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Disorders of Menstruation /
Abnormal Uterine Bleeding
Tory Davis, PA-C
Menstruation Shedding the uterine lining
(endometrium) if pregnancy does not occur.
Necessary (in the absence of hormonal regulation) to insure the endometrium does not become hyperplastic.
Terminology Amenorrhea—lack of menstrual bleeding
– Primary—no menses by age 16– Secondary—absence of 3 or more expected
menstrual cycles
Break-through bleeding (BTB) unexpected bleeding usually occurring while a woman is on exogenous hormonal medication (eg OCPs, patch, or ring)
Terminology (cont.) Menorrhagia—heavy menstrual bleeding.
Prolonged or excessive menstrual blood loss with regular cycles
Metrorrhagia—irregular, frequent bleeding Menometrorrhagia—irregular menses with
prolonged or excessive blood loss Midcycle bleeding—light menstrual
bleeding occurring in ovulatory women at the midcycle estradiol trough
Terminology (cont.) Oligomenorrhea-- menstrual
bleeding/menses occurring less frequently than 36 days apart
Polymenorrhea—frequent menstrual bleeding/menses occurring more frequently than 21 days apart
Contact bleeding/post-coital bleeding Dysmenorrhea- painful menstrual bleeding
Physiologic Requirement?
Hormonal fluctuations of the cycle allow the monthly release of a mature ovum from the ovaries and prepares the endometrium for implantation.
Controlled by GnRH from the hypothalamus, FSH and LH from the pituitary, E2 from the ovary, and P4 from the corpus luteum
Normal Menstrual Cycles Mature, ovulatory women
– 28-29 day average– 21-36 day range– 2-7 days duration– 20-80 cc of blood loss per month
Cycle Variation Women in their middle reproductive
years have the most predictable cycles More pronounced cycle to cycle
variability in the 5-7 years after menarche and 6-8 years before menopause
Cycle Variation (cont.) Adolescents
– Majority range 21-48 days– Usually anovulatory– Mean time from menarche until half the cycles
are ovulatory depends upon the age of menarche
– 12 yrs 1yrs till half cycles are ovulatory– 12-13 3yrs– >13 4.5 yrs
Cycle Variation (cont.) Perimenopause
– Cycles initially shorten– Ultimately (apparently) lengthen, as an
entire cycle will be skipped Average age of menopause is 51
– Cessation of menses for one year
Impact on Health 75% of women experience physical
changes associated with menses PMS (Premenstrual syndrome) PMDD (Premenstrual dysphoric disorder) Direct and indirect health care costs
– Visits to ED, clinic, or office– Time lost from work
Quality of Life Issues Many women seek healthcare related
to menstrual problems– National health survey revealed 66% of
women sought care – 31% had stayed in bed for more than ½
day at least once during the previous year– 12% of all ED visits
PMS
Psychoneuroendocrine d/o with biological, social and psychological impacts
Up to 75% of women experience some level of recurrent sx
Up to 5% may experience severe sx and distress
Common PMS Sx Headache Breast pain Bloating Irritability Fatigue Crying
Abd pain Clumsiness Sleep alteration Labile mood Social withdrawal Libido change Appetite change
Requisite Symptoms for PMDD Diagnosis
Depressed mood Anxiety/tension Mood swings Irritability Decreased interest Concentration
difficulties Fatigue
Appetite changes/food cravings
Insomnia/hypersomnia Feeling out of control Physical symptoms 5/11 symptoms
needed for diagnosis and
Sx disrupt daily functioning
PMS/PMDD Tx Limit caffeine, tobacco, alcohol and
sodium Frequent high-complex carb meals CBT, stress management, aerobic
exercise
PMS/PMDD Tx SSRIs (ie: fluoxetine) 14 days prior to
onset of menses OCPs..not really effective Chaste berry and St John’s wort- more
effective than placebo but less than fluoxetine
Dysmenorrhea Painful menstruation- when pain
prevents normal activity and requires medication
Pain starts when bleeding starts Prostaglandin activity Emotional/psychological factors
Dysmenorrhea tx NSAIDs, starting a day before period
