Gynecology (Tony's) Flashcards
Sex determination
Chromosomal sex determined at conception (XX, XY)
Sex differentiation
Development of male or female urogenital system which involves sex and autosome chromosome genes
Genotypic/primary sex differentiation - development of gonads
Phenotypic/seconday sex differentiation is development of the urogenital system
Male sex differentiation
Y chromosome contains SRY (sex determining region) gene, which encodes TDF (testis-determining factor)
TDF initiates cascade of downstream events to develop male urogenital system (mullerian inhibiting substance (MIS) + testosterone to develop male urogenital system)
Female sex differentiation
Default pathway is female (absence of SRY gene)
Development of the ovaries
- Gonadal ridges in the mesoderm
- Primordial germ cells develop in endoderm of yolk sac and migrate via dorsal mesentary to invade the genital ridges
- Celoemic epithelium gives rise to primitive sex chords, which penetrate the underlying mesenchyme
- In male develop into testis (primitive sex chords develop to form seminiferous tubules and tunica albuginea thickens)
- In female develop into ovaries (primitive sex chords develop to form medulla of ovary and tunica albuginea disappears) and surface epithlium gives rise to secondary sex cords (become follicular cells)
Descent of ovaries location and support
Ovaries move inferiorly and settle just below the rim of the true pelvis.
The superior (cranial) genital ligament forms the suspensory ligament of ovary.
The inferior (caudal) genital ligament (aka gubernaculum) forms the ovarian ligament and round ligament of uterus
Genital duct development
- Indifferent stage - mesonephron (Wolfian) duct develops if male and paramesonephric (Muellerian) duct develops if female
- Sex differentiation of genital duct
MIS and testosterone presence or absence
Role of testosterone in the differentiation of the genital duct
Testosterone stimulates development of mesonephric duct and stimulates development of male external genitalia
Absence results in disintegration of mesonephric duct and development of female external genitalia (labia majora, labia, minora, clitoris and lower 2/3 vagina)
Role of MIS in sex differentiation of genital duct
MIS - inhibits development and stimulates disintegration of paramesonephric duct which develops into uterine tube, uterus and superior part of vagina
Formation of uterus
Bilateral paramesonephric ducts fuse at the distal end to become uterus and superior part of vagina and septae eventually disappears
Formation of vagina
Dual origin where the superior part is derived from paramesonephric duct and the inferior part is derived from urogenital sinus
What are the components that make up the pelvic brim
- Sacral promontory
- Margin of sacral ala
- Arcuate line of ilium
- Pectineal line
- Pubic crest
What is the pelvic outlet
plane bounded by tip of coccyx posteriorly; sacrotuberous ligament posteriolaterally; ischial tuberosities laterally; ischiopubic rami and pubic symphysis anteriorly
What is the pelvic diaphragm and its components
Funnel shaped muscular floor composed of floor of lesser (true) pelvis and roof of perineum
Made by coccyges and levator ani (pubococcygeus, iliococcygeus) muscles
What is the pelvic brim
Divides the superior greater (false) pelvis and inferior lesser (true) pelvis
What are the conjugate measurements of the pelvis
Anatomical (true) conjugate
Obstetric conjugate
Diagonal conjugate
True conjugate
Distance from sacral promontory to superior aspect of pubic symphysis
Obstetric conjugate
distance from sacral promontory to most posterior aspect of pubic symphysis
Diagonal conjugate
distance from sacral promontory to inferior aspect of pubic symphysis
What is the transverse diameter of pelvic outlet
distance between ischial tuberosities (10-11cm)
What is interspinous diameter
distance between ischial spines
What penetrates the pelvic diaphragm
Urethra, vagina, rectum
What is the role of the medial fibers of levator ani (part of pubococcygeus)
Forms sling around rectum (puborectalis)
What is the role of the pelvic diaphragm
supports pelvic viscera, contribute to fecal / urinary continence
What is a lateral episiotomy
Controlled incision of pelvic diaphragm
Pelvic diaphragm compromise and consequences
due to damage during childbirth in female or prostatectomy in males, increasing risk of organ prolapse
in female, primary uterus and bladder prolapse
organ prolapse lead to urinary and fecal incontinence in both genders
Where does the coccygeus muscle run
Inside aspect of sacrospinous ligament
What is the levator plate
pubococcygeus and iliococcygeal muscle form shelf like portion of pelvic floor behind the anus
What is the Pouch of Douglas and its significance
Rectouterine pouch where pus and fluid collects, which can be drained through posterior fornix
Components of broad ligament
Mesoosalpinx
Mesometrium
Mesovarium
What forms the broad ligament of the uterus
Peritoneum drapes over the uterus, uterine tube and ovary superiorly
What is the parametrium
Covering that separates the uterus from the bladder
Pubocervical ligament role
Fascial ligament that anchors side of cervix to pubic symphysis
What are the uterine fascial ligaments
Deep - underneath the broad ligament (peritoneum) that support the position of the uterus
Part of the parametrium
Pubocervical ligament, transverse cervical ligament, uterosacral ligament
Pubocervical ligament
Anchor side of cervix to pubic symphysis
Transverse cervical ligament
aka Mackenrodt or transverse cardinal ligament
Provides central cervical support and carries the uterine artery
Ureter inferior to the transverse cervical ligament/uterine artery
Uterosacral ligament
Anchor cervix posteriorly to sacrum
Ovarian ligament role
Tethers ovary to uterus
Round ligament role
Tethers uterus through inguinal canal to labia majora
What is the isthmus
Initial narrowing from body of uterus to cervix
Layers of uterus
4 layers from superficial to deep
1) Parametrium - supporting fibrous fascia (transverse cardinal/cervical ligament, uterosacral ligament, pubovesical ligament)
2) Perimetrium - peritoneal coat overlying uterus, continuous with mesometrium of broad ligament
3) Myometrium - smooth muscle
4) Endometrium - internal mucosa
What is the angle of version of the uterus
Angle between vaginal and cervical axis
What is the angle of flexion of the uterus
Angle between uterine body axis and cervical axis
What is the most common orientation of the uterus
Anteverted and anteflexed
Components of the uterine tubes
Infundibulum –> ampulla –> isthmus –> intrauterine part –> horns of uterus
Where are the ovaries located
Ovarian fossa, medial to external iliac vessel and anterior to ureter and internal iliac artery
What are located at the vaginal uterine junction
4 vaginal fornices - 1 anterior, 1 posterior, 2 lateral
What is the suspensory ligament of ovary
Mesentery overlying ovarian artery and ovarian vein
Ovarian blood supply and drainage
Ovarian artery from abdominal aorta
Ovarian vein drains into IVC
Uterine blood supply and drainage
Uterine artery from internal iliac artery
Uterine vein drains into internal iliac vein
Vaginal blood supply and drainage
Vaginal artery from internal iliac artery and internal pudendal artery from internal iliac artery (feeds distal vaginal canal in perineum)
Vaginal and internal pudendal veins drain into internal iliac vein
Pelvic blood supply
Internal iliac artery with anterior and posterior division
Anterior - supplies pelvic viscera
Anterior division includes umbilical artery, superior vesicle artery, uterine artery, vaginal or inferior vesicle artery and middle rectal artery and internal pudendal artery
Posterior division goes to body wall, lower limb muscles, perineum
Uterine artery
Pass above ureter
Tortuous
Runs in transverse cardinal ligament
Superior vesicle artery
Feeds superior aspect of bladder and comes off umbilical artery
Vaginal/inferior vesicle artery
Feeds inferior aspect of bladder and superior vagina
Middle rectal artery
Feeds rectum above pelvic diaphragm
Internal pudendal artery
Feeds distal rectum and vagina in perineum
Inferior rectal artery
Feeds rectum below pelvic diaphragm
Innervation of female reproductive organs
Ovaries, uterus, superior vagina innervated by autonomic nerve supply
Sympathetic T12-L2 to pelvic splanchnics
- Synapse at pre-vertebral ganglia or abdominal aortic plexus –> travel with ovarian blood vessels to ovary
- hypogastric/pelvic plexus to uterus and superior vagina
Parasympathetic pelvic splanchnics S2-S4
Distal vagina somatic nerve supply
Motor nerves and sensory innervation from pudendal nerve (S2-4)
What is a splanchnic nerve
splanchnic nerves are paired visceral nerves (nerves that contribute to the innervation of the internal organs), carrying fibers of the autonomic nervous system (visceral efferent fibers) as well as sensory fibers from the organs (visceral afferent fibers).
Visceral pain of the pelvic region
Uterine body above pelvic pain line - visceral pain travels with sympathetics to T12-L2 region
Uterine cervix and upper vagina below pelvic pain line - visceral pain travels with parasympathetic to S2-4
Low vagina travels with somatic pudendal nerve S2-4
Anesthesia blocks for the reproductive system
Spinal block - block lumbar splanchnic nerve (T12-L2), pelvic splanchnic nerve (S2-4) and pudendal nerve (S2-4) blocking all sensation from waist down
Caudal epidural block from pelvic splanchnic (S2-4) and pudendal nerve S2-4 results in loss of sensation of uterine cervix and vagina
Pudendal nerve block of pudendal nerve S2-4 results in loss of somatic sensation of vagina only
Lymphatic drainage of female reproductive system
Most lymph to back body wall to chyle cistern to thoracic duct
Lymph from distal vagina, labia majora and perineum drains superficially to superficial inguinal lymph nodes
Some parts of uterus associated with round ligament can drain to superficial inguinal lymph nodes
Branches of internal iliac artery supplying body wall
Middle sacral artery - midline sacrum, from aorta prior to bifurcation
Lateral sacral artery - feeds sacrum from lateral aspect
Iliolumbar artery - ascends on back body wall
Superior gluteal artery - leaves pelvis above the piriformis between lumbosacral trunk and S1
Inferior gluteal artery - leaves pelvis below piriformis
Internal pudendal artery - leaves pelvis, loops around pelvic diaphragm to access perineum
Obturator artery - travels with obturator nerve through obturator canal
Umbilical artery - obliterated artery that gives off superior vesicle artery prior to becoming occluded
Anterior branching of internal iliac from proximal to distal
- Superior vesicle artery
- Uterine artery
- Inferior vesicle/vaginal artery
- Middle rectal artery
- Internal pudendal artery (penetrates pelvic diaphragm to access perineum)
- Inferior rectal (can alternatively branch off internal pudendal artery)
Hypothalamus Pituitary Ovary Axis
- Hypothalamus secretes GnRH in pulsatilla manner
- GnRH stimulates anterior pituitary to secrete FSH and LH in pulsation fashion
- FSH and LH stimulate ovaries to produce estrogen and progesterone as well as ovulation
Affect of GnRH on LH or FSH secretion
- amplitude and frequency of pulses determines predominant LH or FSH secretion by anterior pituitary
- Follicular phase: GnRH pulses become faster to prepare for the future LH surge and high LH in literal phase
- In literal phase pulses become slower to prepare for future high FSH in follicular
GnRH release regulation
3 negative feedback loops
- Long loop - estrogen and progesterone decrease release
- Short loop - FSH and LH decrease GnRH release
- Ultra short loop - GnRH inhibits its own release
Role of FSH
Targets granulosa cells in ovary causing follicular growth and estrogen production
Role of LH
LH surge stimulates ovulation
LH targets theca cells and corpus luteum
LH stimulate thecca cells to produce testosterone, which can be converted to estrogen by granulosa cells
LH stimulates corpus luteum to produce progesterone as well as estrogen
What’s the deal with estrogen and progesterone levels
Estrogen and progesterone are sex steroid hormone derived from cholesterol and produced in ovarian follicles
Estrogen level varies depending on stage of menstrual cycle
Low (<50) at menstruation
Increases with follicular development and peaks at 200
At end of literal phase, estrogen drops to menstrual levels
Progesterone level varies depending on stage of menstrual cycle
Low <2 before ovulation and high >5 after ovulation
Anatomy of the ovary
Enclosed in germinal epithelium
Outer cortex contains follicles, corpora lutes and corpora albicans
Inner medulla composed of connective tissue where blood vessels, lymph vessels and nerves enter the ovaries
Ovary functions
- Produce oocytes that are ovulated into Fallopian tube
2. Produce reproductive hormones including estrogen and progesterone
Sex hormone production pathway and where each sex hormone is produced
Cholesterol —> progesterone —> testosterone —> estrogen
Progesterone produced in all major ovarian cells (granulosa, theca, interstitial, corpus luteum)
Testosterone produced in theca, interstitial and corpus luteum
Estrogen produced by granulosa cells and corpus luteum
What is required to produce estrogen
Aromatase (lacking in the a cells)
Role of estrogen
Stimulate follicular development and onset of puberty
Main estrogen produced by ovary
Estradiol
Main estrogen produced by placenta
Estratriol
Main estrogen produced by adipose tissue
Estratone
What is the role of the estrogen to testosterone ratio in follicles
Determines the dominant follicle
