohol Syndrome:
■ Presentation: Intellectual disability, thin upper lip, flat philtrum, down-slanting palpebral fissures
■ Diagnosis: Clinical
■ Additional Features: Holoprosencephaly, Ventricular septal defects
Cocaine: Widespread vasoconstriction —► Placental abruption
Cigarettes: Widespread vasoconstriction —► Placental abruption
■ CO —> Hypoxia for fetus
Opioids —► Neonatal Abstinence Syndrome
Features: Uncoordinated suckling responses, high pitched crying and sneezing
Management: Methadone, morphine, buprenorphine
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Pharyngeal Apparatus:
• Pharyngeal Clefts/Grooves:
• Ectoderm derived
• 1st - External auditory meatus
• 2nd - Cervical sinus:
■ Normally obliterates
■ Persistence = Branchial cleft sinus
• Pharyngeal Pouches:
• Endoderm derived
• 1st - Middle ear cells, mastoid air cells, eustachian tube
• 2nd - Epithelium of palatine tonsils
• 3rd - Inferior parathyroid glands (dorsal wing), thymus (ventral wing) HIGH YIELD
•
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4th - Superior parathyroid (dorsal wing), parafollicular cells of thyroid (ventral wing)
• Pharyngeal Arches:
• Mesoderm/neural crest cell derived
• 1st - Mandibular/maxillary process, muscles of mastication, CN V3, anterior½ of tongue
• 2nd - Stapedius/stylohyoid process, facial muscles, CN VII, stapes, lesser horn of hyoid bone
• 3rd - Stylopharyngeus muscle, CN IX, greater horn of hyoid bone
• 4th - Pharyngeal constrictors, superior laryngeal nerve
• 6th- Larynx muscles (except cricothyroid), recurrent laryngeal nerve
• Disorders: Pierre Robin Sequence, Treacher Collins Syndrome
• Aortic Arches:
• 1st - Maxillary artery
• 2nd - Stapedius artery
• 3rd - Common carotid/internal carotid
• 4th - Aortic arch, right subclavian
• 6th - DA,
P DA,pulmonary
pulmonaryarteries
arteries
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Pharyngeal Apparatus:
Cleft Arch Pouch Aortic Arch

1 Meatus (External) Maxillary process Middle ear Maxillary artery

Mandibular process Mastoid air cells
Trigeminal nerve (V3) Eustachian tube
Muscles of mastication
Anterior½ of tongue

2 Sinus (cervical) Stapedius Epithelium Palatine Tonsils Stapedius artery

Stylohyoid
CN 7
Facial muscles

3 - Stylopharyngeus m./n Parathyroid (inferior) Common carotid

Thymus Internal carotid

4 - 4- Pharyngeal constrictors, superior laryngeal n. Parathyroid (superior) 4- Right subclavian, aortic arch
6- Larynx muscles, recurrent laryngeal n. Parafollicular cells of thyroid 6- DA/ Pulmonary arteries
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Sexual Differentiation
Male Development:
• Testes derived from primordial germ cells at gondal ridge
• SRY —> Testis Determining Factor (TDF) —> Testes
■ Sertoli cells = Anti-Mullerian Factor (AMH)
■ Leydig cells = Testosterone
• Mesonephric ducts Undifferentiated Gonad
■ Seminiferous tubules
■ Epididymis
■ Ejaculatory duct Mesonephric
Paramesonephric
Ducts
■ Vas deferens Ovaries
Ducts
Testis
• External genitalia development by DHT
■ Testosterone —> DHT via 5a reductase
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Female Development:
• Ovary derived from primordial germ cells at gondal ridge Leydig Theca Granulosa
Sertoli
■ Granulosa cells —> Estrogen
■ Theca cells —> Androgens AMH
Testosterone Androgens Estrogen
• Absence of SRY gene —> Paramesonephric ducts persist
• Paramesonephric duct
■ Oviduct
■ Uterus DHT
■ Upper vagina
• Estrogen responsible for external genitalia development
Homologs:
• Genital tubercle —> Glans penis, glans clitoris
• Urogenital sinus —> Prostate gland, bartholin’s gland Seminal Vesicle
Oviduct
• Urogenital fold —> Ventral shaft of penis, labia minora Epididymis
Uterus
Ejaculatory Duct
• Labioscrotal swelling —> Scrotum, labia majora Upper Vagina
Ductus Deferens
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Disorders of Genital Embryology

Male Disorders of Development:
♦ Epispadias = Faulty positioning of the genital tubercle —► Urethra opens dorsally
■ Associated with bladder exstrophy and urinary incontinence
Hypospadias = Failure of the urogenital fold —> Urethra opens ventrally
■ Inguinal hernias and cryptorchidism
♦ Cryptorchidism —► Testis fail to descend
Female Disorders of Development:
Mullerian Agenesis —► Failure of the Mullerian duct to develop
■ Presentation: Primary amenorrhea, normal development of breasts, external genitalia and body hair
■ Exam: Absent uterus/upper-vagina/oviduct, functional ovaries
Bicornuate Uterus —> Incomplete paramesonephric duct fusion
Septate Uterus —► Incomplete resorption of septum Undifferentiated Gonad
DES exposure —► Vaginal adenocarcinoma, T-shaped uterus, abnormal fimbriae
Mesonephric
Paramesonephric
Ducts
Ducts
Testis Ovaries

Leydig Sertoli Theca Granulosa

I
AMH
z i

Testosterone Androgens-------► Estrogen

Ini

DHT

Seminal Vesicle
Oviduct
Epididymis
Uterus
Ejaculatory Duct
Upper Vagina
Ductus Deferens
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Chromosomal Disorders
Klinefelter Syndrome, 47XXY:
♦ Meiotic nondisjunction error, advanced paternal age
♦ Pathophysiology:
■ Testicular dysgenesis —► Seminiferous tubule fibrosis —> j Sertoli cells = j Inhibin and f FSH
■ Leydig cell dysfunction —► j Testosterone —► f LH —> Leydig cell hyperplasia
♦ Presentation: Infertility (azoospermia), gynecomastia, f Height (SHOX), testicular atrophy Mesonephric Paramesonephric

♦ Diagnoses: Karyotype
♦ Labs: Hypergonadotropic hypogonadism: f LH, f FSH, f Estradiol, J, Testosterone Leydig Sertoli Theca Granulosa

♦ Biopsy: Seminiferous tubule fibrosis and Leydig cell hyperplasia I

Testostero
I I
Androgens----- ► Estrogen
Inhibin

♦ Associations: f Risk of testicular cancer, f Risk of breast cancer, mitral valve prolapse
Turner Syndrome, 45X0:
♦
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Errors in paternal meiotic nondisjunction or mitotic nondisjunction of embryonic cell (mosaicism) Seminal Vesicle
Epididymis
♦ Presentation: Primary amenorrhea, short stature(SHOX), webbed neck, shield chest HIGH YIELD Ejaculatory Duct Upper Vagina

♦ Diagnosis: Karyotype Frontal

♦ Labs: f FSH, f LH, j Estradiol baldness
absent--------
♦ Associations: Poor beard
growth
Tendency to
■ Cardiac —► Bicuspid aortic valve, coarctation of aorta (“3”sign) grow fewer
Narrow
chest hairs
■ Lymphatic Obstruction —► Cystic hygroma, lymphedema shoulders
Breast------
■ Renal —► Horseshoe kidney
♦ Pregnancy: Possible with IVF and hormone supplementation - - - M Female-type Wide

Double Y, 47XYY:
♦
♦
Presentation: Tall stature, potential motor or language delay
No fertility issues
> Long arms
and legs

V
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Disorders of Sexual Development Part 1:

5a Reductase Deficiency:
• I Conversion of testosterone —> j DHT —> Ambiguous genitalia
• Presentation:
■ Absence of phallus elongation
■ Bifid scrotum
Hypospadias
Undifferentiated Gonad
Lasts until puberty
Labs: Testosterone:DHT ratio >20, karyotype XV, normal estrogen
Autosomal recessive
1 Paramesonephric
Androgen Insensitivity Syndrome:
• XV karyotype Testis
Mesonephric
• Defect in androgen receptor —> Insensitive to androgens Ducts
• V chromosome —> Testes
■
■
Leydig cells —► Testosterone —> No mesonephric ducts
Sertoli cells —► AMH —> No paramesonephric ducts : lh • >
. !....
:•* Granulosa Theca
Leydig
• Presentation: Sertoli ... FSH............. ;

■ Female presenting
' ’ Aromatase
■ Rudimentary vagina AMH
Estrogen ■*---------- Androgens
Testosterone: Inhibin
■ Primary Amenorrhea
■ Cryptorchidism 5a Reductase

■ Absent mesonephric duct structures

DHT
■ Female breast development
■ Absence of pubic hair
• Labs: Karyotype XV, f LH, f Testosterone, f Estrogen Seminal Vesicle
Oviduct
Epididymis
• X-linked recessive Ejaculatory Duct
Uterus
Upper Vagina
Ductus Deferens
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Disorders of Sexual Development Part 2:

Placental Aromatase Deficiency:
• Autosomal Recessive
Aromatase Absent
Inability to convert androgens —> Estrogen
■ $ Androgen —> Fetal masculinization
t Androgens in fetus —> Maternal masculinization
Presentation:
Female Infant: Ambiguous genitalia, primary amenorrhea Undifferentiated Gonad
■ Mother: Voice deepening, hair growth, acne
• Labs: ; Estrogen f Testosterone
Kailman Syndrome:
• Failure of GnRH neurons to migrate to hypothalamus
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1 Paramesonephric
Ducts
Testis
Mesonephric
• Olfactory bulb —> Preoptic nucleus Ducts
• Failure to stimulate gonadotropin hormones
• Hypogonadotropic hypogonadism
• Presentation: Granulosa Theca
. LH
■ Lack of 2° sex characterstics Leydig Sertoli FSH
■ Primary amenorrhea
■ ; Sperm count AMH Aromatase
...Estrogen •*--------- Androgens
Testosterone I Inhibin
■ Cryptorchidism
■ ; Height 5a Reductase

■ Anosmia
DHT
• Labs: ; GnRH -> ; FSH, ; LH -> ; Testosterone (d), ; Estrogen ($)

