Module 3: Menstrual disorders and amenorrhea
REcommend _________________ for all women younger than the age of 30 years who have a diagnosis of ovarian failure
a karyotype test - many causes of premature ovarian failure (including genetic conditions) - autoimmune diseases (Addison's) (check Anti-adrenal antibodies)
while African American women have a 30% decreased incidence of being diagnosed with endometrial cancer (when compared to Caucasian women), they have a 2 ½ times higher risk of death if they are diagnosed with endometrial cancer - Why?
a result of healthcare disparities and the reality that African American women are more likely to be diagnosed with a more advanced stage of the disease
your patient with heavy menstrual bleeding wants contraception as well as fixing the current illness. what medication is the best choice? a. COCs 1pill BID then 1pill a day for 2 weeks and continue b. Progestin-only (Norethindrone) 5mg BID for 3wks and decreasing to Daily dosing c. LNG- IUS (Mirena) d. Tranexamic acid
a. COCs: treatment with an estrogen- progestin contraceptive is a better choice
What exam/test is essential for a woman of any age who is (or has been) sexually active or has abdominal pain, anemia, irregular bleeding, or bleeding that is so heavy her hemodynamic stability is compromised. a. pelvic exam b. CBC c. GC/CT swab d. Blood pressure e. PT/PTT
a. pelvic exam. But, if the patient is an adolescent who is not sexually active, has only recently began menstruating, and has a normal hematocrit, a pelvic examination is most likely unnecessary.
What laboratory tests should you order to rule out vWD causes of AUB a. ristocetin cofactor assay b. General labs + colposcopy w/ biopsy;endometrial bx; hysteroscopy c. General labs + FSH, LH, Prolactin levels, TSH, T3 and T4 d. General labs + MRI, CT scan + cortisol levels
a. ristocetin cofactor assay
contraindication of using estrogen for heavy menstrual bleeding
High estrogen = precipitate thrombotic event : hx of thrombosis, fhx of Idiopathic venous thromboembolism
a woman who presents with severe bleeding from a raw and denuded endometrium may require
High-dose estrogen to stop the bleeding. -- Estrogen therapy will provide rapid growth of a denuded endometrium. then add progesterone (ex: medroxyprogesterone acetate)
Pathologic causes of anovulation
Hyperandrogenic disorders (i.e. PCOS) Hypothalamic dysfunction (secondary to anorexia nervosa) Hyperprolactinemia Iatrogenic (secondary to radiation therapy, chemotherapy or medications) Thyroid disorders Primary pituitary disorders
TSH is ordered to r/o hypo/ hyperthyroidism. What are the expected result if + diagnosis
Hypo: >4.0 hyper: <0.8
Normal menses are governed by what endocrine system? =
Hypothalamic- pituitary- ovarian axis= leading to ovulation
___________is the last resort for women who experience ongoing HMB that has not resolved with other treatments or who do not wish to preserve their fertility
Hysterectomy
Saline infusion sonohysterography (SIS) may offer an even more complete evaluation of the endometrium, but cannot be undertaken if the woman has :
IUD in place
Pharmacologic causes of AUB
IUD, depo provera, Paragard
COEIN- I
Iatrogenic
All women with anovulation require management of this condition: Why?
If left untreated, endometrial cancer can occur, regardless of the woman's age.
Typical treatment of anovulation amenorrhea
Inducing menses using a progestogen such as medroxyprogesterone acetate 5 to 10 mg daily for the first 12 to 14 days of the cycle.
AUB classification and terminology AUB: all-encompassing term referring to any uterine bleeding that is ______________ in amt, frequency, duration or timing (i.e., cycle irregularity)
Irregular
PALM- L
Leiomyoma "fibroids"
PALM [ Structural Abnormalities ] AUB- L: what is the fibromuscular benign tumors in the myometrium called?
Leiomyoma (Fibroids)
If there is no explanation of hypogonadism or hyperprolactinemia, you should order
MRI
____________ and _________ scan may be used to diagnose adnexal masses, adenomyosis, uterine fibroids, and pituitary adenomas.
Magnetic resonance imaging (MRI) and computed tomography (CT) scan
PALM- M
Malignancy and hyperplasia
Pharmacologic mgmt of chronic non-life-threatening heavy menstrual bleeding - Progesterone therapy Medications & dosing & frequency changes & duration
Medroxyprogesterone acetate 10-20mg BID ** usual treatment or Megestrol 20-40mg BID or Norethindrone 5mg BID Only if endometrium is normal or increased in thickness. Treatment should last 3 wks, decreasing to once daily dose after 7-10 days
How can you get adequate information from patient to determine 'out-of-the-ordinary' bleeding of uterus?
Menstrual diary of last 3 months
Examples of AUB-I that causes irregular spotting & bleeding after placement
Mirena, Skyla, Liletta, and paragard (resolves within 3-6 months after placement)
If hemodynamically stable HMB, administering _________________ can also result in the reduction of bleeding within 24 hrs.
Monophasic COC
Myomectomy vs. uterine artery embolization in treating fibroids
Myomectomy is better in improving fertility
MOA of NSAIDs in HMB
NSAIDs interfere with the transformation of arachidonic acid to cyclic endoperoxidase --> blocks the production of prostaglandins = it's also a good painkiller = tx for dysmenorrhea
COEIN- N
Not yet classified
What 2 conditions are associated with an increased risk of endometrial cancer?
Obese PCOS
Outflow tract causes of AUB - what does Uterine or cervical congenital structural abnormalities cause
Obstruction --> menstrual flow impossible or abnormal
Norethindrone
Ortho Micronor, Heather, Camila, Errin, Aygestin
Serum FSH indireclty measures ovarian function. if + progesterone challenge, and FSH level is low in amenorrhea woman, what is the diagnosis?
Ovaries functioning fine (low FSH) - chronic anovulation
the presence of premenstrual symptoms may indicate__________
Ovulation
COEIN- O
Ovulatory dyfx
[ COEIN Nonstructural abnormalities] AUB-O: - many cases stem from ___________________
Ovulatory dysfunction Endocrinopathies
Estrogen breakthrough bleed: common conditions
PCOS (chronic anovulation), Obese (insulin resistance d/t increase circulating insulin level --> elevation in androgen production and anovulation= basically the underlying cause of PCOS = Insulin & androgen), Perimenopausal
Workup for primary amenorrhea
Physiologic causes of amenorrhea - anatomic defects - ovarian failure - chronic anovulation - anterior pituitary disorders - central nervous system disorders
Prolactin is measured to r/o what disease? if + disease, what is the expected level?
