Ovarian disorders Flashcards
Symptoms of functional ovarian cysts are result of:
- Rupture of contents (chemical peritonitis)
- Torsion of enlarged ovaries
- Mechanical pressure
possible symptoms of functional ovarian cysts
- Menstrual irregularities
- Pelvic pressure or pain
- Large - constipation or urinary frequency
*
how to dx functional ovarian cysts
- possible on pelvic exam
- Pelvic US
MC functional ovarian cyst
follicular cysts
causes of follicular cysts
- Due to failure in ovulation
- Incompletely developed - does not rupture
- Fluid does not get completely reabsorbed
s/s of follicular cysts
- Usually asx
- bleeding and torsion
- Large cysts - aching pelvic pain, dyspareunia
- abnml uterine bleeding with disturbance of ovulation
tx for follicular cysts
- observation; symptomatic; resolve spontaneously < 2 mo
- OCPs - may not speed resolution of cysts
- Aspiration - done in past; not thought to help dx or reduce recurrence
- Cystectomy - for large or painful cysts
causes of Corpus Luteum Cysts
- accumulation of fluid inside a corpus luteum
- May be more likely if taking clomiphene (Clomid)
- Failure of corpus luteum to involute
s/s of corpus luteum cysts
- asx or local pain, tenderness,
amenorrhea or delayed menstruation
- May lead to ovarian torsion or cyst rupture and bleeding - Can mimic an ectopic pregnancy
- Severe bleeding/rupture - acute abdomen, hypovolemic shock
tx for corpus luteum cysts
- Symptomatic; resolve spontaneously < 2m
- OCPs - recommended but questionable benefit
- Surgical intervention - if hemorrhaging or torsion
causes of theca lutein cysts
- elevated levels of hCG
- Hydatidiform mole, choriocarcinoma, multiple gestation, hCG therapy
- MC bilaterally, filled with clear fluid
- May occur as multiple simultaneous cysts
s/s of theca lutein cysts
- usually minimal sx
- May have pelvic heaviness or aching
- May see rupture and bleeding or ovarian torsion
tx for theca lutein cysts
- sx; underlying cause
- Gradually resolve as hCG return to normal
- months to resolve
- Surgical intervention - if torsion or hemorrhage
endometric foci on ovarian surface
Seen in pts with endometriosis
May develop fibrous enclosure
Often called “chocolate cysts”
Endometriomas
s/s of Endometriomas
- pelvic pain, dyspareunia, dysmenorrhea, infertility
- CA-125 may be elevated
tx for endometriomas
as for endometriosis
May be removed laparoscopically
- Filled with various types of tissue - Fatty material, hair, teeth, bits of bone, cartilage
- 10-15% of ovarian cysts in premenopausal women
- Rarely neoplastic but may rupture
Dermoid Cysts
- Develop from cells on the outer surface of the ovary
- Benign but can grow very large and cause pain
Cystadenomas
- Persistent anovulation
- Enlarged polycystic ovaries
- Secondary amenorrhea or oligomenorrhea
- Obesity, hirsutism, infertility
PCOS - Stein-Leventhal Syndrome
prevalnce of PCOS?
6.5-10%
- 50% are hirsute
- +50% are obese
cause of PCOS?
- Thought to be complex multivariable disorder, similar to T2DM or MetS
- genetic and environmental factors
- 20-40% prevalence in 1st degree relatives - HPO dysfunction - Altered LH action, altered folliculogenesis
- Insulin resistance and obesity
- Hyperandrogenism
criteria diagnosis for PCOS
At least 2 of the following:
1. Oligo-ovulation (oligomenorrhea) or anovulation (amenorrhea)
1. Hyperandrogenism
1. Polycystic ovaries on US
- “Oyster ovaries” - enlarged and sclerocystic ovaries; smooth, pearl-white surfaces w/o indentations
obstetric symptoms of PCOS
- Leading cause of female infertility
- inc early pregnancy loss - 30-50% (15% baseline)
- inc pregnancy complications
gynecologic symptoms of PCOS
- Menstrual abnormalities
- Ovarian cysts
- Pelvic pain or pressure
- Endometrial neoplasia
psych symptoms of PCOS
- Anxiety, depression
- Low self-esteem
- Negative body image
- Dec quality of life
Constitutional/Endocrine sx of PCOS
- Wt gain or obesity
- Insulin resistance
- Sleep apnea
- NAFLD
- Dyslipidemia
- MetS
- Usually do not see signs of virilization - NO inc muscle mass, dec breast size, deepened voice, clitoromegaly
Dermatologic sx of PCOS
- Hirsutism - coarse, dark hairs in male pattern (face, chest, stomach, back) - 70-80% cases - 2o PCOS
- Acne, oily skin, dandruff
- Hair loss - Male pattern baldness; thinning hair
- Acanthosis nigricans
w/u for PCOS
- Hormonal
- Androgens - mildly elevated
- SHBG - decreased
- Inc LH:FSH ratio - Lipid abnormalities - high LDL and TG, low HDL
- Insulin resistance and type II DM
- Pelvic US - multiple follicles/cysts BL; nml possible
Signs of anovulation on diagnostic testing for PCOS
- Persistently high LH and low FSH
- Low day-21 progesterone level
- Anovulation on sonographic follicular monitoring
observation would be best for what type of PCOS pt?