Non-dominant follicles - inability to convert T to E leading to more androgen and follicular atresia
Dominant follicle - ability to convert
Regulation of FSH secretion
- Activism from granulosa cells stimulates FSH secretion
- Inhibin from granulosa cells inhibits FSH secretion
- Follistatin from granulosa cells neutralizes activism, thereby inhibiting FSH secretion
Oogenesis pathway
1) ovarian germ cells (oogonia) multiplies by mitosis until ~20 weeks gestation
2) at birth, oogonia (2n) enter meiosis I and arrest in prophase, becoming primary oocyte (2n) in a primordial follicle
3) at start of each menstrual cycle ~15-20 primordial follicles are recruited and develop into primary follicles, which is independent of FSH
4) during follicular phase, primary follicles develop into secondary, then one follicle will mature into tertiary follicle
5) before ovulation, LH surge allows primary oocyte (2n) to complete meiosis 1, becoming secondary oocyte (1n) that is halted in meiosis 2 metaphase plus 1st polar body 6) at ovulation, secondary oocyte (1n) exits ovaries and enters fallopian tubes
7) if ovulated secondary oocyte (1n) is fertilized with sperm, then secondary oocyte completes meiosis 2 to become an ovum, which joins sperm to form zygote
Menstrual cycle goal
goal of menstrual cycle is to produce a single, mature, fertilizable oocyte as well as provide right environment for it to implant and develop
Components/phases of menstrual cycle
2 cycles: ovarian and endometrial cycle
normal menstrual cycle usually 28 days
endometrial cycle
- day ~1-5 menstruation, part of proliferative phase
- day ~6-13 proliferative phase
- day 15-28 secretory phase
ovarian cycle
- day ~1-13 follicular phase 2. day ~14 ovulation
- day ~15-28 luteal phase
during menstrual cycle, female is fertile from ovulation day -3 days to ovulation +1 day
-3 days, because sperm can live in fallopian tube for 3 days
+1 day, because ovulated ovum is viable for ~1 day
length of follicular phase may vary, but length of luteal phase should be fixed at ~14 dayS
What occurs during the Follicular Stages
0) all follicles begin as primordial follicle
primordial follicle = oocyte surrounded by layer of flattened granulosa (follicular) cells
ovary start with all of its primordial follicles at birth, which then slowly depletes over time
primordial follicle contain a primary oocyte (2n) (primary oocyte are arrested at meiosis I prophase)
1) primordial follicles will develop into primary follicle, then secondary follicle
development from primordial follicle to secondary follicle is gonadotropin (LH & FSH) independent and occurs with time at any time, only a small portion of primordial follicles are developing to become primary follicle then secondary follicle
primary follicle result in:
- larger primary oocyte with a zona pellucida
- granulosa cells proliferating forming layers around oocyte
- interstitial cells close to growing follicles form the theca cells
2) under high FSH and high LH in follicular phase, a secondary follicle develops into tertiary (Graafian or astral or pre-ovulatory) follicle
high FSH stimulates many primary follicles to start development to secondary follicles
the fastest primary follicle that develops into secondary follicle at first becomes the dominant follicle
dominant follicle increase production of estrogen, that inhibit FSH, such that rest of the developing primary follicles die
non-dominant follicles also cannot convert testosterone into estrogen resulting in high testosterone that stimulates follicular atresia dominant follicle further increase estrogen that trigger LH surge
FSH stimulates proliferation, production of estrogen, increased FSH receptor and inhibin production in granulosa cells LH stimulates testosterone from theca cells, which then is converted to estrogen by granulosa cells
secondary follicle has
-formation of antrum, cumulus granulosa cells (surrounding oocyte) and mural granulosa cells (in the periphery)
-growth of granulosa and theca cell compartments
-increased vascularization of theca layer
-still a primary oocyte
FSH with high estrogen increase expression of LH receptor on granulosa cells, preparing the peripheral granulosa cells to become corpus luteum that is responsive to LH
3) LH surge result in ovulation
the high estrogen (>200) by dominant tertiary follicle cause LH surge
LH stimulates the primary oocyte (2n) to complete meiosis I to become a secondary oocyte (1n)
LH stimulates progesterone production by granulosa cells
LH surge results in ovulation of the tertiary oocyte into fallopian tube by increasing antral fluid and stimulating release of hydrolytic enzymes
the secondary oocyte with corona radiata granulosa cells are released into peritoneal cavity to be picked up into fallopian tube
the rest of follicle (peripheral granulosa and theca cell layers) remains in follicle and become vascularized with capillaries to become corpus luteum
4) corpus luteum forms and produce progesterone and estrogen in luteal phase corpus hemorrhagim -> corpus luteum -> corpus albicans
corpus luteum secretes progesterone and estrogen
corpus luteum contains large luteal cells (granulosa cell derived) and small luteal cells (theca cell derived) that produce progesterone and testosterone the high progesterone increases basal body temperature during luteal phase
corpus luteum is temporary (lasts 14 days) and will disintegrate into corpus albicans due to decline in LH
release of HCG from fertilization and implantation can rescue corpus luteum, which is them taken over by placenta after 4-5 months
What occurs during Endometrium stages
1) menstruation at day 0-5 due to low estrogen and progesterone progesterone withdrawal results in shedding of endometrium
2) proliferative phase at day 5-14 due to high estrogen
follicles produce high estrogen, which stimulate proliferation of endometrial cells increasing endometrial thickness
3) secretory phase at day 14-28 due to high progesterone
corpus luteum secrete high progesterone, which cause endometrial hypertrophy, thickening of spiral arteries and glycogen secretions from glands endometrium is thickest at secretory phase
the endometrium at secretory phase is optimal for implantation
endometrium most optimal for implantation about ovulation + 7 days
4) return to menstruation
disintegration of corpus luteum result in low estrogen and progesterone, causing endometrium to shed progesterone withdrawal is mainly responsible for normal menstrual bleeding
Mechanism of action of OCP
4 MOA by progesterone:
- Inhibiting ovulation (main mechanism)
- Change cervical mucous which blocks sperm
- Cause pseudo decidualization of endometrium to inhibit implantation
- Inhibit tubal peristalsis to inhibit fertilization
Role of estrogen in OCP
Estrogen does not contribute to mechanisms of contraception and is added to prevent breakthrough bleeding
OCP start methods
1) start on 1st Sunday after menses to have period free weekends
2) start on day 1 of that month
3) quick start ASAP (recommended)
Disadvantage to extending hormone days and/or shortening hormone free days with OCP
Can cause unscheduled bleeding
OCP schedule
Any change to traditional 21/7 regimen is reasonable as long as there is no more than 7 days without hormones
Absolute contraindications to OCP, ring and patch
smoker (>15 cigarettes / day) and over age 35
<6 weeks postpartum if breastfeeding
history of current or past venous thromboembolism (VTE)
current breast cancer
uncontrolled hypertension (diastolic >100 or systolic >160)
ischemic heart disease
complicated valvular heart disease
history of cerebral vascular accident (CVA) aka stroke
migraine headache with focal neurological symptoms
over age of 35 and migraine without aura (i.e. focal neurological symptoms)
diabetes with end organ involvement
severe cirrhosis, liver tumor, or active viral hepatitis
known thrombophilia
systemic lupus erythematous (SLE) with positive anti-phospholipid antibody (APLA)
False contraindication
OCP can be prescribed to anyone with family history of cancer
OCP can be prescribed without a pelvic exam
Benefits of OCP, ring and patch
Short term benefits
- regulation of cycle
- decreased bleeding
- decreased dysmenorrhea, premenstual syndrome, acne, hirsutism
Long term benefit
- decrease risk of endometrial and ovarian cancer
- decrease risk of benign breast disease
- decrease risk of colorectal cancer
- decrease risk of acute PID and ectopic pregnancy
- dec risk of ovarian cyst
- amerliorate endometriosis
OCP, ring and patch contraceptive adverse effects
most women using OCP report no adverse effects
common adverse effects: headache, nausea, breast tenderness
usually mild, transient and self resolves in few months
less common adverse effects: decreased libido, unscheduled bleeding, mood changes
rare adverse effects: stroke, MI, VTE, increased risk of cervical cancer
Where should the contraceptive patch not be applied
Breast
When starting a new method of contraception what is the period duration where backup contraception should be used
7 days
Forgiveness period for contraceptive patch
2 days
Nuvaring forgiveness period
2 weeks
Progestin only pill mechanism of action
Thickening of cervical mucous to block sperm
Progestin only pill indication
When combined hormone contraceptive is contraindicated such as breastfeeding women, women with VTE
Use of progestin only pill
1 pill every day at same time (3 hour window) with no sugar pill week
Back up contracceptive x2 days if pill was taken late
Menstruation continues if baseline mensturation is regular
Progestin only adverse effects
Irregular bleeding
Worsening mood disorder such as depression
DMPA injectable progestin mechanism of action
1) inhibit ovulation
2) thickening of cervical mucus to block sperm
3) pseudo-decidualization (atophy) of endometrium that inhibit implantation
Use of injectable progestin DMPA
Intramuscular injection once every 3 months
breakthrough bleeding in first 3-6 months is normal, which usually can be treated with estrogen or NSAID, and can be ameliorated by shorter interval of injection
2 week forgiveness, where injection is still effective up to 14 weeks
if >14 weeks since last injection, do urine pregnancy test to rule out pregnancy, give injection and use back up contraception for 7 days
Absolute contraindication
known or suspected pregnancy (progesterone is not a teratogen, but pregnancy would make injectable progestin meaningless)
unexplained vaginal bleeding
current diagnosis of breast cancer
DMPA adverse effects
menstrual cycle disturbance including irregular non-stop bleeding or amenorrhea especially in first 3 months of use
after 1 year of use, ~50% develop amenorrhea
after 2 years of use, ~75% develop amenorrhea
weight gain due to increased appetite
decreased bone density
delay to fertility: return to fertility after 9 months on average post discontinuation of injectable progestin
Benefits DMPA
injectable progestin also used to treat menorrhagia, dysmenorrhea, endometriosis, chronic pelvic pain
menstrual suppression, inducing amenorrhea to treat menses-related symptoms, anemia and hygienic concerns
decrease risk of ovarian and endometrial cancer
decrease incidence of seizure
IUD contraindication
known or suspected pregnancy puerperal sepsis (infection and fever post childbirth or miscarriage) immediate post septic abortion current pelvic inflammatory disease, purulent cervicitis, chlamydia, gonorrhea cervical or endometrial cancer current breast cancer unexplained vaginal bleeding distorted uterine cavity anatomy malignant trophoblastic disease
Adverse effects of IUD
unscheduled vaginal bleeding, which usually improve with time
LNG-IUS tend to decrease menstrual bleeding
copper IUD tend to increase menstrual bleeding
pain or dysmenorrhea
uterine perforation (0.1% risk)
infection (relative risk of 4 in first 3 weeks after insertion then return to normal baseline)
expulsion of device (5% of cases)
failure resulting in pregnancy, which may have increased risk of ectopic pregnancy
LNG-IUD cause hormonal side effects and functional ovarian cyst
What is the minimum beta hCG to see something in the uterus
1500
Copper IUD MOA
Main mechanism is prevention of fertilization
Other mechanisms:
foreign body reaction
endometrial change that adversely affects sperm transport
copper directly inhibits sperm motility and reduces sperm penetration through cervical mucous
inhibits implantation
Mirena (LNG-IUS) components
Progesterone
Mirena MOA
main mechanism of action is prevention of fertilization
other mechanisms of action include
thickening of cervical mucus by progesterone to block sperm
suppress endometrial estrogen and progestin receptor
inhibit ovulation by progesterone in some women
inhibit implantation
induce endometrial changes
LNG IUS indications
Contraception 3-5 years
Treat heavy menstrual bleeding
Male Vasectomy confirmation
need to use contraception for 3 months after operation and until 2 consecutive semen analysis confirms azospermia
What’s the deal with hysteroscopic tubal occlusion
insertion of alloy coil into fallopian tube via hysteroscope, which induce fibrosis and occlusion in Fallopian tube
need to do hysteosalpingography radiographic imaging to confirm tubal occlusion
must use contraception until occlusion is confirmed
complications include failure to successfully place, perforation of fallopian tube / uterus and expulsion of coil
Emergency contraception methods
Yuzpe method (estrogen + progesterone)
Plan B/Norlevo (Progestin only)
Copper IUD
Most effect emergency contraception method
Most effective emergency contraception (effective up to 7 days post unprotected sex exposure)
Then plan B then Yuzpe
Plan B/Norlevo components
Protesterone only
Plan B MOA
inhibit ovulation