Pituitary adnoma - levels >100ng/ml
the most common cause of amenorrhea? (3)
Pregnancy hypothalamic amenorrhea PCOS
Causes of secondary amenorrhea
Pregnancy Asherman syndrome Cervical stenosis Hormonal contraception Hyperthyroidism/ hypothyroidism Polycystic ovary syndrome (PCOS) Pituitary tumor Premature ovarian failure Menopause Hypothalamic/ central nervous system (CNS) disorders (e.g., lifestyle stress, eating disorder, extreme athleticism)
Causes of Primary amenorrhea
Pregnancy Upper genital tract causes Müllerian agenesis (absence of uterus and vagina, normal secondary sex characteristics) Testicular feminization (absence of uterus, blind ending vaginal pouch, normal breast development, scant pubic and axillary hair) Lower genital tract causes Labial agglutination Imperforate hymen Transverse vaginal septae Hypergonadotropic-hypogonadism Follicle-stimulating hormone (FSH) > 40 mIU/ L Gonadal dysgenesis Ovarian enzyme disorder Resistant ovarian syndrome
Physiologic causes of anovulatory bleeding
Pregnancy Lactation Perimenarche Perimenopause Obesity BMI < 18 Excessive exercise
your adolescent patient who is 15 has not had menarche. She reached thelarche 3 years ago. what is this called?
Primary amenorrhea.
Primary & Secondary amenorrhea
Primary amenorrhea: failure to begin menses by age of 16 Secondary amenorrhea: 3 months without menses once menses has been establisehd
Treatment of anovulation
Progestogen x 10days of each month or COC (pill, patch, or ring)
Who is progestogen indicated for? (compared to estrogen)
Progestogens are not as effective as estrogen in stopping acute bleeding, but are effective for *long-term treatment once the acute bleeding episode has been resolved*. Additionally, progestogens may be the management regimen of choice if the woman has *contraindications to taking estrogen*.
If you are trying to rule out Pregnancy; threatened, missed, or incomplete spontaneous abortion, what test should you order?
Qualitative urine hCG
Hyperthyrodism and abnormal bleeding
Range: varies (spotting, heavy, amenorrhea)
Pharmacologic mgmt of acute non-life-threatening heavy menstrual bleeding - Estrogen therapy
Replenish IV volume CEE 25mg IV q 4-6 hrs as needed, then CEE 2.5 mg-5mg PO x4/day for 2-3 days, then add MPA 10 mg for 10-14 days (Continuous CEE) - COCs x2-x3/ day, then taper [CEE: conjugated equine estrogen] [MPA: medroxyprogesterone acetate]
Candidates of endometrial ablation
Ruled out cancer No previous myomectomy Nondistorted uterine cavity Completed childbearing Refractory to medical therapy
if you are trying to r/o iron-deficiency anemia 2' to bleeding, what should you order? what result should you expect?
SErum iron/ ferritin - Decreased levels
Androgen excess
Symptoms Boys: penile enlargement, hair growth, precocious puberty Girls: ambiguous genitalia (infants), hirsutism, acne, short stature, precocious puberty Women: infertility, hirsutism, acne, male pattern baldness, menstrual irregularities, virility Men: infertility & decreases in following: muscle mass, hair growth, testes size, testosterone production, spermatogenesis
molimina
Symptoms in the premenstrual/ luteal phase that indicate ovulation has occurred These include ovulatory pain (Mittelschmerz), breast tenderness, bloating, and mood swings
T/F: oth hypothyroidism and hyperthroidism can cause amenorrhea, and the cycle returns thyroid level is normalized
TRUE
Why is there no diagnostic tests that clinicians can use to confirm the presence of AUB-E? What do you do to diagnose AUB-E without diagnostic tests?
The exact processes that happen during AUB-E are not well defined --> diagnosis of exclusion
What laboratory tests should you order to rule out Coagulation disorders other than vWD causing AUB a. ristocetin cofactor assay b. renal function tests c. General labs + FSH, LH, Prolactin levels, TSH, T3 and T4 d. Liver function test e. PT, PTT, plt function
e. PT, PTT, plt function
IF HMB is caused by fibroids, which treatment is particularly effective to treat HMB? a. CEE 25mg IV q 4-6 hrs as needed, then CEE 2.5 mg-5mg PO x4/day for 2-3 days, then add MPA 10 mg for 10-14 days (Continuous CEE) b. Medroxyprogesterone acetate 10-20mg BID c. Norethindrone 5mg BID d. Prometrium 200mg for 10-14days repeating 30-40 days e. LNG-IUD (Mirena)
e. Women with fibroids are candidates for the LNG-IUS if the fibroid does not distort the uterine cavity and the uterus is less than 12 weeks' gestation in size.
Pathologic causes of AUB
ectopic pregnancy endometrial cancer endometriosis
Pituitary disease & tumors cause abnormal bleeding pattern d/t
elevated levesl of prolactin - Amenorrhea: prolactin inhibition of pulsatile secretion of GnRH
PALM [ Structural Abnormalities ] AUB- P: ________&___________ are growth on the cervix or endometrium
endocervical polyp endometrial polyps
Women age 45 and older who present with suspected AUB-O should have a β-hCG to rule out pregnancy; if this test is negative, the clinician should follow up with ________________prior to initiating medical management
endometrial biopsy --> so always start with this if not pregnant because it is useful in both anovulatory and ovulatory AUB
What test should be perforemd after progestogen therapy to stop chronic heavy bleeding?
endometrial biopsy in 3-6 months = makesure there is no longer endometrial hyperplasia
What should be performed with woman ages 30 to 45 with a negative β-hCG who have not responded to medical treatment to AUB?
endometrial evaluation / biopsy
Regular/ Irregular interval of bleeding - woman is postmenopausal and reports that she experienced spontaneous, painless, and irregular bleeding, the clinician must include ___________ & evaluate _______________
endometrial hyperplasia in the differential diagnosis and undertake prompt endometrial evaluation.
What is adenomyosis?
endometrial tissue in the myometrium uterine thickening that occurs when endometrial tissue moves into the muscular walls of the uterus (rather than just lining the uterus). tender, symmetric, enlarged "boggy" uterus.
