Flashcards in CM- Abnormal Uterine Bleeding Deck (85):
What is amenorrhea?
What is the difference between primary and secondary?
When should people who do not meet the criteria for primary or secondary be evaluated for amenorrhea?
Amenorrhea is the absence of menstruation.
1. failure to reach menarche by 14 with no secondary sex characteristics
2. failure to reach menarche by 16 with secondary sex characteristics
Absence of menstruation for 6 months or more in a woman with previous periodic menses
If they have amenorrhea but don't fit a category, evaluate if:
1. subject or family is greatly concerned
2. no breasts by 14
3. sexual ambiguity/virilization
What are the 3 general etiologies of amenorrhea?
2. Ovarian failure [hypergonadotrophic hypogonadism]
3. chronic anovulation
What are 6 anatomic causes of amenorrhea?
1. imperforate hymen
2 transverse vaginal septum
3. cervical stenosis
4. intrauterine adhesions [Asherman's]
5. mullerian agenesis
6. labial fusion
What are 6 causes of ovarian failure [hypergonadotrophic hypogonadism]?
3. advanced oocyte atresia [Turner's, X defects]
4. surgical removal
5. premature ovarian insufficiency [POF/POI]
What are the 4 causes of chronic anovulation when estrogen is present [eugonadotrophic eugonadism]?
1. PCOS [polycystic ovarian syndrome]
2. prolactin excess
3. thyroid abnormality
4. ovarian tumors
What are the 3 causes of chronic anovulation when estrogen is absent [hypogonadotrophic hypogonadism]?
1. hypothalamic disorders [eating disorders, stress, over exercise]
2. inherited hypo-pituitary disorders [kallman or IHH]
3. hypothalamic-pituitary lesions [brain tumor]
Patients with ______________ usually present with primary amenorrhea, while patients with _______________ usually present with secondary amenorrhea.
Anatomic abnormalities usually present with primary whereas patients with chronic anovulation usually present with secondary amenorrhea
What is the "rule of pregnancy"?
Pregnancy MUST be ruled out as the most common reason for missed menses in reproductive age women before you look for anatomic, ovarian failure or chronic anovulation causes of amenorrhea.
What are the 5 main categories of abnormal uterine bleeding?
1. amenorrhea [absence of menstruation]
2. ovulatory bleeding [regular, cyclic, predictable]
3. anovulatory bleeding [unpredictable in amount and timing, because endometrium doesn't get a signal to slough]
4. postcoital bleeding
5. postmenopausal bleeding
What is menorrhagia?
Is it usually ovulatory or anovulatory?
What are potential causes?
It is cyclic [ovulatory] menstrual bleeding that is:
1. excessive in duration [over 7 days]
2. excessive in amount [over 80ml]
Potential causes are usually secondary to anatomic uterine abnormalities like:
Rarely it can be chronic anovulatory and caused by endometrial hyperplasia
A patient presents with bleeding that is light and spotty and occurs for longer than 35 days. What is this called?
A patient presents with bleeding that occurs at irregular intervals. What is this called?
A patient presents with bleeding that is excessive and prolonged and occurs at irregular intervals. What is this called?
What is the PALM-COEIN classification system for AUB in reproductive age women?
All classifications are started with AUB [abnormal menstrual bleeding] and are followed by one of the following:
1. HMB [heavy menstrual bleeding]
2. IMB [intermenstrual bleeding]
After that the etiology of the bleeding is named:
Structural causes of bleeding = PALM
-Leiomyoma [submucosal, other]
Non-structural causes of bleeding = COEIN
-Coagulopathy [menometrorrhagia since menarche]
-Iatrogenic [iuds, oral contraceptives]
-Not yet classified
What are the 4 things associated with post-coital bleeding?
1. Cervical cancer
2. cervical erosion
3. cervical polyp
4. cervical OR vaginal infection [trichomoniasis]
A teen has had exessive and prolonged episodes of irregular bleeding since menarche. What is your initial concern?