change endometrium to inhibit implantation
disrupt luteal phase
effect on tubal transport time
however, does not disrupt an established pregnancy, so it is not effective with more time elapsed from sexual intercourse
Use of Plan B
earlier use increase effectiveness, best within 5 days of unprotected sexual intercourse
plan B have 2 tablets
both tablets at same time (preferred method) or one table followed by the other 12 hours later
Amenorrhea definition
absence of menstruation for at least 3 cyclic lengths
Oligomenorrhea definition
Cyclic length >35 days
Primary amenorrhea definition
failure to reach menarche (amenorrhea and no pubertal development by 14 years of age; or amenorrhea with secondary sexual characteristics by age 16)
Secondary amenorrhea definition
previously menstruating and cessation of menses (cessation of regular menses for 3 normal menstrual cycles or 6 months), typically in patient age <40
Major cause of amenorrhea
causes can be classified to physiologic, other endocrinopathies, medication, hypothalamus - pituitary - ovary - uterus - outflow tract
physiologic: pregnancy, breast feeding, menopause
other endocrinopathies: thyroid disease (hypothyroidism, hyperthyroidism), adrenal disease (adrenal insufficiency, adrenal hyperplasia), hyper-androgenism (congenital adrenal
hyperplasia, androgen secreting tumor), Cushing’s syndrome, constitutional delay of puberty
medication: contraception containing estrogen and / or progesterone, anti-depressants, anti-hypertensive, anti-psychotics, opiates
hypothalamus: hypothalamic tumor, functional suppression of hypothalamus, gonadotropin releasing hormone (GnRH) deficiency, infection (meningitis, TB, syphilis), traumatic
brain injury
functional suppression of hypothalamus-pituitary-varian axis due to physical stress on body including rapid weight loss, eating disorder, malabsorption, excessive
exercise, stress
pituitary: tumor (prolactinoma), empty sella syndrome, infiltrative disease (sarcoidosis), post-partum hypopituitarism (Sheehan syndrome)
ovary: polycystic ovary syndrome, ovarian insufficiency, ovarian insufficiency, ovarian tumor
ovarian insufficiency can be due to idiopathic causes, auto-immune destruction, chemotherapy, radiation, congenital causes (Turner’s syndrome, gonadal dysgenesis)
outflow tract obstruction: congenital (complete androgen resistance, imperforate hymen, Mullerian agenesis, transverse vaginal septum), acquired (Asherman syndrome, cervical
stenosis)
Amenorrhea history
HPI
menstruation history: onset of amenorrhea, previous menses if any (primary vs. secondary), previous menstrual cycle (length, pattern, consistency of pattern)
hypothalamus / pituitary tumor symptoms: headache, loss of vision, vomiting, galactorrhea
thyroid symptoms: temperature, heart rate, bowel movement
symptoms of androgen excess: acne, hirsutism, hair thinning, deepening of voice
primary ovarian insufficiency: vasomotor symptoms (hot flush, night sweats)
hyperandrogenism: acne, hirsutism
uterine or outflow tract obstruction symptoms: cyclic or acute pelvic pain
PMH
thyroid disease
surgery, radiation, chemotherapy
OB/GYN History
GTPAL
past sexually transmitted infections
OB/GYN surgery
Medication
contraception
dopamine antagonist including psychiatric medications
FH
age at menarche for mom and sisters
family history of genetic syndrome, autoimmune disease
SH
eating and exercise pattern
change in weight
sexual history
Amenorrhea physical exam
general: height, weight, BMI, inspection for dysmorphic feature (Turner’s syndrome)
Tanner staging
skin: inspect for hyperandrogenism (hirsutism, acne, male pattern hair loss), striae (Cushing’s syndrome)
head & neck: vision test (pituitary tumor), thyroid exam
abdomen: palpation for mass (ovarian or adrenal tumor)
genital: inspection for outflow tract obstruction, missing or malformed organ, thin vaginal mucosa (low estrogen), virilization (clitoral enlargement)
Amenorrhea investigations
blood work: CBC, b-hCG, LH, FSH, prolactin, TSH, serum estrodiol
pelvic ultrasound to rule out abnormal anatomy
Progesterone withdrawal challenge
Other: if estrogen not evidence from physical exam (normal vaginal discharge suggest normal estrogen level), then measure serum estradiol
if chronic disease suspected, CBC and metabolic panel
if history or physical exam suggest hyper-androgen, then serum testosterone
if Turner’s syndrome suspected, chromosome karyotype
if hypothalamus or pituitary cause suspected, then MRI head
Progesterone withdrawal challenge
not routinely done, because it can be substituted with estradiol (E2) to measure estrogen and pelvic ultrasound to measure outflow tract
progesterone for course of 10 days then stop to simulate luteal phase and see if bleeding ensues after withdrawal
withdrawal bleeding confirms adequate estrogen production and functional anatomy (responsive endometrium and patent outflow tract)
failure to bleed on progesterone withdrawal can be due to low estrogen from ovary, hypothalamic pituitary dysfunction, non-reactive endometrium, no uterus or anatomical
abnormality with uterine outflow tract
if failure to bleed, give estrogen then progesterone
failure to bleed with estrogen then progesterone confirms anatomic abnormality
bleeding with estrogen and progesterone confirms low estrogen, which need to be worked up to see if it is due to ovarian insufficiency or hypothalamic or pituitary disorder
Amenorrhea treatment
treatment always should address underlying cause
primary amenorrhea with no internal female reproductive organ usually have no viable treatment
pituitary dysfunction: symptom relief with estrogen and progesterone replacement (e.g. oral contraceptive pill), LH & FSH injection for fertility
hypothalamus dysfunction: if functional hypothalamic suppression, then need to correct underlying cause, otherwise symptom relief with estrogen and progesterone replacement
pituitary or hypothalamus tumor: consider surgical resection, LH & FSH injection for fertility
ovarian dysfunction: symptom relief with estrogen and progesterone replacement (e.g. oral contraceptive pill), egg donor and in-vitro fertilization for fertility
obstructive tract should be treated with surgical repair
other endocrinopathy: address and treat endocrinopathy (e.g. thyroid replacement for hypothyroidism)
Primary amenorrhea top differential diagnoses
Chromosomal abnormalities leading to primary ovarian insufficiency - Turner’s syndrome, Fragile X syndrome
Other genetic conditions - androgen insensitivity, congenital adrenal hyperplasia
Anatomic abnormalities - Mullerian agenesis
Constitutional delay
Primary amenorrhea with normal breast development - androgen insensitivity syndrome, Mullerian agenesis, Mullerian uterine septum
Pathophysiology amenorrhea due to Turner’s syndrome
45 X lacking 1 X chromosome
Pathophysiology amenorrhea due to fragile X syndrome
abnormal X chromosome
Androgen insensitivity
46XY karyotype with androgen receptor defect leading to female external genitalia, no uterus, no cervix, no fallopian tube, little hair growth
Normal functioning testes secreting normal male testosterone
Pathophysiology amenorrhea due to congenital adrenal hyperplasia
Excessive androgen production leading to anovulation
Pathophysiology amenorrhea due to Mullerian agenesis
46XX karyotype, female phenotype, no uterus, no cervix, no fallopian tube
Normal ovaries
Approach to primary amenorrhea
- History and physical
Growth curve, wrist xray for bone age
If normal growth and delayed wrist xray with normal work up then constitutional delay - TSH - fu with thyroid hormone
Prolactin - MRI of head
bhCG - Further tests depend on presence of uterus on u/s
- No uterus suggests genetic syndrome (fu with karyotype and testosterone)
46XX with female range testosterone is Mullerian agenesis
46XY with male range testosterone is androgen insensitivity
- Normal uterus base diagnosis on FSH level
High FSH suggests primary ovarian insufficiency (repeat in 1 month to diagnose with POI, order karyotype to evaluate Turner or presence of Y chromatin, test for fragile X)
Low FSH can be physiologic (functional amenorrhea, constitutional delay) or pathologic (MRI) hypothalamus pituitary disorder
Normal FSH can be due to ovarian tumour, adrenal tumour or congenital adrenal hyperplasia - High 17-OH-progesterone =CAH
- High testosterone =u/s for ovarian tumour
- High DHEAS = adrenal imaging for tumour
- Normal testosterone and DHEA consider PCOS
How do adrenal tumours cause amenorrhea
Glucocorticoid secreting tumours likely secrete cortisol, which suppresses GnRH production
Secondary amenorrhea top differential
Hypothalamic - eating disorder, stress
Pituitary - prolactinoma
Thyroid - hypothyroidism
Ovary - PCOS, POI
Approach to secondary amenorrhea
- History and physical - review medications including contraceptive and illicit drugs
- TSH (thyroid hormone if abnormal), prolactin (MRI if abnormal)
- Further tests depend on level of FSH
a) high FSH suggests POI
Repeat in 1 month, measure serum estradiol, order karyotype to rule out Turner’s syndrome
b) Normal or low FSH/LH
Functional amenorrhea
MRI head to rule out hypothalamus/pituitary abnormality if h/a, vomiting, vision changes
Hx OB/GYN procedure do withdrawal bleed or hysteroscopy to evaluate for Asherman’s syndrome
Signs of hyperandrogenism (virilization such as hirsutism, acne, hair thinning, enlarged clitoris) - order serum testosterone (high PCOS, very high or rapid onset imaging for adrenal and ovarian tumour), DHEA-S and 17-hydroxyprogesterone (CAH if very high)
Ovarian insufficiency is associated with
other autoimmune diseases
Ovarian insufficiency causes
90% are idiopathic
Chromosomal abnormalities
Environmental insult (chemo, radiation, infection, surgery)
Tumour
Empty sella syndrome
Autoimmune
Infiltrative process
Ovarian insufficiency pathophysiology
Inadequate follicles to sustain menses due to failure to form enough primordial follicles or accelerated loss of follicles or damage to follicle by autoimmunity or toxins
Ovarian insufficiency clinical presentation
Primary or secondary amenorrhea
Menses with cycle interval >90 days
Oligo-menorrhea (<9 cycles per year)
Investigations in ovarian insufficiency
Normal TSH, prolactin
Can have normal anatomy on ultrasound
Consistently high FSH and LH
Consistently low estradiol
Ovarian insufficiency diagnosis
Patient diagnosed with POI if patient meets all of criteria:
- Primary or secondary amenorrhea for 3 months or change from regular menstruation for 3 months
- High FSH>40 on 2 occasions a month apart
- Age <40
POI complications
Leads to low estrogen, resulting in increased risk of osteoporosis as well as atherosclerosis and its consequent cardiovascular diseases
POI lead to infertility
POI management
- Pre-pubertal POI
- slowly increasing estrogen for 2 years or until breakthrough bleeding
- then add progesterone to induce cyclic withdrawal bleed - Post puberty POI
Hormone therapy of estrogen for day 1-26 of menstrual cycle and progesterone for day 14-26 (OCP, patch, ring, copper + hormone replacement therapy, IUS + estrogen replacement therapy)
weight bearing exercise and calcium and vitamin D supplement to prevent osteoposrosis
BP, lipid monitoring to assess cardiovascular disease risk + diet, no smoking, exercise
Psychosocial support for patient to deal with infertility, but recommend contraceptive if not wanting to conceive because there is still 5% chance of spontaneous pregnancy
Consider egg/embryo donor or adoption if patient wants children
What is the purpose of estrogen replacement in post puberty POI
Prevent osteoporosis, CVD, vasomotor symptoms
Normal and abnormal duration menstruation
4-7 days
<2 days and >7 days is abnormal
Normal and abnormal volume menstrual flow
30 mL
>80 mL is abnormal
Normal and abnormal length of menstrual cycle
24-35 days is normal
<24 or >35 days is abnormal
Menorrhagia
regular normal interval with excessive volume >80mL and / or duration of flow (i.e. heavy menstrual bleeding) >7 days
Metrorrhagia
irregular intervals with normal or reduced volume and duration of flow (i.e. irregular menstrual bleeding)
Menometrorrhagia
irregular intervals and excessive volume and duration of flow (i.e. irregular heavy menstrual bleeding)
Polymenorrhea
cyclic length <24 days
Types of AUB
Menorrhagia Metrorrhagia Menometrorrhagia Polymenorrhea Post-menopausal bleeding Amenorrhea Oligomenorrhea
Dysmenorrhea
Pain with menstruation
What are some conditions that could mimic AUB
Vaginal bleeding
Hematuria
Hematochezia
AUB differential diagnosis during reproductive years
- Pregnancy and its complications
- Functional- Blood dyscrasia, hypothyroidism, luteal dysfunction
- Pathological (PALM COEIN)
Pathological causes of AUB for women in reproductive years
PALM - structural abnormalities
Polyps Adenomyosis Leiomyoma (ie fibroids) Malignancy Hyperplasia
Malignancy or hyperplasia = endometrial cancer, endometrial hyperplasia, cervical cancer
COEIN are non-structural abnormalities
Coagulopathy
Ovulatory dysfunction - all differential diagnosis for oligomenorrhea and amenorrhea
Endometrial dysfunction - endometrial hemostasis disorder, endometritis, abnormal local inflammatory response, abnormal vasculogenesis of endometrium
Iatrogenic - medications, IUD
Not yet classified (ie idiopathic)
Medications that can cause AUB in reproductive years
Hormone medication - androgen, estrogen, progesterone
Hormone related therapy medication - GnRH agonist, aromatase inhibitor, SERM, SPRM
Other medications: SSRI, TCA, anti-psychotics, corticosteroids, anti-platelet agents, anti-coagulants
How do structural abnormalities causing AUB generally present
(PALM)
Inter menstrual bleeding
Anovulatory or ovulatory AUB?