Leiomyomas are further classified by a secondary category that labels their location within the uterus. - It is important to determine if the leiomyoma interferes with the_______________, because this type is most likely to cause AUB. - what is 'other' category?
endometrium (submucosal) - subserosal - intramural leiomyomas
The anovulatory woman is always in the _____________ of the ovarian cycle and in the ________________ of the endometrial cycle. There is no __________or ___________because there is no ovulation or cycle.
follicular phase & proliferative phase No Luteal phase or secretory phase
underweight, over-exercised, stress adolescent is mostly likely to have what kind of amenorrhea?
functional amenorrhea
A progesterone challenge test that produces withdrawal bleeding is indicative of ________________ because bleeding will occur only if a sufficient amount of circulating estrogen is present.
functioning ovaries - use micronized progesterone (Prometrium) x 7-10 days - use medroxyprogesterone (Provera) x 7-10 days = withdrawal bleeding within 7-10 days after progesterone discontinued if enough endogenous estrogen to produce a withdrawal bleed
Work up of outflow track causes of AUB?
genotype & phenotype
after using COCs to stop the HMB, what should be used to initiate withdrawal bleeding during the last 10 days of therapy?
give 2.5mg of conjugated equine estrogen (CEE) daily --> + add 10mg medroxyprogesterone acetate (Provera)
When prescribing progestin therapy for heavy mestrual bleeding, withdrawal will result in
heavy menses
What is hematometra, hematocolpos, and hemoperitoneum?
hematometra:blood in uterus hematocolpos: blood in vagina hemoperitoneum: blood in peritoneum
anovulatory uterine bleeding tends to be heavy secondary to
high and sustained levels of unopposed estrogen ---> endometrial hyperplasia --> amenorrhea , heavy menstrual bleeding, and intermenstrual bleeding (IMB)
pregnancy complications associated with uterine artery embolization
higher rate of miscarriage and pregnancy complications
hair loss, changes in breast size, hirsutism, headache, breast discharge indicate
hormone-secreting tumors
Contraindication of tranexamic acid (TXA; Lysteda)?
hx or at risk of thrombosis
What are medications that can cause hyperprolactinemia? a. antidepressant b. Opiates C. calcium channel blocker d. Estrogen e. beta blocker f. Testosterone g. a,b,c, h. a,c,d,f, i. a,b,c,d j. all of the above
i a,b,c,d antidepressants, opiates, calcium-channel blockers, and estrogens,
Treatment of amenorrhea
identify and manage underlying cause - COCs: pills, vaginal ring, patch - Medroxyprogesterone acetate (Provera) : 5-10mg daily for 10-12 days - Norethindrone acetate (Aygestin): 5mg daily for 10 days monthly - Micronized progesterone (Prometrium): 200mg @ HS for 10 days
Outflow tract causes of AUB What happens when segments of the mullerian tube fail to devleop?
imperforated hymen lack of a vaginal orifice lapses in the continuity of the vaginal canal absent uterus, cervix, uterine cavity, or endometrium
Advantages of hysterectomy
improved quality of life
progestogen is given for 7-12 days each month to ______________________.
induce normal bleeding
Normal physiologic event that causes AUB
irregular bleeding w/ menarche or perimenopause (d/t irregular ovulation) Pregnancy
Why is age important criterion in diagnosing amenorrhea?
it is an important criterion in making the differential diagnosis of primary vs. secondary amenorrhea
Although D & C is the quickest way to stop acute bleeding, not considered a _______________for HMB.
long-term treatment for HMB the choice of surgical modality is based on a number of factors, including the woman's initial response to medical management and her desire for future fertility.
Critical weight theory hypothesizes that some critical weight and amount of body fat exist that must be maintained for women to experience regular menstrual cycles. how do they impact the bleeding cycle?
low body fat + decreased secretion of GnRH --> decreased LH & FSH --> decrease amt of estrogen by ovaries
What are the causes of ABU-I?
medications or devices that act on the endometrium
hx of hot flushes, cessation of menses, or vaginal dryness suggest
menopause
hot flushes or the sensation of a racing heartbeat are present— these signs accompanied by abnormal bleeding may indicate_________________.
menopause is approaching,
What age does adenomyosis occur? - pregnancy status?
multiparous and older than age 40
what procedure puts women at risk that cause outflow tract AUB?
multiple cervical procedures (dilation, curettage [D&C]), significant endometrial infections --> scarring --> outflow tract AUB
High dose estrogen: common side effect
nausea --> concurrent treatment w/ an antiemetic is recommended
Dysfunctional uterine bleeding is now called
nonstructural causes of AUB: causes not related to structural abnormalities of the uterus
Goal of treatment in functional hypothalamic amenorrhea
offset the bone loss that occurs during the estrogen-deficient periods
Ectopic pregnancy classic symptoms
pelvic and abdominal pain Amenorrhea/ unexplained vaginal bleeding vague, sharp, diffuse, or unilateral. The woman may have had a time of amenorrhea, and pregnancy may or may not already be diagnosed. Cervical motion tenderness, a uterus that is not enlarged, normal size Adnexal mass, and adnexal tenderness.
3 categories of causes of AUB
physiologic pathologic pharmacologic
Ovulatory abnormal uterine bleeding typical age
post-adolescent years & during the premenopausal years
Disadvantages of hysterectomy
postsurgical fatigue Wt change changes in sexual satisfaction
When is TVS (transvaginal ultrasonography) performed in relation to mesntrual cycle?
premenopausal: day 4-6 of the menstrual cycle (at the end of menstrual cycle or after = almost shed, or finish sheding) Postmenopausal: anytime.
the goal of treatment of amenorrhea
prevent endometrial hyperplasia, malignancy
Physiology and Patterns of normal menses - Regular, ovulatory menstrual cycles often include premsntrual symptoms caused by ______________(hormone)
progesterone
After giving high-dose estrogen therapy to stop HMB, less than 25 days, what should you prescribe to this treatment?
progesterone (medroxyprogesterone acetate) 10mg x 10 days
Progesterone breakthrough bleeding: what hormone imbalance?
progesterone- estrogen ratio becomes elevated
HX of headaches and galactorrhea with amenorrhea is indicative of (2)
prolactin-secreting tumor or hypothyroidism
Prometrium 200mg is a treatment of what? what precaution should you be aware?
prometrium 200mg for 10-14days repeating 30-40 days is to treat chronic menorrhagia (abnormally heavy bleeding during menstruation) - peanut allergies (peanut oil is used in manufacturing process)
If you are trying to rule out *ectopic Pregnancy*; threatened, missed, or incomplete spontaneous abortion, what test should you order?
quantitative serum hCG - level lower than expected for gestational age: ectopic pregnancy - lack of significant increase in 48 hrs and/or plateuing : ectopic pregnancy
COEIN- E 1st step of AUB workup in childbearing age
r/o pregnancy via H&P, including pelvic and culture - they are considered pregnant until proven otherwise
Malignancy and atypical hyperplasia are rare in women of ____________ and in women who have a normal _____________and who do not have ________________
reproductive age body mass index (BMI) polycystic ovarian syndrome (PCOS).