Coagulopathy is associated with menometrorrhagia
On physical exam, what do the following presentations clue you in to?
1. irregular uterus
2. symmetrically enlarged uterus
3. decidual reaction of the cervix with velvety, friable erythematous lesions on the ectocervix
1. leiomyoma [fibroids]
2. adenomyosis or endometrial cancer
When is it appropriate to order a Pap smear for abnormal menstrual bleeding?
Pap smear is most useful for diagnosing asymptomatic intraepithelial lesions of the cervix and can help screen for invasive cervical [ecto] lesions.
Cytobrush allows cells to be obtained from the endocervix too.
Abnormal cytological findings must be further evaluated.
When is it appropriate to order pelvic ultrasound in a woman with abnormal menstrual bleeding?
If you think the problem is uterine especially and you want to evaluate the endometrial lining.
helpful if the uterus is large [fibroids] or there is a large ovarian mass
- provides more detail bc of close proximity of the probe to the pelvic organs
- hysterosonography uses saline to create the cavity to evaluate endometrial lining
- good for diagnosing fibroids
- endometrial polyps
Describe the procedure of endometrial biopsy. When is it appropriate to order?
Pipelle device or Novak suction curette sample small areas of the endometrial lining to help diagnose uterine bleeding.
Cervical dilation is NOT necessary.
What is the most direct way to assess the endometrium?
Hysteroscopy- and biopsy by direct visualization can be done at the same time
Good for visualizing endometrial polyps
When is bHCG assay used?
1. check for pregnancy
2. complications of pregnancy
3. trophoblastic disease
What are the 5 sources of bleeding in the female genital tract?
1. vagina and vulva [atrophic vaginitis, trauma lacerations, infection, cancer]
2. cervix- erosion, polyp, cancer, myoma
3. Uterus - endometriosis, adenomyosis, hyperplasia, cancer, OCPs, IUDs, pregnancy, Asherman's
4. fallopian tubes - ectopic
5. ovaries - estrogen producing tumors, cysts
What is Asherman syndrome?
What is the pathogenesis?
What are thought to be causes?
It is amenorrhea, hypomenorrhea or recurrent pregnancy loss due to intrauterine scarring [uterine synechiae]
1. destruction of the basal endometrium prevents endometrial proliferation in response to ovarian steroids [estrogen]
2. since no tissue is produced, nothing passes at the end of the luteal phase when progesterone is withdrawn with atresia of corpus luteum
Scarring and basal endometrium damage is caused by:
1. vigorous curette [postpartum hemorrhage, miscarriage]
2. uterine surgery leaving adhesions
3. severe infection
What is the most common solid pelvic tumor in women?
What percent of women have them?
What race is more likely to have them?
What is the cause?
What change occurs in these tumors during pregnancy?
Leiomyomas [fibroids] are benign smooth muscle tumors of the uterus.
25-50% of women have them and they are more common in African American women
The cause is unknown but suggested that the fibroid arised from a single neoplastic cell in the myometrium that goes linear to circular.
In pregnancy, the tumor responds to estrogen and enlarges
What are the 4 locations where leiomyomas can be?
How is diagnosis of leiomyoma confirmed?
1. subserosal - under the serosa/outer margin of the uterus distorting external contours of the uterus
2. submucosal - enters the endometrial cavity distorting the contours of the cavity
3. intramural- entirely within the myometrium
4. pedunculated- on a stalk into the cavity
Diagnosis is confirmed with transvaginal sonography
Only 20-40% of patients with fibroids report symptoms, the most common of which is _____________.
What complaints will this woman typically present with?
menorrhagia- heavy cyclic bleeding
1. frequent changing of sanitary protection
2. interruption of daily life
3. iron deficiency anemia
4. if the fibroid is submucousal it could cause metrorrhagia
What is adenomyosis?
What are the 2 largest risk factors?
What are the 2 most common complaints?
What is the diagnostic gold standard?