Seminal Vesicle
Oviduct
Epididymis
Uterus
Ejaculatory Duct
Upper Vagina
Ductus Deferens
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Male Anatomy
Organs:
♦ Testis, seminal vesicle, ejaculatory duct, epididymis, ductus deferens, prostate, penis
Blood Flow:
♦ Testicular artery branch of abdominal aorta
■ Pampiniform plexus
♦ Other portions supplied by the internal iliac branches
♦ Nutcracker syndrome
■ Left renal vein trapped —► Backflow of blood
■ Symptoms: Left varicocele, hematuria, flank pain
■ Cause: Renal cell carcinoma or massive weight loss
Lymphatics:
HIGH YIELD Testis —► Para-aortic nodes
♦ Scrotum —► Superficial inguinal nodes
♦ Prostate/Corpus Cavernosa —► Internal iliac nodes
Sexual Response
♦ Erection —► Parasympathetic nerves
♦ Emission —► Hypogastric nerves
♦ Expulsion —► Pudendal nerves
Anterior Urethral Injury
♦ Damage to bulbar urethra
♦ Straddle injury
♦ Presentation: Blood at urethral meatus, scrotal hematoma (Dartos fascia)
Posterior Urethral Injury:
♦ Damage to membranous urethra
♦ Pelvic fracture
♦ Fluid leak into retropubic space
♦ Presentation: Blood at urethral meatus, high riding prostate
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Female Anatomy
• Organs:
• Ovaries
• Oviduct, uterus, vagina
• Labia majora, minora, greater bartholin gland
• Blood Flow:
• Ovarian artery - Abdominal aorta
• Rest supplied by branches of the internal iliac artery
■ Uterine, vaginal
• Lymphatics:
• Ovaries - Para-aortic nodes
• Labia Majora/Minora - Superficial inguinal nodes AfraTafreeh.com
• Uterus/Cervix - External iliac nodes
• Nerves:
• Peritoneal fold - Pelvic pain line
■ Pelvic sympathetics above
■ Parasympathetics (S2-S4) below
• Landmarks
■ lschial spine - lschioanal fossa - Pudenda! block
• Ligaments Pudenda! nerve is the primary sensory innervation to the genitalia
• Suspensory ligament - Contains ovarian vessels HIGH YIELD
■ Risk of damaging ureter during hysterectomy
• Broad Ligament
■ Mesometrium, mesosalpinx, mesovarium
• Cardinal Ligament - Cervix to lateral pelvic wall
• Round ligament - Uterine horn to labia majora
■ Travels through inguinal canal
■ Round ligament pain
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OUTLINE (g
1. Gametogenesis 6. Placenta and Umbilical Cord
A. Spermatogenesis A. Placenta

Reproductive: 1.
B. Folliculogenesis
C. Oogenesis
Pregnancy Hormones
B. Umbilical Cord
C. Umbilical Cord Disorders
D. Fetal Circulation

Pregnancy and A. Estrogen

B. Prolactin
6. Fetal Circulation
A. Ductus Venosus
C. □-hCG B. Foramen Ovale

Menstruation 1.
D. Human Placental Lactogen
Menstrual Cycle 6.
C. Ductus Arteriosus
Childhood Development
A. Ovarian Cycle A. Tanner Stages
B. Uterine Cycle
1. Menstrual Cycle Disorders
A. Primary Amenorrhea
B. Secondary Amenorrhea
C. Dysmenorrhea
D. Mittelschmerz
1. Pregnancy Physiology
A. Fertilization
B. Changes By System
C. Lactation

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Gametogenesis
Spermatogenesis
♦ Occurs in seminiferous tubules
♦ Spermatogonia —► Mitosis —► One 1 ° Spermatocyte
♦ 1 ° spermatocyte undergoes meiosis —► Two 2° spermatocytes
♦ 2° spermatocyte —► Meiosis II —► Four spermatids
♦ Maturation process called spermiogenesis
■ Occurs in epididymis
■ Spermatid —► Spermatozoa
■ Creation of acrosome, development of flagellum
Folliculogenesis:
♦ Maturation of ovarian follicle
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Primordial follicle —► Secondary follicle —► Tertiary follicle
Tertiary follicle —► Oocyte component ovulated
Empty tertiary follicle —> Corpus Luteum
■ Releases progesterone
■ Fertilization —► f DhCG —► Sustain Corpus Luteum
Oogenesis:
Immature oocyte —► 2° Oocyte or mature ovum
■ Immature oocyte created in fetal period
■ Oogonium —► 1° Oocytes
1° Oocyte arrested in Prophase I until puberty
Ovulation —► Released oocyte arrested in Metaphase II
■ If unfertilized —► Menstruation
■ If fertilized —► Zygote
Post-fertilization
Secondary oocyte —► Meiosis II completion —► Mature Ovum + 2nd Polar Body
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Hormones of Pregnancy
Estrogen:
♦ Steroid hormone —► Intracellular receptor
♦ Synthesized in ovaries —► Granulosa cells
■ Additional sites of synthesis: Placenta and adipose tissue
♦ Conversion of androgen —> Estrogen via aromatase
■ Estradiol (ovary) > Estrone (fat) > Estriol (placenta)
♦ Sexual Development
■ Stimulates growth of breast, endometrium and vagina
♦ Extragenital Development
■ f Clotting factors, f HDL and j LDL, f Osteoclast apoptosis
Progesterone:
♦ Steroid hormone —► Intracellular receptor
♦ Synthesized by corpus luteum + Placenta
■ 10th week gestation —► Placenta
♦ Sexual Charactersites
■ Endometrial spiral artery and glandular development, inhibit prolactin, cervical mucus thickening
♦ Extragenital Characteristics
■ f Body temperature, inhibits estrogen receptors —> Inhibits endometrial hyperplasia
phCG:
♦ GPCR -»■ CAMP
♦ Maintains corpus luteum —> Continued progesterone production
■ Secreted day 6 post-fertilization, peaks during weeks 8-10
♦ Diagnostics
■ High: Multiple pregnancy, Choriocarcinoma, Molar pregnancy, Trisomy 21
■ Low: Ectopic pregnancy, abortion, trisomy 18, trisomy 13 HIGH YIELD
Human Placental Lactogen:
♦ Contributes to insulin resistance
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Menstrual Proliferative Secretory

Menstrual Cycle
Overview: Follicular Luteal
♦ Normal cycle is around 28 days
♦ Menses lasts 3-7 days
♦ 12 months without menstruation —► Menopause
Ovarian Cycle:
♦ Days 1-14: Follicular Phase
■ FSH —► 1 Ovarian follicle development
■ Granulosa cells produce estrogen —► j FSH
■ 1'1' Estrogen —► f FSH —► T LH —► Ovulation HIGH YIELD
♦ Days 15-28: Luteal Phase
■
■
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LH surge —► Ovulation —► Rupture of tertiary follicle
Tertiary follicle remnant —► Corpus luteum
■ Corpus luteum maintained by D-hCG —► 1 Progesterone
■ No fertilization —► Corpus Luteum regresses —► J. Progesterone
Uterine Cycle:
♦ Days 1-7: Menstrual Phase
■ Absence of fertilization —► Corpus luteum regress
■ j Progesterone —► Vasospasm spiral arteries —► Bleed
♦ Days 7-14: Proliferative Phase
■ Growth of endometrium via estrogen
■ Follicle produces estrogen —► Endometrium proliferates
♦ Days 14-28: Secretory Phase
■ Corpus luteum produces progesterone
■ Progesterone —> Preparation of endometrium
■ Spiral arteries extending full length of endometrium
■ Endometrial glands become more tortuous
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Menstrual Cycle Disorders

Menstrual Proliferative Secretory
Primary Amenorrhea:
♦ Absence of menarche by age 16 Follicular Luteal
♦ Hypogonadotropic hypogonadism (Kallmann syndrome)
■ | GnRH —> J, LH, J, FSH -► | Estrogen
G
♦ Hypergonadotropic hypogonadism (Turner’s)
■ 1 GnRH —> 1 LH, f FSH —> j Estrogen
♦ Anatomical Abnormalities
Estrogen
■ Mullerian Agenesis —► Normal GnRH —► Normal LH, normal FSH —► Normal Estrogen Progesterone
LH
■ Imperforate hymen (bulging blue membrane) FSH

♦ Enzymatic/Receptor dysfunction
■ Complete Androgen Insensitivity —► f LH, J Testosterone, f Estrogen
■ Congenital Adrenal Hyperplasia —> Variable
Secondary Amenorrhea:
♦ Absence of menses for 3 month in an individual with normal cycle
♦ Absence of menses for 6 months in an individual with previously irregular cycles
Day 7 Day 14 Day 28
♦ Uterine Disorders: Uterine scarring post curettage —> Asherman syndrome
♦ Ovarian Disorders Undifferentiated Gonad

■ PCOS, premature ovarian failure Mesonephric

Paramesonephric
♦ Pituitary dysfunction Ovaries
Ducts

■ Sheehan syndrome, prolactinoma

■ Functional hypothalamic amenorrhea: (disordered eating / amenorrhea / osteoporosis) Leydig Sertoli Theca Granulosa
I I I
• j Leptin or f Cortisol —► j GnRH —► j LH, j FSH —► j Estrogen high yield Testosterone
Inhibin Androgens------ ► Estrogen

Dysmenorrhea
♦ Painful menses
♦ Primary —► f PGF2-a —► Vasoconstriction, f Uterine contractions
Mittelschmerz
Seminal Vesicle
Oviduct
Ovulatory pain —► Ruptured follicular cyst Contraction of oviduct —► Peritoneal irritation Epididymis
Ejaculatory Duct
Ductus Deferens 0 Uterus
Upper Vagina
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Pregnancy Physiology
• Fertilization:
• Ampulla of oviduct
• Acrosome reaction - Penetration of zona pellucida
• Cortical reaction - Granule release - Prevention of polyspermy
• Changes By System:
• Cardiac: j Cardiac output due to 1 Afterload, jPreload, j Stroke volume, j Heart rate
• Respiratory: Dyspnea, respiratory alkalosis, j Tidal volume, 1 TLC
• Hematologic: j Plasma volume - Dilutional anemia, j Clotting factors, j Folate and j Iron demand
• Renal: j Renal plasma flow - j GFR - 1 Creatinine, Glycosuria
Gastrointestinal: 1 LES tone - GERO, 1 Motility - Constipation, hemorrhoids
Endocrine: j Insulin levels - Insulin resistance
• Lactation:
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• Suppressed during pregnancy by progesterone
• Delivery of placenta - 1 Progesterone - j Prolactin
Prolactin
• Prolactin inhibited by dopamine and progesterone
■ Suckling stimulates arcuate nucleus - Inhibits dopamine
■ Suckling - j Oxytocin release from supraoptic and paraventricular nuclei
• Oxytocin - Milk ejection
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Placenta & Umbilical Cord