Diagnosis of AUB-C
review of hx confirmed by hematologic testing
Endometrial ablation can make ___________________challenging
screening for endometrial cancer (i.e., endometrial biopsy) = risk for endometrial cancer should be counseled prior to endometrial ablation about this potential risk
Endocervical polyps bleeding is often associated
sexual intercourse
PALM-COEIN system
standardized classification of AUB PALM: acronym for the 4 basic system that are visually objective structrual criteria (*P*olyp, *A*denomyosis, *L*eiomyoma, *M*alignancy and hyperplasia COEIN: acronym of 5 categories unrelated to structural abnormalities (*C*oagulopathy, *O*vulatory dysfunction, *E*ndometrial, *I*atrogenic, and *N*ot yet classified)
Leiomyoma is divided into women who have at least 1 ____________ and those whose myomas do not impact the _____________
submucosal myoma endometrial cavity
What is Uterine Artery Embolization used for?
surgical intervention to address fibroids & relieve HMB. = occlude blood flow to the fibroids, shrinking the fibroids & decrease their associated symptoms
Many cases of AUB-O stem from endocrinopathies including_______________, _________________, ________________, or __________________
thyroid disorders polycystic ovarian syndrome excessive exercise extreme mental distress
Contraindications of NSAIDs
ulcers bonchospastic lung disease
36 y.o. G3P3 s/p BTL c/o heavy, prolonged menses 30 # weight gain and dysmenorrhea x 4 months Gyn: Menarche 11, monthly cycles, 4 days flow until 4 months go BP: 11062, P64, T98.6 BMI48 Abdomen: +bs, soft, nontender, no rebound/guarding Speculum-os closed, no bleeding, no CMT BME: Difficult due to body habitus, no uterine or adnexal masses EMB path: proliferative phase endometrium. Diagnosis?
unopposed estrogen
COEIN- N AUB-N not yet classified
used while other causes are explored.
Adverse effects of tranexamic acid (TXA; Lysteda)?
venous thromboembolism (VTE) [ serious] nausea, leg cramps (rare)
PT, aPTT, bleeding time should be ordered to r/o
von Willebrand's disease, leukemia, prothrombin deficiency= increased bleeding time
your new patient, Women presenting with complaint of heavy menstrual bleeding who have history of easy bruising and prolonged bleeding following dental work or surgery. What should be your plan of care?
warrant further follow-up for VWD.
endometrial ablation contraindication
woman who desires to maintain her fertility (it is not considered sterilization because pregnancy after ablation is rare, but does occur) + known suspected uterine cancer + Uterine hyperplasia + thin myometrium + IUD + Pregnancy + previous classical c-sec birth + pelvic, uterine, cervical, and vaginal infection + Uterus sounds to <4cm or uterus sounds outside of the device parameter + disorder of Mullerian fusion or absorption
Progesterone breakthrough bleeding commonly occurs in what population?
women using progestin-only pills or progestin-only contraception (pills, IUD, Nexplanon, etc.)
Candidates of Uterine Artery Embolization
women who desire to retain their fertility
what is the diagnosis of a woman who experiences amenorrhea with positive progesterone challenge, denies galactorrhea, normal prolactin level? a. pituitary tumor b. anovulation
b. Anovulation( like PCOS)
if Denuded endometrium is the cause of the HMB, what should you prescribe, initially? a. COCs b. Estrogen therapy c. Progestin- only therapy d. levonorgestrel-releasing IUD
b. Estrogen therapy --> stimulates rapid endometrial proliferation = resolution of the bleeding from a denuded endometrium
What laboratory tests should you order to rule out Cervical or uterine pathology causes of AUB a. General labs + GC/ CT+ wet mount; b. General labs + colposcopy w/ biopsy;endometrial bx; hysteroscopy c. General labs + ultrasound d. General labs + MRI, CT scan + cortisol levels
b. General labs + colposcopy w/ biopsy; endometrial bx; hysteroscopy
What laboratory tests should you order to rule out endocrine causes of AUB a. General labs + FSH, LH, Prolactin levels, TSH, T3 and T4 b. General labs + prolactin, FSH, LH c. General labs + adrenal studies, testosterone levels d. General labs + MRI, CT scan + cortisol levels
b. General labs + prolactin, FSH, LH --> r/o premature ovarian failure
NSAIDS are used for a. anovulatory HMB b. Ovulatory -idiopathic HMB
b. Ovulatory -idiopathic HMB - the heavier the bleeding, the better the effectiveness of NSAIDs
What laboratory tests should you order to rule out renal disease causes of AUB a. ristocetin cofactor assay b. renal function tests c. General labs + FSH, LH, Prolactin levels, TSH, T3 and T4 d. Liver function test e. PT, PTT, plt function
b. renal function tests
hx of multiple D&C etiology, significant endometrial infections, and cervical treatments (cryotherapy) may indicate
cervical stenosis r/t Asherman syndrome --> subsequent amenorrhea
Level I evidence consistently demonstrates that the treatment of choice for abnormal uterine bleeding is pharmacologic treatment with ____________________
combined contraceptives.
Common cause of AUB in women of reproductive age --> this is the reason why clinicians treating women of childbearing age w/ AUB to first exclude __________
complication of pregnancy - threatened or incomplete abortion - ectopic pregnancy - retained products of conception - gestational trophoblastic disease --> Exclude pregnancy or complication of pregnancy first!
