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Chase Findley, MSIV
Gonadal Drainage, 454
Venous
Left ovary/testis, left gonadal vein, left renal
vein, IVC
Lymphatic
Ovaries/testes,
para-aortic
lymph nodes
Derivation of Sperm Parts, 455
Acrosome
Golgi apparatus
Neck
Contains mitochondria
Utilizes fructose
Tail (flagellum)
Centrioles
Autonomic Innervation of Male
Sexual Response, 455
Erection
Parasympathetic, pelvic nerve
Nitrous oxide, smooth muscle relaxation,
vasodilation, erection
Emission
Sympathetic, hypogastric nerve
Ejaculation
Visceral, somatic, pudendal nerve
Male Reproductive Anatomy, 455
Semiferous Tubules, 456
Spermatagonia (germ cells)
Maintain germ pool, produce primary
spermatocytes
Sertoli cells
Secrete inhibin, inhibits FSH
Secrete androgen-binding protein
○ Maintains local testosterone levels
Forms blood-testis barrier
○ Isolates gametes from autoimmune attack
Regulate spermatogenesis
Sertoli cells
Secrete testosterone
Regulation of Spermatogenesis,
457
GnRH
From hypothalamus,
stimulates FSH, LH
release from
pituitary
LH
Stimulates Leydig
cells to synthesize
testosterone
FSH
Stimulates Sertoli
cells to create sperm
Androgens, 458
Testosterone, DHT (testis)
Andostenedione (adrenal gland)
Testosterone function
Differentiation of epididymis, vas deferens,
seminal vesicles
Increase muscle, growth spurt, size of penis,
libido, spermatogensis
Close epiphyseal plates (via estrogen)
Deepen voice
Androgens, 458
DHT function
Differentiate penis, scrotum, prostate
Balding
Increased sebaceous gland actitivity
Prostate growth
Androgens, 458
Potency
DHT>testosterone>androstenedione
5 α reductase
Converts testosterone to DHT, inhibited by
finasteride
Aromatase
Converts testosterone/androstenedione to
estrogen in adipose tissue and Sertoli cells
Estrogens, 458
17β estradiol (ovary)
Estriol (placenta)
Functions:
Growth of follicle
Endometrial proliferation
Development of genitalia, breasts
Female fat distribution
Hepatic synthesis of transport proteins
Feedback inhibition of FSH/LH
LH surge
Myometrial excitability
Increase HDL, decrease LDL
Progesterone, 458
From corpus luteum, adrenal cortex, testes
Functions:
Stimulate endometrial glandular secretions and
spiral artery development
Maintenance of pregnancy
Decrease myometrial excitability
Production of thick cervical mucous, inhibits
sperm entry to uterus
Increase body temperature
Inhibit FSH/LH
Uterine smooth muscle relaxation, prevent
contractions
Menstrual Cycle, 459
Oogenesis, 460
Pregnancy, 460
Fertilization most commonly occurs in
upper fallopian tube, within 1 day of
ovulation
Implantation in wall of uterus 6 days
after fertlization
Trophoblasts secrete βHCG, detectable
in urine 1 week after conception
Pregnancy, 460
Lactation
After labor, decrease in steroids induces
lactation
Suckling maintains milk production by
increasing oxytocin and prolactin
Prolactin
Induces, maintains lactation, inhibits ovulation
Oxytocin
Involved in milk letdown and uterine
contractions
hCG, 461
From synctiotrophoblast of placenta
Maintains corpus luteum
○ Maintains progesterone production
○ Acts like LH, stimulates luteal cells
Used as pregnancy marker, appears in urine
Elevated in pathologic states
○ Hydatidiform moles, choriocarcinoma,
gestational trophoblastic tumors
Menopause, 461
Age related decline in ovarian follicles
Decreased estrogen production
Increased FSH/LH, GnRH
Symptoms include hot flashes, vaginal
atrophy, osteoporosis, coronary artery
disease
Average age is 51
Klinefelter’s Syndrome, 461
XXY (male)
Presence of inactivated X chromosome (Barr
body)
Testicular atrophy, eunuchoid body shape,
tall, long extremities, female hair
distribution
Common cause of hypogonadism
Dysgenesis of seminiferous tubules
Decreased inhibin, increased FSH
Abnormal Leydig cell function
Decreased testosterone, increased LH,
increased estrogen
Turner’s Syndrome, 461
XO (female)
Short stature, ovarian dysgenesis (streak
ovary), webbing of neck, preductal
coarctation of aorta,
Most common cause of primary amenorrhea
Decreased estrogen
○ Increased LH and FSH
Sex Chromosome Disorders, 461