– Ibuprofen, naproxen Anti-prostaglandins much less
effective after pain is established Continuous heat to abd OCPs for 6-12 months have lasting
benefit
Abnormal Uterine Bleeding
Menorrhagia Oligomenorrhea Metrorhhagia Polymenorhhea Menometrorhhagia Oligomenorrhea Contact bleeding
Ddx of Abnormal Uterine Bleeding
Blood Dyscrasias Anatomic causes of bleeding, including
pregnancy Anovulation Malignancy Non-uterine causes of bleeding
AUB work-up Hx PE with cytology Pelvic ultrasound Endometrial biopsy Hysteroscopy D & C
Blood Dyscrasias Von Willebrand Idiopathic thrombocytic purpura (ITP) Leukemia Clotting factor deficiencies
Anatomic causes Pregnancy—cessation of menstrual
bleeding for 40 weeks– 1 in 5 pregnancies end in spontaneous abortion– First symptom is usually bleeding
Gestational trophoblastic disease (molar pregnancy)– Non-viable pregnancy with a large, grapelike
placenta that sloughs off and causes heavy bleeding
Infection– Cervicitis—leads to bleeding from the cervix– Endometritis—leads to sloughing off of
endometrial blood and mucous
Anatomic causes (cont.) Endocervical or endometrial polyps
– Esp post-coital bleeding IUD
– Bleeding likely with Paragard, extremely rare with Mirena (progestin-containing)
Leiomyoma (fibroids)– Subserosal (in wall of myometrium)– Intramural (most common “bump on top”)– Submucosal (can be pedunculated)
Leiomyomas (Fibroids) Benign neoplasms arising from uterine wall
smooth muscle cells 20-25% of reproductive age women Can be small to quite large, single or
multiple. Surrounded by pseudocapsule. Often asx, but can cause metrorrhagia,
menorrhagia, dysmenorrhea and infertility Cause unknown, but hormone responsive
Fibroid Sx Prolonged, heavy bleeding, can cause
anemia– (which type?)
Pain- from vascular compression Sensation of fullness, heaviness in pelvis Infertility or spontaneous abortion PE:
– Distorted uterine contour– Confirm with ultrasound
Fibroid Tx Depends on sx, age, parity,
reproductive plans, general health, and size/location of leiomyomas
GnRH agonists- to shrink fibroid OCPs control bleeding but do not treat
the fibroid Progestin-releasing IUD for multiple
small leiomyomata
Fibroid Tx - Surgical Myomectomy- preserves fertility, high risk
for fibroid recurrence Hysterectomy- eliminates sx and chance of
recurrence. Also eliminates uterus. Uterine fibroid embolization (UFE)
– Embolic occlusion of uterine arteries– As effective as above, few recurrences, few
major complications
Anovulation Patient History—very important to
diagnosis– Ovulatory cycles—consistent number of
days from beginning of one cycle to the next, breast tenderness, and dysmenorrhea usually present
– Anovulatory cycles—variation in number of days per cycle, no breast tenderness, and dysmenorrhea is not consistent from one cycle to the next
Anovulation Hypothalmic disorder related to:
– Stress– Diet– Exercise– Body fat
Pituitary-ovarian axis very sensitive to any bodily changes
Anovulation: Endocrinopathies
Thyroid– Both hypo- and hyperthyroidism may
present with AUB– TSH
Anovulation, endocrinopathies
Prolactin– Pepperell evaluated 304 patients with
oligoamenorrhea and found 7.6% had increased prolactin
– Interrupts menstrual function by inhibiting pulsatile release of GnRH
– Note: causes for falsely elevated prolactin levels Recent breast exam or breast stimulation Recent pelvic exam
Anovulation: POF Premature Ovarian Failure (Early
Menopause)– Diagnosed if woman of child-bearing age
develops amenorrhea and FSH level is found to be greater than 35
– This is an indication that the ovaries are no longer producing sufficient hormone levels to allow ovulation to occur
Other Causes of Anovulation
Any medication that affects the cytochrome P-450 cycle, eg psychotropic drugs
Ovarian tumors that produce steroids:– Granulosa cell tumors– Sertoli Leydig cell tumors
Malignancy as a Cause of AUB
Uterus—endometrial cancer Cervix--severe dysplasia, carcinoma in
situ, or invasive cancer will lead to bleeding.