maintenance?
- with regular cycle intervals (8-12/yr) and mild hyperandrogenism who do not desire to conceive
- Regular screening for lipids, DM, weight
lifestyle changes for PCOS
- 5-10% wt loss can restore normal ovulatory cycles in some patients
- Reduces insulin and androgen levels
- Well-balanced hypocaloric diet instead of low-carb/high-protein - Limited processed foods and foods with added sugars
- Regular aerobic exercise
types of hormonal therapy for PCOS
- COC
- progesterone-only therapy
MOA of COC for PCOS
- Induce regular menses and antagonizes endometrial proliferation
- Reduce androgen lvl → suppress FSH/LH release, increase SHBG
- Chose COCs with progestins that have less androgenic properties
- Norethindrone, norgestimate, desogestrel, drospirenone - vaginal ring/patch - not well studied
- If not pregnant - progesterone to cause withdrawal bleed before COC
for suspected PCOS, If pt has not had menses for > 4 weeks what must you obtain?
pregnancy test
- Oral OR IUD
- Mainly used in patients who cannot take COC
- Helps prevent endometrial hyperplasia/cancer
- Some forms can be used for contraception
- Does not tx hyperandrogenic sx
Progesterone-only therapy
Insulin sensitizing agents for PCOS?
- metformin - May inc spontaneous ovulation induction; GI upset, lactic acidosis
- rosiglitazone (Avandia) / pioglitazone (Actos) - Less well-studied, concerns over SE; Category C in pregnancy
- GLP-1 agonists - wt loss
tx for NAFLD/NASH in PCOS?
- Metformin - can reduce risk, reduce progression
- Weight loss can also improve metabolic/hepatic function
tx for hirsutism
- COCs - lower androgens, inc SHBG; 1st-line/initial tx
- GnRH agonists - lower androgen lvl; Expensive and undesirable SE of bone loss, menopausal s/s
- Depilation - hair removal above skin surface; Shaving, topical chemical depilatories
- Epilation - removal of entire hair shaft; Mechanical, electrolysis, laser
- Eflornithine Hydrochloride (Vaniqa)
- Spironolactone
- Finasteride, dutasteride
Antimetabolite topical cream applied BID
Inhibits enzyme for hair follicle division and function
Does not permanently remove hair
Expensive
which tx for hirsutism
Eflornithine Hydrochloride (Vaniqa)
SE and CI of Eflornithine Hydrochloride (Vaniqa)
- SE - acne, burning, redness, ingrown hair
- CI - patients with known hypersensitivity
Often used in combination with contraceptives
6-month trial of COC followed by this medication
May cause metrorrhagia
Not safe to fetus if patient should become pregnant
what hirsutism tx?
spironolactone
Decreased testosterone conversion; may cause decreased libido
May also help with male-pattern hair loss
Not safe to male fetus if pt becomes pregnant
which hirsutism tx?
Finasteride, dutasteride
5-alpha-reductase inhibitors
tx for acne in PCOS
involves lowering androgen levels
- COC
- Antiandrogen agents - spironolactone, 5-ɑ reductase inhibitors
- Adjuvant - topical retinoids, BPO, isotretinoin, topical or systemic abx
tx for acanthosis nigricans in PCOS?