It is symmetric, globular uterine enlargement caused by ectopic rests of endometrium in the myometrium.
It is though to be caused by downward invagination of the basal endometrium into the myometrium [because there is no submucosa]
Age and parity [number of times given birth] are the largest risk factors
1. menorrhagia - due to vascularization of endometrial lining
2. dysmenorrhea with large clots in menses [due to PGs in myometrial tissue in response to endometrium]
MR is the diagnostic gold standard
What are the 3 biggest risk factors for the development of endometrial polyps?
What factors are associated with malignant transformation?
Maligancy = the above risks, plus postmenopausal age, large polyp size
What are the 5 causes of bleeding in early pregnancy?
1. threatened abortion [bleeding but fetus is alive]
2. incomplete abortion [some fetal/placental tissue]
3. first trimester demise [retained dead fetus]
4. ectopic pregnancy
5. gestational trophoblastic disease
How do you differentiate between threatened abortion and ectopic pregnancy?
Both present with pain in the absence of bleeding.
Threatened abortion: cramping/colicky, mild and intermittent
Ectopic pregnancy: unilateral pain in the lower abdominal quadrant
SONOGRAPHY is used because it can demonstrate a gestational sac within the uterus and a cystic mass in the adenexal area.
In the absence of bleeding it is best classified as threatened abortion and managed by observation
A patient has acute and intense pain associated with syncope. There is recovery and gradual diminuation of the lower ab pain but then it gradually resurges.
The patient experiences shoulder pain.
What is this patient presenting with?
ruptured ectopic pregnancy
What 3 things are highly suggestive of an ectopic pregnancy?
1. positive pregnancy test
2. empty uterus via transvaginal sonography
3. adnexal mass by vaginal sonography
What is the DDx for post menopausal bleeding?
What is the most serious?
What is the most common?
1. atrophy of the endometrium - most common
2. exogenous hormones
3. tumors of the reproductive tract- most serious
4. vaginal atrophy/vulvar lesions
*must be considered endometrial cancer until proven otherwise
What causes atrophy of the endometrium in post menopausal women?
The atrophy is secondary to hypoestrogenism.
The collapsed atrophic endometrium has no fluid/mucus to prevent intracavitary friction which leads to microerosions.
Microerosions cause chronic inflammatory reaction which is prone to light spotting
What is the first step that should be done if there is bleeding in a post-menopausal woman?
sonography and if warranted endometrial tissue sampling to rule out endometrial cancer
You are doing examination on a postmenopausal woman who presents with a complaint of bleeding. You note thin vaginal tissue with ecchymosis. What is the likely diagnosis?
What is the DDx of gynecological bleeding in pre-pubertal girls?
vaginal tumor [sarcoma botryoides]
What is the DDx of abnormal bleeding in an adolescent?
Bleeding dyscrasias [coagulopathy]-heavy bleeding/hemorrhage]
Breakthrough bleeding on OCPs
What is the DDx of abnormal bleeding in a woman of reproductive age?
1. pregnancy complication
2. cancer [cervix, endometrium, vulva/vagina]
4 structural problems [polyps, adenomyosis, leiomyomas]
5. breakthrough bleeding on OCPs
What is the DDx of abnormal bleeding for a postmenopausal woman?
2. structural problems -polyps, leiomyoma
3. endometrial hyperplasia
5. breakthrough bleeding on HT/ET
What is the LH/FSH levels, estrogen levels, and primary defect in hypergonadotrophic hypogonadism?
LH/FSH is high
Estrogen is low
Primary defect is in the ovaries
What are the LH/FSH levels, estrogen levels, and primary defect in hypogonadotropic hypogonadism?
LH/FSH is low
Estrogen is low
Primary defect is in the HP axis
What are the LH/FSH levels, estrogen levels and primary defect in eugonadotropic eugonadism?
LH/FSH is normal
Estrogen is normal
Primary defect is acyclicity due to:
2. increased prolactin
3. thyroid disease
4. chronic illness
What are the anatomic developmental defects and acquired defects that can cause irregular bleeding?