When should you obtain progesterone level?
cycle day 22-24
What laboratory tests should you order to rule out hormone producing tumor causes of AUB a. General labs + FSH, LH, Prolactin levels, TSH, T3 and T4 b. General labs + prolactin, FSH, LH c. General labs + adrenal studies, testosterone levels d. General labs + MRI, CT scan + cortisol levels
d. General labs + MRI, CT scan + cortisol levels
What laboratory tests should you order to rule out infectious causes of AUB a. General labs + GC/ CT+ wet mount; b. General labs + prolactin, FSH, LH c. General labs + ultrasound d. General labs + MRI, CT scan + cortisol levels
d. General labs + GC/ CT+ wet mount; consider need for WBC
What laboratory tests should you order to rule out Liver disease causes of AUB you order to rule out vWD causes of AUB a. ristocetin cofactor assay b. renal function tests c. General labs + FSH, LH, Prolactin levels, TSH, T3 and T4 d. Liver function test e. PT, PTT, plt function
d. Liver function test
You have given monophasic COCs to hemodynamically stable woman with HMB. You expected the bleeding today (within 24hrs) but pt reports it hasn't stopped. What should you do? a. Transfuse 2 packs of RBCs b. Order CT scan c. switch to high-dose estrogen therapy d. wait until 48 hrs to evaluate further
d. wait until 48 hrs to evaluate further: you need to give COCs at least 48 hrs before trying something else / looking for something else
Endometrial ablation
destruction of the endometrium using heated fluid (either contained within a balloon or circulating freely within the uterine cavity), tissue freezing, microwave, or radiofrequency electricity
Cause: Genetic abnormalities causing outflow track issues are uncommon, except in women whose mothers were given ___________________during pregnancy typically between the years of 1938 and 1971
diethylstilbestrol (DES)
Unopposed estrogen
during the normal menstrual cycle estrogen and progesterone cyclically take turns acting as the dominant hormone. Because estrogen is the predominant hormone stimulating proliferation of the endometrium it plays a role in the development of endometrial cancer --> Exogenous estrogen (Estrogen replacement therapy) --> Endogenous estrogen: - increased secretion: feminizing ovarian tumors (granulose cell tumor) - increased androgen precursor: androgen secreting tumors, liver diseases, chronic anovulation (PCOS), stress - Increased aromatization: obesity, liver disease, or hyperthyroidism - Increased free estrogen: decreased level of SHBG
Ovulatory dysfunction AUB is the new name for the category that was once termed ________________
dysfunctional uterine bleeding
Megestrol
(Megace) - Breast/endometrial cancer treatment - Breakthrough bleeding, hot flashes, mood swings - If female, use appropriate birth control - can harm fetus
Special consideration of AUB with trauma of genital tract - Examples
(Tampons, hymeneal tearing, sexual assault)
In terms of cycle variation over 12 months, what constitutes - Absent - Regular - Irregular
- Absent: No bleeding - Regular: Variation +/- 2~20 days - Irregular Variation >20 days
Risk factors for Ectopic Pregnancy
- Age 15- 19 years , Age > 35 years (HPO axis issues in the beginning and end of menstruation) - Racial minorities - Previous ectopic pregnancy - Any previous tubal surgery or tubal deformity - History of pelvic inflammatory disease (Scarring and adhesions = traveling of fertilized egg blocked) - History of infertility - Past or current use of intrauterine device - Use of low-dose progestins or postcoital estrogens for contraception - Assisted reproduction - History of therapeutic abortion especially with complications
why is Gonadotropin releasing hormone agonists used short-term and not long term, although it is very effective in stemming the bleeding with resultant amenorrhea?
- GnRHas has a lot of side effects related to estrogen deficiency - expensive
In terms of Amount of flow, what constitutes - Heavy flow - Normal flow - Light flow
- Heavy flow: >80ml - Normal flow: >5-80ml - Light flow: <5ml
Pathophysiology of progesterone breakthrough bleeding
- Imbalance in both the vasoconstriction & vasodilating properties of prostaglandins - Imbalance in both platelet aggregation and inhibition = abnormal microvasculature = abnormal bleeding
criteria requiring evalution for amenorrhea
- No menses by age 14 in the absence of growth or development of secondary sexual characteristics - No menses by age 16 regardless of the presence of normal growth and development of secondary sexual characteristics - In women who have menstruated previously, no menses for an interval of time equivalent to a total of at least three previous cycles, or 6 months
When diagnosin Amenorrhea, what to do/ order 1st: r/o pregnancy - Outflow tract abnormalities: - Ovarian function abnormalities: - Thyroid disease: - hyperprolactinemia :
- Outflow tract abnormalities: bimanual exam - Ovarian function abnormalities: estrogen, progesterone, FSH levels - Thyroid disease: TSH level - hyperprolactinemia : prolactin level
In terms of Duration of flow, what constitutes - Prolonged flow - Normal flow - Shortened flow
- Prolonged flow: > 8 days - Normal flow: 4.5-8.0 days - Shortened flow: <4.5 days
First trimester complications causing abnormal uterine bleeding
- Spontaneous Abortion( SAB)/ Abortion (loss before 20 wks gestation) - Ectopic pregnancy (Implantation in fallopian tube, or any other location other than th uterine cavity - high risk for pregnancy loss, tubal rupture, scarring, future infertility ) ==> reason why we need to do the pregnancy test
Characteristic of ovulatory abnormal bleeding
- abnormal bleeding that are cyclic & regular - bleeding patterns are abnormal (prolonged, heavy bleeding common)
predominant predisposing factor for adenomyosis
- more than 1 pregnancy (multiparous) - hx of miscarriage, curettage, endometrial resection, C-section or tamoxifen use
4 management goals for treating AUB
1) normalize the bleeding 2) correct any anemia 3) prevent cancer 4) restore quality of life
often the menstrual history is sufficient for making a diagnosis. Nevertheless, an endometrial biopsy or hysteroscopy should always be included in the assessment of abnormal bleeding in women who are
1) perimenopausal, 2) postmenopausal, 3) obese adolescents with long-term (3 or more years) unexplained abnormal bleeding 4) any woman whose endometrium has been exposed to unopposed estrogen.
