Flashcards in Day 10.1 Reproductive Deck (149):
Gonadal venous drainage
Left ovary/testes --> L gonadal vein --> L renal vein --> IVC
(the adrenals also go thru the left renal vein to get to the IVC. left = longer!)
Right ovary/testes --> R gonadal vein --> IVC
Lymphatic drainage of the ovaries/testes
Para-aortic lymph nodes
Lymphatic drainage of distal (lower) 1/3 of vag, vulva, and scrotum
Superficial inguinal nodes
Lymphatic drainage of the proximal (upper) 2/3 of vag, uterus
Obturator, external iliac, and hypogastric nodes
Which is a varicocele and on which side is it more commonly found?
Enlargement of the vein in the scrotum that drains the testes. (pampiniform plexus).
Can cause infertility
Bag of worms
Varicocele is more common on the left bc of the way that the left testis drains (L gonadal to L renal, at a 90 degree angle)
What do the suspensory ligaments of the ovaries do?
connect ovaries to lateral pelvic wall
contain ovarian vessels w/in it
What does the cardinal ligament do?
Connects the cervix to the side wall of the pelvis
contains uterine vessels inside of it
What does the round ligament of the uterus do?
Connects the uterine fundus (top) to the labia majora.
Derivative of the gubernaculum, travels through the (round) inguinal canal
Does not carry any structures w/in it.
What does the broad ligament do?
Connects uterus, fallopean tubes, and ovaries to the pelvic side wall
Contains the fallopean tubes, ovaries inside of it, as well as the round ligament
What does the ligament of the ovary do?
connects to the ovary to the uterus
Pathway of sperm during ejaculation
How does erection take place (proerectile, antierectile processes)
Erection is caused by the PNS (pelvic nerve).
NO causes increased cGMP --> smth musc relaxation --> vasodilation --> erection
NE causes increased intracellular Ca2+ --> smth musc contraction --> vasoconstriction --> no erection
What nervous system is responsible for emission?
Sympathetic Nervous System- Hypogastric Nerve
What nervous system is responsible for ejaculation?
Visceral and somatic nerves: pudendal nerve
How do sildenafil and vardenafil work?
They inhibit cGMP breakdown.
More cGMP = more relaxation, vasodilation, erection
What are the parts of the sperm and when does derivation of the parts occur?
Happens during final phase of spermatogenesis:
Spermatid --> Spermatozoa
Acrosome - derived from the golgi, is at the very tip
Head, contains nucleus
Middle piece- contains mitochondria
Tail (flagellum) comes from centrioles.
The sperm Feeds on Fructose
What are the types of estrogen, and where do they each come from?
Estradiol - from ovaries (strongest potency)
Estrone - from fat
Estriol - from placenta (weakest)
How does estrogen change in pregnancy?
50-fold increase in estradiol (ovaries) and estrone (fat)
1000-fold increase in estriol (placenta)- this is an indicator or fetal well-being.
Where are estrogen receptors located?
They are expressed in the cytoplasm, but when they are bound by ligand they get translocated to the nucleus.
What are the sources of estrogen?
What organs does estrogen contribute to the devt of?
Genitalia and breast
Female fat distribution
How does estrogen affect the follicle?
How does estrogen affect endometrium?
Excess estrogen is a precursor to endometrial hyperplasia, which can lead to endometrial carcinoma
How does estrogen affect the myometrium?
Increases myometrial excitability
How does estrogen affect receptors and other hormones?
Estrogen causes upregulation of estrogen, LH, and progesterone receptors.
It causes feedback inhibition of FSH and LH, then the LH surge
It stimulates prolactin secretion in general, but BLOCKS the action of prolactin at the breast- so don't give a breastfeeding mom OCPs or you will decrease her milk production.
How does estrogen affect proteins and lipids?
Increases transport of proteins,
Encourages favorable lipid profile:
Increased HDL, decreased LDL
What is the process of making estrogen in the ovary? Which enz, which cells?