Placenta:
♦ Anatomy
■ Decidua Basalis —► Maternal component
■ Intervillous Space —► Mix of maternal and fetal components
■ Chorionic Plate —> Fetal component
♦ Hormone production —> □-hCG, HPL, Progesterone HIGH YIELD
♦ Fetal gas exchange
Umbilical Cord:
♦ Derived from allantois
■ Allantois —► Urachus —► Median umbilical ligament
♦ Two arteries —► Deoxygenated blood
♦ One vein —► Oxygenated blood
♦ Vitelline duct: Connects yolk sack to midgut lumen
Umbilical Cord Disorders
♦ Vitelline fistula
■ Vitelline duct persists—* Meconium from umbilicus
♦ Vitelline cyst
■ Partial obliteration of vitelline duct —► Cyst around umbilicus
♦ Meckel diverticulum
■ Partial obliteration of vitelline duct —► Small bowel obstruction
♦ Single umbilical artery
■ Chromosomal abnormalities
♦ Patent Urachus
■ Complete —► Urine from umbilicus
■ Partial —* Urachal sinus
 Reproductive System: Pregnancy and Menstruation Bootcamp.com

Fetal Circulation
Oxygenated Blood
• Placenta —► Umbilical vein —► Ductus venosus —► IVC —► Right atrium
o Ductus venosus bypasses the liver
o Connects umbilical vein —► IVC
o Ligamentum venosum after birth
• Right atrium —► Foramen ovale —► Left Atrium —► Left ventricle —► Aorta —► Systemic Circulation
o Foramen ovale bypasses the lungs
o Closure —► Fossa ovalis
o Persists —► Patent foramen ovale
Deoxygenated Blood
•
o Ductus arteriosus bypasses lung
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Extremities —► SVC —► Right atrium —► Right ventricle —► Pulmonary artery—* Ductus arteriosus
Ductus a.

o Ligamentum arteriosum after birth Foramen a

Foramen Ovale „Ductus

, ven
o Closure after birth by increase left atrial pressure
o Failure of septum primum and septum secundum to fuse —► PFO
o Patent in 25% of patients —► Embolic risk
Ductus Arteriosus
o Derivative of 6th aortic arch
o Kept open during pregnancy by j 02 and f Prostaglandin E2 or Rubella HIGH YIELD
o Alprostadil will keep ductus arteriosus open
o Indomethacin will close ductus arteriosus
o Machine like murmur at left infraclavicular area
Sinus Venosus
o Right horn: Smooth portion of the right atrium
o Left horn: Coronary sinus
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Childhood Development
Tanner Stages:
• Stage 1: No sexual development
• Stage 2: Lightly pigmented pubic hair develops
■ Male: f Testis size
■ Female: Breast bud
• Stage 3: Coarsening of pubic hair
■ Male: f Penis size
■ Female: Breast mound
• Stage 4: Pubic hair sparing inner thighs
■ Male: ] Penis width
■ Female: Raised areola, “mound on mound”
• Stage 5: Pubic hair spreads to inner thighs
■ Male: Penis/testis reach maturity
■ Female: Flattened areola

IV

V
REVIEW OUTLINE

1. Ectopic Pregnancy 8. Postpartum Hemorrhage

A. Etiology A. Etiology
Reproductive B.
C.
Presentation
Management
B.
C.
Presentation
Management

System: 2.
D. Differential Diagnosis
Molar Pregnancy
D. Differential Diagnosis

Pathologies of A.
B.
Etiology
Presentation
C. Management
Pregnancy 3.
D. Differential Diagnosis
Hypertension in Pregnancy
A. Table
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4. Supine Hypotension Syndrome
A. Etiology
B. Presentation
5. Polyhydramnios and Oligohydramnios
A. Table y
6. Twin-twin Transfusion Syndrome
A. Etiology
B. Presentation
7. Placental Pathology
A. Placenta Previa
B. Vasa Previa
C. Placenta Accreta Spectrum
D. Placental Abruption

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Ectopic Pregnancy
Etiology:
• Fertilized egg implantation outside of uterine cavity —> +/- Rupture
o Fallopian tube (ampulla most common) HIGH YIELD
o Abdomen or cervix less common
• Risk factors: Previous ectopic, PID, IUD, IVF, f Age, endometriosis
Presentation:
• Usually presents 4-6 weeks after last period
• Symptoms of pregnancy (morning sickness, breast tenderness)
• Vaginal bleeding
• Abdominal pain (can be variable depending on location of implantation)
o Acute rupture: Acute abdomen / signs of shock
• Labs: Urine pregnancy (+), p-hCG f Slower than expected (should double every 48 hrs)
• US: No evidence of intrauterine gestation
Management:
• Methotrexate (contraindicated in breastfeeding mother)
• RhoGAM
• Surgery
Differential Diagnosis:
• Appendicitis
• Ovarian cyst rupture
• Molar pregnancy
• Spontaneous abortion
 Reproductive System: Pathologies of Pregnancy Bootcamp.com

Molar Pregnancy
Etiology:
• Trophoblastic (syncytiotrophoblast + cytotrophoblast) disease of pregnancy
Complete mole: 46XX (most common) or 46XY
o Enucleated ovum (P57-) —► Fertilized by 1 sperm —► Paternal DNA duplicated
o TTT P-hCG —> TTT Hydropic villi + Circumferential proliferation —> TTT Risk of choriocarcinoma
Partial mole: 69XXX. 69XXY. 69XYY
o Normal ovum (P57+) —► Fertilized by 2 sperm
o t p-hCG —► Minimal hydropic villi and proliferation —► Minimal risk of choriocarcinoma
Presentation:
• ftt P-hCG > 100k mIU/mL —> Pregnancy symptoms
o Morning sickness AfraTafreeh.com
o Pelvic discomfort
o First semester Vaginal bleeding (prune juice)
• j Uterine fundus size for gestational age (more common in complete mole)
• +/- “Grape-like” mass in vagina or adnexa
• US: Central heterogeneous mass with multiple discrete anechoic spaces
o Complete mole: “Snowstorm” / “Grape cluster” / “Honeycomb appearance” HIGH YIELD
o Partial mole: Fetal parts, amniotic fluid
• Choriocarcinoma: Malignancy of trophoblastic tissue in mother or baby during or after pregnancy
o f p-hCG, no chorionic villi present, +/- bilateral theca lutein cysts
o Hematogenous spread to lungs (cannon ball metastasis) —> SOB + Hemoptysis
o Treat with methotrexate
Management: RhoGAM + Dilation and curettage
Differential Diagnosis:
• Normal ortwin pregnancy, miscarriage, ectopic pregnancy
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Hypertension in Pregnancy
Stage Presentation Etiology Management

Chronic -HTN prior to 20 weeks -Obesity -Antihvpertensives:

Hypertension -HTN persists post delivery -Diabetes -Hydralazine, Labetalol, Methyldopa, Nifedipine

Gestational -HTN after 20 weeks -Increased blood volume -“Hypertensive Moms Love Nifedipine”
Hypertension -Normal BP 6 weeks post delivery
Risk with multiple gestations -Increased circulatory load -Delivery at 37-39 weeks

Preeclampsia -Gestational hypertension -Abnormal placental spiral arteries -Antihypertensives

(+) -Magnesium sulfate
-Proteinuria OR Organ dysfunction -Placental vasoconstriction -Prompt delivery

-Placental ischemia -Maternal Complications:

-Renal failure
-Increased systemic vascular tone -Intracerebral hemorrhage —> Stroke
-ARDS

Eclampsia -Preeclampsia -Risk factors: -Fetal Complications:

(+) -Immunological intolerance (APS) -Uteroplacental insufficiency
-Seizures -Improper implantation -Placental abruption
-Inflammatory changes, advanced age, HTN

HELLP -Hemolysis -Liver thrombotic microangiopathy -Complications:

Syndrome -Elevated Liver Enzymes -Liver capsule hematomas —> Hypovolemia
-Low Platelets -Liver failure —> Lab abnormalities -Tissue factor exposure —> DIC
 Reproductive System: Pathologies of Pregnancy Bootcamp.com

Transient Complications of Pregnancy

Supine Hypotensive Syndrome:
Also called aortocaval compression syndrome
Compression of maternal aorta by growing fetus —> | Placental blood flow —> Possible pregnancy loss
Compression of maternal IVC by growing fetus —> Hypotension while supine
Peripheral Edema:
• Maternal dilutional anemia —> | Oncotic pressure —> f Fluid leak to interstitial space
Gestational Thrombocytopenia:
• Secondary to dilutional anemia.
• Must rule out ITP or HELLP if other symptoms present
Nausea and Vomiting:
• f p-hCG —> f Nausea and vomiting AfraTafreeh.com
• If severe and unremitting —> Reclassified as hyperemesis gravidarum
Hyperthyroidism:
• p-hCG has a similar structure to TSH
• f p-hCG —> f Thyroid stimulation —> $ T3 and T4
• Hyperthyroidism: Tachycardia, diarrhea, heat sensitivity, anxiety
Gestational Diabetes:
Human placental lactogen —> f Insulin production —> Insulin resistance —> Gestational diabetes
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Polyhydramnios and Oligohydramnios

Amniotic Fluid: Protects fetus and supports growth throughout pregnancy
• Produced from fetal urine —> Cleared by fetal swallowing

Etiology Presentation

Polyhydramnios • -Congenital anomalies —> Interruptions in ingestion -Frequently asymptomatic

J Amniotic fluid -Tracheoesophageal anomalies Uterine size
-Intestinal atresia Amniotic fluid on US
• Anencephaly —> Absent swallowreflex
• Fetal anemia —> f CO —» f Fetal urine output
• Maternal Diabetes —> J Fetal urine output
• Multiple gestation
• Twin-twin transfusion syndrome
4 Blood volume in recipient twin

Oligohydramnios • Uteroplacental insufficiency —> j, CO —> J, Fetal urine output Pulmonary hypoplasia
J, Amniotic fluid • Renal agenesis —> No fetal urine production -Chest wall compression
• ACE inhibitors —> Kidney damage —> gFetal urine output -Lack of pulmonary fluid for aspiration
• Obstructive uropathy —> Kidney damage —> j Fetal urine output Oligohydramnios (root cause)
-Posterior urethral valves Twisted face
• ARPKD —> Kidney damage —> j. Fetal urine output -Low set ears, retrognathia, flat nose
• Twin-twin transfusion syndrome Twisted skin
volume in donor twin Extremity defects
-Shortened limbs, clubbed feet
Renal failure
 Reproductive System: Pathologies of Pregnancy Bootcamp.com

Twin-twin Transfusion Syndrome

Etiology:
• Monochorionic diamniotic gestations
o Occurs when zygote splits after morula stage (after day 4)
o Abnormal arteriovenous connections form between weeks 16-25
• Unbalanced vasculature in placenta —> Unbalanced blood supply between fetuses
o “Donor” fetus shunts blood to “recipient” fetus
Presentation:
o Donor fetus: Hypovolemia, anemia, oligohydramnios, birth defects, death
o Recipient fetus: Hypervolemia, polycythemia, polyhydramnios, favorable prognosis