1. imperforate hymen
2. transverse vaginal septum
3. Mullerian agenesis
1. leiomyomas and polyps
2. Asherman's syndrome
What is premature ovarian failure/insufficiency?
What will FSH, LH, and estrogen levels be?
How is diagnosis of this condition made?
Loss of ovarian function prior to age 40 [after age 40 is just considered menopause]
Loss of negative feedback from ovarian steroids and inhibin will elevate plasma LH/FSH
Diagnosis is made by demonstrating 2 elevated FSH levels >40 drawn 1 month apart
What are the 8 etiologies for premature ovarian failure?
1. chromosomal [turners]
2. fragile X
3. iatrogenic [chemo, radiation, surgery]
4. infectious [mumps oophoritis]
Describe chromosomal causes of POF.
Gonadal dysgenesis in which the germ cells undergo accelerated atresia and the ovary is replaced with a fibrous streak.
1. Turner's 45X
2. chromosomal mosaicism with or without structural abnormalities of X. 45X, 46XX
What causes fragile X syndrome?
How does this contribute to POF?
triple repeat sequence mutation [CGG] in the X-linked FMR1 gene. >200 repeats = fully expanded mutation.
The repeat sequence is hypermethylated, silencing the gene expression.
Pre-mutation [50-200 repeats] is associated with POF in females
What should all women with unexplained POF be evaluated for?
the presence of autoimmune disorders at regular intervals.
Anti-ovarian Ab often present with adrenal insufficiency, hypothyroidism, SLE, DM, and parathyroid disorders [serum Ca and P]
How does galactosemia contribute to POF?
It is an impairment of the GALT enzyme to metabolize galactose from milk based foods.
POF occurs in 85% of untreated patients.
Treat with dietary restriction.
What enzymatic deficiency is associated with primary amenorrhea, sexual infantilism, and hypertension?
17a-hydroxylase deficiency because it blocks cortisol and adrogen pathways in the adrenal gland.
Only aldosterone is made -->hypertension
What are the etiologies of chronic anovulation with low estrogen?
Will these women experience progesterone withdrawal bleeding?
1. functional [stress, anorexia, exercise]
2. inherited HP abnormalities
3. HP lesions
5. thyroid disease
6. chronic illness
They will NOT experience withdrawal bleeding after progesterone treatment because the endometrium will be thin from lack of estrogen.
What is the mechanism by which functional hypothalamic amenorrhea may result in abnormal menstrual cyclicity?
Eating disorders -
1. decrease leptin which increases NPY and hunger
2. insulin, glucagon, catecholamines
These lead to abnormal pulsatile GnRH--> abnormal pulsatile LH/FSH -->anovulatoin amenorrhea
increased CRH-->increased cortisol--> abnormal pulsatile GnRH->abn LH/FSH--> anovulation/amenorrhea
increase opioids [endorphins] which leads to abnormal GnRH-->LH/FSH--> anovulation/amenorrhea
What are the 2 inherited HP abnormalities?
How do they differ?
1. Idiopathic hypogonadotropic hypogonadism [IHH]
2. Kallmann syndrome
In addition to hypogonadotropic hypogonadism, Kallmann syndrome patients also have defects in the ability to smell [thought to be due to mutated X-linked KAL-1 that is critical for migration of GnRH and olfactory nerves from the olfactory placode]
A young woman presents with delayed puberty, irregular menses, anosmia, eunuchoid habitus and unilateral renal agenesis. What is the likely cause?
What are the 4 main hypothalamic lesions that can lead to hypogonadotropic hypogonadism?
1. Tumors [craniopharygiomas, germinoma, glioma, teratoma ,etc]
2. Inflammation [TB, sarcoidosis
3. CNS trauma
Post-partum, a patient presents with failure to lactate and ovulate. She has lost axillary and sexual hair. She has secondary hypothyroidism and adrenal insufficiency. What is the cause?