Double Y males
XYY (male)
Phenotypically normal, normal fertility
Tall, acne, antisocial behavior
True hermaphroditism
46,XX or 47,XXY
Both ovary and testicular tissue present
Ambiguous genitalia
Pseudohermaphroditism, 462
Disagreement between phenotypic and
gonadal sex
Female (XX)
Ovaries present
External genitalia virilized or ambiguous
Excessive of exposure to androgenic
steroids during gestation
Caused by congenital adrenal hyperplasia or
exogenous administration of androgens
Pseudohermaphroditism, 462
Male (XY)
Testes present, external genitalia feminized or
ambiguous
Most common form is androgen insensitivity
○ Defect in androgen receptor
○ Normal appearing phenotypic female
○ Female external genitalia, rudimentary vagina
○ Internal genitalia absent (uterus, fallopian tubes)
○ Develop testes (internal), remove to prevent
malignancy
○ Increased sex hormones, LH
5α Reductase Deficiency, 462
Unable to convert testosterone to DHT
Ambiguous genitalia until puberty
Increased testosterone causes
masculinization of external genitalia
Testosterone/estrogen levels normal
Abruptio Placentae, 463
Premature detachment of placenta
Presents as painful bleeding in 3rd
trimester
May be associated with DIC
Increased risk with smoking,
hypertension, cocaine
Placenta Accreta, 463
Defective decidual layer
Placenta attaches to myometrium
Increased risk with prior c-section or
uterine inflammation
Massive bleeding after
delivery
Placenta Previa, 463
Abnormal attachment of placenta to
lower uterine segment
Presents as painless bleeding in any
trimester
May occlude internal os
Increased risk with
prior c-section
Ectopic Pregnancy, 463
Extrauterine implantation of pregnancy, most
often in fallopian tube
Presents as abdominal pain without bleeding
Increased risk with salpingitis
Suspect with increased hCG and sudden
lower abdominal pain, confirm
with ultrasound
Differentiate from appendicitis
Amniotic Fluid Abnormalities,
463
Polyhydramnios
>1.5-2 L amniotic fluid
Associated with esophageal/duodenal
atresia (inability to swallow amniotic fluid)
and anencephaly
Oligohydramnios
<0.5 L amniotic fluid
Associated with bilateral renal agenesis and
posterior urethral valves (inability to secrete
urine)
Cervical Pathology, 463
Dysplasia and carcinoma in situ
Disordered epithelial growth
Begins at basal layer of squamo-columnar
junction, extends outward
CIN 1-3 depending on dysplasia
Associated with HPV
16,18
May progress to
invasive carcinoma
Cervical Pathology
Invasive carcinoma
Often squamous cell carcinoma
Pap smear used for early detection of
dysplasia (koilocytes)
Lateral invasion can
block ureters, lead to
renal failure
Endometriosis, 464
Non-neoplastic glands/stroma in abnormal
locations outside uterus
Cyclic menstrual bleeding from ectopic
tissue
Results in blood filled “chocolate cysts”
Presents as severe menstrual related pain
May cause infertility
Adenomyosis
Endometrium within myometrium
Endometrial Proliferation, 464
Endometrial hyperplasia
Endometrial gland proliferation caused by
increased estrogen stimulation
Increased risk of endometrial carcinoma
Presents as post-menopausal bleeding
Risk factors include anovulatory cycles,
HRT, PCOS, granulosa cell tumor
Endometrial Proliferation, 464
Endometrial carcinoma
Most common gyn malignancy
Most common in 55-65 years
Presents as vaginal bleeding
Preceded by endometrial hyperplasia
Risk factors are unnopposed estrogen
therapy, obesity, diabetes, HTN, nulliparity,
late menopause
Deeper myometrial invasion worsens
prognonsis
Myometrial Tumors, 464
Leiomyoma
Most common female tumor
Benign, smooth muscle tumor, with rare
malignant transformation
Multiple tumors with well demarcated
borders
Most common in 20-40’s, blacks
Estrogen sensitive
○ Increase in size with pregnancy, decrease
with menopause
Myometrial Tumors, 464
Leiomyoma
May be asymptomatic or cause abnormal
uterine bleeding
○ May cause iron deficient anemia
Whorled pattern of smooth muscle bundles
Myometrial Tumors, 464
Leiomyosarcoma
Bulky, irregular shaped tumor
Areas of necrosis, hemorrhage
Highly aggressive, likely to recur