Dosing : tranexamic acid (TXA; Lysteda)
1,300mg TID x 5 days per menstrual cycle
[ COEIN Nonstructural abnormalities] AUB-O: 3 types of ovulatory dysfunction steming from endocrinopathies
1. Anovulatory uterine bleeding 2. Amenorrhea 3. Ovulatory abnormal uterine bleeding
3 subcategories of AUB-O
1. Anovulatory uterine bleeding 2. Amenorrhea (absence of bleeding) 3. Ovulatory uterine bleeding
Progestogen therapy for chronic anovulation
1. Medroxyprogesterone acetate (provera) 10 mg X 10 days (repeat every 30-40 days) 2. Depo provera 150mg IM every 12 weeks 3. northindrone 5 mg 2X day X 10 days 4. oral micronized progesterone (prometrium) -take at night - 200 mg/day X 10 days 5. LNG-IUD REPEAT endometrial biopsy in 3-6 months to ensure that hyperplasia has resolved
General tests to consider for all types of AUB
1. Pregnancy test (urine or serum hCG [ serum to diagnose specific pregnancy disorders) 2. CBC : if anemia suspected 3. TSH: hypothyrodism/ hyperthyrodism, other thyroid abnormalitiy suspected 4. Prolactin level: headaches, galactorrhea, and/or peripheral vision changes 5. Pap >21 yo 6. Nucleic acid amplification test (NAAT): GC/ CT if + sexually active 7. microscopic exam of vaginal secretions w/ saline & KOH 8. Coagulation studies (PT, aPTT): suspicious hx of bleeding or easy bleeding; unexplained menorrhagia 9. serum progesterone: menstrual hx indicate whether the woman is ovulating
SAB diagnosis
1. assessing uterine size = physical examination or ultrasound 2. fetal heart tone 3. examination of cervical Os (dilated) 4. serial b-hCG measurement
Ectopic pregnancy management
1. before confirmed diagnosis: close observation to avoid the medical emergency of tubal rupture - Rhogam administration, monitoring b-hCG levels, emotional care for pregnancy loss, future fertility counseling. 2. early diagnosis: Use of methotrexate to dissolve products of conception & avoid tubal ruptures 3. presence of signs & symptons of rupture: prompt medical attention w/ surgical capabilities surgical resolution is most common
methotrexate in ectopic pregnancy requirement
1. mass under 4cm 2. no heart beat 3. no rupture 4. quant hCG under 5000**** 5. compliance 6. no comorbidities ( bleeding problem, immunocom)
NSAID therapy for heavy menstrual bleeding
1. mefnamic acid 500 mg 3x daily ** 2. ibuprofen 600 mg 3x daily 3. Naproxen sodium 550 loading dose, then 275 every 6 hours *initiate 3 days prior to menses
COEIN- E Etiology
1. premature release of blood from the endometrium 2. disorders of local endometrial hemostasis
FSH is ordered to r/o what? what is the expected result if + diagnosis ?
Amenorrhea d/t menopause Premature ovarian failure FSH >30mlU/ml; (some 40)
Ovulatory abnormal uterine bleeding range:
Amenorrhea to Irregular heavy menstrual period
Progesterone is ordered to r/o what? what is the expected result if +diagnosis
Anovulatory amenorrhea - Levels <10ng/ml
Which type of ovulatory bleeding is predictable bleeding frequently leads to abnormal cycle intervals, excessively heavy bleeding, or lighter than normal amounts of bleeding?
Anovulatory uterine bleeding
COEIN- I What medications cause a disturbance in the HPOA (not endometrium) and cause AUB-I?
Antidepressant therapies (tricyclics, phenothiazines, serotonin reuptake)
Pharmacologic mgmt of acute non-life-threatening heavy menstrual bleeding - Combined Estrogen- Progestin therapy
Any monophasic COC beginning w/ 1 pill BID x first day--> decrease to 1 pill daily --> continue for minimum 2 wks
what is leiomyoma
Benign neoplastic proliferation (tumor) of smooth muscle arising from myometrium
COEIN- I what type of bleeding do women have when using gonadal steroidal medications (hormonal contraception)?
Breakthrough bleeding (BTB)
If you are trying to rule out Anemia, what should you order? Clotting abnormalities? what are the results expected?
CBC w/ plt Anemia: hgb <10mg/dL Clotting: plt <150,000 cells/mm3
Pharmacologic mgmt of acute non-life-threatening heavy menstrual bleeding
COCs Progestogen-only therapy levonorgestrel-releasing IUD
Alternative treatments for HMB
Chinese herbal medicine (CHM): more research needed. Purslane: herbal treatment commonly used in Iran; may be beneficial, but studies are lacking.
COEIN- E what infection is associated with endometritis? what is the bleeding pattern of endometritis caused by this infection?
Chlamydia trachomatis --> intermenstrual bleeding
[ COEIN Nonstructural abnormalities] AUB-C
Clotting disorders (many diseases)
[Nonstructrual abnormalities] COEIN- C
Coagulopathy
Pharmacologic mgmt of - Long-term / chronic managementheavy menstrual bleeding
Cyclic MPA 10mg/day x10-14 days --> q 30-40 days COC (Oral, patch, ring) Oral micronized progesterone 300mg for 10-14 days, q 30-40 days *at night*(s/e: fatigue) Depo medroxyprogesterone acetate (Depo-Provera) 150mg IM q 3 months LNG- IUS (Mirena) NSAIDs Tranexamic acid
When medical therapy fails, surgical management options for HMB include
D&C Endometrial ablation uterine artery embolization hysterectomy
Androgen precursor
DHEA
COEIN- E Pathophysiology
Decrease of local endometrial vasoconstrictors (endothelin-1 & prostaglandin F2) --> Vasodilation and HMB (heavy menstrual bleeding) Excessive amt of plasminogen activator or decreased amt of plasminogen activator inhibitor --> HMB
Medroxyprogesterone Acetate
Depo-Provera
What is the diagnosis of the adolescent who is underweight, overexercises, and is experiencing a great deal of stress?
Diagnosed with functional amenorrhea = energy deficit = negative impact on the HPOA
treatment of hyperprolactinemia
Dopamine agonist
Feminist perspective views women holistically -If uterine bleeding diagnosed as abnormal is actually a variation of normal, treat with_______,__________ & ______________ intervention
Education, reassurance, and nonpharmacologic intervention. - many are not sure about what is normal and not normal = reassuarance - education should be given because many are not aware of anatomy & function of uterus
[Structural Abnormalities] PALM- P what is a benign growth on the cervix that are easily visualized with a speculum, appearing as smooth, deep to bright red growths that are fragile and bleed with little encouragement during examination?
Endocervical polyps
how can you differentiate AUB-E from other causes?