Sheehan syndrome - severe postpartum hemorrhage leads to hypotension and decreased perfusion of the pituitary.
How do large tumors of the ant. pituitary cause amenorrhea?
Any cell type:
1. damage to the pituitary stalk
2. compression of gonadotropes
3. complications of surgery/radiation
1. direct production of excess prolactin
What are the 5 etiologies of chronic anovulation with normal estrogen?
3. thyroid disease
4. chronic illness
5. tumors of ovary or adrenals
What are 3 causes of hyperprolactinemia?
How is prolactin regulated in the HP axis?
1. small prolactinomas
2. sleep, eating, pregnancy, coitis
3. chest wall stimulation
1. dopamine - inhibitory
2. seratonin, NE,opioids, estrogen, TRH - stim.
What is the mechanism by which hyperprolactinemia may result in abnormal menstrual cyclicity?
1. Elevated prolactin will stimulate a reflex increase in dopamine.
2. GnRH neurons have dopamine receptors which disrupt their normal pulsatile secretion.
3. This disrupts normal LH/FSH secretion.
Prolactin also has direct effects on the ovary
What is the effect of pregnancy on a prolactinoma of the pituitary?
In late pregnancy, the estrogen induced hyperplasia of gonadotropes will expand the tumor leading to headaches and compression of the optic chiasm
Thyroid disease can be associated with amenorrhea or menorrhagia. What are the classic associations?
Amenorrhea/oligomenorrhea = hyperthyroidism
Menorrhagia = hypothyroidism
What are the 2 mechanisms by which hypothyroidism may result in abnormal menstrual cyclicity?
1. Hypothyroid results in a reflexive increase in TRH in the hypothalamus.
TRH stimulates prolactin production--> increased dopamine via reflex--> disrupted GnRH -->LH/FSH--> anovulation/amenorrhea
2. Thyroid hormone also increases SHBG.
In hypothyroidism, there will be low thyroid hormone and low SHBG so more free estrogen. This can lead to anovulation with menorrhagia
What 3 chronic illnesses tend to lead to hypogonadotropic hypogonadism?
3. malabsorption syndrome
What is the most common endocrine disorder in reproductive age women?
What is the Rotterdam criteria?
To be diagnosed with PCOS, patients must have 2 out of the following 3 criteria:
1. oligo or anovulation
-clinical = hirsutism, acne
-biochemical = increased testosterone, DHEAS
3. polycystic ovaries on sonogram
-over 12 cysts that are under 10mm each
Why is PCOS considered a diagnosis of exclusion? What other disorders can present in a similar fashion?
The following disorders can also present with oligo/anovulation and/or hyperandrogenism:
2. thyroid disease
4. Cushing syndrome
5. androgen-secreting tumors
What are the characteristics of polycystic ovaries?
1. mildly enlarged
2. smooth, white, thick capsule
3. multiple subcapsular follicular cysts in various stages of atresia
4. hyperplastic stroma
5. absent corpora albicans
You do an ultrasound and note >12 cysts of under 10mm each. The ovarian volume is over 10 ml.
The ovaries have a black pearl necklace appearance with fluid filled follicles forming a ring around the periphery of the ovary .
What is the likely diagnosis?
Describe PCOS-associated obesity.
It is android [apple shaped] pattern obesity with increased hip-to-waist ratio
What are the major repercussions of PCOS?
- menstrual irregularity
- endometrial hyperplasia/cancer
2. hirsutism/acne [hyperandrogenism]
3. metabolic disorders
- insulin resistance/diabetes
4. pregnancy complications
5. depression, sleep apnea
When can the presence of PCOS be suspected?
A few years after puberty.
The majority of adolescents will start with irregular anovulatory cycles, but will become regular in a few years.
PCOS will develop persistant oligomenorrhea [<8 periods a year] or amenorrhea
What physiologically is the cause of why women with PCOS have long periods w/o bleeding followed by severe menorrhagia at unpredictable intervals [menometrorrhagia]?