a) coagulopathy
b) iatrogenic
c) ovulatory dysfunction
d) endometrial dysfunction
a) either
b) either
c) anovulatory
d) ovulatory
Anovulatory AUB presentation
Unpredictable and irregular menstrual cycle with prolonged or heavy bleeding
Ovulatory AUB presentation
Predictable and cyclic menses with normal duration
Top things on differential for post-coital bleeding
Cervical dysplasia
Polyp
Approach to AUB in Pre-menopausal women
- Confirm uterus as source of bleeding
- Rule out pregnancy
- Rule out coagulopathy, ovulatory dysfunction, iatrogenic of COEIN
- Rule out structural causes (PALM) with TVUS, saline infusion sonography and hysteroscopy
- Determine if ovulatory or anovulatory based on history
Anovulatory consider endocrinopathy and follow route for oligomenorrhea/amenorrhea
Ovulatory consider endometrial dysfunction (workup with hysteroscopy and endometrial biopsy)
Approach to AUB in post-menopausal women
AUB in post-menopausal women is malignancy, likely endometrial cancer until proven otherwise
1) rule out cause due to medication including hormone replacement
2) rule out structural causes with endometrial biopsy, trans-vaginal ultrasound / saline infusion sonography and hysteroscopy
3) consider neoplasia elsewhere in vagina, cervix, fallopian tube, bladder / urethra and rectum
4) based on exclusion (no findings in previous steps), diagnose with post-menopausal AUB most likely due to endometrial / vaginal atrophy
General medication management for AUB
Medication is 1st line therapy if non-structural abnormality
Non-hormonal and/or hormonal for regular menorrhagia
Hormonal for irregular menorrhagia
Non-hormonal treatment of AUB
- Iron supplement
Indication - iron deficient anemia - NSAID
MOA - decrease blood loss by vasoconstriction
Indication - menorrhagia, pain relief for dysmenorrhea
Less effective than other forms of therapy - Anti-fibrinolytics TXA
MOA - inhibit plasminogen activator to decrease bleeding
Indication - menorrhagia
Contraindication - thromboembolism (DVT, PE)
Side effects - nausea, GI upset, leg cramps, retinal vascular occlusion
Hormonal treatment AUB
- Combined hormone (estrogen progestin) contraceptive
Indication - menorrhagia (regular or irregular), irregular menstrual cycle
Most prescribed treatment for AUB
MOA - progestin suppress ovulation and estrogen to support endometrium preventing breakthrough bleeding thereby decreasing blood loss (also regulate cycle, contraception, prevent hyperplasia and treat dysmenorrhea)
Contraindication - heavy smoking, DVT, stroke, uncontrolled hypertension, migraine with neurological symptom, breast cancer, CAD, liver disease - Progestin (oral, injection, IUS)
Indication - irregular menstrual cycle, menorrhagia (irregular or regular)
MOA - progestin inhibits ovarian steroid synthesis causing endometrial atrophy, decreasing blood loss, cyclical withdrawal can induce endometrial shedding
Oral progestin is not effective for regualr menorrhagia and less effective than NSAID and TXA
IUS decrease menstrual blood loss and decrease frequency of period, which is more effective than other progestin treatment and can treat dysmenorrhea - GnRH agonist (Lupron)
Indication - menorrhagia (regular or irregular), shrinkage of fibroid, dysmenorrhea
MOA: induce reversible menopause by inducing endometrial atrophy and amenorrhea
Side effects - menopausal symptoms (hot flash, mood fluctuation, vaginal dryness, bone effects)
Surgical management of AUB
Non structural - endometrial ablation or hysterectomy (definitive treatment)
Structural abnormality - specific surgical management
Medications that can cause vaginal bleeding
Contraception - hormone contraceptives, IUD
Post menopausal hormone therapy
Tamoxifen
Anti-coagulants
Corticosteroids
Chemotherapy
Phenytoin
Antipsychotic drugs
Life threatening causes of vaginal bleeding
Early pregnancy - ruptured ectopic, spontaneous abortion
Late pregnancy - placental abruption, placenta previa
Post-partum - PPH
Ovary - ruptured ovarian cyst - ovarian torsion
Uterus - acute severe menorrhagia
Trauma to genital tract, foreign body in genital trat
Infection to genital tract including PID, salpingitis
Gynecologic malignancies
Approach to vaginal bleeding
- Stabilize patient
- Rule out pregnancy
- Rule out bleeding source outside genital tract (urinary, GI)
- Rule out vulva, vagina, cervix causes on physical exam
- Consider ovarian, fallopian tube and uterus causes
Gynecologic emergencies that present with acute pelvic pain
Ectopic pregnanc
Ruptured ovarian cyst
Ovarian torsion
PID
What is the Ring of Fire sign indicative of on ultrasound
The ring of fire sign, also known as ring of vascularity, signifies a hypervascular lesion with peripheral vascularity on color or pulsed Doppler examination of the adnexa due to low impedance high diastolic flow 1.
This sign can be seen in:
corpus luteum cyst (more commonly)
ectopic pregnancy
What is the double sac sign indicative of on ultrasound
The double decidual sac sign (DDSS) is a useful feature on early pregnancy ultrasound to confirm an early intrauterine pregnancy (IUP) when the yolk sac or embryo is still not visualized. It consists of the decidua parietalis (lining the uterine cavity) and decidua capsularis (lining the gestational sac) and is seen as two concentric rings surrounding an anechoic gestational sac. Where the two adhere is the decidua basalis, and is the site of future placental formation.
What may be seen on ultrasound if a ruptured ovarian cyst is present
Ovarian cyst (thin wall, posterior acoustic enhancement, no blood flow)
Fluid in pouch of Douglas or Morrison’s pouch or LUQ
What is the Pouch of Douglas
An extension of the peritoneal cavity between the rectum and the back wall of the uterus. Also known as the rectouterine pouch
What is Morrison’s pouch
The hepatorenal recess (subhepatic recess, pouch of Morison or Morison’s pouch) is the space that separates the liver from the right kidney
What might you see on imaging with Ovarian Torsion
Enlarged ovary, ovarian mass, multiple small peripheral follicles (often in context of adnexal mass)
Abnormal ovarian location
Decreased/no Doppler flow in ovary
Ovarian torsion management
Immediate surgery to detorse viable ovary
Otherwise salpingoophorectomy for non-viable ovary
PID pathophysiology
Infection of upper genital tract structure (uterus, Fallopian tube, ovaries) by STI (commonly Gonorrhea or Chlamydia), which may cause endometritis, salpingitis, oophoritis, tubo-ovarian abscess, peritonitis, peri-hepatitis
PID clinical presentation
Pelvic pain (classifcally during or shortly after menses)
Vaginal discharge or bleeding
Dysuria
Fever, chills
PID management
Antibiotic therapy (ex. Ceftriaxone 250 mg IM single dose + Doxycycline 100 mg PO BID x 14 days)
Chronic pelvic pain definition
Pelvic pain below umbilicus for >6 months duration, which causes functional disability or requiring treatment
Risk factors of chronic pelvic pain
History of previous sexual abuse or assault in 20%
Red flags on hx and PE for chronic pelvic pain
- Constitutional symptoms
- GI symptoms - hematochezia
- ObGyn symptoms - peri menopausal irregular vaginal bleeding, post menopausal vaginal bleeding, post coital bleeding
Investigations for chronic pelvic pain
Blood work - beta-hCG (repeat in 48 h if positive), CBC, ESR
Vaginal swab for STI
Urinalysis r&M C&S for UTI or renal calculus
Chronic pelvic pain syndromes
- Pelvic pain dysfunction/chronic pelvic pain syndrome
- Vestibulitis vulvodynia syndrome
- Pelvic congestion syndrome
Pathophysiology of pelvic pain dysfunction/chronic pelvic pain syndrome
Idiopathic spasm of pelvic floor muscles (elevator ani)
Pelvic pain dysfunction/chronic pelvic pain syndrome symptoms
Pelvic pain out of proportion to pathology, dyspareunia, vaginismus (spasm of vagina), dysuria, dyschezia, pain elsewhere (back, lower abdomen, groin, leg)
Impact of pelvic pain dysfunction/chronic pelvic pain syndrome
Impaired function at home/work
Decreased libido -> decreased sexual activity
Signs of pelvic pain dysfunction/chronic pelvic pain syndrome
Tight, tender, band-like muscle in vagina and rectum
Symptoms Vestibulitis vulvodynia syndrome
Vulvar discomfort or pain
Dyspareunia (superficial —> deep)
Perineal burning or rawness
Urinary symptoms (urgency, frequency, dysuria)
Vestibulitis vulvodynia syndrome Signs
Erythema of Bartholine openings and hymen
Tenderness on q tip probe into vestibule, vaginismus and pelvic pain dysfunction
Pelvic congestion syndrome Risk factors
Multiparity
Sedentary lifestyle
Constipation
Sexual dissatisfaction
Pelvic congestion syndrome Pathophysiology
Pelvic vein varicosities
Pelvic congestion syndrome Symptoms
Dull aching pain in pelvis and lower abdomen aggravated by standing and relieved with lying down
May progress to dyspareunia, dysmenorrhea, back pain, vaginal discharge
Pelvic congestion syndrome Investigations
Us showing pelvic veinvaricosities
Non specific treatment of chronic pelvic pain
Medication -
Acetaminophen, NSAID, opioids
If cyclic consider combined OCP, progesterone oral, IM or IUS, GnRH agonist (Lupron), Danazol
If non-cyclic consider gabapentin or amitriptyline
Surgery - laparoscopy, lysis of severe adhesions, total abdominal hysterectomy for failed medical treatment
Special cases for pap tests
- Patients previously treated for cervical dysplasia - annual screening
- Immune compromised - annual screening
- Total hyserectomy including cervix for benign disease - none
- Visual cervical abnormality on speculum exam or abnormal symptoms - colposcopy regardless of pap test cytology findings
LSIL
Low grade squamous intraepithelial lesion
Minor dysplasia not likely to become cancer, probably due to HPV infecion
Equivalent to cervical intraepithelial neoplasia (CIN 1)
HSIL
High grade squamous intraepithelial lesion
Severe dysplasia that is more likely to progress to cancer
Equivalent to CIN 2 or 3
Glandular cell abnormalities
AGC - atypical glandular cells
AIS - adenocarcinoma in situ
ASCUS for patient age <30 follow up
repeat Pap test cytology every 6 months x 2
if any of the Pap tests cytology every 6 months is abnormal (i.e. >ASCUS), then colposcopy
if both Pap tests cytology every 6 months are negative, then return to routine screening every 3 years
ASCUS for patient age >30 with HPV testing available follow up
A) HPV testing available
1) HPV testing
if HPV testing is negative, then proceed to 2
if HPV testing is positive, then colposcopy
2) Repeat Pap test cytology in 1 year
if repeat Pap test cytology is abnormal (i.e. >ASCUS), then colposcopy
if repeat Pap test cytology is negative, then return to routine screening every 3 years
B) HPV testing not avaiable
follow same algorithm as ASCUS for patient age <30 with repeat Pap test cytology every 6 months x 2
LSIL follow up
straight to colposcopy or follow same algorithm as ASCUS for patient age <30 with repeat Pap test cytology every 6 months x 2
HSIL: straight to colposcopy
ASC-H: straight to colposcopy
AGC: straight to colposcopy
HSIL
straight to colpo
ASC-H
straight to colpo
AGC
straight to colpo
Satisfactory colposcopy
Only when transformation zone between stratified squamous epithelium and glandular epithelium is visualized
type 1 transformation zone = entire transformation zone visualized on colposcopy
type 2 transformation zone = entire transformation zone fully visualized when cervix is opened
type 3 transition zone = entire transformation zone is not visualized even when cervix is opened
type 1 and 2 transformation zone is satisfactory
type 3 transformation zone is not satisfactory
What is the cervical intraepitheliual neoplasia system
colposcopy biopsy classified by cervical intraepithelial neoplasia system (CIN 1, 2 and 3), which signify premalignant transformation and dysplasia that is not cancer but may progress
to cancer
What to biopsy during colposcopy
if any abnormal appearing tissue such as abnormal vascular pattern, mosiacism, punctate lesion, nodular lesion or turns white with acetic acid on colposcopy, then biopsy
if no abnormal lesion identified, then biopsy transition zone
Management post colpo < CIN1
if biopsy is less than CIN 1, then return to screening protocol (Pap test very 3 years)
What is an excisional biopsy
excisional biopsy mentioned above can be loop electrosurgical excision (LEEP), laser, cryotherapy or cone biopsy
Management post colpo CIN 2 or 3
CIN 2 or 3 have risk of cancer
CIN 2 or 3 usually treated with excisional biopsy
Management post colpo CIN 1
CIN 1 biopsy rarely progress to cancer
a) if satisfactory (type 1 or 2 transformation zone) colposcopy, then observe with pap test at 12 months and then manage according to cytology
b) if unsatisfactory (type 3 transformation zone) colposcopy, then observe with pap test and colposcopy at 6 months and 12 months
i) if colposcopy and pap test at both visits are negative for CIN, then return to screening protocol
ii) if CIN persist or progress, then treat by ablation
c) if CIN 1 after HSIL or AGC on pap test, then review biopsy histology with pap test cytology
if discrepancy, then excisional biopsy
Management post unsatisfactory colpo
if unsatisfactory (type 3 transformation zone) colposcopy and cytology was AGC or HSIL, then diagnostic excisional biopsy with LEEP or cone biopsy with endocervical curretage
STIs tested for with vaginal culture and microscopy
Yeast
Bacterial vaginosis
Trichomoniasis
STIs tested for with cervical culture
Chlamydia
Gonorrhea
STIs tested for with blood work
HIV
Hepatitis B - HBSAg
Hepatitis C - HCV RNA testing