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Placental Pathology
Placenta Previa:
Etiology: Improper implantation location —> Placenta extends over cervical os
Risk factors: C-section, f Maternal age, multiple gestations, previous placenta previa
Presentation: Found on routine US —> Painless 3rd trimester vaginal bleeding +/- pain or contractions
o No fetal distress (as opposed to vasa previa)
Management: Digital vaginal exam contraindicated (hemorrhage risk)
Vasa Previa
• Etiology: Fetal vessels cover the cervical os —> Associated with velamentous umbilical cord
• Presentation Triad: Membrane rupture, fetal bradycardia (cord compression), painless vaginal bleeding (vessel rupture)
Placenta Accreta Spectrum:
• Etiology: f Depth of invasion of chorionic villi —> Invasion past decidua into myometrium
• Risk factors: Poor decidualization: f Maternal age, multiple gestations, infertility procedures, uterine surgery, C-section
• Degree:
■ Accreta: Attachment to uterine myometrium without penetration
■ Increta: Penetration into uterine myometrium
■ Percreta: Penetration of uterine serosa and pelvic organs
Placental Abruption (Abruptio Placentae):
• Etiology: Blood vessel failure in decidua basalis +/- trauma —> Placenta detaches from uterine wall
• Risk factors: Smoking, cocaine, hypertension (preeclampsia), uterine abnormalities (fibroids / bicornuate uterus)
• Presentation: Sudden pain and bleeding in 3rd trimester with contractions
o Possibility of DIC (tissue factor activation)
o Unstable vitals and fetal distress
o Retroplacental hematoma on US
Differential Diagnosis: Uterine rupture, postpartum hemorrhage (Sheehan syndrome)
 Reproductive System: Pathologies of Pregnancy Bootcamp.com

Postpartum Hemorrhage
Etiology: Post delivery blood loss:
o Usually post delivery of placenta
o Tone (most common): Atony presents as a “soft and boggy” uterus
o Trauma / Lacerations: Cervical (forceps delivery), vaginal (episiotomy), uterine rupture
o Thrombin: Underlying coagulation disorder
o Tissue: Retained products of conception / Tissue factor exposure (010)
Presentation:
• Bleeding: >500mL vaginal or >1000mL C-section
• Hypovolemia —> Hypotension, tachycardia, SOB, pallor
Management:
• Treat underlying cause AfraTafreeh.com
• Supportive care
 AfraTafreeh.com
REVIEW OU TUNE <Z)
1. Internal Vaginal Pathology 7. Uterine Cancer
A. Bartholin Gland Pathology A. Endometrial Carcinoma
Reproductive B.
C.
Imperforate Hymen
Vaginismus
B.
C.
Endometrial Polyps
Leiomyoma (Fibroids)

System: 2.
D. Atrophic Vaginitis
Vaginal Skin Pathology 8.
D. Leiomyosarcoma
Cervical Pathology

Female Pathology A.
B.
Lichen Sclerosus
Lichen Simplex Chronicus
A.
B.
Cervical Dysplasia Spectrum
Cervicitis
C. Lichen Planus 9. Ovarian Cysts
3. Vaginal Cancer A. Follicular Cyst
A. Extramammary Paget’s B. Theca Lutein Cyst
B. Vulvar Carcinoma C. Chocolate Cyst
C. Clear Cell Adenocarcinoma D. Complications
D. Sarcoma Botryoides 10. Ovarian Cancer Overview
4. Polycystic Ovarian Syndrome 11. Ovarian Cancer Subtypes
A. Pathophysiology A. Epithelial Tumors
B. Presentation B. Germ Cell Tumors
C. Diagnostics C. Sex Cord Tumors
D. Management 12. Breast Cancer Overview
5. Uterine Pathology 1 13. Benign Breast Conditions
A. Adenomyosis 14. Benign Breast Tumors
B. Endometrial Hyperplasia 15. Invasive Carcinomas
C. Asherman Syndrome
6. Uterine Pathology 2
A. Endometriosis

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Internal Vaginal Pathology

Bartholin Gland Cyst / Abscess:
• Etiology: Bartholin gland blockage —> Fluid accumulation (cyst) —> Infection (abscess)
• Presentation: Reproductive age females
o Classically unilateral
o Vaginal pain especially with sitting or intercourse
• Management: Abscess drainage + Word catheter insertion
• Differential: Gartner duct cyst
Imperforate Hymen:
Etiology: Failure of hymen to canalize during development
Presentation:
o AfraTafreeh.com
Pubertal age patient with cyclic monthly abdominal pain (primary amenorrhea)
o Blue/purple hymenal bulge
• Management: Hymenectomy
Vaginismus:
• Etiology: Involuntary vaginal contraction during intercouse or pelvic exams —► Vaginal pain
• Risk factors: Sexual trauma, anxiety disorders, depressive disorders
• Presentation:
o Pain during intercourse or pelvic exams, despite willingness
o Clinically diagnosed by visualization of vaginal contraction during pelvic exam
Atrophic Vaginitis:
• Etiology: | Estrogen —> | Vaginal blood flow and secretions —> Vaginal atrophy
• Presentation: Women in low estrogen state (menopause, pituitatry dysfunction, aromatase inhibitors)
o Thin and dry vaginal skin +/- Itching/Pain
o Altered vaginal pH E
• Management: Topical estrogen cream + Water based lubricant Cribriform hymen Microperforate hymen Imperforate hymen
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Vaginal Skin Pathology

Lichen Sclerosus:
Etiology: Inflammatory condition of unknown cause
Epidemiology: Most common in perimenopausal and post-menopausal females
Presentation: “Porcelain” white plaques with violaceous borders —► Plaques can flake or slough
o Severe pruritus
o Pain with intercourse and or defecation
• Histology: Atrophy of epidermal tissue, hyperkeratosis, dermal fibrosis
• Management: Benign disease with slight risk of SCC —► Punch biopsy confirms diagnosis and rules out SCC —» Steroid cream
Lichen Simplex Chronicus:
• Etiology: Habitual scratching or rubbing often secondary to another condition
• Epidemiology: Patients with pruritic ano-pelvic disease
• Presentation: Thick “leathery” vulvar skin +/- Signs of excoriation
• Histology: Hyperplasia of squamous epithelium
• Management: No cancer risk —> Treat underlying condition
Lichen Planus:
• Etiology: T-cell mediated (CD8+) —> Dermal-epidermal junction (interface dermatitis)
• Epidemiology: Associated with hepatitis C, vitiligo, ulcerative colitis
• Presentation: “Lacy” white reticular deposits (Wickham striae)
o 6 P’s :Pruritic, Pink/Purple, Planar, Polygonal, Papules, Plaques
o Bilateral and symmetric
• Histology: Hypergranulosis, saw-tooth rete ridges, lymphocytic infiltrate
• Management: Topical steroids
Vulvar and Vaginal Cancers
Extramammary Paget's Disease:
• Pathophysiology: Adenocarcinoma of the vulvar tissue
o Low risk of underlying invasive carcinoma vs Paget's disease of the breast
• Presentation: Pruritus, redness, crusting, +/- ulcers
• Histology: Paget cells: lntraepithelial adenocarcinoma in situ
Vulvar Carcinoma:
• Pathophysiology: HPV infection (Types 16, 18, 31, 33), smoking, or long standing lichen sclerosus
o Squamous cell carcinoma most common - Often contiguous spread from cervical sec
• Presentation:
o Very thin shiny vu Ivar tissue
o Atrophic vaginal introitus AfraTafreeh.com
0 Dyspareunia
0 Painful/itchy/bleeding vulvar ulcers
0 Histology: Squamous cell carcinoma: Keratin pearls
Clear Cell Adenocarcinoma:
• Pathophysiology:: Diethylstilbestrol exposure in utero - Vaginal adenosis (persistence of glandular columnar epithelium)
• Presentation: Upper½ of the Vagina
Sarcoma Botryoides:
• Pathophysiology: A subtype of embryonal rhabdomyosarcoma
• Epidemiology: Females < 4 years old
• Presentation: Clear "grape-like" segmented mass protruding from vagina HIGH YIELD
• Histology: Desmin(+) spindle shaped cells
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Polvcvstic Ovarian Syndrome

Pathophysiology:
t Adipose tissue —> f Estrogen, f Insulin resistance —> f Insulin
• J LH —► Disruption of LH/FSH balance —► Anovulation, cyst formation
• f Androgen production (ovarian theca interna cells)
• | SHBG —> f Free estrogens and androgens
• f Estrogen, | Progesterone —> Endometrial hyperplasia
Presentation:
• Signs of polyendocrinopathy in a reproductive age female HIGH YIELD
o f Insulin resistance: Obesity + Acanthosis nigricans
o f Androgens: Hirsutism + Acne
o f Estrogen, j Progesterone: Amenorrhea/Oligomenorrhea, enlarged ovaries, and infertility
Diagnostics:
• Labs: LH, f FSH, f Estrogen, f Testosterone
• US: Enlarged ovaries with multiple cysts
Management:
Weight loss + Metformin
Hormonal contraceptives: Establish estrogen/progesterone balance
Spironolactone: Steroid receptor antagonist —► Androgen blocking effects
Finasteride: Inhibition of 5-a-reductase —> j Conversion of testosterone to DHT
Letrozole: Blocks conversion of androstenedione to estrone
Flutamide: Androgen receptor antagonist
Clomiphene: Promotes ovulation
 Reproductive System: Female Pathology Bootcamp.com