Increased incidence in blacks
May protrude from cervix
Premature Ovarian Failure, 464
Premature atresia of ovarian follicles in
reproductive age women
Presents with menopause between
puberty and age 40
Decreased estrogen
Increased LH, FSH (decreased
feedback inhibition)
Polycystic Ovarian Syndrome,
465
Increased LH/FSH ratio leads to
anovulation
Hyperandrogenism
Enlarged, bilateral cystic ovaries
Presents with amenorrhea, infertility,
obesity, hirsutism
Associated with insulin resistance,
increased risk of endometrial cancer
Treat with weight loss, OCP’s,
gonadotropin analogs, clomiphene, surgery
Ovarian Cysts, 465
Follicular cyst
Distentension of unruptured graafian follicle
Associated with hyperestrinism, endometrial
hyperplasia
Corpus luteum cyst
Hemorrhage into persistent
corpus luteum
Associated with menstrual
irregularity
Ovarian Cysts, 465
Theca-lutein cyst
Bilateral/multiple, due to gonadotropin
stimulation
Associated with choriocarcinoma and moles
“Chocolate cyst”
Blood containing cyst from
ovarian endometriosis
Varies with menstrual cycle
Ovarian Germ Cell Tumors, 465
Dysgerminoma
Malignant, equivalent to male seminoma
Sheets of uniform cells
hCG tumor marker
Choriocarcinoma
Rare, malignant
Can develop in pregnancy (mother or fetus)
Large hyperchromatic synctiotrophoblastic cells
Increased frequency of theca-lutein cysts
hCG tumor marker
Ovarian Germ Cell Tumors, 465
Yolk sac (endodermal sinus) tumor
Aggressive malignancy in ovaries,
sacrococcygeal area (children)
Teratoma
Contains 2-3 germ layers
Mature teratoma (dermoid cyst)
○ Most common benign tumor
Immature teratoma
○ Aggressively malignant
Struma ovarii
○ Contains functional thyroid tissue
Ovarian Non-germ Cell Tumors,
466
Brenner tumor
Benign, looks like bladder
Fibromas
Bundles of spindle-shaped fibroblasts
Meig’s syndrome
○ Ovarian fibroma, ascites, hydrothorax
Pulling sensation in groin
Ovarian Non-germ Cell Tumors,
466
Granulosa cell tumor
Estrogen secreting
○ Precocious puberty
○ Endometrial hyperplasia or carcinoma
Call-exner bodies
○ Small follicles with
eosinophilic secretions
Ovarian Non-germ Cell Tumors,
466
Krukenberg tumor
GI malignancy that metastasizes to ovary
Mucin-secreting signet cell adenocarcinoma
Ovarian Non-germ Cell Tumors,
466
Serous cystadenoma
Benign, bilateral, lined with fallopian tube
Serous cystadenocarcinoma
Malignant, bilateral
Mucinous cystadenocarcinoma
Malignant
Pseudomyxoma peritonei
○ Accumulation of mucinous material from
ovarian or appendiceal tumor
Vaginal Carcinoma, 466
Squamous cell carcinoma
Secondary to cervical SCC
Clear cell adenocarcinoma
Associated with in utero exposure to DES
Sarcoma botyroides
Girls <4 years
Spindle shaped tumors
Desmin positive
Benign Breast Tumors, 466
Fibroadenoma
Small, mobile, firm mass with sharp edges
Most common in <25 years
Increase in size and tenderness with
estrogen
Not pre-malignant
Benign Breast Tumors, 466
Intraductal papilloma
Small, grows in lactiferous ducts
Typically beneath areola
Serous/bloody discharge
Slightly increases risk of carcinoma
Benign Breast Tumors, 466
Phyllodes Tumor
Large, bulky mass of connective tissue and
cysts
“Leaf-like” projections
Most common in 6th decade
May become malignant
Malignant Breast Tumors, 467
Common in post-menopause
Arise from mammary duct epithelium or
lobular glands
Overexpression of
estrogen/progesterone receptors erb-B2
affects therapy and prognosis
Axillary lymph node involvement is most
important prognostic factor
Malignant Breast Tumors, 467
Ductal carcinoma in situ
Fills ductal lumen
Early malignancy without basement
membrane penetration
Malignant Breast Tumors, 467
Invasive ductal
Firm, fibrous mass
Small, glandular, duct-like cells
Most invasive and common
Malignant Breast Tumors, 467
Invasive lobular
Orderly rows of cells
Multiple, bilateral
Medullary
Fleshy, cellular,
lymphatic infiltrate
Good prognosis
Malignant Breast Tumors, 467
Comedocarcinoma
Ductal, caseous necrosis
Inflammatory
Dermal lymphatic invasion
by breast carcinoma
Peau d’orange
Poor survival rate
Common Breast Conditions, 468
Fibrocystic disease
