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8th Edition APGO Objectives for Medical Students
Normal and Abnormal Bleeding
Rationale
The occurrence of bleeding at times other than expected menses is a common event. Accurate diagnosis of abnormal uterine bleeding is necessary for appropriate management.
Objectives
The student will be able to: Describe endocrinology and physiology of the
normal menstrual cycle Distinguish abnormal uterine bleeding from
dysfunctional uterine bleeding List causes of abnormal uterine bleeding Evaluate and diagnose abnormal uterine
bleeding Describe therapeutic options
Normal Menstrual Cycle
Basic functional components Hypothalamic-pituitary unitOvaries Uterus-endometrium
Normal Menstrual Cycle
Normal parametersCycle interval 28 days + 7 daysDuration of menstrual flow - 4-7 daysAverage blood loss - 30-45 mLOvulatory bleeding is cyclic and
predictable
Normal Menstrual Cycle
Follicular phase (days 1-13) Rapid endometrial growth due to
stimulation by ovarian estrogen Regeneration in region of glandular
stumps Maximum thickness in late follicular
phase
Normal Menstrual Cycle
Luteal phase (days 14-28) Dependent upon ovulation (day 14) and
development of corpus luteum, progesterone production
Progesterone inhibits further endometrial thickness
Microvasculature becomes well-differentiated (spiral arterioles)
Normal Menstrual Cycle
Menstrual phase Fall in progesterone as corpus luteum
involutes Vasoconstriction → ischemia and hemorrhage Release of PGF2α
Hemostasis Platelet plugs Vasoconstriction Regeneration of functional layer (estrogen
stimulation)
Normal Menstrual Cycle
Hormonal changes LH peaks day 14 FSH is slightly increased day 14 and
day 27-28 Estradiol peaks day 12-13 Progesterone peaks day 18-22, then
falls Inhibin increased in luteal phase
Normal Menstrual Cycle
Pathways of ovarian steroidogenesis ∆ 4 → Estradiol, testosterone
androstenedione ∆ 5 → Dehydroepiandrosterone;
Dihydrotestosterone
Abnormal uterine bleeding
DefinitionExcessive flow or prolonged bleeding Frequent bleeding episodes Prolonged intervals between bleeds Organic cause (structural or systemic) vs.
hormonal dysfunction
Abnormal uterine bleedingTerminology Hypermenorrhea/menorrhagia
Regular bleeding Prolonged bleeding >7 days Excessive bleeding >80 mL
Metrorrhagia - irregular bleeding at frequent intervals Polymenorrhea - regular uterine bleeding at intervals
<21 days Intermenstrual - bleeding between regular and
identifiable periods Oligomenorrhea - bleeding at intervals >40 days
Menorrhagia
Affects approximately 15% of adult womenEtiology - pathologic conditions
Bleeding disorders Leiomyomas Adenomyosis Thyroid dysfunction Chronic endometritis Endometrial polyps or hyperplasia Estrogen-producing tumors Cervical or endometrial
cancer Intrauterine device Anovulation (dysfunctional uterine bleeding)
Menorrhagia
Laboratory evaluation Urine pregnancy test CBC with platelets EMB (endometrial biopsy) Thyroid functions (TSH) Coagulation studies Pelvic sonography
Menorrhagia
Medical management Prostaglandin synthetase inhibitors Combination hormonal contraceptives Progestins Correct medical conditions
Menorrhagia
Surgical management D&C - if clinically indicated Myomectomy - if leiomyomata are cause
and fertility desired Hysteroscopy with lesion resection Endometrial ablation Hysterectomy
Intermenstrual bleeding Unpredictable Generally associated with structural abnormalities Differential diagnosis
Ovulatory (Mittelschmerz) Inflammatory - endometritis Structural
• Malignancy • Leiomyomas • Polyps
Iatrogenic • Oral contraceptives • Hormone Replacement Therapy (HRT)
Anovulatory (dysfunctional) uterine bleeding
Etiology Obesity Adrenal hyperplasia Polycystic ovary syndrome (PCO) - increased
ovarian production of androgens, insulin resistance, chronic anovulation Increased circulating androgens aromatized to E1
(estrone) providing negative feedback to pituitary Low FSH (due to chronic elevation of estrogens) and
high LH - static levels do not trigger ovulation
Anovulatory (dysfunctional) uterine bleeding Etiology Obesity Adrenal hyperplasia Polycystic ovary syndrome (PCO) - increased ovarian
production of androgens, insulin resistance, chronic anovulation Increased circulating androgens aromatized to E1 (estrone)
providing negative feedback to pituitary Low FSH (due to chronic elevation of estrogens) and high LH -
static levels do not trigger ovulation
Anovulatory (dysfunctional) uterine bleeding
Laboratory evaluation Urine pregnancy test CBC with platelets DHEAS and testosterone, if symptoms of
hirsutism Endometrial biopsy (R/O neoplasia) Thyroid stimulating hormone (TSH)
Anovulatory (dysfunctional) uterine bleeding
Medical management Combination hormonal contraceptives Progestins (cyclic or continuous) Weight reduction/exercisesMetformin
ReferencesButtram VC Jr, Reiter RC. Uterine leiomyomata: etiology,
symptomatology, and management. Fertil Steril 36:433-445, 1981.