- Tx aimed at improving insulin sensitivity
- Topical treatments usually do not improve
2 Novel and Emerging Therapies for PCOS
-
Myo-Inositol - dietary supp; Second messenger - may help improve insulin sensitivity
- maybe help ovulatory frequency, wt loss -
NK34 antagonists / Kappa-receptor agonists - slows GnRH pulses
- showed improved LH and testosterone lvls - No effect on ovulation noted to date
before Ovulation Induction, what conservative tx should always be attempted first?
wt loss and exercise
what 4 medications help with ovulation induction
- Letrozole (Femara) - 1st-line
- Clomiphene citrate (Clomid) - formerly 1st-line
- Metformin - used alone or in combo with clomiphene
- Exogenous gonadotropins
MOA of Letrozole (Femara)
- inhibits aromatase
- inc production of GnRH → FSH/LH
- Given days 3-7 of menstrual cycle to produce a larger amount of FSH
SE and CI of Letrozole (Femara)
SE - hot flashes, fatigue, dizziness, joint pain - tolerable due to short duration
CI - pregnancy (category X), hypersensitivity to drug
DDI of letrozole
methadone/levomethadone, tamoxifen
Pros of letrozole
as compared to clomiphene citrate
- More monofollicular development
- Shorter half-life (48 hours vs. 2 weeks for Clomid)
- No direct antiestrogenic adverse effects on endometrium
- Lower serum estradiol levels
- Higher rates of live birth, esp in obese women
which ovulation induction medication is a SERM and binds to hypothalamus, blocking estrogen receptors
Increased production of GnRH → FSH/LH
Acts as an estrogen agonist if estrogen is absent
Clomiphene citrate (Clomid) - formerly first-line
SE and CI of Clomiphene citrate (Clomid)
-
SE - ovarian enlargement and cysts, hot flashes, bloating, GI upset, breast discomfort, abnormal menses, HA
- Serious - alopecia, inc risk of ovarian or endometrial CA, ovarian hyperstimulation syndrome, uterine fibroid enlargement - CI - pregnancy (category X), liver disease, undiagnosed abnormal uterine bleeding, ovarian cysts (not due to PCOS)
DDI of clomiphene citrate
drugs that act on HPO axis - estrogens, SERMs, aromatase inhibitors, gonadotropins, GnRH agonists
clomiphene citrate Induces ovulation in ?%, but successful pregnancy in only %
- 75
- 40
used alone or in combo with clomiphene
Category B in pregnancy
which ovulation induction medication
metformin
- cause ovulation in 72% and pregnancy in 45%
- High risk for ovarian hyperstimulation syndrome
which ovulation induction medication
Exogenous gonadotropins
Main cause of symptoms in Ovarian Hyperstimulation Syndrome?
Vascular hyperpermeability - 3rd spacing of fluid
s/s of mild ovarian hyperstimulation syndrome
- bloating, N/V/D, weight gain
- Ovaries enlarged 5-12 cm; mild ascites
pt with ovarian hyperstimulation syndrome has increased weight gain (>2 lbs/d), N/V/D, dark urine, oliguria, thirst, dry skin and hair
what is the severity of her s/s?
moderate
s/s of severe ovarian hyperstimulation syndrome
SOB, pleural effusion, severe oliguria, pain in the calf / chest / abdomen, hemoconcentration, thrombosis, respiratory distress
tx for Ovarian Hyperstimulation Syndrome
Supportive; resolves 1-2 wks after d/c meds
Lower incidence with Clomid than synthetic FSH
surgical tx options for PCOS?
- Laparoscopic ovarian surgery - SE: adhesions
- Oophorectomy
Creates focal areas of damage in ovary
Cauterization, laser “drilling,” biopsies
May induce ovulation in patients unresponsive to medical therapy
what surgery?
Laparoscopic ovarian surgery
MCC of ovarian torsion?
ovarian enlargement - 50-80%
10-22% of ovarian torsion cases occur during ?
pregnancy
- A surgical emergency - ischemic condition
- Prompt dx critical for preserving function
- May involve ovary alone or oviduct (adnexal torsion)
Ovarian Torsion
- sudden onset, severe, unilateral, lower abd. pain
- Over 50% on right side; may radiate to flank, thigh or groin
- May develop after episodes of exertion
- fever, N/V, adnexal mass on exam, vaginal bleeding possible
Ovarian Torsion
atypical presentation of Ovarian Torsion
- Bilateral, mild or intermittent pain
- No tenderness on examination
w/u for ovarian torsion
- sonography - Disruption of normal doppler blood flow to ovary
- hCG
on sonography you see
Multiple follicles rimming an enlarged ovary
“Bulls’-eye”, “whirlpool”, “snailshell”
Rounded, enlarged ovary +/- heterogeneous stroma
dx?