Uterine Pathology
Adenomyosis:
• Pathophysiology: Hyperplasia endometrial basalis layer —> Invasion of endometrial tissue into the uterine myometrium
• Etiology: POOL, hormone replacement therapy, ovarian producing tumors
• Presentation:
o Women 30-50
o Dysmenorrhea and menorrhagia
o Soft “boggy”, uniformly enlarged “globular” uterus +/- tenderness HIGH YIELD
• Management: GnRH agonists (leuprolide), hysterectomy
Endometrial Hyperplasia:
• Pathophysiology: f Estrogen —> Hyperplasia of endometrial glandular tissue
• AfraTafreeh.com
Etiology: POOL, estrogen supplementation, nulliparity, late menopause, estrogen producing tumors
• Presentation: Post menopausal bleeding / AUB
• Diagnostics: Proliferation of glandular cells with atypical cells showing extensive loss of cell polarity
• Management: Progesterone (progestin) supplementation, hysterectomy if evidence of cellular atypia i
Asherman Syndrome:
• Pathophysiology: Uterine trauma —► Destruction of endometrial basalis layer —► Adhesions/Fibrosis —► Failure of endometrial regeneration
• Etiology: Prior dilation and curettage or uterine surgery
• Presentation: Amenorrhea, infertility, abnormal uterine bleeding, pelvic pain, recurrent pregnancy loss
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Uterine Pathology
Endometriosis:
Pathophysiology: Extrauterine endometrial tissue —> Ovaries (most common), uterosacral ligaments, rectouterine pouch peritoneum
o Retrograde blood or lymphatic flow
o Metaplastic change of multipotent cells Endometriosis
Fallopian tube
• Etiology: Reproductive age females +/- family history, nulliparity, early menarche
• Presentation:
o Dysmenorrhea, dyspareunia, dyschezia, cyclic pelvic pain (estrogen sensitive tissue)
o Infertility
o AUB
Uterus
o Nodular adnexa, normal sized retroverted uterus
• Diagnostics:
o Can be visualized on US
o Surgical pathology extrauterine endometrial tissue
■ Peritoneum: Yellow-brown “Powder burn” lesions
■ Ovary (endometrioma): Blood filled “chocolate cysts” HIGH YIELD
• Management: NSAIDs, OCPs, GnRH agonists, progestins, danazol, surgical removal
Postpartum Endometritis
• Pathophysiology:: Retained uterine contents —> Inflammation +/- infection of the endometrial lining
• Etiology: Reproductive age women with recent delivery, miscarriage, abortion, IUD, multiple cervical exams
• Presentation: Fever, vaginal discharge, abdominal pain, uterine tenderness, foul smelling lochia
• Diagnostics
o Acute: Growth of group B Streptococcus
o Chronic: Growth of N. gonorrhoeas or A. israelii + Evidence of plasma cells on endometrial histology
Management: Clindamycin + Gentamicin +/-Ampicillin
Complication: Postpartum sepsis, surgical site infection, peritonitis
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Uterine Cancer
Endometrial Carcinoma:
Pathophysiology: Prolonged estrogen exposure —> Endometrial transformation
Etiology: Post-menopausal women with history of estrogen exposure (obesity, PCOS, late menopause, nulliparity)
• Presentation: AU B
o Endometrioid type: Unopposed estrogen + PTEN/Mismatch repair protein loss —> Transformation
■ Histology: Abnormally arranged endometrial cells
o Serous type: Endometrial atrophy —> Transformation (aggressive)
■ Histology: Papillae and tufts +/- Psammoma bodies
Endometrial (Uterine) Polyps:
• Pathophysiology: Prolonged estrogen exposure —> Discrete collection of benign endometrial tissue
• AfraTafreeh.com
Etiology: Post-menopausal women with history of estrogen exposure
• Presentation: AU B
Leiomyoma (Fibroids:)
• Etiology: f Estrogen —> f Growth of uterine myometrium —> Benign smooth muscle tumor
o Does NOT transform into leiomyosarcoma
• Epidemiology: Females aged 20-40, f Incidence in Black patients
• Presentation: AUB (iron deficiency anemia), pelvic pain, miscarriage, urinary frequency, constipation
o Enlarged, asymmetric, nontender uterus HIGH YIELD
• Histology: Multiple discrete tumors displaying “whorled” well-demarcated smooth muscle bundles
Leiomyosarcoma:
• Etiology: Malignant neoplasm of the myometrium
o Does NOT transform from leiomyoma
• Epidemiology: Most common in post menopausal females
• Histology: Single tumor displaying areas of necrosis
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Cervical Pathology
Cervical Dysplasia Spectrum:
Pathophysiology:: HPV infection —> Disordered epithelial growth at transformation zone —> Transformation to progressive malignancy
o Disordered growth —► CIN 1, CIN 2, CIN 3 —► Invasive squamous cell carcinoma
Etiology: HPV exposure, multiple partners, smoking, DES exposure, immunocompromised states
• Presentation:
o Typically asymptomatic +/- Vaginal bleeding after intercourse
o Abnormal cells identified on routine screening pap smear
o Invasive carcinoma can obstruct ureters
■ Hematuria, hydronephrosis, renal failure
• Microbiology: Associated with HPV strains 16, 18, 31, 33 high yield

o HPV strain 16: Expresses E6 gene protein —► Inactivation of p53

o HPV strain 18: Expresses E7 gene protein —► Inactivation of Rb
• Histology: Koilocytes: Pathognomonic HPV infected cells with a “raisenoid” nucleus and perinuclear “halo” high yield

• Management: Routine pap smear screening

• Incidence: Endometrial > Ovarian > Cervical
Cervicitis:
• Pathophysiology: Infection of cervix
• Presentation:
o Pelvic pain
o CervicalA/aginal discharge
o Erythematous/Friable cervix
• Management: Antimicrobials
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Ovarian Cvsts:
Follicular Cyst:
• Pathophysiology: Failure of Graafian follicle rupture —> Cystic fluid accumulation
• Etiology:
o Associated with f Estrogen state and endometrial hyperplasia
o Most common ovarian mass in young females
Theca Lutein Cyst:
• Pathophysiology: f p-hCG —► Stimulation of theca interna cels —► Bilateral cyst formation
• Etiology:
o Common complication of choriocarcinoma or molar pregnancy
o Resolve after 0-hCG levels normalize
Chocolate Cyst: AfraTafreeh.com
• Pathophysiology: Endometriosis localized to the ovary
• Etiology:
o Underlying endometriosis
Ovarian Cyst Rupture:
• Cyst rupture —► Collection of fluid in rectouterine pouch
• Acute onset unilateral abdominal pain
Ovarian Torsion:
• Twisting of ovary and fallopian tube around infundibulopevic and/or ovarian ligament —► Compression of ovarian vessels
o Venous, lymphatic compression —► Edema
o Arterial compression —> Ischemia and necrosis
o Ovarian necrosis: Dual blood supply from ovarian and uterine arteries
Acute onset unilateral abdominal pain
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Ovarian Cancer
Ovarian Tumors:
• Pathophysiology: Neoplastic transformation of ovarian tissue
• Etiology:
o Most common adnexal mass in females > 55
o Historical risk factors: f Age, PCOS, endometriosis, infertility
o Risk factors: BRCA 1/2 mutations, Lynch syndrome, family history, CA-125
o Protective factors: Multiparity, breast feeding, OCPs, tubal ligation
• Epithelial tumors (ovarian surface epithelium)
o Ovarian surface epithelium
o Serous or mucinous (fluid producing)
o Usually benign
• Germ cell tumors (egg/follicle)
o Primordial germ cells
o Yolk sac tumor (Extraembryonic), Teratoma (Somatic), Dysgerminoma (Undifferentiated)
o Benign or malignant
• Sex cord tumors (follicle/stroma)
o Sertoli or granulosa cells
o Stromal variants —> Fibroblasts or primitive gonadal stroma
o Benign or malignant
• Incidence: Endometrial > Ovarian > Cervical
 Reproductive System: Female Pathology Bootcamp.com

Epithelial Tumors
Epidemiology + Presentation Tumor Characteristics Histopathology

Serous -Most common ovarian neoplasm -Fallopian tube like epithelium •

tJ
•
•
�
�-
Cystadenoma -Psammoma bodies ' • @· le'
(Benign) �(J ·'•
' ,<1> · .

Mucinous -Can cause pseudomyxoma peritonei -Mucus secreting epithelium

Cystadenoma -Large + Multiloculated
(Benign)
AfraTafreeh.com
Brenner Tumor -Encapsulated appearance
(Benign) -Solid
-Yellow-tan color
-Coffee bean nuclei on H+E
-Resembles bladder epithelium
-Transitional epithelium

Serous -Most common malignant ovarian neoplasm -Psammoma bodies

Carcinoma -Often bilateral
(Malignant)

Mucinous -Metastatic from other GI tumors (appendix)

Carcinoma -Can cause pseudomyxoma peritonei
(Malignant)
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Germ Cell Tumors

Epidemiology + Presentation Tumor Characteristics Histopathology

Mature Cystic -Most common ovarian tumor in young females -Cystic mass HIGH YIELD
Teratoma -Large tumors can cause pain / torsion -All 3 germ layers (heterogeneous)
“Dermoid Cyst” -Hyperthyroidism in struma ovarii o Hair, teeth, sebaceous tissue
(Benign) -Monodermal type (struma ovarii)
o Thyroid tissue

Immature -Aggressive tumor presenting before age 20 -Fetal tissue component (neuroectoderm)
Teratoma -Large + Multi loculated
(Malignant)

Dysgerminoma -Most common tumor of adolescents -Uniform sheets of “fried egg " cells
(Malignant) -Tumor markers f LDH and f hCG

Yolk Sac Tumor -Aggressive tumor of children and young females -Yellow, friable, bloody —> Hemorrhagic
“Endodermal -Schiller-Duval bodies (glomerular pattern)
Sinus Tumor” -Tumor marker: f AFP
(Malignant)
 Reproductive System: Female Pathology Bootcamp.com

Sex Cord Stromal Tumors

Epidemiology+ Presentation Tumor Characteristics Histopathology

Fibroma -Meigs syndrome -Spindle shaped fibroblasts in bundles

(Benign) o Ovarian fibroma, pleural effusion, ascites
-Presents with "pulling" sensation in groin

Thecoma -Presents with AUB in post-menopausal female -Can produce estrogen

(Benign)

Sertoli-Leydig -Androgen producing

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-Small tumor -Grey, yellow, or brown in color
Cell Tumor -Virilization -Testicular type histology
(Benign) -Hirsutism -T ubules and cords lined with pink sertoli eels
-Male pattern baldness -Reinke crystals
-Clitoral enlargement Rod-like eosinophilic inclusions

Granulosa Cell -Most common malignant sex cord stromal tumor -Call-Exner bodies HIGH YIELD
Tumor -Post menopausal females with AUB -Centrifugal granulosa cells
(Malignant) -Children with precocious puberty -Eosinophilic fluid
-Breast tenderness
- j Testosterone, j Estrogen
-Resemble primordial follicles
-Tumor marker: j lnhibin
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Breast Cancer:
Pathophysiology:
• Neoplastic transformation of breast tissue
o Ductal
o Lobular
Etiology:
• Risk factors:
o f Incidence with f Age
o Family history
o White patients more common
o Black patients more common for triple negative breast cancer
o BRCA 1/2 mutations
o f Estrogen exposure: Nulliparity, no breastfeeding, early periods, late menopause
o Alcohol use
o Male risk factors: Klinefelter's and BRCA2 mutation
• Prognosis guided by axillary lymph node biopsy
Diagnostics:
• Overexpression of estrogen and progesterone receptors c-erB2, HER2, EGF
o Triple negative cancer is the most aggressive
Presentation:
• Variable
• +/- Mass
• Blood tinged nipple discharge
• Breast ulcerations, edema of arm, lymphadenopathy (axillary classically)
Invasive tumors —► Pectoral muscle and Cooper ligaments involvement —► Skin dimpling + Nipple retraction/inversion
 Reproductive System: Female Pathology Bootcamp.com