Syphilis - VDRL
When to perform bloodwork testing for STIs
Can perform immediately, but HIV, Hep B and Hep C have a latency period so need to repeat bw at 3 and 6 months
STI Urine testing
Urine PCR for chlamydia and gonorrhea
b-hCG
No voiding for 2h then beginning of ‘dirty’ urine (20mL)
Herpes testing
Open intact vesicle with needle, then culture liquid with special swab with liquid virus transport
Send to lab within hours
HPV diagnosis
Diagnosed clinically based on warts on clinical exam
HPV testing indication
Testing for triage of ASCUS pap test for patient 30+ years
HPV testing technique
concomitant with cervical pap test with Dacron swab or cervical brush
STI pharynx testing
Gonorrhea
Insertion of regular swab and rub against posterior pharynx and tonsillar crypts
Rectum STI testing
Testing for gonorrhea and chlamydia
Insertion of regular swab 2-3 cm into anal canal pressing laterally to avoid feces
Need to repeat and obtain another specimen if visible fecal contamination
Urethra STI testing
Testing for gonorrhea and chlamydia
no voiding for 2 hours then regular swab moistened with water inserted 1-2 cm up female urethra and 3-4 cm up male urethra
Vulvovaginitis pathophysiology
inflammation of vulva and/or vagina
Vulvovaginitis clinical presentation
vaginal discharge
vulvo-vaginal pruritus
vulvovaginal pain
most common cause of Vulvovaginitis
infection (BV, vaginal candidiasis, trichomoniasis)
How does vaginal discharge vary throughout the menstrual cycle
Low estrogen in follicular phase results in thick and sticky vaginal discharge
high estrogen in luteal phase results in clearer, wetter and more stretchy vaginal discharge, which is more conducive to sperm travelling
BV epidemiology
Most common cause of abnormal vaginal discharge
Increases risk of acquiring STIs
BV risk factors
African American
Changing sex partner, lesbian partner with BV, douching
Change to vaginal environment: IUD, antibiotic use, co-existing STI
BV pathophysiolgy
normal flora in vagina includes Lactobacillus, which produce hydrogen peroxide to prevent multiplication of other vaginal microorganism
bacterial vaginosis is not an infection, but polymicrobial replacement of normal flora and multiplication in vagina without inflammation
polymicrobial includes anaerobes (Prevotella, Mobiluncus, Bacteroides), Gardrerella, Ureaplasma and Mycoplasma
BV presentation
most asymptomatic
increased thin, white and homogeneous vaginal discharge with a foul odor
BV investigations
Whiff test - fishy odor when alkali (10% KOH) is added to a wet mount containing vaginal discharge
pH >4.5 (normal 4)
Miscroscopy of wet mount containing vaginal discharge - clue cells (vaginal squamous epithelial cells coated with bateria around its edges)
BV diagnosis
Amsel’s criteria - 3/4 of following
- Thin white homogeneous vaginal discharge
- pH >4.5
- Positive Whiff test
- Clue cells on microscopy
BV treatment
Treat only if symptomatic
Treat with antibiotics (oral better than topical)
1st line - Metronidazole 500 mg PO BID x 7 days
2nd line - Metronidazole gel or Clindamycin cream
If pregnant treat with metronidazole oral or clindamycin oral
testing and treating sexual partner not recommended
Vulvovaginal Candidiasis (VVC) epidemiology
2nd most common vaginal infection after BV
Vulvovaginal Candidiasis (VVC) risk factors
change in vagina microbiological environment: uncontrolled diabetes, systemic antibiotic use
immunocompromised state
high estrogen level: pregnancy, obesity, oral contraceptive pill (OCP)
low estrogen (menopause, pre-puberty) decreases risk of VVC
VVC pathogenesis
candida yeast is part of normal vaginal flora, where overgrowth can cause symptoms under changed vagina environment
infection of vagina and vulva by candida fungal species
95% cases are candida albicans, which respond well to usualy therapies
less common infections by non-albicans candida species which is harder to treat: candida glabrata (torulopsis), candida parapsilosis, candida krusei, saccaromyces cerevisiae
VVC clinical presentation
vaginal symptoms: thick white clumpy “curdy and cottage cheese like” vaginal discharge which is usually odorless
skin symptoms: vulval itch, burning, pain or soreness; skin fissures, erythema, edema or satellite lesions (sores in surrounding skin) of vulva
VVC investigations
pH litmus paper test in vagina: pH usually within normal range and <4.5 (normal vaginal pH is ~4)
vaginal swab KOH wet mount / culture: yeast with hyphae and spores
VVC diagnosis
diagnosis by microbial culture of vaginal swab showing Candida (bud + hyphae) plus symptoms of vulvovaginitis
VVC treatment
treat only if symptomatic
oral antifungal: Fluconazole 150mg PO in single dose
topical antifungals: azoles (Clotrimazole, Miconazole, Terconazole) suppository or cream for 3 days if uncomplicated cases; 7 days if complicated cases (diabetes,
immunocompromised, atypical Candida)
oral is preferred over topical treatment for women except when pregnant
only topical treatment is recommended for pregnant women
if resistant to azoles or atypical (not Candida albicans), then topical boric acid powder
gentian violet is effective
other alternatives treatments are not effective including Lactobacillus, probiotics, garlic tampons, tea tree oil, echinacea, golden seal, yeast guard suppositories
Trichomoniasis pathogenesis
trichomoniasis is a disease caused by trichomonas vaginalis, a unicellular flagellated parasite motile protozoa
transmission by genital sexual contact, which is reduced by condom
trichomonas can infect vagina, bladder or urethra
Trichomoniasis clinical presentation
50% of women are asymptomatic
onset of symptoms usually 1 week after contact
vagina symptoms: yellow-green malodorous diffuse frothy vaginal discharge, pruritus, dyspareunia
urinary symptoms: dysuria, increased urinary frequency
complication: rarely may cause pelvic inflammatory disease
Trichomoniasis on physical exam
vaginal discharge
strawberry cervix (petechiae) due to punctate hemorrhage
Trichomoniasis investigation
Microscopy of vaginal swab - motile flagellated organism, many WBC, inflammatory cells (PMNs)
Trichomoniasis diagnosis
trichomoniasis diagnosed by trichomonas visualized on microscopy of vaginal swab sample
Trichomoniasis management
not a reportable disease
treat even if asymptomatic
oral antibiotic therapy: Metronidazole 2g PO single dose or 500mg PO BID x 7 days
sexual partners should also be treated
Post menopasual atrophic vaginitis pathogenesis
post menopausal women have low estrogen, leading to atrophy of vagina
atrophy of vagina usually only lead to vaginal dryness, but can cause an inflammation within the vagina resulting in vaginal discharge
Post menopasual atrophic vaginitis clinical presentation
vagina symptoms: yellowish vaginal discharge, feeling of dry and irritated vagina despite discharge, dyspareunia, pruritus, itching, burning, may cause vaginal bleeding
speculum exam: vaginal petechiae
Post menopasual atrophic vaginitis treatment
vaginal estrogen (ring, tablet or cream) is most effective, which need to be applied for life and achieves full effect in 3 months
systemic estrogen is less effective than vaginal estrogen with more side effects and contraindications
Hirsutism definition
excessive male-pattern hair growth in women
Virilization definition and presentation
excessive development of exaggerated masculine characteristics in women
usually presenting with clitoromegaly, deepening of voice, acne, hirsutism, baldness, increased muscularity
Pathophysiology of hirsutism and virilization
hirsutism and virilization are caused by excess androgen secretion (hyper-androgenemia) including testosterone and dihydrotestosterone (DHT)
usually high androgen level results in hirsutism first, and very high androgen level results in virilization
excess androgen may be from ovary, adrenal gland or exogenous source
ovary secrete testosterone and androstenedione
adrenal gland secrete dehydroepiandrosterone sulfate (DHEA-S) and androstenedione
Hirsutism and virulization differential diagnosis
1) Pituitary
a) Cushing’s disease, resulting in increased ACTH that stimulate secretion of adrenal androgen
b) acromegaly
2) Excess Androgen from Adrenal Gland
a) neoplasm: androgen secreting adrenal tumors
b) genetic: 21-hydroxylase deficiency (aka congenital adrenal hyperplasia), which stop synthesis pathway of mineral-corticoid and glucocorticoid, resulting in excess precursor converted to androgen
3) Excess Androgen from Ovary
a) polycystic ovarian syndrome (PCOS)
b) ovary hyperthecosis
c) androgen secreting ovarian tumors: Sertoli-Leydig cell, Granulosa-theca cell, Hilus cell
4) Exogenous
a) exogenous androgens: testosterone, DHEA
5) Other
a) pregnancy due to luteoma or theca-lutein cyst
b) severe insulin resistance syndromes
c) idiopathic hirsutism
Clinical presentation of excess androgen
hirsutism: excess terminal hair growth (dark coarse hair) in androgen dependent area (upper lip, chin, mid-sternum, upper abdomen, back, buttocks)
hirsutism can be graded based on Ferriman-Gallwey score, which grade 9 androgen dependent body areas from 0 (no hair) to 4 (frankly virile)
hirsutism defined as >8 for black or white women, >2 for Asian women, >9-10 for Mediterranean, Hispanic and Middle Eastern Women
Skin - acne
Virilization - frontal balding, deepening of voice, increased muscle mass, clitoromegaly
Excess androgen physical exam
body habitus
inspection: hair for balding and hirsutism (Ferriman-Gallwey score), skin acne, acanthuses nigricans, Cushingoid feature (moon face, buffalo hump, striae, thin skin, bruising), muscle mass
acanthosis nigricans = grey-brown discolouration of skin at neck, groin, axillae and vulva, which is marker of insulin resistance and hyper-insulinemia
abdominal exam: palpate for mass (ovary)
pelvic exam: inspect clitorus for clitoromegaly, bimanual pelvic exam for ovarian mass
Excess androgen investigations
blood work for amenorrhea / oligo-menorrhea: b-hCG, prolactin, TSH, FSH
blood work for hirsutism: total and free serum testosterone, androstenedione, DHEA-S, 17-OH progesterone, dexamethasone suppression test or 24 hour urine for free cortisol
very high 17-OH progesterone (>200) in congenital adrenal hyperplasia
high cortisol despite dexamethasone suppression test or high 24 hour urine cortisol in Cushing’s syndrome
very high DHEA-S (>700) suggests androgen secreting adrenal tumor
high total testosterone (>150) suggest androgen secreting ovarian tumor
high androstenedione and high free & total testosterone suggest polycystic ovarian syndrome
if high total testosterone >150, trans-vaginal ultrasound for ovarian tumor
if high DHEA-S >700, abdominal CT with IV contrast for adrenal tumor
Excess androgenism treatment
Oral Contraceptive Pill
indication: 1st line for treatment of acne and hirsutism
mechanism of action: estrogen increases steroid hormone binding globulin and progestin inhibits LH secretion, thereby decreasing ovarian androgen production
takes >6 months to be effective, usually stopped after 1-2 years and observe for return of ovulatory cycles
Spironolactone
indication: treats hirsutism
mechanism of action: inhibit ovarian and adrenal biosynthesis of androgen, androgen receptor antagonist, inhibit 5-alpha reductase activity
side effects: diuresis, theoretical risk of feminizing male fetus
Cyproterone Acetate
indication: treats acne and hirsutism
mechanism of action: inhibit androgen secretion, androgen receptor antagonist
side effect: fatigue, edema, loss of libido, weight gain, mastalgia
Dexamethasone
indication: congenital adrenal hyperplasia
mechanism of action: suppression of endogenous ACTH
Flutamide
mechanism of action: non-steroidal anti-androgen
side effect: hepatotoxicity
Finasteride
mechanism of action: inhibit 5-alpha reductase
Mechanical Methods
plucking, waxing, shaving or exfoliants, which do not destroy dermal papillae
electrolysis or laser, which destroy dermal papillae
PCOS epidemiology
common endocrine problem in women of reproductive age
affects 5-10% of women of reproductive age (12-45)
PCOS risk factors
Family history
metabolic syndrome (obesity, diabetes, dyslipidemia, hypertension)
PCOS pathophysiology
insulin resistance -> decreased sex hormone binding globulin -> increased free testosterone
increased testosterone production by theca cells -> follicular atresia -> anovulation
anovulation results in no secretion of progesterone due to no corpus luteum, increased testosterone in ovary is converted to estrogen
thus high estrogen unopposed by progesterone lead to continuous endometrial proliferation that never shed, increasing risk of endometrial cancer
increased testosterone production and increased free testosterone -> secondary male sexual characteristics (hirsutism, virilization)
PCOS signs and symptoms
onset usually around menarche, but can be after puberty
irregular menstruation or amenorrhea
infertility
acne, hirsutism, deepened voice
weight gain
vitals: hypertension
body habitus: overweight or obese
general: hirsutism, acne, male pattern baldness, acanthosis nigricans
pelvic exam: enlarged clitoris, large ovaries on palpation
PCOS investigations
blood work: normal b-hCG, prolactin, TSH, FSH, normal to slightly high free & total testosterone <150, normal 17-OH progesterone, normal
dexamethasone suppression test, normal 24 hour urine cortisol test
high androstenedione
pelvic ultrasound: polycystic ovaries
PCOS diagnosis
1) Exclude other causes for hyperadrogenism and amenorrhea
PCOS is diagnosis of exclusion
hyperandrogenism differential diagnoses