American College of Obstetricians and Gynecologists Practice Bulletin #16, Surgical Alternatives to Hysterectomy in the Management of Leiomyomas, ACOG: Washington, DC, May 2000.
Adapted from Association of Professors of Gynecology and Obstetrics Medical Student Educational Objectives, 7th edition, copyright 1997
Clinical Case
Normal and Abnormal Uterine Bleeding
Patient Presentation41-year-old G2P0020 LMP=10 days ago presents with persistent
heavy vaginal bleeding. She denies dizziness, but complains of feeling weak and fatigued. Her cycles have been heavy for a long time, but seem to be worsening over the last several months. Her cycles come every 28-35 days and she bleeds for 7-10 days. She describes bad cramps, passing clots and using 2 boxes of maxi pads each cycle. She is worried about losing her job if the bleeding is not better controlled. She only gets designated break times from the assembly line to use the bathroom. She takes Ibuprofen every 4-6 hours for cramps. She denies any bleeding disorders in the family. She uses condoms for contraception. She also complains of a pressure sensation and increased urinary frequency.
Allergies: None; Medications: Ibuprofen as needed
Patient PresentationOb-Gyn history Menarche 13/cycles 28-35 days/ 7-10 days.
Normal pap smears. History of Gonorrhea once and treated1 elective termination at 16-years-old and 1 miscarriage at 10 weeks, about 2 years ago
Past medical history NonePast surgical history D & C for miscarriage; tonsils and adenoids as
a childSocial history Nonsmoker. Occasional alcohol. No drugs. Works
at a factory for machine parts assembly.Family history Hypertension in mother and father. Mother had 1
miscarriage and 3 sons. Her brothers are healthy and one has sickle trait. Her paternal grandfather died of lung cancer.
Patient presentationROS Negative, except as noted above.Physical exam VS: BP=130/88; Pulse= 110; Respirations= 18; Ht=5’6’;
Wt=150 poundsAfrican-American women who appears pale and with bags under her eyes
HEENT: NC and ATLungs: clear to auscultation and percussionCV: rapid rate, no murmursBreasts: Non-tender, no masses, no dimpling, retraction or discharge Abdomen: Non-tender, No hepatomegaly, firm palpable mass in the lower
abdomenExtremities: Non-tender, no edema, 2+/= DTRs bilaterallyPelvic exam: Normal external genitalia; moist and pink vagina with rugae
and dark blood in the vault; cervix is non-tender, no lesions, and nullipara; uterus is 16 weeks size, firm, mobile, non-tender; adnexae: non-tender, no palpable masses
Patient presentation
Laboratory/studiesHbg: 9.0, HCT: 27%HCG: negativeTSH: 3.5 uIU/mL (Normal range: 0.4-4.0)Prolactin: 19 ng/dl (Normal range <20)PT/PTT: normalUrinalysis: negative for infectionEndometrial biopsy: Proliferative endometriumPelvic Ultrasound: Multiple myomas (intramural and
submucosal in location), Normal ovaries
Diagnoses
MenorrhagiaAnemiaLeiomyomatous uterusPossible anovulation (when her cycles
are greater than or equal to 35 days)
TreatmentThis patient was treated with GnRH analog for three months.
Her hemoglobin increased to 12. She had some minor spotting during therapy. She complained of hot flushes and irritability. Her follow-up examination at 2.5 months of therapy showed a decrease in uterine size to 12-14 weeks size. Her repeat ultrasound confirmed these findings. She was counseled regarding medical management with oral contraceptives, progestins or continued GnRH analog with hormonal add-back. Given the presence of submucosal myomas, it is likely that this treatment may not be effective in the long run. However, she has had an optimal response thus far.
Treatment
She was also counseled regarding surgical management. If she is interested in maintaining her fertility, her options include: hysteroscopic resection of submucosal myomas only or abdominal myomectomy. If fertility is not desired and she wants a definitive therapy, then a hysterectomy is indicated. Risks and benefits for these medications and surgeries were discussed. This patient is at increased risk for requiring a blood transfusion if the bleeding recurs and is heavy, or if the bleeding is significant during surgery. She will think about her options and decide over the next week.
Teaching points1. Leiomyomas occur with a high prevalence of 25-50% of women
(Buttram and Reiter). They are more common in the African-American population.
2. If this patient did not respond to the gonadotropin agonist therapy and the bleeding worsened, she would have been a candidate for high dose oral contraceptives, high-dose Premarin intravenously or a D&C to control her bleeding. If none of these options were effective, a uterine artery embolization or hypogastric artery ligation could be options prior to hysterectomy. In the near future, other medical therapies may become standard. Currently, gonadotropin-releasing hormone antagonists and progesterone antagonist mifepristone (RU 486) are under investigation. Gene therapies may be developed as we learn more about leiomyoma formation and growth.
Teaching points3. After a myomectomy, the recurrence rate of
leiomyomas ranges from 27-51%. Approximately, 15% require another operative procedure. The incidence of re-operation is increased with multiple myomas (26%) as opposed to a single myoma (11%).
4. It is important to rule out the other differential diagnoses in women with leiomyomas, i.e. pregnancy with possible incomplete abortion or ectopic, thyroid disease, endometrial cancer, etc). These disorders are also present in these women and we cannot assume we have the correct diagnosis unless tested.
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