Fallopian tubes—much less common Ovarian—not usually associated with
bleeding
DUB “Dysfunctional uterine bleeding” Abnormal uterine bleeding with
pathologic causes ruled out So..you’ve done all that stuff, and it’s
all okay Usually tx with hormones (ie OCPs) to
control bleeding
Non-uterine causes Genital neoplasms of the vulva or vagina
– To avoid missing vaginal lesions, stainless steel speculum blades should be rotated on removal to fully evaluate the vaginal mucosa
– Better: use plastic speculum with good light source
Genital trauma/foreign objects Rectal bleeding or urinary tract source
Evaluation History
– Menstrual pattern (duration, changes in quality, color of menses)
– Dysmenorrhea, mittleschmerz, breast changes
– Post-coital spotting– Dietary practices, change in weight,
exercise, stress– Evidence of systemic disease
Evaluation (cont.) Physical Exam
– Vital signs, height, weight, body phenotype, BMI– Skin, hair (acne, hirsutism pattern)– Fat distribution, striae– Thyroid – Breast exam to check for galactorrhea– Complete pelvic exam– Tanner stage for teens
Evaluation--testing All patients:
– Pregnancy test– CBC with platelets– Recent Pap
Over 35 yrs:– Endometrial sample
Documented drop in hgb <10– PT, PTT– Bleeding time
As indicated:– TSH– Prolactin– Testosterone– LH/FSH– 17-OH progesterone– Overnight
dexamethasone suppression test or 24 hr urinary free cortisol
– Hysteroscopy or ultrasound
Proposed Treatment Scheme
Begin evaluation and diagnostic testing, rule out pregnancy, check hgb
Hospitalize for low hgb (<7), and strongly consider blood dyscrasia, submucosal fibroid, or malignancy
Acute Bleeding: Control Oral progestins:
– Micronized Progesterone 200 mg (Prometrium) or Medroxyprogesterone 10 mg (Provera) or Norethindrone 5 mg (Aygestin)
– 1 po q4 hrs or until bleeding stops, then– 1 qid x 4 days– 1 tid x 3 days– 1 bid x 2 weeks, then – Cycle monthly with progestin or low dose oral
contraceptive
AUB Long Term Control Cycle with low dose OCP, patch, or vaginal
ring Cycle with a progestin, eg Prometrium Use of progestin-containing IUD (Mirena) Choice depends upon:
– Contraceptive need– Smoking status– Medical history– Patient preference
Long Term Control Danazol or other androgen agents will shut
down the hypothalamic-pituitary-ovarian axis
GnRH analogs (Lupron, Nafarelin) (x 6 months)
Ibuprofen and other NSAIDs decrease bleeding and cramping
Endometrial thickness of 4 mm or less is needed to eliminate intermenstrual bleeding
Endometrial Ablation Uterine thermal balloon
– Out-patient procedure– Regional anesthesia (spinal or epidural)– Balloon catheter inserted into uterus– Very hot fluid (87C) is inserted for 8 minutes
Post-Procedure– Cramping, bleeding for 1 week, serous discharge
for 4-6 weeks– Amenorrhea is the intended result
Endometriosis Abnormal growth of endometrial tissue
in locations other than the uterine lining
3-10% of women of reproductive age 30% of infertile women
Pathogenesis Cause unknown, but theories: Retrograde menstruation
– Viable endometrium shed during menses, flows thru fallopian tubes to peritoneal cavity
– Solid theory that does not explain all cases (ie: endometriosis in non-menstruating women or in non-peritoneal endometriosis)
Pathology This is a SURGICAL diagnosis Characteristic diagnostic surgical gross
appearance Small petechial lesions to larger “powder
burn” lesions 5-10 mm– Multiple lesions
On ovary, can enlarge to several centimeters– Endometriomas, or “chocolate cysts”
Implantation MC site: ovary Also round and broad ligaments,
uterus, fallopian tubes, sigmoid colon, appendix
Can implant on bowel, bladder, ureters– Or deep in tissue; cervix, posterior fornix,
wounds Also brain, thoracic cavity...
Pathophys Pelvic pain- secondary to hormonal
stimulation of endometrial tissue Implants enlarge and then bleed
– But implants are surrounded by fibrotic tissue that prevents escape of hemorrhagic fluid
Leads to inflammation, adhesions, mass effects
BUT Many pts with endometriosis do not
have significant pain Maybe pain is assoc with depth of
invasion?