- normal 17-OH progesterone ruling out congenital adrenal hyperplasia
- normal 24 hour urine free cortisol ruling out Cushing’s syndrome
- normal DHEA-S and normal abdomen ultrasound ruling out androgen secreting (adrenal or ovarian) tumor
amenorrhea differential diagnoses
- negative b-hCG ruling out pregnancy
- normal prolactin ruling out hyperprolactinemia
- normal TSH ruling out thyroid disorder
- no signs of structural abnormality besides polycystic ovaries on pelvic ultrasound
- normal or low FSH ruling out primary ovarian insufficiency
2) diagnose PCOS based on Rotterdam’s criteria or AE-PCOS criteria
a) Rotterdam Criteria
patient diagnosed with PCOS if patient satisfies >2 of the 3 criteria
1. anovulation presenting as oligomenorrhea or amenorrhea
2. hyperandrogenism from clinical signs or high testosterone
3. polycystic ovaries (>12 cysts or large ovarian volume >10mL of at least one ovary) on ultrasound
b) Androgen Excess PCOS (AE-PCOS) Criteria
patient diagnosed with PCOS if patient satisfied all of the criteria below:
1. hyperandrogenism: hirsutism and / or hyperandrogenia
2. ovarian dysfunction: oligo or anovulation and / or polycystic ovaries on ultrasound
3. exclusion of other androgen excess disorders and related disorders
note that polycystic ovary on ultrasound is not enough to diagnose PCOS and patient without polycystic ovary on ultrasound can still have PCOS
PCOS consequences
1) Short Term Consequences infertility irregular menses hirsutism, acne, androgenic alopecia metabolic syndrome: insulin resistance, glucose intolerance, acanthosis nigricans, hypertension, obesity, dyslipidemia obstructive sleep apnea
2) Long Term Consequences PCOS increases risk of type 2 diabetes mellitus endometrial cancer cardiovascular disease: coronary artery disease, myocardial infarction, stroke
PCOS workup
work up need to assess for metabolic syndrome and cardiovascular disease risk
body habitus: BMI, waist circumference
blood pressure
diabetes screening: HbA1C and / or fasting blood glucose
lipid profile: total cholesterol, LDL, HDL, triglycerides
PCOS treatment
1) Restore menorrhea
menorrhea restored by cyclic progesterone with withdrawal to stimulate cyclic shedding of endometrium
if patient does not want children, then combined oral contraceptive pill (OCP)
if contraception is not needed, then cyclic progesterone
2) Contraception
patients with PCOS can still get pregnancy, so need to use contraception if the patient does not want baby
3) Hyperandrogenism
OCP and Cyproterone acetate can be used to treat acne and hirsutism
Spironolactone can be used to treat hirsutism
hirsutism can be treated by mechanical means
Management of PCOS complications
1) Metabolic Syndrome
regular assessment for metabolic syndrome including fasting glucose / HbA1C; lipid profile; blood pressure
healthy lifestyle: exercise, diet, weight loss
address each risk factor
antihypertensive if hypertensive
lipid lowering medication if hyperlipidemia
diabetes medication if diabetes mellitus
metformin can be used to treat impaired glucose tolerance
2) Endometrial Hyperplasia and Cancer
restore menorrhea by replacing progesterone to shed endometrium
endometrial biopsy to screen for endometrial cancer if age >35 and abnormal uterine bleeding
3) Infertility
contraception if patient does not want to get pregnant
ovulation induction with SERM (selective estrogen receptor modulator) as needed when patient want to get pregnant
Infertility definition
failure to conceive after 1 year of frequent unprotected intercourse (frequent ~2-3 times during fertile time window, which is at ovulation around 14 days before menstruation)
Infertility risk factors - female
- demographics: female age is single biggest risk factor for infertility, where chance of successful pregnancy dramatically decreases and miscarriage dramatically
increases at age >35
increasing age -> decreased follicle cells and lower quality of oocyte with higher risk of aneuploidy - body habitus: very high or very low body mass index
- OB&GYN history: oligomenorrhea, amenorrhea, pelvic inflammatory disease, endometriosis
- past surgical history: previous abdominal or pelvic surgery
- medication: chemotherapy
Risk factors for infertility - male
- demographics: age >40 years
- past medical history: history of undescended testes
- past surgical history: previous urogenital surgery
- medication: chemotherapy
- social history: recreational drugs
Top 3 causes of infeertility not accounted for by female age
- Ovulation defect (oligomenorrhea or amenorrhea) in ~25% cases
- Male factor (ie abnormal semen quantity and/or quality) in 25% cases
- Fallopian tube defect in ~25% cases
What is congenital bilateral absence of vas deference associated with
cystic fibrosis carrier
Clinical evaulation for infertility is indicated for any of the following
couple in which female age <35 after 1 year of unprotected and frequent sexual intercourse
couple in which female age >35 or with specific medical history after 6 months of unprotected and frequent sexual intercourse
Female causes of infertility
- Tubal factors- obstruction from surgery, inflammation, anatomical abnormality
- Ovulatory dysfunction - hypothyroidism, prolactinoma, hypothalamic amenorrhia, PCOS, POI
- Uterine structural abnormality - congenital uterine malformation, fibroids, adhesions, polyps
Male causes of infertility
- Abnormal semen quantity and/or quality - lube, chronic disease, surgery, chemo, testosterone, smoking, alcohol, drugs, heat, Kleinfelter, CF, chromosome Y microdleetion
- Low or absent semen volume
- failed emission, incomplete collection, short abstinence period, CBAVD, ejaculatory duct obstruction, hypogonadism, retrograde ejaculation - Acidic semen -CBAVD, ejaculatory duct obstruction
- Azoospermia - obstruction, testicular failure
- Oligospermia - variocele, hypogonadism, T-chromosome microdelection
- Asthenospermia (poor sperm motility) - anti sperm antibodies, genital tract infection, partial obstruction of ejaculatory ducts, site of vasectomy reversal, varicele, prolonged abstinence
Investigations of infertility
For all infertility all of the following assessment should be done:
- Assessment of ovulation by history and serum progesterone 7 days prior to expected period
- Ovarian reserve testing by FSH, estradial and pelvic ultrasound (us also assesses anatomy of uterus, uterine tube and rest of pelvis)
- Uterus and uterine tube anatomy on saline infusion sonogram or hysterosalpingogram
- Semen analysis
- TSH for thyroid dysfunction
investigation for oligo/anovulation only if positive history of olig/amenorrhea or low serum progesterone 7 days prior to expected period
Assessment of ovulation
ovulation can be assessed by history, basal body temperature charting, urine LH detection kit or luteal phase progesterone
a) History
on history, a regular and predictable menstrual cycle lasting 21-35 days with signs of molimina (impending period) predict ovulation in 95% of women
signs of molimina include breast tenderness, cramping, mood changes and headaches
14 days before menstruation = ovulation
if patient has regular predictable period on history, then ovulation can be clearly predicted and no further investigation is required
b) Basal Body Temperature Testing
basal body temperature charting is tracking of basal body temperature throughout menstrual cycle with an accurate digital thermometer
increase of 0.3-0.5 C of body basal temperature correspond to 2-3 days after ovulation
having intercourse when basal body temperature have already increased is too late because it is 2-3 days after ovulation
charting of body basal temperature allows patient to track pattern of ovulation so that she can predict the next one given the same pattern
c) LH Surge
urine LH detection kit measures LH surge at ovulation, which can be used to detect current ovulation
having intercourse at LH surge as detected by LH detection is effective
d) Luteal Phase Serum Progesterone
progesterone need to be measured ~7 days before the expected menstrual period, which measure the elevated progesterone at the luteal phase if ovulation
Investigations for oligo/anovulation
serum LH, FSH
serum estradiol (at day 3 of menstrual cycle)
serum progesterone (at 7 days before expected menstrual cycle)
serum b-hCG for pregnancy
serum TSH for thyroid function
serum prolactin for prolactinoma
pelvic ultrasound for any anatomical abnormalities
Common causes of oligo/anovulation as determined by investigations
hypogonadotropic (low LH, FSH) hypogonadism (low estradiol, low progesterone) suggest central cause such as hypothalamic amenorrhea
normagonadotropic (normal LH, FSH) satisfying Rotterdam criteria (2/3 of polycystic ovaries on ultrasound, oligo / a-menorrhea and hyperandrogenism) suggest polycystic
ovarian syndrome
hypergonadotropic (high LH, FSH) hypogonadism (low estradiol, progesterone) suggest primary ovarian insufficiency
high TSH suggest hypothyroidism
high prolactin suggest prolactinoma
Ovarian reserve definition
number of eggs remaining in ovary that have potential to ovulate and be fertilized
How to count ovarian reserve
FSH and estradiol on day 3 of menstrual cycle
pelvic ultrasound which can count antral follicle as well as assess anatomy
low ovarian reserve if
high FSH and low estradiol and
low antral follicle count
ovarian reserve testing are not very reliable in predicting fertility potential
How to confirm tubal patency
tubal patency assessed by hysterosalpingogram, saline infusion sonogram, or diagnostic laparoscopy
a) Hystersalpingogram (HSG)
HSG = injection of radio contrast dye into uterus and image on radiograph
normal patent uterine tube lead to contrast going from uterus to tube and into abdominal cavity, making uterus, uterine tube and some of the abdominal cavity visible on
radiograph
in tubal obstruction, the dye cannot enter uterine tube nor the abdominal cavity, so uterine tube and abdominal cavity is invisible
abnormal hysterosalpingogram leads to laparoscopic assessment
HSG best done in day 2-5 after menses (to avoid blood / clot, to ensure not pregnant) with NSAID and antibiotic (Doxycycline) prophylaxis (optional) prior to HSG due to 1-3% risk
of infection
b) Saline Infusion Sonogram (SIS)
SIS = infusion of saline into uterus, which can be visualized on ultrasound
SIS can be used as substitute for hysterosalpingogram
same principles and findings as hysterosalpingogram, where saline infusion in saline sonogram ~ contrast dye in hysterosalpingogram
SIS is better at assessing uterine cavity, but cannot assess tube structures
NSAID prior to SIS
c) Laparoscopy
laparoscopy is the gold standard test for assessing tubal factors
diagnostic laparoscopy is laparoscopic visualization of abdominal cavity while injecting dye (indigo carmine or methylene blue) into uterus
abnormal uterus / uterine tube anatomical abnormality can be visualized on laparoscopy such as fibrosis of uterus post pelvic inflammatory disease
normal patent uterine tube leads to dye going through uterine tube and exiting into abdominal cavity, which is visualized on laparoscope
obstructed uterine tube prevent dye from entering abdominal cavity, so it is not visualized on laparoscope
laparoscopy needs to be done under general anaesthesia, so it has operative risks
laparoscopic assessment indicated if patient has any of the below:
1. abnormal hysterosalpingogram
2. known endometriosis
3. previous ectopic pregnancy or tubal surgery
4. previous ruptured appendicitis
5. abnormal physical pelvic exam findings
6. previous pelvic inflammatory disease
How to assess uterine factor for infertility
uterine factor is an uncommon cause of infertility
uterine factor usually already assessed by assessing for tubal patency and ovarian reserve with the following test:
1. pelvic ultrasound (3D ultrasound is better for assessing uterine malformation and space filling defects)
- HSG or SIS (can assess for space filling masses or intra-uterine adhesions)
- hysteroscopy, which is gold standard for definitive diagnosis of uterine abnormality
Semen analysis
semen analysis is analysis of the male partner’s
semen sample which assess volume, concentration of sperm, sperm motility and sperm morphology
semen analysis should be at least 2 properly performed semen analysis obtained at least 4 weeks apart with abstinence 2-3 days prior to semen collection, which are transported at
body temperature and analyzed within an hour
normal semen analysis according to WHO criteria is:
- volume >1.5mL
- pH >7.2
- sperm concentration >15 million/mL of semen
- sperm motility >40% progressive
- sperm morphology >4% normal
Hypospermia definition
small semen volume
oligospermia definition
low sperm count
azoospermia definition
absence of sperm in semen
asthenozoospermia definition
low sperm motility
teratospermia definition
sperm with abnormal morphology
oligoasthenoteratozoospermia definition
low sperm count with low motility and abnormal morphology
Hypogonadotropic (low LH, FSH) hypogonadism (low estradiol, low progesterone) such as hypothalamic amenorrhea treatment
weight gain
GnRH pump or gonadotropin (FSH) SC infection to induce ovulation
In-vitro fertilization
Normagonadotropic (normal LH, FSH) normoestrogenic such as polycystic ovarian syndrome (PCOS) treatment
Weight loss
1st line - Clomiphene citrate (SERM acting as estrogen antagonist thereby increasing FSH) to induce ovulation
Aromatase inhibtor
insulin sensitizing agent (Metformin)
Laparoscopic ovarian drilling to induce ovulation