Benign Breast Pathology:

Key Points Histopathology

Fibrocystic -Premenopausal females 20-50 -Papillary apocrine changes

Changes -Most common benign breast lesion -Sclerosing adenosis
-Bilateral/Multifocal lumps +/- pain o Stromal fibrosis and acini +/- Calcification
-Cystic structures -Epithelial hyperplasia
o Fluid filled ducts o Terminal duct cells +/- Lobular epithelium
o “Blue domes”
-Small f Cancer risk

Fat Necrosis -Painless lump +/- Recent breast trauma -Mammography: “Calcified oil" cysts
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-Histology:
o Necrotic fat
o Lipid laden macrophages (foam cells)

Lactational -Recent breastfeeding -Treat with antibiotics

Mastitis -Milk stasis —> Bacterial breeding -Continue breastfeeding
-Bacteria infiltrate cracks in skin overlying nipple
-Painful, red, worse with breastfeeding
-Staph. Aureus most common HIGH YIELD

Gynecomastia -Male breast tissue development -Newborn period, puberty, elderly

-Due to hormonal imbalance -Hypogonadism, cirrhosis
o f Estrogen -Spironolactone, finasteride, ketoconazole, cimetidine
o ; Testosterone -Exogenous steroids
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Benign Breast Tumors:

+ Presentation Key Points Histopathology

Fibroadenoma -Females < 35 -Small, mobile, well defined mass

-Most common breast tumor in women <35 y/o -Fibrous tissue and glands
-No f Cancer risk -f Estrogen —> f Size + f Tenderness

Intraductal -Small f Cancer risk -Fibroepithelial tumor within lactiferous ducts

Papilloma -Classically sub-areolar
-Serous or bloody discharge

Phyllodes -Common at age 50-60 -Large mass (connective tissue + cysts)

Tumor -Some progress to malignancy -"Leaf-like " lobulations HIGH YIELD
-Usually painless
 Reproductive System: Female Pathology Bootcamp.com

Non-invasive Breast Carcinomas

Epidemiology + Presentation Key Points Histopathology

Ductal -Ductal atypia —> Fills ductal lumen

Carcinoma In-Situ -Microcalcifications on mammography
-No basement membrane penetration
-Comedocarcinoma:
o High grade nuclei
o Central necrosis
o Dystrophic calcification

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Paget Disease -Eczematous patches on nipple and areola -DCIS extension to skin of nipple
-Paget cells:
o Intraepithelial adenocarcinoma cells

Lobular -Found incidentally on biopsy -j E-cadherin expression

Carcinoma In-Situ -f Cancer risk in either breast -p120 catenin positive
ELM
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Invasive Breast Carcinomas

Epidemiology + Presentation Key Points Histopathology

Invasive Ductal -Most common invasive breast cancer -Rock hard mass with well defined margins
-Often bilateral and multifocal -Firm and fibrous
-Desmoplastic stroma
-Small, glandular, duct-like cells

Invasive Lobular -Frequently with bilateral symmetry -j E-cadherin expression

Carcinoma -“Single file” cells HIGH YIELD
-Lack of duct formation
-Frequently without desmoplastic response

Medullary -Large anaplastic cells in sheets

Carcinoma -Lymphocytes and plasma cells present
-Well circumscribed
-Mimic of fibroadenoma

Inflammatory -Poor prognosis -Invasion of dermal lymphatics

Carcinoma -50% survival at 5 years -Hair follicles —> Peau d’orange HIGH YIELD
-Mimics Paget’s or mastitis
-Painful
-Warm swollen erythematous skin
-Often no palpable mass
REVIEW OUTLINE

1. Cryptorchidism and Testicular Torsion b. Benign Prostatic Hyperplasia

A. Cryptorchism A. Pathophysiology

Reproductive 2.
B. Testicular Torsion
Testicular Fluid Collections
B.
C.
Etiology
Presentation
A. Spermatocele D. Diagnosis
System: B.
C.
Congenital Hydrocele
Acquired Hydrocele S.
E. Management
Prostate Adenocarcinoma
A. Pathophysiology
Male Pathology 3.
D. Varicocele
Testicular Cancer
A. Pathophysiology
B.
C.
Etiology
Presentation
B. Etiology D. Diagnosis
C. Presentation E. Management
D. Diagnosis
E. Management
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4. Germ Cell Tumors
5. Non-Germ Cell Tumors
6. Penile Pathology
A. Peyronie Disease
B. Ischemic Priapism
C. Squamous cell carcinoma
7. Inflammatory Pathology
A. Epididymitis
B. Orchitis
C. Prostatitis

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Cryptorchidism and Testicular Torsion

Cryptorchidism:
• Pathophysiology: Testicles fail to descend into scrotum —> f Temperature —> Impaired testicular function
• Sertoli cells = Temperature sensitive vs. Leydig cells largely unaffected
• Risk factors:: f Risk with prematurity, low birth weight
• Presentation: Absence of one or both testes in the scrotum
• Diagnostics:
o Labs: j Sperm count, j Inhibin, f FSH, f LH, j Testosterone when bilateral, normal testosterone when unilateral
o US: Testicles in the inguinal region
• Management and complications:
o Infertility and cancer risk
o Often resolves spontaneously —► If persistent, orchiopexy between 6 months and 2 years of age
Testicular Torsion:
• Pathophysiology: Processus vaginalis error —> Rotation of testicle around spermatic cord —> Testicular necrosis
• Etiology:
o Horizontally aligned testicles “bell clapper deformity”
o Males 12-18 years old +/- groin trauma
• Presentation:
o Acute and severe testicular pain, high riding testicle with absent cremasteric reflex HIGH YIELD
o Neonates with firm blue unilateral scrotal mass
o Negative Prehn sign —► No relief of pain with manual elevation of the testicle (+ in epididymitis)
o Nausea, vomiting, and abdominal pain
• Diagnostics: Ultrasound with doppler showing absence of testicular blood flow
• Management:
o Bilateral orchiopexy within 6 hours or manual detorsion if surgical management unavailable within 6 hours
• Differential: Epididymitis, testicular trauma
 Reproductive System: Male Pathology Bootcamp.com

Testicular Fluid Collections

Spermatocele:
Pathophysiology: Dilation of rete testis or epididymal ducts —> Accumulation of sperm —> Cyst formation
• Presentation: Normal Hydrocele Spermatocele Varicocele
o Fluctuant non-tender paratesticular nodule, + Transillumination test
Congenital Hydrocele:
• Pathophysiology:
o Incomplete obliteraton of processus vaginalis —► Scrotal accumulation of peritoneal fluid
• Etiology: Most common cause of scrotal swelling in infants
• Presentation: Fluid filled scrotum, + Transillumination test
• Management: Spontaneous resolution by age 1
Acquired Hydrocele: AfraTafreeh.com
• Pathophysiology: Infection, trauma, neoplastic activity —► Fluid accumulation in scrotum
o Blood laden scrotum = Hematocele
• Etiology: All age groups are susceptible, as opposed to congenital hydrocele (infants only)
• Presentation: Fluid filled scrotum, + Transillumination test can be negative if fluid is chylous
• Management: Treat underlying cause
Varicocele:
• Pathophysiology: Distal blockage or testicular vein —> Venous accumulation in pampiniform plexus —>
• Etiology: Most common cause of scrotal enlargement in adult males
• Presentation:
o Left sided most common (due to differential left renal vein architecture)
high yield o "Bag of worms” pampiniform dilation —> Larger with standing/valsalva, will not transilluminate
• Diagnostics: US showing pampiniform plexus dilation
• Management: Surgical ligation or embolization if causing pain or infertility
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Testicular Cancer
Pathophysiology: Primary neoplasm of testicular tissue
• 95% arise from germ cell tissue (sperm progenitors)
• 5% arise from sex cord stroma (Leydig and Sertoli cells)
Etiology:
• Most commonly occurring in young males
• Risk factors:
o Cryptorchidism
o Klinefelter syndrome
o Contralateral testicular cancer
Presentation:
• Testicular mass +/- Scrotal edema
Diagnostics:
• Lab abnormalities and histology vary by tumor type (see tables)
• Negative transillumination test
Management:
• Radical orchiectomy
• Biopsy is contraindicated due to risk of spread
 Reproductive System: Male Pathology Bootcamp.com

Germ Cell Tumors

Epidemiology + Presentation Tumor Characteristics Histopathology

Seminoma -Homogenous testicular enlargement -Male analog of ovarian dysgerminoma

-Painless -Large cells in lobules with watery cytoplasm
-Malignant, late to metastasize (good prognosis) • ’’Fried egg” cells
-Most common testicular tumor -f Placental ALP
-Does not affect infants -Radiosensitive tumor

Embryonal -Painful mass with hemorrhage and necrosis -Glandular/Papillary on histology

Carcinoma AfraTafreeh.com
-Malignant, early to metastasize (poorer prognosis)
-Commonly mixed with other tumor types (not pure)
-t hCG
-f AFP (mixed), normal AFP (pure)

Mature Teratoma -Differential presentation with age and sex -Cystic mass
• Adult male: Malignant or benign -All 3 germ layers (heterogeneous)
• Pediatric males: Benign • Hair, teeth, sebaceous tissue
• All females: Benign

Yolk Sac -Also called “endodermal sinus tumor” -Male analog of ovarian yolk sac tumor
Tumor -Most common testicular tumor in children < 3 yrs -Yellow and mucinous
-Malignant and aggressive -Primitive glomeruli (Schiller-Duval bodies)
AFP

Choriocarcinoma -Malignant tumor —> Hematogenous spread -Disordered trophoblastic tissue

-Metastasis to lungs and brain (cannonball mets) • Syncytiotrophoblast and cytotrophoblast
-Gynecomastia and hyperthyroidism (due to f hCG) -fff hCG
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Non-Germ Cell Tumors

Epidemiology + Presentation Tumor Characteristics Histopathology

Leydig Cell -Benign -Produce androgens or estrogens 1 »

Tumor -Precocious puberty -Golden brown 1 < *
-Gynecomastia -Eosinophilic cytoplasmic inclusions
• Reinke crystals ' T.’ '
____ < * * ,
Sertoli Cell -Also called “androblastoma” -Composed of sex cord stromal tissue
Tumor -Benign
WWWKM