2 cell theory of estradiol: must use both theca cells and granulosa cells
Pulsatile GnRH goes to the Ant Pit, which releases LH and FSH
LH goes to the theca cells, and causes cholesterol to be converted (--> > >) to androstenedione. However, the theca cell does not have aromatase, so the androstenedione has to leave and go to the granulosa cell.
FSH goes to the granulosa cell and stimulates aromatase. So, while the granulosa cell does not have desmolase, it has to get the androstenedione from the theca cell. Then, it converts androstenedione to estrogen using its aromatase.
Then estrogen goes out of the granulosa cell.
What is the difference bt pulsatile GnRH and constant GnRH
Pulsatile GnRH will stimulate the ant pit to rls LH and FSH
Constant GnRH is inhibitory
What are the sources of progesterone?
If progesterone is elevated, what phase of the menstrual cycle is it?
but note: progest peaks around day 21 in cycle. however, around ovulation is when it first starts rising.
What effect does progesterone have on the endometrium?
Stimulates endometrial glandular secretions
(and spiral artery devt)
How does progesterone affect cervical mucus?
Produces thick mucus, which inhibits entry of sperm (don't need sperm bc already prego)
What effect does progesterone have on pregnancy?
It maintains it.
It also decreases myometrial excitability so that pregnancy is maintained, as well as causing uterine smooth musc relaxation (which prevents contractions)
How does progesterone increase body temp?
It increases it (think of increased body temp on ovulation day- progesterone means you're ovulating)
What effect does progesterone have on gonadotropins?
It inhibits LH and FSH
How does progesterone affect estrogen receptors?
It decreases estrogen receptor expressivity
What causes menstrual cramps? Drug of choice?
DoC = NSAIDs
Women who have a lot of early miscarriages may have a deficiency in what hormone?
Progesterone (it maintains pregnancy)
Hormone sequence for the menstrual cycle
FSH causes follicle maturation
Follicle produces estradiol
This causes LH surge
Ovulation and production of progesterone (and estradiol)
Progest inhibits LH and FSH
So the corpus luteum declines
No more estradiol and progesterone
So FSH is no longer inhibited...
and it starts over.
When is follicular growth the fastest?
During the 2nd week of the proliferative phase
What stimulated endometrial proliferation?
What maintains the endometrium to support implantation?
How is fertility affect by progesterone levels?
Decreased progesterone means decreased fertility
How long is the follicular phase?
How long is the luteal phase?
Follicular is the first part of the cycle and it varies in length.
Luteal is the second part and it is usually a constant 14 days. So no matter when ovulation takes place, menstruation will occur 14 days later.
What is the endometrial phase equivalent for the follicular phase? for the luteal phase?
Follicular - proliferative phase (first part of the cycle)
Luteal - secretory phase (second part of the cycle)
What is oligomenorrhea?
Oligo: >35 day cycle
Poly: s frequent
In what order do these occur? Estrogen, LH, Menstruation, Ovulation, Progesterone?
Progesterone peaks (from corpus luteum)
Menstruation (apoptosis of endometrial cells)
What triggers ovulation?
(and the LH surge is caused by increased estrogens)
the LH surge causes rupture of the follicle (ovulation)
When does progesterone start to rise, wrt the menstrual cycle?
24 hrs after ovulation
T/F Sperm take 24 hrs to get to the oocyte
How does increased estrogen cause the LH surge?
Increased estrogen causes increased GnRH receptors on the Ant Pit. So, increased estrogen stim's LH surge bc more receptors for GnRH are there, and GnRH causes rls of LH.
How is temp affected by ovulation?
basal body temp rises 24 hrs after ovulation, induced by progesterone
Blood from ruptured follicle can irritate the peritoneal lining and cause pain (mimicing appendicitis in worst case)
What hypothalamic nucleus is involved in ovulation?
Arcuate nucleus of the hypothalamus.
This rls's GnRH, which stim's the Ant Pit to release LH. --> LH surge
Layers of endometrium
Bottom to top:
Stratum Spongiosum (shed)
Stratum Compactum (shed)
When is the corpus luteum formed, what does it produce, and what is its lifespan?
Formed after ovulation
Produces progesterone and estrogen (during the luteal (2nd) phase.