Gonadotropin (FSH) SC injection to induce ovulation
In-vitro fertilization
hypergonadotropic (high LH, FSH) hypogonadism (low estradiol, progesterone) such as primary ovarian insufficiency treatment
in-vitro fertilization
donor egg
adoption
treatment of tubal factor infertility
consider tubal surgery
in-vitro fertilization
treatment of uterine factor infertility
surgical removal of masses or adhesions within uterine cavity
treatment of male factor infertility
lifestyle modification: avoid excessive heat, limit caffeine intake, stop smoking, stop marijuana and other recreational drugs, decrease alcohol intake, vitamins (C, E, Selenium, Zinc,
Folic acid)
abnormal sperm production: gonadotropin or exogenous pulsatile GnRH for hypothalamic dysfunction
abnormal sperm function: intra-uterine insemination, in-vitro fertilization
obstruction: in-vitro fertilization with testicular sperm aspiration / extraction (TESA / TESE)
Treatment modalities of infertility in order of increasing success rate and invasiveness
Ovulation induction –> OI with IUI –> superovulation with IUI –> IVF
Ovulation induction definition, indications, contraindications and method
ovulation induction = supra-ovulation = inducing ovulation of 1 egg
ovulation induction / supra ovulation stimulate ovulation followed by sexual intercourse with partner to improve chance of pregnancy
ovulation induction / supra-ovulation indicated in oligo / an-ovulation
ovulation / supra-ovulation should not be used in
- premature ovarian insufficiency
- regular menstruation and ovulation where ovulation is not the cause for infertility
- mild male factor as cause of infertility
- unexplained infertility
ovulation / supra ovulation can be induced by clomiphen citrate, tamoxifen, letrazole, gonadotropin (FSH) or ovarian drilling
Clomiphene citrate mechanism
selective estrogen receptor modulator (SERM) that acts as an estrogen antagonist at the hypothalamus
estrogen antagonism at hypothalamus remove negative feedback of estrogen, increasing FSH
increased FSH stimulate follicular development and thus stimulate ovulation
Tamoxifen MOA
SERM that block estrogen effect on hypothalamus to increase FSH and stimulate follicular development & ovulation
Letrazole MOA
aromatase inhibitor that decrease synthesis of estrogen level, stimulating FSH release and triggering follicular development & ovulation
Gonadotropin (FSH) administration for infertility
given as a daily subcutaneous injection in follicular phase with ultrasound monitoring of developing follicles to trigger ovulation
SERM risk
repetitive cycles of SERM >12 increase risk of ovarian and breast cancer
Ovarian drilling method for infertility
surgical caudery of tiny holes in stroma of ovary, decreasing androgen release from theca cells, stimulating ovulation
ovarian drilling associated with risk of bleeding and tubal obstruction
Superovulation definition, indication, method
superovulation = inducing ovulation of 2-4 eggs
superovulation artificially induce ovulation followed by usually intrauterine insemination
superovulation is a more extreme version of ovulation induction, so it is usually used in combination with intrauterine insemination when ovulation induction with intrauterine
insemination fails
superovulation is done with daily subcutaneous FSH injection under concomitant ultrasound to track follicular development (high FSH dose induce maturation and ovulation of >1 egg)
What’s the deal with IUI (pairing, method, benefit)
IUI usually paired with OI or SO to increase chance of conception
in IUI, sperm sample is taken from the male partner, which is then washed to filter and keep only the viable and mobile sperm
the washed sperm sample is then inserted via an insemination catheter into the uterus at same time as OI or SO
IUI is better than natural sexual intercourse at conception because it is an optimal placement of washed sperm
OI with IUI indications and disadvantages
indicated in
unexplained infertility
oligo / ano-ovolation where OI alone failed
moderately low sperm counts
disadvantages include
time consuming with frequent visits, tests and procedures
emotionally demanding
expensive
risk of multiple pregnancy and ovarian hyperstimulation
SO with IUI indications and disadvantages and success rates
indicated in
cases where OI with IUI failed
same disadvantages as OI with IUI
success rates are moderate
20% success rate in women age <35
10-15% success rate in women aged 35-39
<10% success rate in women aged 40
note that success rate of SO with IUI is greater than OI with IUI
IVF definition, indication, procedure, success rates
in vitro fertilization is stimulation of follicle which is then retrieved and fertilized with sperm in-vitro followed by re-insertion of fertilized embryo back into uterus to be implanted
indication for in-vitro fertilization
- tubal obstruction
- severe endometriosis
- severe oligo-azoospermia (very low sperm count)
- polycystic ovarian syndrome with failed medical therapy
- failed SO with IUI at least 3 times
- donor egg is needed (e.g. primary ovarian insufficiency)
- advancing maternal age (>40)
general procedure have 4 steps
1) FSH stimulation by subcutaneous injection to grow multiple follicles under close ultrasound and bloodwork monitoring
2) egg is aspirated with needle inserted through vagina into ovary under ultrasound guidance
3) retrieved egg is fertilized with sperm to make embryo by standard in-vitro fertilization or intra-cytoplasmic sperm injection (ICSI)
a) in standard in-vitro fertilization, egg is mixed with solution of millions of sperm and one of those sperm will fertilize the egg, resulting in embryo
b) in ICSI, 1 sperm is chosen and then inserted into the egg resulting in embryo
c) standard in-vitro fertilization or ICSI depend on sperm count, motility and morphology where ICSI preferred if male partner sperm sample have low count, low motility and low
percentage of normal morphology
d) the fertilized embryo will be grown in petri-dish for 3-5 days (emulating days embryos traverse through uterine tube before implantation)
e) good quality fertilized embryos can be frozen (cryoperserved) for future use
4) fertilized embryo is then inserted via catheter into uterus under ultrasound guidance, so that it can implant into uterus and start pregnancy
a) in young women (<38), 1 or 2 fertilized embryos is inserted into uterus hoping 1 will implant
b) in older women (>42), 5 fertilized embryos is inserted into uterus hoping 1 will implant
IVF have highest success rate overall success rate ~40% in all women ~50% success rate in women age <35 ~40% success rate in women age 35-39 ~20% success rate in women age >40
Time limit for collecting forensic evidence and using rape kit in suspected domestic violence case
72h
When is STD prophylaxis administered in suspected domestic violence cases
Within 72h of potential exposure (contact with perpetrator’s genitalia)
Gonorrhea prophylaxis
Ceftriaxone 250 mg IM 1 dose
or Cefixime 400 mg PO 1 dose
Chlamydia prophylaxis
Azithromycin 1g PO 1 dose
or Doxycycline 100 mg PO q12h for 7 days
Trichomoniasis and BV prophylaxis
Metronidazole 2g PO 1 dose
Hep B prophylaxis
hep b vaccine if unvaccinated (asap, then repeat doses at 1-2 months and 4-6 months after 1st dose)
HIV
Zidovudine (AZT) 200mg PO Q8H or 106mg/m2 per dose Q8H for 4 weeks PLUS Lamivudine 150mg per dose Q12H or 4mg/kg per dose Q12H for 4 weeks
consider HIV prophylaxis if assailant is known to be HIV positive or is at high risk for being HIV positive
alternative for adolescents: 300mg AZT / 150mg Lamivudine Q12H for 4 weeks
Emergency contraception
Levonorgestrel 0.75 mg once then repeated in 12h
Components of the pelvic floor
Peritoneum Pelvic viscera Endopelvic fascia Elevator ani muscle Perineal membrane Superficial genital muscles Vulvar subcutaneous fascia Fat Skin
What is the genital hiatus
Oval opening between the levator crura through which passes the vagina and urethra
How does the vaginal uterine axis change with position
vaginal uterine axis is parallel to long axis of body when supine, but when standing, lower 1/3 vagina is parallel to the long axis of body but the upper 2/3 vagina & uterus are
perpendicular to long axis of body
Support of vagina and uterus
Structural Support
anterior support: lower 1/3 vagina supported by pubouretral and urethropelvic ligament, which contains elastin and collagen with smooth muscle
lateral support: lower 1/3 vagina supported by endopelvic fascia which attaches to the arcus tendineus; upper 2/3 vagina & uterus supported by cardinal (Mackenrodt’s) ligament
posterior support: uterus supported by uterosacral ligament
apical support: uterosacral ligament and upper support of arcus tendons
2) Mechanical Support
constant levator ani muscles contraction activity pulls rectum anteriorly & superiorly, help maintain urinary & fecal incontinence
(levator ani muscle involuntarily contracts during cough)
cardinal and uterosacral ligaments, pubo-cervical fascia
flap valve closure: upper vagina covers opening in levator plate
once one of the supports fails, then progressive damage to other supports over time due to extra strain, leading to pelvic organ prolapse
Overactive bladder definition
syndrome of urgency, frequency, nocturia, urinary incontinence
Risk factors for all urinary incontinence
Immobility
Risk factors for stress incontinence
Chronic valsalva maneuvers
Pelvic floor relaxation
Pregnancy and childbirth
Risk factors for urgency incontinence
Medication
Smoking
Obesity
Risk factors for overflow incontinence
Neurologic problems
Medication
Etiology of urgency incontinence
a) detrusor overactivity
- neurologic (spinal cord injury)
- inflammation (cystitis, stone, tumour)
- structural (bladder neck obstruction tumour stone, BPH)
- idiopathic
b) decreased bladder compliance
- fibrosis of bladder
- non-functioning bladder neck or proximal urethra: neurological disease, trauma, surgery, aging
Stress incontinence etiology
a) Urethral hypermobility
- childbirth
- pelvic surgery
- aging
- levator muscle weakness
b) intrinsic sphincter deficiency
- aging
- hypoestrogen state
- pelvic surgery
- neurologic problem
Urethral hypermobility definition
weakened pelvic floor allowing bladder neck and urethra to descend with increased intra abdominal pressure
Overflow incontinence clinical presentation
Supra-pubic pressure
Over distended bladder
Continuous incontinence
What medications can contribute to urinary incontinence
anti-histamine anticholinergics ACE inhibitor, diuretics anti-depressants, antipsychotics alpha agonists, alpha 1 blockers
What is the q tip test
for urinary incontinence
insert cotton swab into urethra, where positive test = movement of swab by >30 degrees with straining which suggest urethra hyper mobility causing stress urinary
incontinence
What is a bulbocavernosal reflex and what levels does it test
(S2-4): anal sphincter contraction with squeezing of clitoris, bulb penis or tugging of Foley catheter
What is an anal wink and what levels does it test
(S2-4): ipsilateral contraction of anal sphincter upon stroking of the peri-anal skin
Investigations with urinary incontinence
Urine analysis R&M, C&S
Suspected overflow - post void residual u/s
suspected urgency - cystometry to diagnose detrusor overactivity
severe voiding symptoms - urine flow rate and urodynamic testing
suspected structural disease within urethra or bladder - cystoscopy
Urgency incontinence diagnosis
Based on history and urodynamics study
Stress incontinence diagnosis
History and positive stress test on physical
Overflow incontinence diagnosis
bladder u/s showing PVR > 200 cc
Stress incontinence management
1st line = lifestyle modification, weight loss, pelvic floor exercises (Kegel, vaginal cones, biofeedback, electrical stimulation), bulking agents, estrogen replacement therapy
2nd line = pessary for female (medical device to provide structural support of vagina)
last line = surgical treatments
open or laparoscopic Burch Retropubic Urethropexy (RPU), where placing surgical suture at bladder neck and tying it to Cooper ligament
pubo-vaginal sling procedures, where a band of sling is placed under bladder neck that tightens (closing urethra) during Valsalva maneuver
mid-urethral slings, which can be retropubic tension-free vaginal tape (TVT) or obturator TVT, where a sling is placed around mid urethra that tightens (closing urethra) during
Valsalva maneuver
surgical treatments have 80-90% cure rate at 5 years
Urgency incontinence
1st line = lifestyle modification (decrease fluid intake, limit caffeine intake, smoking cessation, weight loss), bladder habit training, estrogen replacement therapy
2nd line = medication: anti-cholinergics (Tolterodine, Oxybutynin, Trospium, Solifenacin, Darifenacin, TCA)
last line = Botulinum toxin, sacral neuromodulation
no role for surgery
Mixed incontinence management
combination of management for urgency and stress incontinence
Overflow incontinence management
lifestyle changes
catheterization
treat underlying cause
Pelvic organ prolapse definition
herniation of pelvic organs to or beyond the vaginal walls
anterior compartment prolapse definition
herniation of anterior vaginal wall often associated with descent of bladder (cystocele) and urethra (urethrocele)
posterior compartment prolapse definition
herniation of posterior vaginal wall often associated with descent of rectum (rectocele) and / or intestines (enterocoele)
apical compartment prolapse definition
descent of apex of vagina (uterus and cervix, cervix alone or vaginal vault) into lower vagina to hymen or beyond vaginal introitus, can be associated