History Infertility Dysmenorrhea Dyspareunia Constant pelvic pain or low sacral back
pain
Physical Tender nodules in posterior fornix Pain with uterine motion
Or – most likely- normal exam
Diagnosis What kind of diagnosis is it? Can suspect and even tx based on
clinical findings But if you need to know, go in- usually
laparoscopically No need for other studies usually
Endometriosis Tx Take into account:
– Desire for fertility– Age– Symptoms– Stage of disease
Tx Analgesics (ibu) Hormones
– OCPs or progestins– Danazol- prevents gonadotropin release, inhibits
midcyle LH and GSH. Androgenic side fx– GnRH agonists (Lupron)- with continuous admin,
suppresses gonadotropin secretion Assisted reproduction when desired
Prognosis Can offer significant relief from sx Can help achieve pregnancy Cannot cure
– Although extensive surgery can come close
– Conservative surgery has 10-35% recurrence
Amenorrhea Absence of menses Primary amenorrhea- no menses by age 16
with otherwise nl development Secondary amenorrhea- absence of
menses for 3 or more cycles or 6 months in a previously menstruating female– MC cause??– 3% in genl population– 100% under extreme stress
Examples?
Why bother? Dx and tx amenorrhea important
– Implications for future fertility– Risks of unopposed estrogen or
hypoestrogen
Ddx Hypothalamic defects
– Abnl GnRH pulse discharge, transport– Congenital GnRH deficiency
Idiopathic hypogonadotropic hypogonadism
Pituitary defects (less common)– Congenital or acquired
ie pituitary adenomas
Ddx Ovarian Dysfunction
– Gonadal dysgenesis- MC cause of primary amenorrhea
ie: Turner’s syndrome
– POF– PCOS
XY karyotype (androgen insensitivity syndrome)
Work-up
Download Amenorrhea pdf posted to shared files
Progesterone challenge Indirectly determines if ovary is
producing estrogen If endometrium has been primed,
exogenous progestin will produce menses
Tx Desiring pregnancy?
– Ovulation induction Not desiring pregnancy?
– If hypoestrogenic, combo tx with estrogen and progesterone to maintain bone density and prevent genital atrophy
– Normal progestin challenge: needs occasional progestin to prevent endometrial hyperplasia and cancer
– OCPs work well for either, and can decrease hirsutism
– Calcium, too!
Infertility vocab Infertility: Inability of a couple to conceive
for 12 months. (implies decrease in ability to conceive)– Primary vs secondary
Sterility: intrinsic inability to conceive Fecundity: probability of achieving live
birth from one menstrual cycle– Fecundability- likelihood of conception per
month
Very few infertile patients are sterile (1-2%)
Epi 13% of women (range 7-28%, age
dependant) Incidence of primary and secondary
infertility increasing– Why?
90% of couples having regular unprotected intercourse will conceive in 1 year
Normal fecundability 20-25%
Infertility etiology Either or both partners
– Cause found in 80% with even split between partners
So start with thorough hx of conception attempts and thorough hx of BOTH partners
Key Aspects Sperm Oocyte- ovarian reserve and ovulation Transport- fallopian tubes Implantation- uterus
Dudes History
– Prior paternity– Congenital abnormalities or undescended testes– Prev surgery or infections
PE– Varicocele (MC cause)
Semen analysis– Sperm count– Motility– Morphology
Chicas Hx
– Menarche– Cycle length and characteristics– S/s systemic ds (hypothyroid)– Exercise, weight– Age
Girl exam Pelvic, pap, etc Confirmation of ovulation
– History– U/S ovulation confirmation– Basal body temp– Cervical mucus monitoring
Pelvic U/S, hysterosalpingogram, maybe laparoscopy
Treatment Understanding that infertility can be a
devastating diagnosis Emotional roller coaster Damaging to self-image, relationships,
intimacy
Tx
Sperm factor- can use donor sperm or intrauterine insemination using “prepared” sperm
Ovulatory factor– Clomiphene citrate (Clomid) for ovulatory
induction– Good place to start– IVF (most invasive/expensive)
Referral is most appropriate