Primary -Malignant and aggressive -Diffuse large B cell lymphoma most common
Testicular -Most common testicular cancer in older males
Lymphoma
 Reproductive System: Male Pathology Bootcamp.com

Penile Pathology
Peyronie's Disease:
• Pathophysiology: Penile trauma —> Fibrous scar tissue deposition in tunica albuginea —> Distortion of penile architecture
• Etiology:
o Repeated trauma during intercourse
• Presentation:
o Curved penis +/- Pain and erectile dysfunction
o Sexual/Performance anxiety
Management: Collagenase injections or surgical repair
Differential: Penile fracture —> Traumatic rupture of corpora cavernosa during extreme bending
Ischemic Priapism:
• AfraTafreeh.com
Pathophysiology: Continuous erection (> 4 hours) —► Mechanical obstruction of blood flow —► Penile ischemia
• Etiology:
o Sickle cell disease —> Sickled RBCs block venous drainage
o Medications: Sildenafil, trazodone
• Presentation:
o Erection > 4 hours + Pain
• Management:
o Immediate treatment with corporal aspiration, intracavernosal phenylephrine, surgical decompression
Squamous Cell Carcinoma:
• Pathophysiology: Precursor lesions (in situ) —► Transformation to squamous cell carcinoma
• Etiology:
o Bowen disease: Leukoplakia (white plaque) of the penile shaft
o Erythroplasia of Queyrat: Erythroplakia (red plaque) of the penile glans
o Bowenoid papulosis: Reddish papules throughout entire penis
o HPV and uncircumcised males
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Inflammatory Pathology
Epididymitis:
Pathophysiology: Inflammation of the epididymis, usually secondary to infection^ Can progress to involve the entire testicle
o Young sexually active males (C. trachomatis and N. gonorrhoeae)
o Older males +/- UTI (E. coli, Pseudomonas)
o Behcet's disease —> Autoimmune granuloma formation in seminiferous tubules
• Presentation: Posterior testicular pain with + Prehn sign +/- dysuria
Orchitis:
• Pathophysiology: Inflammation of the testicle usually secondary to infection
o Young sexually active males (C. trachomatis and N. gonorrhoeae)
o Older males +/- UTI (E. coli, Pseudomonas)
o Mumps —► Infertility risk
o Behcet's disease —► Autoimmune granuloma formation in seminiferous tubules
• Presentation:
o Testicular pain and swelling +/- dysuria
o Uncommon in males under 10 yrs
Prostatitis:
• Pathophysiology: Bacterial infection—* Inflammation of the prostate
o Acute:
■ Younger males (C. trachomatis and N. gonorrhoeae)
■ Older Males (E. coli)
o Chronic: Bacterial or non-bacterial (nerve damage or irritation from previous infection)
• Presentation
o Dysuria, frequency, lower back pain
o Swollen, warm, tender prostate
 Reproductive System: Male Pathology Bootcamp.com

Benign Prostatic Hyperplasia

Pathophysiology: f DHT —> Hyperplasia of stromal and epithelial cells of middle and lateral prostate lobes —> Urethral compression
• Complications: Bladder distension/hypertrophy, hydronephrosis, UTIs,
Etiology:
• Males > 50 years old, obesity, type 2 diabetes, hypertension
• f Levels of DHT
Presentation:
• Urinary frequency, dysuria, difficulty with initiation and termination of urination (dribbling)
• Smooth, elastic, uniformly enlarged non-tender prostate on digital rectal exam
• UTIs or Post-renal AKI
Diagnostics:
• f Prostate specific antigen (PSA), f Fraction of free PSA AfraTafreeh.com
• Urinalysis (infection or blood)
• Lab values reflect post-renal AKI (f BUN, f Or, BUN/Cr ratio < 20)
• f Post-void residual urine
Management:
• a-1 antagonists (terazosin/tamsulosin) —► Smooth muscle relaxation
• PDE5 inhibitors —> ; Hydrolysis of cGMP —> f NO —> Smooth muscle relaxation
• 5-a-reductase inhibitors (finasteride) —> ; Conversion of testosterone to DHT
• Surgical resection (TURP)
Differential: Prostate adenocarcinoma
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Prostate Adenocarcinoma (80% in peripheral zone)

Pathophysiology: Malignancy arising from prostatic glandular tissue
• Complications: Bladder distension/hypertrophy, hydronephrosis, UTIs, metastasis to spine via vertebral venous plexus
Etiology:
• f Incidence with f Age (>65 years old)
• More common in Black men
Presentation:
• Mostly asymptomatic
• Signs of obstruction: Dysuria, UTIs, or post-renal AKI
• Nodular, asymmetric, and indurated prostate on digital rectal exam
• Metastasis —> Back or bone pain HIGH YIELD
Diagnostics:
• T Prostate specific antigen (PSA), j Fraction of free PSA
• f Alkaline phosphatase suggests osteoblastic bony metastasis
• Lab values reflecting post-renal AKI (f BUN, f Or, BUN/Cr ratio < 2
• Biopsy —> Gleason scale (tumor staging system)
Management:
• Dependent on patient age and disease severity
• Androgen deprivation therapy
o GnRH analogs (leuprolide, goserelin, nafarelin, histrelin): Augment HPAaxis
o Flutamide, bicalutamide: Competitive inhibition at androgen receptors
o Ketoconazole: 17a-hydroxylase inhibitor —> ; Steroid hormone production
• Radiation / Chemotherapy
Differential:
• Benign prostatic hyperplasia
REVIEW OUTLINE

1. GnRH Modulators
A. GnRH Agonists

Reproductive 2.
B. Degarelix
Selective Estrogen Receptor Modulators
A. Clomiphene
System: B.
C.
Tamoxifen
Raloxifene

Pharmacology 3. Androgen Modulators

A.
B.
Aromatase Inhibitors
Danazol
C. Testosterone/Methyltestosterone
D. Antiandrogens
4. Hormone Replacement Therapy
A. Estrogens
AfraTafreeh.com
B. Progestins
5. Contraception
A. Combined contraception
B. Copper Intrauterine Device
C. Antiprogestins
6. Tamsulosin, Minoxidil, Tocolytics
A. Tamsulosin
B. Minoxidil
C. Tocolytics

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GnRH Modulators
Gonadotropin Releasing Hormone Agonists:
• Mechanism of action: GnRH analog
o Pulsatile Interval: Physiologic GnRH agonist
high yield o Continuous Interval: Transient GnRH agonist (tumor flare) —► Followed by J.GnRH receptor expression in pituitary —► j LH/FSH
• Agents: Leuprolide, goserelin, nafarelin, histrelin
• Indication: Uterine fibroids, endometriosis, precocious puberty, prostate cancer, infertility
• Adverse effects: Hypogonadism, ; Libido, osteoporosis, erectile dysfunction, nausea, vomiting
Degarelix:
• Mechanism of action: GnRH antagonist —> | LH/FSH
• Indication: Prevents startup flare during initiation of GnRH analog therapy for prostate cancer
• Adverse effects: Hot flashes, liver toxicity

Hypothalamus

Pituitary
gland
 Reproductive System: Pharmacology Bootcamp.com

Selective Estrogen Receptor Modulators (SERMs)

Clomiphene:
• Mechanism of action: Antagonist of estrogen receptors in the hypothalamus —> f Release of FSH and LH —> Promotes ovulation
• Indication: Infertility due to anovulation (PCOS)
• Side effects: Hot flashes, ovarian enlargement, visual disturbances, multiple simultaneous pregnancies
Tamoxifen:
Mechanism of Action: Estrogen antagonist at the breast, partial agonist at uterus and bone
Indication:
o ER+/PR+ breast cancer Clomiphene
o Treating gynecomastia during prostate cancer therapy
• Adverse effects:
o AfraTafreeh.com
f Risk of thromboembolic events (especially with smoking), hot flashes
o Endometrial cancer
Raloxifene:
Mechanism of action:
o Estrogen antagonist at the breast and uterus.
o Estrogen agonist at the bone
Indication: Osteoporosis
Adverse effects:
o f Risk of thromboembolic events (especially with smoking)
o Hot flashes
o No increased risk of endometrial cancer
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Androgen Modulators
Aromatase Inhibitors:
• Mechanism of action: Aromatase inhibition —> J, Peripheral conversion of androgens to estrogen
• Agents: Anastrozole, letrozole, exemestane
• Indication: Estrogen receptor positive breast cancer
• Adverse effects: Hot flashes, sweating, weakness
Danazol:
• Mechanism of action: Synthetic androgen that acts as partial agonist at androgen receptors
• Indications: Endometriosis, hereditary angioedema, leiomyoma
• Adverse effects: Weight gain, edema, acne, hirsutism, masculinization, J, HDL levels, hepatotoxicity, idiopathic intracranial hypertension
Testosterone/Methyltestosterone:
• Mechanism of action: Agonist at androgen receptors
• Indication:
o Hypogonadism
o Promotion of 2° sex characteristics
o Stimulates anabolism to promote recovery after burn or injury
Adverse effects: Masculinization, J, Testicular testosterone production, premature epiphyseal plate closure, f LDL, J, HDL
Reproductive System: Pharmacology Bootcamp.com

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Testosterone / Methyltestosterone
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Antiandroaens
Agent Mechanism of Action Indication Adverse Effects

Finasteride 5-a-reductase inhibition —> j. Conversion of testosterone to DHT -BPH -Gynecomastia

-Male pattern baldness -Sexual dysfunction

Flutamide, Nonsteroidal competitive inhibitors at androgen receptors —Steroid binding -Prostate cancer -Gynecomastia
bical utamide -Sexual dysfunction

Abiraterone 17-a-hydroxylase inhibition —> j. Steroid production -Prostate cancer -Hypertension

-Hypokalemia
17/20 lyase-inhibitor —> Steroid production -Adrenal Insufficiency

Ketoconazole 17a-hydroxylase/17,20-lyase inhibitor —> J (Steroid production -Prostate cancer -Gynecomastia

-PCOS -Amenorrhea

Spironolactone Androgen receptor inhibitor -PCOS -Gynecomastia

17a-hydroxylase/17,20-lyase inhibitor —> JJ ‘Steroid production -Amenorrhea
 Reproductive System: Pharmacology Bootcamp.com