with enterocele
uterine procidentia
anterior, posterior and apical compartment prolapse
Pelvic organ prolapse risk factors
demographics: age
OB&GYN history: pregnancy, vaginal childbirth (which stretches pelvic muscle and fascia that may cause permanent damage)
body habitus: obesity
past medical history: previous pelvic surgery
other: hypo-estrogenic state (post-menopause), connective tissue disorder
social history: smoking
Pelvic organ prolapse pathophysiology
contributing factors lead to weakness in pelvic floor that hold pelvic organs in place including aging declining quality of collagen estrogen withdrawal constipation chronic cough
weakness in pelvic floor structures lead to prolapse of organs herniating into vaginal wall, which descends into what was originally vaginal canal
Pelvic organ prolapse clinical presentation
sensation of fullness, pressure or bulge in vagina
organs falling out of vagina
urinary symptoms: urinary incontinence or retention (may be complicated by urinary tract infection or renal impairment)
– pelvic organ prolapse may mask stress urinary incontinence by organ compressing on urethra, which is important, because any surgery fixing pelvic organ prolapse will create
new problem of stress incontinence
GI symptoms: constipation
OB&GYN symptoms: vaginal bleeding or discharge from erosions or ulcerations
Stages of pelvic floor prolapse
grade 0 = no prolapse
grade 1 = prolapse descending to upper 1/3 of vagina
grade 2 = prolapse descending to mid vagina
grade 3 = prolapse descending to level of hymenal ring or introitus
grade 4 = prolapse descending past hymenal ring
Pelvic organ prolapse management
treatment is indicated for any symptomatic pelvic organ prolapse
1st line = pelvic floor exercises (Kegels, vaginal cones, biofeedback, electrical stimulation of pelvic floor), estrogen replacement therapy (systemic or local)
2nd line = pessary (medical device inserted into vaginal canal to provide structural support to return and hold prolapsed organ to its original place)
last line = surgery
Absolute indication for surgery in pelvic organ prolapse
urinary retention due to organ prolapse (which may lead to hydronephrosis and renal failure), otherwise all other surgeries are elective procedures
At what stage is surgery considered for pelvic organ prolapse
Stage 3-4
What are the options for surgery for pelvic organ prolapse
surgery can be reconstructive or obliterative
reconstructive aims to correct and restore normal anatomy, which can be via open or vaginal approach
in reconstructive surgery, supporting structures (uterosacral ligament, sacrospinous ligament) are reattached or shortened; or organs are pexed (tethered) to other internal
pelvic structures to prevent prolapse via mesh
vault prolapse: sacralcolpopexy, sacrospinous fixation, uterosacral ligament suspension
cystocele: anterior colporrhaphy (plication of pubovervical fascia), may use graft to provide support which can be sutured to cardinal uterosacral ligament, endopelvic
fascia or obturator fascia
rectocele: posterior colporrhaphy (posterior repair), plication of endopelvic fascia and perineal muscle approximated in midline to support rectum and perineum
enterocele: contents reduced, neck of peritoneal sac ligated, uterosacral ligament and levator ani muscle approximated
obliterative removes and / or closes off all or portion of vaginal canal by colpocleisis (closure of vagina) or colectomy to reduce viscera back into pelvis, which is only via
vaginal approach
Potential complications of pelvic organ prolapse surgery
urinary incontinence, dyspareunia, recurrence of relapse (30% risk)
Fistula etiologies
Obstetric
Iatrogenic
Local disease causing inflammation
Pathophysiology of obstetric fistula
obstetric fistula usually result from prolonged, obstructed labour without timely medical intervention
1) prolonged, obstructed labour result in sustained pressure of baby’s head on mother’s pelvic bone, damaging pelvic soft tissue
2) damage of pelvic soft tissue result in fistula from vagina to bladder or rectum
Gynecological fistula clinical presentation
vesicovaginal or rectovaginal fistula: recurrent vaginitis, irritation of vulva, vagina and perineum, dyspareunia
vesicovaginal fistula: uncontrolled leakage of urine into vagina (“urinary incontinence” or “increased vaginal discharge” by patient), recurrent urinary tract infection, abnormal urinary
stream, hematuria
rectovaginal fistula: uncontrolled leakage of feces into vagina (“fecal incontinence” or “foul smelling vaginal discharge” by patient), flatus into vagina
Gynecological fistula management
A) Vesicovaginal fistula
if small fistula, then trans-urethral or supra-pubic catheter to drain bladder, allowing fistula to heal
if large fistula, then surgical repair (lysis of fistula and then closure of fistula with sutures), which can be via vaginal or abdominal open approach
B) Rectovaginal fistula
surgical repair (lysis of fistula and then closure of fistula with sutures), which can be via vaginal or abdominal open approach
Menopause definition
last natural menstrual period, defined as 12 months of amenorrhea after the last natural menstrual period, typically occurring at age 45-55
Early menopause time frame
40-45 years
Primary ovarian insufficiency / premature ovarian failure time frame
menopause before age 40
Late menopause time frame
after 55 years
peri- menopause definition
transition period of altered ovarian hormone leading up to menopause and 1 year after menopause
Peri-menopause time frame
progression from regular cycles to shortened cycles to irregular cycles then to menopause
peri-menopause can start as early as mid 30s and last 2-8 years up to menopause
average age of menopause
51 years
Physiology of menopause
in time around menopause, there is narrowing of thermoneutral zone, which result in regulatory response of sweating or shivering in response to small change in temperature
loss of estrogen lead to atrophy of vagina and bladder incontinence
low estrogen lead to dyslipidemia, increase plaque development and inhibit vasodilation, thereby increasing risk of cardiovascular disease
Menopause clinical presentation
symptoms can be throughout peri-menopause and post-menopause
there is spectrum of symptoms, where menopause can range from asymptomatic to symptomatic severely affecting quality of life
Symptoms
vasomotor: hot flashes, night sweats
affect ~60% of menopausal women
majority of post-menopausal women will experience hot flashes <7 years, but hot flashes can persist for >15 years
exacerbated by obesity, smoking
usually have trigger such as alcohol, warm ambient environment, hot drinks
cognitive: poor memory, poor concentration
psychiatric: depression, irritability, emotional lability, sleep disturbance
menopause can initiate de novo psychiatric disorder or worsen existing psychiatric disorder
urogenital: vaginal dryness, urinary frequency & urgency, diminished libido
vaginal dryness often 1st sign of menopause and progressive with time, leading to discomfort, dyspareunia, bleeding, post-coital bleeding or discharge
general: fatigue, myalgia & athralgia
complication due to low estrogen in post-menopause: increased risk of cardiovascular disease, osteoporosis, colorectal cancer
Contraindication for hormonal therapy in menopause
hormone dependent cancer: breast cancer, endometrial cancer
arterial thromboembolic disease: myocardial infarction, angina
venous thromboembolism: deep vein thrombosis, pulmonary embolism
cardiovascular disease: coronary artery disease, myocardial infarction, stroke
severe active liver disease
un-investigated abnormal uterine bleeding due to possible endometrial cancer and hormone replacement worsening uterine bleeding
Hormonal profile in menopause
FSH, LH, and E2 tend to fluctuate during menopause and usually not used, also due to the fact that peri-menopause and menopause are clinical diagnoses
usually menopause have high FSH, high LH and low E2
Investigations in menopause
cardiovascular disease risk factors: lipid profile, blood glucose / HbA1C
cancer risk factor: mammogram
osteoporosis risk factor: BMD
pelvic ultrasound as baseline, which can be used to compare and detect endometrial hyperplasia post hormone replacement
diagnosis of menopause
clinical retrospective diagnosis which rarely requires investigation - diagnosed if amenorrhea for 1 year and in normal age range (45-55)
Management of menopausal symptoms
lifestyle modification recommended for everyone
reducing core body temperature (fan, reduce room temperature, lighter clothing)
regular exercise
weight loss
smoking cessation
avoid known trigger such as hot drinks or alcohol
for vasomotor symptoms, consider prescribing systemic hormonal therapy (HT)
45
for urogenital atrophy, prescribe local vaginal estrogen
What is the systemic hormonal therapy used in menopause
Estrogen and progesterone if patient has an uterus OR estrogen only if patient does not have an uterus
Systmeic hormonal therapy vs oral contraceptive pill
HT is not equivalent to OCP
HT is at a lower dose which only partially replaces the estrogen and progesterone hormone level to a level below normal whereas OCP is at a higher dose which increases estrogen
and progesterone hormone to a level above normal
HT is safer than OCP due to lower doses
contraindication for HT and OCP are not the same
HT indication
indication: menopausal symptoms (vasomotor, vaginal dryness) that is negatively impacting quality of life to be started in critical window (3-5 years after last menstrual
period) for maximum of 5 years therapy
in patients with premature ovarian failure, HT should be used up until normal menopause age (i.e. age 50) for its cardio-protective effect
HT is not recommended for prevention of coronary heart disease or osteoporosis due to risk of breast malignancy and cardiovascular disease
HT contraindication
cardiovascular disease: stroke, coronary artery disease, myocardial infarction
VTE related: smoking, previous VTE including DVT, PE
malignancy: previous breast cancer, endometrial cancer
acute liver disease
HT mechanism in menopause
hormonal therapy replaces low estrogen in menopause, negating menopausal symptoms as well as negating health risks associated with low estrogen
progesterone is added to lower risk of endometrial cancer from unopposed estrogen
estrogen only HT can be considered in patients with total hysterectomy
Types of HT
types of estrogen
oral conjugated equine estrogen (CEE/premarin), which is not bio-identical
oral estrase, which is bio-identical
transdermal estradiol, which is bioidentical
types of progesterone
oral micronized progesterone, which is bio-identical
progestin, which is a synthetic drug and not bio-identical
HT routes of administration
estrogen can be delivered orally or transdermally (gel, patch)
oral estrogen is inferior to transdermal, because it increases risk of VTE
the transdermal patch bypass liver to avoid VTE risk, are relatively stable in blood and permit measurement of serum estradiol for dose adjustment
transdermal estrogen route includes gel and patch
progesterone is usually delivered orally
HT and CVD risk
no convincing evidence that HT increase risk of CVD in newly menopausal women starting HT
HT started in critical window (3-5 years after last menstrual period) do not increase CVD risk
HT initiated outside critical window (>5 years after last menstrual period) can increase CVD risk
HT and VTE risks
HT only increase VTE risk by a minimal amount (2-3 additional cases per 10,000 users) with greatest risk in 1st year of use
risk of VTE decreases with lower dose and transdermal route of estrogen
HT and Stroke and dementia risks
HT as risk for stroke and dementia is unclear
risk factors for stroke should be addressed
HT should be on the lowest dose
HT and breast cancer risk
longer duration of HT increases risk of breast cancer (8 additional cases per 10,000 person years)
usually breast cancer risk increases after 5 years of HT
patients taking HT should undergo regular screening for breast cancer
HT General usage guidelines during menopause
start HT with a low dose and then slightly increase until menopausal symptoms improve thus to be at minimally effective dose
while on HT, reassess risk for CVD, VTE and breast cancer regularly
stop HT by age of 60 or after 5 years of HT due to increased risk for CVD and breast cancer
if possible, use transdermal estradiol to decrease risk of VTE
if patient have uterus, add micronized progesterone
HT side effects
mood symptoms
breast soreness
bloating
vaginal bleeding
alternative therapies to HT
if hormonal therapy is contraindicated or not desired, then 2nd line treatments may be considered for vasomotor symptoms
anti-depressant: venlafaxine (Effexor), desvenlafaxin
anti-epileptics: gabapentin
anti-hypertensives: clonidine
venlafaxine and gabapentin are most commonly used
complementary and alternative therapy is not recommended due to lack of evidence for efficacy and safety
Local vaginal estorgen indication
1st line treatment for vaginal atrophy in absence of vasomotor symptoms
can be added to HT if HT does not resolve vaginal atrophy
Types of local vaginal estrogen
cream: premarin vaginal cream, estragyn cream
vaginal suppository: vagifem
vaginal ring: estring
Local vaginal estrogen risks
Due to only local effect, local vaginal estrogen not associated with CVD, VTE nor breast cancer
Local vaginal estrogen general guidelines
local vaginal estrogen need to be taken life-long