Lifespan is 14 days (ovulation - menstruation)
But, if B-hCG from the placenta is present, this will rescue the CL and extend the lifespan to 6-7 weeks
(after that, the placenta can make its own progesterone)
What cells of the CL secrete progesterone and estrogen in the luteal phase?
Lutein cells- Granulose lutein cells and Theca lutein cells
Stages of oogenesis- names, ploidy, 2N or 4N
1. Oogonium, Diploid, 2N (46 single chromosomes)
2. Primary oocyte, Diploid, 4N (46 sister chromatids)
3. Secondary oocyte, Haploid, 2N (23 sister chromatids). This also made one polar body in addition to the secondary oocyte.
Ovum, Haploid, N (23 single chromatids)
When do primary oocytes begin Meiosis I? When do they complete it?
Begin Meiosis I during fetal life
Complete it just prior to ovulation.
In what phase of Meiosis I are primary oocytes arrested?
Primary oocytes arrest in Prophase I until ovulation.
In what phase of Meiosis II are secondary oocytes arrested?
Secondary oocytes arrest in metaphase II until fertilization.
The egg MET a sperm at fertilization
What happens to the secondary oocyte if fertilization does not occur?
It degenerates- it does not go to ovum!
Make sure you can draw out oogenesis, ploidy, etc.
Where and when does fertilization occur?
Usu in upper fallopian tube (ampulla), within one day after ovulation.
When does implantation occur?
Implantation is into uterine wall, 6 days after fertilization (so 3 weeks after LMP)
When is B-hCG detectable? What secretes it?
Trophoblasts secrete B-hCG.
Detectable in blood 1 week after conception
Detectable in urine home test 2 weeks after conception (so at time of missed period)
What induces lactation, what maintains milk production?
After labor, the decreased progesterone induces lactation
Suckling maintains milk production (is required to do so), bc increased nerve stimulation increases oxytocin and prolactin
How does prolactin affect lactation and reproductive fn??
Prolactin induces and maintains lactation
It decreases reproductive fn (so breastfeeding is protective)
What does oxytocin do?
Helps w milk letdown
Involved in uterine contractions
Where does B-hCG come from?
Synctiotrophoblast of the placenta
Fn of B-hCG?
Maintains the CL (and therefore maintains progesterone secretion) for the 1st trimester by acting like LH.
If B-hCG didn't do this, there would be no luteal cell stimulation and abortion would result.
Why does the CL degenerate in 2nd and 3rd trimester?
The placenta synthesizes its own estrogen and progesterone, so it's not needed.
What does elevated hCG indicate?
1. Pregnancy (this is how it is detected in urine)
Gestational trophoblastic tumors (aka testicular choriocarcinoma)
What are the hormonal changes that take place in menopause?
FSH increases (a lot)
LH increases (but no surge)
The big increase in FSH is used as a confirmatory test.
What is menopause?
Decreased estrogen production d/t age-linked decline in the number of ovarian follicles. Avg onest is 51 years, but earlier in smokers. Usu preceeded by 4-5 years of abn (oligomen) menstrual cycles.
What is the source of estrogen after menopause?
Estrone- peripheral conversion of androgens.
Increased androgens cause hirsutism
Physical changes caused by menopause
Menopause causes HHAVOC:
Atrophy of vag
What is premature ovarian failure?
Premature atresia of ovarian follicles in women still in reproductive age. See signs of menopause at <40yo.
Decreased estrogen, increased FSH and LH.
What is hormone replacement therapy?
Used for relief/prevention of menopausal sx (hot flashes, vag atrophy) and osteoporosis- it increases estrogen, so it decreases osteoclast activity.
Unopposed ERT estrogen replcmt therapy increases the risk of endometrial cancer, so progesterone is added. (In pts that have a uterus)
There is a possible risk of CV problems.
What is the mechanism and clinical use of exogenous estrogens?
Ethinyl estradiol, DES, mestranol all work by binding estrogen receptors.
Used in hypogonadism or ovarian failure, menstrual abnormalities, HRT in post-menopausal women
Can also use in men w androgen-dependent prostate cancer
What is the toxicity of exogenous estrogens?