Hormone Replacement Therapy

Estrogens:
• Mechanism of action: Agonism at estrogen receptors
• Agents: Ethinyl estradiol, mestranol, diethylstilbestrol (DES)
• Indication: Menstrual abnormalities, ovarian failure, hypogonadism, menopausal hormone replacement, combined OCRs
• Adverse effects: f Risk of thrombi, post-menopausal bleeding, clear cell adenocarcinoma (DES), endometrial cancer (unopposed by progesterone)
• Contraindications: Smoking in age > 35, DVT history, cardiovascular disease, ER positive breast cancer, migraine with aura high yield
Progestins:
• Mechanism of action: Agonism at progestin receptors —► J. Endometrial growth, f Endometrial vascularization, f Cervical mucus thickness
Agents: Levonorgestrel, medroxyprogesterone, etonogestrel, norethindrone, megestrol
Indications
o AfraTafreeh.com
Contraception: Pills, subdermal implant, depot injection, IUD
o Endometrial cancer
o Abnormal uterine bleeding
o Progestin challenge: Bolus of progestin followed by withdrawal
■ Bleeding:
• Amenorrhea due to anovulation
■ Lack of bleeding:
• Hypoestrogenism
• Anatomic defects (Asherman syndrome)
• Chronic anovulation without estrogen

Day 7 Day 14 Day 28

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Contraception
Combined Contraception:
• Mechanism of action:
o f Estrogens and f Progestins —► J. LH/FSH Prevents Estrogen/LH surge —► No ovulation
o f Progestins —► f Cervical mucus thickness —► Blockage of sperm entry
o f Progestins —> | Endometrial proliferation —> | Odds of viable implantation
• Agents: Combination of progestins and ethinyl estradiol:
o Delivery routes: Pill, patch, and vaginal ring
Indication: Menstrual abnormalities, ovarian failure, hypogonadism, menopausal hormone replacement
• Adverse effects: Breast tenderness, breakthrough menstrual bleeding, VIE, hepatic adenomas
• Contraindications: Smoking in patients age > 35, DVT, stroke, CAD, migraine with aura, breast cancer, liver disease
Copper Intrauterine Device:
• Mechanism of action: Local inflammatory reaction in uterus —► Toxic to egg and sperm —► Prevents fertilization and implantation
• Indications
o Contraception:
■ Long term
■ Emergency (most effective)
Side effects: Menorrhagia and dysmenorrhea
Contraindications: Active PID
Antiprogestins:
• Mechanism of action: Antagonism at progestin receptors —► f Endometrial growth, j Endometrial vascularization, j Cervical mucus thickness
• Agents: Mifepristone, ulipristal
• Indications
o Pregnancy termination (mifepristone + misoprostol)
o Emergency contraception (ulipristal)
 Reproductive System: Pharmacology Bootcamp.com

Tamsulosin. Minoxidil. Tocolytics

Tamsulosin
• Mechanism of action: a1-antagonist —> Smooth muscle relaxation —> Promotes urethral dilation
o Selective for a1 A/D receptors (found on prostate) vs vascular al B receptors
• Indication: Benign prostate hyperplasia
Minoxidil
• Mechanism of action: Direct arteriolar vasodilation
• Indication: Androgenetic alopecia (male pattern baldness), severe refractory hypertension
Tocolytics
• Mechanism of action:
o Terbutaline: (p2-agonist) —> J, Contractions
o AfraTafreeh.com
Nifedipine (Ca2+ channel blocker) —> J, Contractions
o Indomethacin: (NSAID) —> J, Prostaglandin synthesis —> J, Contractions
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References
• Created with BioRender.com

• https://commons.wikimedia.Org/wiki/File:Pregnancy_ultrasound_110325143136_1432470.jpg

• https://c0mm0ns.wikimedia.0rg/wiki/File:BI0b_sign_0f_ect0pic_pregnancy.svg

• https://commons.wikimedia.Org/wiki/File:2906_Placenta_Previa-02.jpg

• https://c0mm0ns.wikimedia.0rg/wiki/File:Neural_crest.svg

• NikNaks, Public domain, via Wikimedia Commons

• https://c0mm0ns.wikimedia.0rg/wiki/File:Anencephaly-web.jpg

• https://c0mm0ns.wikimedia.0rg/wiki/File:Ph0t0_0f_baby_with_FAS.jpg

• Teresa Kellerman, CC BY-SA 3.0 <https://creativecommons.0rg/licenses/by-sa/3.O >, via Wikimedia Commons

• Created with biorender.com

• https://c0mm0ns.wikimedia.0rg/wiki/File:PharyngealArchHuman.jpg

Loki austanfell, CC BY-SA 3.0 <https://creativecommons.0rg/licenses/by-sa/3.O >, via Wikimedia Commons

 Reproductive System: Fetal Development Bootcamp.com

References
• https://upload.wikimedia.Org/wikipedia/commons/e/ee/pitt-rogers-danks_syndrome.jpg

• Created with BioRender.com

• Case courtesy of Dr Bahman Rasuli, <a href="https://radiopaedia.org/?lang=us">Radiopaedia.org</a>. From the case <a
href="https://radiopaedia.org/cases/62784?lang=us">rlD: 62784</a>

• Case courtesy of Dr Bahman Rasuli, <a href="https://radiopaedia.org/?lang=us">Radiopaedia.org</a>. From the case <a
href="https://radiopaedia.org/cases/62784?lang=us">rlD: 62784</a>
AfraTafreeh.com
• Created with Biorender.com

• https://commons.wikimedia.Org/wiki/File:Klinefelter%27s_syndrome.jpg

• http://smithperiod6.wikispaces.com/Klinefelter's+Syndrome, CC BY-SA 3.0 <https://creativecommons.Org/licenses/by-sa/3. 0>, via

Wikimedia Commons

• <a href="https://commons.wikimedia.org/wiki/File:Turner_syndrome_webbed_neck.png">Johannes Nielsen</a>, <a

href="https://creativecommons.org/licenses/by/2.0">CC BY 2.0</a>, via Wikimedia Commons

Slide 14: Sexual Differentiation

o Created with BioRender.com
 AfraTafreeh.com
Reproductive System: Fetal Development Bootcamp.com

References
• Slide 20: Sexual Differentiation
o Created with BioRender.com

• Created with BioRender.com

• Dixon, A. Traumatic urethral injury. Case study, Radiopaedia.org. (accessed on 09 Apr 2022) https://doi.org/10.53347/rlD-31648

• Created with BioRender.com

• https://commons.wikimedia.Org/wiki/File:Male_and_female_anatomy.svg

Tsaitgaist, CC BY-SA 3.0 <https://creativecommons.0rg/licenses/by-sa/3.O >, via Wikimedia Commons

 Reproductive System: Pregnancy and Menstruation Bootcamp.com

References
• Spermatogenesis & Oogenesis
o Created with BioRender.com

• Menses
o Created with BioRender.com

• Pregnancy Physiology
o Created with BioRender.com

• AfraTafreeh.com
Umbilical Cord: <a href="https://commons.wikimedia.org/wiki/File:The_Umbilical_Cord.jpg">Ed Uthman, MD</a>, <a
href="https://creativecommons.org/licenses/by-sa/2.0">CC BY-SA 2.0</a>, via Wikimedia Commons>

• Fetal Circulation: https://c0mm0ns.wikimedia.0rg/wiki/File:Fetal_circulati0n.png Vandyke Carter, Public domain, via Wikimedia

Commons

• Childhood Development: https://c0mm0ns.wikimedia.0rg/wiki/File:Tanner_scale-female.svg

o M.Komorniczak, polish wikipedist.Illustration by : Michal KomorniczakThis file has been released into the Creative Commons
3.0. Attribution-ShareAlike (CC BY-SA 3.0)lf you use on your website or in your publication my images (either original or
modified), you are requested to give me details: Michal Komorniczak (Poland) or Michal Komorniczak (Poland).For more
information, write to my e-mail address: [email protected], CC BY-SA 3.0
<https://creativecommons.0rg/licenses/by-sa/3.O >, via Wikimedia Commons
 AfraTafreeh.com
Reproductive System: Pathologies of Pregnancy Bootcamp.com

References
• <https://commons.wikimedia.Org/wiki/File:Pregnancy_ultrasound_110325143136_1432470.jpg>

• <https://c0mm0ns.wikimedia.0rg/wiki/File:BI0b_sign_0f_ect0pic_pregnancy.svg>

• <a href="https://commons.wikimedia.org/wiki/File:Molar_pregnancy.jpg">Mikael Haggstrdm. When using this image in external works, it

may be cited as:Haggstrdm, Mikael (2014). &quot;Medical gallery of Mikael Haggstrdm 2014&quot;. WikiJournal of Medicine 1 (2).
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• <a href="https://commons.wikimedia.org/wiki/File:Molar_pregnancy_0001.jpg">Mme Mim</a>, <a

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• <a href="https://commons.wikimedia.org/wiki/File:Supine_hypotensive_syndrome_2.jpg">Bonnie Urquhart Gruenberg</a>, <a

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• <a href="https://commons.wikimedia.org/wiki/File:Twin_to_Twin_transfusion_syndrome.svg">Kevin Dufendach</a>, <a

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Created with BioRender.com

 Reproductive System: Female Pathology Bootcamp.com

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Reproductive System: Female Pathology Bootcamp.com

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20. <a href="https://commons.wikimedia.org/wiki/File:Histopathology_of_uterine_leiomyoma_(Van_Gieson%27s_stain).jpg">Mikael Haggstrbm, M.D. -Author info - Reusing images- Conflicts
of interest: NoneMikael HaggstrbmConsent note: Consent from the patient or patient&#039;s relatives is regarded as redundant, because of absence of identifiable features (List of
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21. <a href="https://commons.wikimedia.org/wiki/File:ThinPrep_Pap_smear_HPV.jpeg">Photomicrograph by Ed Uthman, MD. 20 July 2006 Euthman 20:24, 29 November 2006 (UTC)</a>,
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22. <a href="https://commons.wikimedia.org/wiki/File:CIN_1-HPV_on_ThinPrep.jpg">Ed Uthman</a>, <a href="https://creativecommons.org/licenses/by-sa/2.0">CC BY-SA 2.0</a>, via

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24. <ahref="https://commons.wikimedia.org/wiki/File:Keratin_PearlsJn_Squamous_Cell_Carcinoma_of_the_Larynx_(35398275972).jpg">Ed Uthman from Houston, TX, USA</a>, <a

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25. <a href="https://commons.wikimedia.org/wiki/File:PCO_polycystic_ovary.jpg">Je Hyuk Lee</a>, <a href="https://creativecommons.org/licenses/by-sa/3.0">CC BY-SA 3.0</a>, via
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27. <a href="https://commons.wikimedia.org/wiki/File:Brenner_tumor_with_annotated_coffee_bean_nuclei.jpg">Mikael Haggstrbm, M.D. -Author info - Reusing images- Conflicts of interest:
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Reproductive System: Male Pathology Bootcamp.com

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2. <a href="https://commons.wikimedia.org/wiki/File:Scrotal_ultrasonography_of_varicocele.jpg">Chee-Wai Mak and Wen-Sheng

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