Endometrial AUB usually occurs in a predictive and cyclical manner with heavy menstrual bleeding (sometimes it presents with intermenstrual or prolonged bleeding patterns)
In postmenopausal women, TVS can reliably meausre endometrial thickness and rule out _________________ in thin endometrium defined as _______________ mm or less
Endometrial carcinoma thin endometrium : <5mm = if >5mm in postmenopausal woman --> follow up
PALM [ Structural Abnormalities ] AUB- M: AUB is common symptom of ______________
Endometriual cancer
COEIN- E
Endometrium
Estrogen breakthrough bleeding occurs as a result of
Estrogen breakthrough bleeding occurs as a result of the endometrium being stimulated by long-term, chronic unopposed estrogen, such as that observed in women experiencing chronic anovulation.
The amount of breast development is an indicator of production or exposure to what?
Estrogen production or exposure to exogenous estrogen
etiology of anovulatory bleeding
Estrogen withdrawal Estroben Breakthrough Progesterone bleed through -->
T/F: If a woman presents with amenorrhea with no history of infection or trauma and her pelvic examination and bimanual examination are normal, then an abnormality of the outflow tract is likely.
FALSE - NOT LIKELY
T/F: using progestogen therapy is safe to use if pt thinks she may be pregnant
FALSE - do not use progestogen therapy if the woman thinks she might be pregant, even if her pregnancy test is negative
Outflow tract causes of AUB - Obstruction of menses do not cause pain
FALSE - obstruction of menses may lead to painful distention d/t a menstrual blood collection (i.e., hematometra, hematocolpos, or hemoperitoneum)
T/F: hyperprolactinemia is always accompanied by glactorrhea (
FALSE - not always accompanied, but can be diagnosed by obtaining a serum prolactin level in women with amenorrhea
T/F: Women with coagulopathy disorders taking anticoagulant medications are classified AUB-I (iatrogenic)
FALSE. because of the rationale (coagulopathy disorder) for the drug therapy, it is considered AUB- C
T/F: The current biomedical standard for measuring the amount of blood lost during menstruation is counting tampon/pad saturation at home
FALSE: --> alkaline hematin method, which is quite expensive and can be inconvenient for women The ratio of the hemoglobin concentration in the total menstrual discharge to the peripheral blood is considered the volume of menstrual blood loss
What system are polyps classified?
FIGO classification system : asking Present y/n - not how many, how large,
Primary amenorrhea
Failure of menses to occur by age 16 years, in the presence of normal growth and secondary sexual characteristics. If by age 13 menses has not occurred and the onset of puberty, such as breast development, is absent, a workup for primary amenorrhea should start.
T/F: intensive training regimen & exercise in general causes amenorrhea
False - it is not exercise in general that causes the amenorrhea, but rather the specific type of exercise. - For example, swimming is less likely to cause amenorrhea than long-distance running. - low BMI & low body fat combo + high level intensity physical activity = highest risk
T/F: AUB is most always related to menstrual cycle
False. it may or may not be related to woman's menstrual cycle
T/F: leiomyomas are the most common benign pelvic tumors in women and the leading indication for hysterectomy
True
T/F: menstrual cycle is a vital sign of adolescents overall heatlh
True
SIS has higher sensitivity and specificity than TVS
True - sensitivity and specificity of TVS in diagnosing endometrial pathologies were 83% and 70.6%, respectively, whereas the sensitivity and specificity of SIS in the diagnosis were 97.7% and 82.4%,
irregular bleeding during first 2 years after menarche and 3 years prior to menopause may be a reflection of normal functioning.
True HPOA is most affected during this period
T/F: the diagnosis of AUB can be confidently made in women with a history of irregular, unpredictable bleeding for 6 months or longer in the absence of premenstrual symptoms. But women with REGULAR/IRREGULAR bleeding that is heavy, and prolonged, menstrual hx alone is likely to be inadequate for making an accurate diagnosis
True. Regular
T/F: long-term use of hormonal contraceptives can lead to amenorrhea
True. d/t endometrial atrophy
How do you diagnose adenomyosis
Ultrasonography MRI (NOT histopathologic detection)
_____________________should be considered in all women (particularly adolescents) with abnormal bleeding if the bleeding does not respond to treatment and is not able to be explained.
Underlying coagulopathies (Evidence level III)
Regular/ Irregular interval of bleeding A woman who reports having regular cycles that have now become heavy, accompanied by the passage of clots,and who says she has noticed a sensation of pelvic fullness, may be experiencing AUB secondary to _____________.
Uterine fibroids
prolonged, heavy bleeding in ovulatory uterine bleeding is commonly associated with pelvi pathology such as
Uterine fibroids (leiomyomas) Adenomyosis Endometrial polyps
Approximately 13% of women with AUB will have a blood clotting disorder. What is the more commonly inherited bleeding disorder?
VWD (von Willebrand's disease)
When do you perform culture and/or microscopic examination of vaginal secretion?
Vaginal infection - GC, CT, Vulvovaginal candidiasis
The most common times for a woman to experience irregular menstrual cycles are (2)
at the beginning and the end of her reproductive life cycle: Postmenarche & perimenopause
how does age impact the evaluation of amenorrhea?
can interrupt/ cause the dysfunction of the HPOA --> Amenorrhea
COEIN- I woman taking anticoagulant for a blood clotting disorder is placed AUB-C? AUB-I?
AUB-C: disorder is the rationale for needing anticoagulant therapy, then causing dysfunctional bleeding
What is the medical term describing bleeding that is considered out of the ordinary by the woman or the clinician.
Abnormal Uterine Bleeding (AUB)
SEcondary amenorrhea
Absence of menstrual bleeding in a woman who had been menstruating but later stops menstruating for three or more months
PALM [ Structural Abnormalities ] AUB- A: what is the small areas of endometrial tissue within the myometrium called?
Adenomyosis
PALM- A
Adenomyosis
Risk factors for Endometrial cancer
Age 40 years or older Anovulation Polycystic ovary syndrome (PCOS) Family history of endometrial cancer New onset of heavy irregular bleeding, particularly after menopause Nulliparity Overweight Unopposed estrogen stimulation of endometrium Tamoxifen therapy Infertility Type 2 diabetes
Treatment of SAB
1. referral to a physician for management 2. Rhogam administration following a SAB is indicated for women who have an Rh-negative blood type.
withdrawal of progesterone causes?