Increased risk of endometrial cancer
Bleeding in post-menopausal women
Clear cell adenocarcinoma of vag in females that were exposed to DES in utero (so whose moms took it while preg)
Increased risk of DVT, PE
Contraindicated if ER-positive breast cancer or hx of DVTs
What is the mechanism and use of exogenous progesterones?
Mech- bind progesterone receptors, reduce growth, and increase vascularization of the endometrium
Used in OCP and in Rx of endometrial CA and abn uterine bleeding
Which IUD has progesterone?
Mirena. 5 years, prevents menstruation, and used as Rx for menorrhagia
Copper one is Paraguard, for 10 yrs but no hormones.
IM injection every 3 mo
A/w bone mineral density loss esp if long-term, so not ideal for >2yrs of use
But good choice for pts w MR
How do OCPs work?
Prevent estrogen surge, so the LH surge does not occur. Therefore, no ovulation.
Which has a lower does of estrogen, HRT or OCPs?
Advantages vs Disadvantages of OCPs
reliable, decreased risk of endometrial and ovarian cancer, decreased ectopic pregnancy, decreased pelvic infections, decreased dysmenorrhea (regulation of menses), decreased acne
Disadv: take every day, no STD protection, increased TGs, deprsn/weight gain/nausea/HTN*, hypercoagulable state (DVT, PE)
*young woman w HTN- always ask abt OCP use
When are OCPs contraindicated?
Smoker >35yo (increased risk for clots)
Migranes w aura (increased risk for stroke)
Mifepristone mech, clinical use, toxicity
Competitive inhibitor of progestins at progesterone receptors (so anti-progesterone, anti-gestation)
Use- abortion. Given w misoprostol (PGE-1) bc prostaglandins cause contractions of uterus, which is what you want if trying to abort.
Toxicity- heavy bleeding, GI effects (naus/vom/anorexia), abd pain
How does cervical dysplasia progress?
Dysplasia --> Carcinoma In Situ --> Invasive carcinoma
Where does cervical dysplasia and CIN start?
Dysplasia is disordered epithelial growth, it begins at the basal layer of the squamo-columnar jn and extends outward.
It's classified as CIN 1, 2, or 3 (carcinoma in situ) based on the extent of the dysplasia. Can progress (slowly) to invasive carcinoma if left untreated.
Risk factors for cervical dysplasia
Assoc w HPV 16, 18 (vaccine preventable)
Mult sex partners
Early sexual intercourse
Invasive carcinoma of the cervix
Often sq cell carcinoma
Pap smear can catch cervical dysplasia (koilocytes) before it progresses to invasive carcinoma.
Lateral invasion can block ureters, causing renal failure. (Primarily locally invasive.)
Avg age 40-45 yo
Appearance of koilocytes
Have a perinuclear cytoplasmic clearing (fried egg appearance)
Vulvar intraepithelial neoplasia (VIN)
Very similar to CIN except vulvar location
Grades I, II, III
A/w HPV 16, 18 (also 31)
Precursor to vaginal carcinoma
What are the 3 kinds of vaginal carcinoma?
1. Sq cell carcinoma (secondary to cervical carcinoma)
2. Clear cell adenocarcinoma (affects women who were exposed to DES estrogen in utero)
3. Sarcoma botryoides (a variant of rhabdomyosarcoma)- affects girls <4yo. Spindle-shaped tumor cells that are desmin-positive (desmin is a muscle stain)
What are Bartholin's gland cysts?
Cyst causing pain in labia majora from clogged gland. Must be drained and treated w Abx. Can result from previous infection.
What are the layers of the uterus?
Non-neoplastic endometrial glands/stroma in abn locations outside of the uterus.
Have cyclic bleeding (follows menstrual cycle) from the ectopic endometrial tsu, which results in blood-filled "chocolate cysts."
Usu in ovary or on peritoneum.
Causes severe menstrual-related pain (bc it is irritating peritoneum), often results in infertility (d/t fallopian tube scarring)
Can be d/t retrograde menstrual flow or ascending infection
Endometrium within the myometrium
A type of endometriosis.