Most common “breast lumps” from age 25-
menopause
Premenstrual breast pain, multiple bilateral
lesions, fluctuating size
Does not indicate increased risk of
carcinoma
Common Breast Conditions, 468
Fibrocystic disease
Fibrosis
○ Hyperplasia of breast stroma
Cystic
○ Fluid filled, blue dome
Sclerosing adenosis
○ Increased acini and intralobular fibrosis
Epithelial hyperplasia
○ Increased epithelial cell
layers in terminal duct lobule
○ Increased risk of carcinoma with
atypical cells
Common Breast Conditions, 468
Acute Mastitis
Breast abscess
Associated with breast feeding
○ Bacterial infection through cracks in nipples
Most common pathogen is S. aureus
Common Breast Conditions, 468
Fat Necrosis
Benign painless breast lump
Secondary to injury to breast tissue
Common Breast Conditions, 468
Gynecomastia
Results from hyperestrogenism
○ Cirrhosis, testicular tumor, puberty, old age
Klinefelter’s syndrome
Drugs
○ Estrogen, marijuana, heroin, psychoactive
drugs, spironolactone, digitalis, cimetidine,
alcohol, ketoconazole
Benign Prostatic Hyperplasia,
468
Common in men >50
Related to age-related increase in
estradiol, sensitization of prostate to DHT
Nodular enlargement of periurethral (lateral
and middle) lobes, compresses urethra into
vertical slit
Presents with frequency, nocturia,
hesitancy, dysuria
May lead to distention/hypertrophy of
bladder, hydronephrosis, UTIs
Increased PSA, not premalignant
Prostatitis, 469
Symptoms
Dysuria, frequency, urgency, low back pain
Etiology
Acute: bacterial
Chronic: abacterial (most common),
bacterial
Prostatic Adenocarcinoma, 469
More common in men >50 years
Usually develops in posterior lobe
(peripheral zone) of prostate
Diagnosed by DRE and biopsy
Prostatic Adenocarcinoma, 469
PSA tumor marker
Increased PSA, decreased fraction of free
PSA
Osteoblastic metastasis
Low back pain
Increased serum
alkaline phosphatase
Cryptorchidism, 469
Undescended testis
Decreased spermatogenesis secondary
to increased body temperature
Increased risk of germ cell tumors
Prematurity increases occurrence
Testicular Germ Cell Tumors, 469
95% of all testicular tumors
Seminoma
Malignant, most common testicular tumor
Painless testicular enlargement
Males 15-35
Radiosensitive, late metastasis
Excellent prognosis
Testicular Germ Cell Tumors, 469
Seminoma
Large cells in lobules with watery cytoplasm,
“fried egg” appearance
Testicular Germ Cell Tumors, 469
Embryonal carcinoma
Malignant
Painful testicular enlargement
Worse prognosis
Glandular/papillary
morphology
Can differentiate to
other tumors
Testicular Germ Cell Tumor, 469
Yolk sac (endodermal sinus) tumor
Analogous to ovarian yolk sac tumor
Schiller-Duval bodes
○ Central vessel surrounded
by tumor cells
Primitive glomeruli
Increased AFP
Testicular Germ Cell Tumors, 469
Choriocarcinoma
Malignant
Increased hCG
Teratoma
Usually malignant
Testicular Non-germ Cell Tumors,
469
5% of testicular tumors, mostly benign
Leydig cell tumor
Intracytoplasmic Reinke crystals,
Androgen producing
○ Gynecomastia
○ Precocious puberty
Testicular Non-germ cell Tumors,
469
Sertoli cell tumor
Androblastoma from
sex cord stroma
Testicular lymphoma
Most common testicular
cancer in older men
Tunica Vaginalis Lesions, 469
Lesions in serous covering of testes
Present as testicular masses that
transilluminate
Varicocele
Dilated vein in pampiniform
plexus “bag of worms”
May cause infertility
Tunica Vaginalis Lesions, 469
Hydrocele
Increased fluid secondary to incomplete
fusion of processus vaginalis
Spermatocele
Dilated epididymal duct
Penile Pathology, 470
Carcinoma in situ
Bowen’s disease
○ Gray, solitary, crusty plaque
○ Usually on shaft of penis or scrotum
○ Peak incidence in 5th decade
○ Progresses to sqamous cell carcinoma in
<10% of cases
Penile Pathology, 470
Carcinoma in situ
Erythroplasia of Queyrat
○ Red, velvety plaques
○ Usually involves glans
○ Similar to Bowen’s disease
Penile Pathology, 470
Carcinoma in situ
Bowenoid papulosis
○ Multiple papular lesions
○ Affects younger age group
○ Usually not invasive
Penile Pathology, 470
Squamous cell carcinoma
More common in uncircumcised men
