Disorders of Menstruation / Abnormal Uterine Bleeding

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Disorders of Menstruation / Abnormal Uterine
Bleeding

• Tory Davis, PA-C

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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.

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Terminology

• Amenorrhealack of menstrual bleeding
• Primaryno menses by age 16
• Secondaryabsence 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)?

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Terminology (cont.)?

• Menorrhagiaheavy menstrual bleeding. Prolonged
  or excessive menstrual blood loss with regular
  cycles
• Metrorrhagiairregular, frequent bleeding
• Menometrorrhagiairregular menses with prolonged
  or excessive blood loss
• Midcycle bleedinglight menstrual bleeding
  occurring in ovulatory women at the midcycle
  estradiol trough

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Terminology (cont.)?

• Oligomenorrhea-- menstrual bleeding/menses
  occurring less frequently than 36 days apart
• Polymenorrheafrequent menstrual bleeding/menses
  occurring more frequently than 21 days apart
• Contact bleeding/post-coital bleeding
• Dysmenorrhea- painful menstrual bleeding

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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

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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

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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

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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
• gt13 4.5 yrs

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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

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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

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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

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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

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Common PMS Sx

• Headache
• Breast pain
• Bloating
• Irritability
• Fatigue
• Crying

• Abd pain
• Clumsiness
• Sleep alteration
• Labile mood
• Social withdrawal
• Libido change
• Appetite change

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Requisite Symptoms for PMDD Diagnosis

• Appetite changes/food cravings
• Insomnia/hypersomnia
• Feeling out of control
• Physical symptoms
• 5/11 symptoms needed for diagnosis and
• Sx disrupt daily functioning

• Depressed mood
• Anxiety/tension
• Mood swings
• Irritability
• Decreased interest
• Concentration difficulties
• Fatigue

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PMS/PMDD Tx

• Limit caffeine, tobacco, alcohol and sodium
• Frequent high-complex carb meals
• CBT, stress management, aerobic exercise

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PMS/PMDD Tx

• SSRIs (ie fluoxetine) 14 days prior to onset of
  menses
• OCPs..not really effective
• Chaste berry and St Johns wort- more effective
  than placebo but less than fluoxetine

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Dysmenorrhea

• Painful menstruation- when pain prevents normal
  activity and requires medication
• Pain starts when bleeding starts
• Prostaglandin activity
• Emotional/psychological factors

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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

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Abnormal Uterine Bleeding

• Menorrhagia
• Oligomenorrhea
• Metrorhhagia
• Polymenorhhea
• Menometrorhhagia
• Oligomenorrhea
• Contact bleeding

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Ddx of Abnormal Uterine Bleeding

• Blood Dyscrasias
• Anatomic causes of bleeding, including pregnancy
• Anovulation
• Malignancy
• Non-uterine causes of bleeding

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AUB work-up

• Hx
• PE with cytology
• Pelvic ultrasound
• Endometrial biopsy
• Hysteroscopy
• D C

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Blood Dyscrasias

• Von Willebrand
• Idiopathic thrombocytic purpura (ITP)?
• Leukemia
• Clotting factor deficiencies

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Anatomic causes

• Pregnancycessation 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
• Cervicitisleads to bleeding from the cervix
• Endometritisleads to sloughing off of
  endometrial blood and mucous

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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)?

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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

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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

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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

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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

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Anovulation

• Patient Historyvery important to diagnosis
• Ovulatory cyclesconsistent number of days from
  beginning of one cycle to the next, breast
  tenderness, and dysmenorrhea usually present
• Anovulatory cyclesvariation in number of days
  per cycle, no breast tenderness, and dysmenorrhea
  is not consistent from one cycle to the next

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Anovulation

• Hypothalmic disorder related to
• Stress
• Diet
• Exercise
• Body fat
• Pituitary-ovarian axis very sensitive to any
  bodily changes

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Anovulation Endocrinopathies

• Thyroid
• Both hypo- and hyperthyroidism may present with
  AUB
• TSH

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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

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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

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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

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Malignancy as a Cause of AUB

• Uterusendometrial cancer
• Cervix--severe dysplasia, carcinoma in situ, or
  invasive cancer will lead to bleeding.
• Fallopian tubesmuch less common
• Ovariannot usually associated with bleeding

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DUB

• Dysfunctional uterine bleeding
• Abnormal uterine bleeding with pathologic causes
  ruled out
• So..youve done all that stuff, and its all okay
• Usually tx with hormones (ie OCPs) to control
  bleeding

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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

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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

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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

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Evaluation--testing

• All patients
• Pregnancy test
• CBC with platelets
• Recent Pap
• Over 35 yrs
• Endometrial sample
• Documented drop in hgb lt10
• 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

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Proposed Treatment Scheme

• Begin evaluation and diagnostic testing, rule out
  pregnancy, check hgb
• Hospitalize for low hgb (lt7), and strongly
  consider blood dyscrasia, submucosal fibroid, or
  malignancy

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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

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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

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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

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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

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Endometriosis

• Abnormal growth of endometrial tissue in
  locations other than the uterine lining
• 3-10 of women of reproductive age
• 30 of infertile women

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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)?

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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

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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...

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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

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BUT

• Many pts with endometriosis do not have
  significant pain
• Maybe pain is assoc with depth of invasion?

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History

• Infertility
• Dysmenorrhea
• Dyspareunia
• Constant pelvic pain or low sacral back pain

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Physical

• Tender nodules in posterior fornix
• Pain with uterine motion
• Or most likely- normal exam

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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

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Endometriosis Tx

• Take into account
• Desire for fertility
• Age
• Symptoms
• Stage of disease

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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

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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

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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?

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Why bother?

• Dx and tx amenorrhea important
• Implications for future fertility
• Risks of unopposed estrogen or hypoestrogen

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Ddx

• Hypothalamic defects
• Abnl GnRH pulse discharge, transport
• Congenital GnRH deficiency
• Idiopathic hypogonadotropic hypogonadism
• Pituitary defects (less common)?
• Congenital or acquired
• ie pituitary adenomas

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Ddx

• Ovarian Dysfunction
• Gonadal dysgenesis- MC cause of primary
  amenorrhea
• ie Turners syndrome
• POF
• PCOS
• XY karyotype (androgen insensitivity syndrome)?

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Work-up

• Download Amenorrhea pdf posted to shared files

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Progesterone challenge

• Indirectly determines if ovary is producing
  estrogen
• If endometrium has been primed, exogenous
  progestin will produce menses

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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!

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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)?

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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

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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

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Key Aspects

• Sperm
• Oocyte- ovarian reserve and ovulation
• Transport- fallopian tubes
• Implantation- uterus

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Dudes

• History
• Prior paternity
• Congenital abnormalities or undescended testes
• Prev surgery or infections
• PE
• Varicocele (MC cause)?
• Semen analysis
• Sperm count
• Motility
• Morphology

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Chicas

• Hx
• Menarche
• Cycle length and characteristics
• S/s systemic ds (hypothyroid)?
• Exercise, weight
• Age

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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

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Treatment

• Understanding that infertility can be a
  devastating diagnosis
• Emotional roller coaster
• Damaging to self-image, relationships, intimacy

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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