On histo see smooth musc w sawtooth appearance, spiral arteries in the middle of it.
Abn endometrial gland proliferation
Usu caused by excess estrogen stimulation
Increased risk for endometrial carcinoma.
Causes post-menopausal vag bleeding
Risk factors for endometrial hyperplasia
granulosa cell tumor
basically, anything that causes increased estrogen
What is the most common gynecologic malignancy?
Most common gyn malignancy!
Px w vaginal bleeding (typically preceeded by endometrial hyperplasia)
Peak occurance 55-65 yo
Increased myometrial invasion means worse pgx.
Risk factors for endometrial carcinoma
Prolonged use of estrogens w/o progesterone (so only ERT)
What is the most common tumor in women?
Aka fibroid, most common tumor in women.
Benign smooth musc tumor of the myometrium (malignant txformation is rare)
Pften px's w mult tumors w well-demarcated borders.
Estrogen sensitive- tumor size can increase in pregnancy when there is more estrogen and decrease w menopause, when there is less
Peak occurence 20-40 yo; increased incidence in blacks
Can be asympt, or may cause abn uterine bleeding or result in miscarriage. If severe bleeding, can cause iron deficiency anemia.
Does NOT progress to leiomyosarcoma.
Whorled pattern of smooth musc bundles
Bulky, irreg-shaped tumor of the myometrium
Tumor has areas of necrosis and hemorrhage
Typically arises de novo (does NOT come from leiomyoma)
Most commonly in middle-aged women, increased in blacks
Highly aggressive, tendency to recur.
May protrude from cervix and bleed.
Rx for Endometrial carcinoma
Rx for leiomyoma
Removal if indicated (if severe iron-def anemia)
Medical mgmt- induce menopausal state w continuous GnRH- this will suppress FSH and LH. Leuprolide (GnRH analog) does this when administered continuously.
GnRH analog- so can be used as an agonist if given pulsatile, or an antagonist if given continuously.
LEUprolide can be given in LIEU of GnRH.
Use pulsatile for infertility
Use continuous for uterine fibroids (so basically, induce menopause)
Also use continuous in prostate cancer (use w flutamide)
Can cause anti-androgen sx, naus/vom, menopausal sx.
How do you dx leiomyosarcoma?
Rx for leiomyosarcoma
Which tumor has highest incidence in US? Cervical, Endometrial, Ovarian
Endometrial > Ovarian > Cervical
elsewhere cervical is worse d/t decreased screening.
Which tumor has the worst pgx?
Cervical, Endometrial, Ovarian
Ovarian > cervical >endometrial
ovarian is usu detected late.
Most common causes of anovulation
HPO axis abn
premature ovarian failure
hyperprolactinemia (causes hypogonadism)
What is Asherman's syndrome?
Endometrial fibrosis (so certain areas of the endometrium just have fibrotic tsu instead of endometrial tsu.
Often d/t surgery, esp D&C, if basalis layer is scraped, it won't regenerate.
(but still ovulate)
What is the hormonal profile of PCOS?
The increased LH increases the androgens in the thecal cells- these then get converted peripherally (in fat) to estrogens (estrone), which has a positive(!) fdbk on LH, making even more LH.
Increased LH production causes anovulation and hyperandrogenism d/t deranged steroid synth by theca cells of ovary.
Enlarged bilateral cystic ovaries
Clincally: amenorrhea, infertility, obesity, hirsutism
A/w insulin resistance
Increased risk of endometrial cancer
Rx for PCOS
Dx criteria for PCOS
1. Androgen excess (causes the acne, hirsutism)
2. Ovulatory dysfn (no ovulation causes amenorrhea, infertility)
3. Polycystic ovaries on ultrasound
What is virilism?