1. shedding of the endometrium = progesterone withdrawal bleeding 2. production of Arachidonic acid --> stimulates the production of PGF2 alpha --> vasoconstriction and contraction of smooth muscle --> dysmenorrhea
Medroxyprogesterone acetate is given 5-10mg daily for 10-12 days, sometimes 14 days. minimum duration of treatment of MPA is?
10 days
Assessment of AUB: Hx - obtaining menstruation and contraception history is very important in identifying the cause of AUB. Depo provera can take how long to return to normal cycle after discontinuation
18 months - Age; age at menarche and menopause; cycle length, duration, and flow important; change in menstrual pattern - Contraceptive: type, length of use, side effects
Administration timining NSAIDs to treat HMB
3 days prior to the start of menses (or start of the menses)
A random serum estradiol level that is greater than _____pg/ mL indicates functioning ovaries.
40pg/ml - ovarian function abnormalities are the most common cause of amenorrhea = check estrogen production = if low: ovarian failure or hypothalamic amenorrhea
COEIN- I how does medication cause AUB-I?
= Work on endoetrium itself or interferes with ovulation cycle
Categories of amenorrhea
= depends on the site of the disturbance 1. Disorders of the genital outflow tract 2. Disorders of the ovary 3. Disorders of the anterior pituitary 4. Disorders of hypothalamus or CNS
______________provides the opportunity to assess for the presence of tumors, cervical polyps, ovarian cysts, uterine tenderness or enlargement, and adnexal pain or masses.
A bimanual examination
Common symptoms of endometrial cancer
AUB postmenopausal bleeding
In terms of cycle interval and frequency, what constitutes - Frequent cycle - Normal cycle - Infrequent cycle ?
Frequent: <24 days Normal: 24-38 days Infrequent: >38 days
what is the absence of menses due to the suppression of HPOA in which no anatomic organic disease is identified
Functional hypothalamic amenorrhea
what can be used to treat HMB while watiting for surgical treatment?
Gonadotropin-releasing hormone agonists (GnRHas) - leuprolide acetate (Lupron), - nafarelin acetate (Synarel), - goserelin acetate (Zoladex) may be used for a short period of time while a woman is awaiting surgical treatment for her heavy bleeding.
COEIN- E what infection is associated wth endometritis that cause irregular spotting d/t irritation and inflammation of the tissue of the cervix or endometrium?
Gonorrhea
Primary amenorrhea in young woman:
HPOA disorder Anatomic factors (i.e., outflow tract obstruction)
Endocrine disorder causing bleeding abnormalities
Thyroid disorders (Hypo & Hyper thyroidism) Pituitary disease/ tumors (prolactin-secreting pituitary adenomas)
T/F: Amenorrhea is part of the spectrum of ovulatory disroder (AUB-O).
True
T/F: HPOA is intact and steroid hormone profile is normal in ovulatory AUB
True
T/F: Normal menses vary in length, duration, and amt of flow from woman to woman, but menses in women tend to have patterns
True
SAB / miscarriage risk factors
advancin maternal age endocrine disorders viral and bacterial infections anatomic reproductive disorders chronic diseases
*Asherman Syndrome* --
aggressive scraping results in the loss of the basalis layer, the regenerative stem cell layer of the endometrium. surgical removal of stratum basalis, causing scarring and secondary amenorrhea
AUB is a common reason women seek healthcare. - bleeding patterns range from
amenorrhea (no menses) to heavy menstural bleeding (HMB)
Ovulatory dysfunction include
amenorrhea, light or heavy menses that are frequent, less frequent, occuring in regular menstrual patterns.
clitoral hypertrophy and other signs of
androgen excess
lack of progesterone in the luteal phase leading to an unstable, excessively vascular endometrium is part of ______________
anovulatory uterine bleeding
What is tranexamic acid (TXA; Lysteda)?
antifibrinolytic agent to reduce menstrual bleeding by 45-60% --> FDA approval for heavy bleeding = second-line option who do not want use hormonal option = first-line to treat vWD related HMB
Pharmacologic mgmt of acute non-life-threatening heavy menstrual bleeding - Estrogen- Progestin therapy
any monophasic COC x1 pill BID x 5-7 days --> decrease to 1 pill daily --> finish the 21 days active pills &7 day placebo pills (finish the pack) = x 2 wks minimum
an example of AUB-N
arterial-venous malformation related AUB (doesn't fit into any AUB categories)
Ectopic pregnancy and serial b-hCG measurement
beta hCG level q48 hrs: decrease Beta hCG levels usually double about every 2 days for the first four weeks of pregnancy = Intrauterine pregnancy (IUP)
Intermenstrual bleeding
bleeding between periods
What are examples of premenstrual symptoms caused by progesterone?
bloating fatigue constipation mood changes = Molimina
A Pap test is used to detect A) pregnancy. B) the time of ovulation. C) cervical cancer. D) a prolapsed uterus. E) ovarian cancer.
c. Cervical cancer = dysplasia; carcinoma - may have atypical cells suggestive of dysplasia and/or carcinoma
What laboratory tests should you order to rule out amenorrhea causes a. General labs + GC/ CT+ wet mount; b. General labs + colposcopy w/ biopsy;endometrial bx; hysteroscopy c. General labs + FSH, LH, Prolactin levels, TSH, T3 and T4 d. General labs + MRI, CT scan + cortisol levels
c. General labs + FSH, LH, Prolactin levels, TSH, T3 and T4
What laboratory tests should you order to rule out adrenal causes of AUB a. General labs + FSH, LH, Prolactin levels, TSH, T3 and T4 b. General labs + prolactin, FSH, LH c. General labs + adrenal studies, testosterone levels d. General labs + MRI, CT scan + cortisol levels
c. General labs + adrenal studies, testosterone levels (may be add CT scan of abd, cortisol levels)
What laboratory tests should you order to rule out Structural abnormalities causes of AUB a. General labs + GC/ CT+ wet mount; b. General labs + prolactin, FSH, LH c. General labs + ultrasound d. General labs + MRI, CT scan + cortisol levels
c. General labs + ultrasound = r/o polyps, submucosal fibroids, measuring endometrial thickness, pregnancy complications, ovarian masses
what imaging technique should you order if ovarian or endometrial cancer is suspected? a. Ultrasound b. CT c. MRI d. PET
c. MRI