Ovarian Torsion
tx for ovarian torsion
- Surgery - laparoscopy or laparotomy
- Cystectomy at surgery or after
- necrotic - oophorectomy - post-op monitoring - f, leukocytosis, peritonitis
- mgmt similar during pregnancy
- progestational support If ovary removed prior to 10 weeks,
MC source of ovarian cancer?
Epithelial ovarian cells - >90% of all malignant ovarian tumors
ovarian CA typically occur in pts near or at what stage of their menstrual cycle?
menopause
MC carcinoma of ovarian CA?
75% - serous cystadenocarcinomas
ovarian CA is associated with what serum marker?
CA-125
other causes/tumors of ovarian CA?
- Germ cell tumors - present in 20s-30s
- Sex Cord-Stromal Tumors - 5-8%
- 5% of ovarian cancers - due to metastases
which tumor has a Better prognosis than EOC cancers
30-40% - dysgerminomas
Associated with AFP, hCG, LDH
Germ cell tumors
positive RF for ovarian CA
-
Positive family hx
- Strongest risk - 10-15% of pts - Increased age
- Caucasians
- smoking
-
GYN-related
- Early menarche (< 12 yrs)
- Late menopause (> 50 yrs)
- Endometriosis
- Nulligravidity - Possible - obesity, talcum powder use
negative RF of ovarian CA?
- Oral contraceptive pill use
- Longer duration - more protective
- Reduced to half by 15 years of use - Breastfeeding
- Progesterone therapy
- Tubal ligation
- Hysterectomy/Salpingectomy
lifetime risk of ovarian cancer?
%
1.7%
which BRCA is MC for ovarian cancer?
Breast-Ovarian Cancer Syndrome
BRCA1
Breast-Ovarian Cancer Syndrome MC affects what pt demographic?
MC in women of Ashkenazi Jewish, French Canadian, Icelandic descent
Hereditary Nonpolyposis Colorectal Cancer syndrome not only has a risk for ovarian CA but what other CAs?
higher risk of colon, breast, endometrial CA
possible tx for women with any known genetic predisposition for CA?
prophylactic bilateral salpingo-oophorectomy
Better to do by age 35 if possible
s/s of early ovarian CA?
poorly defined or vague symptoms
- GI - bloating, abdominopelvic pain, early satiety, indigestion
- GU - urinary frequency or urgency, dyspareunia
- Other - fatigue, back pain
- does not prompt pt to seek help
s/s of late ovarian CA?
70% of cases
- Early sx + inc abdominal girth (ascites), nausea, anorexia, dyspnea (pleural effusions)
- 15% of reproductive-age patients - menstrual abnormalities
solid, fixed, irregular adnexal mass
Unilateral cystic masses are benign in 95% of cases
Abdominal distention, upper abdominal mass, ascites
LAD - inguinal, Sister Mary Joseph’s nodule
dx?
ovarian CA
Metastatic disease to the skin is rare but possible
w/u for ovarian CA?
- CA-125
- Younger pts - serum AFP, LDH, hCG
- HE4 - similar sensitivity to CA-125; Approved for monitoring ovarian CA but not screening
- Other markers - CEA, CA 19-9, apolipoprotein A - not specific
- Panel tests - OVA1, Overa
- Algorithms - ROMA, RMI, ADNEX
- abnml hormone levels
- pelvic US - Limited in making definitive dx
- CT/MRI
- Dx: BX and tissue pathology
elevated CA-125 can be seen in what other conditions?
endometriosis, leiomyoma, PID, cirrhosis
rare for healthy women to have elevated CA-125
what pelvic US findings would indicate cancer?
solid, septations, ascites
tx for EOC cancers?
-
Surgery - Required unless pt status cannot tolerate surgery
- Definitive dx and staging
- Removal of tumor and contralateral adnexa even if grossly normal
- + hysterectomy and infracolonic omentectomy -
Medical
- chemo - 4-6 wks after surgery
what predicts persistent EOC cancer?
Elevated CA-125 level
tx for germ cell CA
- Surgery
- dx at earlier stage > EOC
- Removal of involved adnexa
- May preserve normal-appearing contralateral adnexa, uterus
- Still perform surgical staging -
Medical
- MC curable
- Chemotherapy and radiation can be helpful
Second MC GYN malignancy
MCC of death in GYN malignancies
ovarian CA
prognosis of ovarian CA
- Stage 1 EOC - 5-yr survival 83-90%
- Stage 4 EOC - 5-yr survival 19%
- Germ cell tumors better rates > EOCs
- Dysgerminomas - 5-year survival 95%