Seen with really really high testosterone (eg ovarian tumor that produces estrogens)
Deepening of voice, male pattern baldness, clitoromegaly
What are the 4 kinds of ovarian cysts? (physiological)
Corpus luteum cyst
Chocolate cyst (endometrioma)
Follicular cyst of the ovary
Unruptured graafian follicle- if it doesn't let go of egg, can stay around, become distended, and make estrogens
A/w hyperestrinism and endometrial hyperplasia
Corpus luteal cyst of the ovary
Normal in pregnancy (until 6-7 weeks)
Otherwise, can occur when there is hemorrhage into a persistent CL
Theca-Lutein cyst of the ovary
Due to increased B-hCG; pregnancy-related
A/w chriocarcinoma, moles, multiple pregnancies (at the same time), and ovarian hyperstimulation syndrome (IVF)
Chocolate cyst of the ovary
Blood-containing cyst, from ovarian endometriosis
Varies w menstrual cycle
What are the 4 main categories of ovarian tumors?
Epithelial (most common)
Metastatic (from GI, breast, endometrium)
List the epithelial ovarian tumors
My Med Students Consistently Beat Exams
Clear cell (DES exposure in utero)
Serous, Mucinous, Endometrioid are the most common
Epithelial ovarian tumor
Lined w fallopian tube-like epithelium
Epithelial ovarian tumor
50% of the malignant ovarian tumors are this type.
Have psamomma bodies (concentric rings of calcification)
Epithelial ovarian tumor
Multi-locular cyst lined by mucus-secreting epithelium.
Intestine-like tsu (looks like GI)
Epithelial ovarian tumor
Pseudomyxoma peritonei- intraperitoneal accumulation of mucinous material from an ovarian or appendiceal tumor.
Epithelial ovarian tumor
Looks like bladder
List the germ cell ovarian tumors
Endodermal sinus (yolk sac) tumor
What are the markers for germ cell ovarian tumors?
hCG and LDH - dysgerminoma
hCG - choriocarcinoma
AFP - Yolk sac tumor (endodermal sinus)
90% of ovarian germ cell tumors are what type?
Ovarian germ cell tumor
Contains cells from 2 or 3 germ layers
Mature teratoma - benign. most freq benign ovarian tumor. aka dermoid cyst. see in younger adults
Immature teratoma - aggressively malignant. anaplastic (undifferentiated).
Struma ovarii - contains functional thyroid tsu, so can cause hyperthyroidism.
Ovarian germ cell tumor
Sheets of uniform cells
Tumor markers: hCG and LDH
Equivalent to male seminoma (but more rare)
Ovarian germ cell tumor
Malignant, but rare.
Large hyperchromatic synctiotrophoblastic cells- this is a placental cancer.
Tumor marker: hCG
Develops in pregnancy either in mother or fetus.
Increased freq of theca-lutein cysts (which are d/t increased B-hCG)
This is a gestational trophoblastic neoplasia (as are moles)
Yolk sac tumor (endodermal sinus tumor)
Ovarian germ cell tumor (or testes in boys)
Tumor marker: AFP
Occurs in kids
Can also be sacrococcygeal area.
Yellow, friable, solid masses
50% have Schiller-Duval bodies (resemble glomeruli bc they are blood vessels enveloped by germ cells)
What ovarian germ cell tumor has LDH as a tumor marker?
Dysgerminoma (LDH and hCG)
What ovarian germ cell tumors have AFP as a tumor marker?
Yolk sac tumors
aka endodermal sinus tumors
What ovarian germ cell tumors have hCG as a tumor marker?
Dysgerminoma has both hCG and LDH.
List the stromal/sex cord ovarian tumors
Granulosa-Theca cell tumor
Sertoli-Leydig cell tumor
Granulosa cell tumor (granulosa-theca cell tumor)
Stromal ovarian tumor
Causes precocious puberty in kids bc of the estrogen
Can cause endometrial hyperplasia or carcinoma in adults.
Classic: Call-Exner bodies(!!)- small follicles filled w eosinophilic secretions.
Abn uterine bleeding.
Sertoli-Leydig cell tumor (of the ovary)
Stromal ovarian tumor.
Tumor of the ovary with high androgens, causes hirsutism (and sometimes even virilism)
Stromal ovarian tumor
Bundles of spindle-shaped fibroblasts.
Meigs' syndrome = triad:
1 ovarian fibroma
3 hydrothorax (pleural effusion)
Have a pulling sensation in groin