Why are obese women with PCOS more likely to experience menorrhagia?
Estrogens result in the progressive thickening of the endometrial lining.
Without normal ovulation, the usual progesterone-mediated mechanism for slowing growth and mediating synchronous sloughing is absent.
Estrogen fluctuates somewhat and can sometimes cause "estrogen withdraw bleeding" OR if the endometrium becomes unstable with overgrowth it will cause bleeding
Adipose tissue converts androgens to estrogen in the peripheral tissue which can cause gonadotropin suppression and 'estrogen withdraw"
What causes hirsutism, acne and alopecia in patients with PCOS?
There is an elevated LH/FSH ratio due to irregular pulse from the hypothalamus favoring LH or irregular androgen/estrogen feedback.
LH causes the thecal cells to make androgens
FSH causes granulosa cells to aromatize the androgens to estrogen. It can't keep up with the number of androgens produced and some leak to the periphery.
Androgens in the periphery can cause hirsutism, acne and alopecia but NOT virilization [deep voice, clitoromegaly].
The amount of hirsutism depends on:
1. Testosterone converting to DHT in target tissue
2. end organ specificity such as familial pattern or 5areductase activity
What factors can elevate levels of SBHG in serum?
What decreases levels [increasing free androgens]?
SBHG is increased by thyroid hormones.
SBHG is decreased by :
What 2 metabolic disorders/problems are women with PCOS at risk to develop?
1. Insulin resistance/diabetes- it is an independent risk factor from obesity because the lean PCOS women get it too. It is associated with acanthos nigricans - velvety thick brown plaques at the back of neck, under breast, armpit
2. hyperlipidemia- increased LDL, decreased HDL
What pregnancy risks are associated with PCOS?
1. increased rate of miscarriage [due to elevated insulin?]
2. gestational diabetes
3. pregnancy-induced hypertension
The etiology of PCOS is currently unknown but what is the "common denominator" in the pathogenesis of PCOS?
Self-perpetuating non-cyclic hormonal pattern either from primary defects or defects in the HP axis.
What is the proposed pathophysiology behind PCOS?
1. Alterations in GnRH release lead to relative increase of LH versus FSH so there is decreased aromatase conversion of testosterone to estrodiol
2. increased intrafollicular androgen levels result in follicular atresia, and increased circulating androgens lead to hirsutism, acne, alopecia, lipid profile
3. Elevated androgens are converted in the periphery to estrogens in the stromal cells of adipose tissue resulting in chronic feedback on the hypothalamus and pituitary
4. unopposed estrogen stimulation can lead to endometrial hyperplasia
5. insulin resistance leads to follicular atresia and acanthos nigricans
6. lack of follicular development results in oligo-anovulation
What serum tests should be done to evaluate PCOS?
What other tests?
1. hCG - rule out pregnancy
2. prolactin/TSH- rule out causes of anovulation
3. Testosterone, 17OH-P, DHEAs - rule out other causes of hyperandrogenism
4. 2hr glucose tolerance - evaluate diabetes
5. fasting lipid panel - evaluate hyperlipidemia
6. FSH levels
1. pelvic ultrasound - check ovaries for PCOS
2. endometrial biopsy- eval. for endometrial hyperplasia
In the initial examination of amenorrhea, what 3 features are key to look at?
1. degree of sexual maturation [breasts, hair] which can differentiate amenorrhea vs. delayed puberty
2. presence/absence of a uterus [anatomic vs. functional]
3. current estrogen status [hypo vs. eu]
What are the fundamental treating concepts for a person with hormonal causes of abnormal menstrual bleeding?
1. treat the underlying disease
-hyperprolactinemia --> dopamine ag
- hypothyroid --> levothyroxine or leiothyronine
2. if not making estrogen, give estrogen
3. if giving estrogen, give progesterone to prevent endometrial hyperplasia
4. treatment varies depending on whether the patient wants to get pregnant