More common in Asia, Africa, S. America
Associated with HPV
Penile Pathology, 470
Peyronie’s disease
Bent penis
Aquired fibrous tissue formation
Anti-androgens, 471
Finasteride
5 α reductase inhibitor
Decreases conversion of testosterone to
more potent DHT
Used in BPH, male pattern baldness
Flutamide
Non-steroidal competitive inhibitor of
testosterone receptor
Used in prostate carcinoma
Anti-androgens, 471
Ketoconazole
Inhibits steroid synthesis
Spironolactone
Inhibits steroid binding
Both used in treatment of PCOS and
hirsutism
May cause gynecomastia, amenorrhea
Leuprolide, 471
Pulsatile administration
GnRH analog with agonist properties
Continuous administration
GnRH analog with antagonist properties
Used in
Infertility (pulsatile), prostate cancer
(continuous with flutamide), uterine fibroids
May have anti-androgen effects, nausea
vomiting
Sildenafil, vardenafil, 471
Inhibit cGMP phosphodiesterase, causing
increased CGMP, smooth muscle
relaxation in corpus cavernosum,
increased blood flow, erection
Used in treatment of impotency
May cause headache, flushing, dyspepsia,
impaired blue/green colorvision
Risk of life threatening hypotension if taken
with nitrates
Mifepristone (RU-486), 471
Competitive inhibitor of progesterone
receptors
Used in termination of pregnancy
Makes uterus inhospitable to fertilized egg
Administered with misoprostole
May cause heavy bleeding,
nausea/vomiting, anorexia, abdominal
pain
Oral Contraception, 471
Prevent estrogen surge
Estrogen surge, LH surge do not occur
Pros:
Reliable
Decrease risk of endometrial/ovarian cancer,
ectopic pregnancy, pelvic infections,
regulation of menses
Cons:
Increased triglycerides, weight gain, nausea,
hypertension, hypercoaguable state
Hormone Replacement Therapy,
471
Used in:
Treatment of menopausal symptoms
○ Hot flashes, vaginal atrophy
Prevention of osteoporosis
Unopposed estrogen (without
progestins) increases risk of endometrial
cancer
Give progestins if patient has not had
hysterectomy
Increase in CV risk (pro-thrombotic)
Induction/delay of Labor, 472
Dinoprostone
PGE2 analog
Causes cervical dilation, uterine contraction
Induces labor
Ritodrine/terbutaline
B2 agonists
Relax uterus
Reduce premature uterine contractions
Delay labor
Anastrozole/exemestane, 472
Aromatase inhibitors
Aromatase converts androgens to estrogens
Used in post-menopausal breast cancer
Adjuvant therapy after surgery
Metastatic disease
Testosterone, 472
Agonist at androgen receptors
Used in:
Treatment of hypogonadism
Promotion of development of secondary
sexual characteristics
Stimulation of anabolism (burn, injury)
Treatment of ER-positive breast cancer
Testosterone Toxicity, 472
Masculinization in females
Exogenous use reduces intratesticular
testosterone, inhibits Leydig cells, leads
to testicular atrophy
Premature closure of epiphyseal plates
(short stature)
Dyslipidemia
Estrogens, 472
Bind estrogen receptors
Used in:
Treatment of hypogonadism/ovarian failure
Treatment of menstrual abnormalities
Hormone replacement therapy in post-
menopause
Treatment of men with androgen-dependent
prostate cancer
Estrogen Toxicity, 472
Increased risk of endometrial cancer
Increased bleeding in post-menopause
Increases risk of clear cell
adenocarcinoma with prenatal DES
Increased risk of thrombi
Contraindicated in estrogen-receptor
positive breast cancer
Progestins, 472
Bind progesterone receptors
Reduce growth and increase
vascularization of endometrium
Used in:
Oral contraceptives
Treatment of endometrial cancer
Treatment of abnormal uterine bleeding
Estrogen Partial Agonists, 472
Clomiphene
Partial agonist at estrogen receptors in
pituitary
Prevents estrogen feedback inhibition of
LH/FSH release from pituitary
Increased LH/FHS stimulates ovulation
Used in treatment of PCOS and infertility
May cause hot flashes, ovarian
enlargement, multiple simultaneous
pregnancies, visual disturbances
Estrogen Partial Agonists, 472
Tamoxifen
Estrogen antagonist in breast tissue
Used to treat and prevent recurrence of ER-
positive breast cancer
Raloxifene
Estrogen agonist in bone
Used to treat osteoporosis