1. Normal & Abnormal Uterine Bleeding
Syamel Muhammad

2. Objectives
Recognize the characteristics of Normal Menstrual Bleeding (The LMP as the fourth vital sign!)
Describe the etiologies of Abnormal Uterine Bleeding (AUB.)
Understand etiologies of AUB with respect to the life stages of women.
Understand the diagnostic tools to identify the etiology of the AUB.
State the medical & surgical options available in primary care and gynecology settings.

3. Normal Menstruation The Menstrual Cycle
In the normal menstrual cycle, orderly cyclic hormone production and parallel proliferation of the uterine lining prepare for implantation of the embryo.
Berek & Novak’s Gynecology, 2012, p.145
A sound understanding of the female reproductive cycle is the first step in becoming a women’s health specialist. Starting with a definition is a good start, but as we read a text book definition we know that we also need a lay person definition for counseling our patients.

4. Normal Menstruation
“The menstrual cycle starts with the first day of bleeding of one period and ends with the first day of the next. In most women, the cycle last about 28 days. Cycles that are shorter or longer by 7 days are normal.”
ACOG Website: FAQ095
Online sources are good. I like to know a few that I can refer patients for education. “Menstruation, or period, is normal vaginal bleeding that occurs as part of a woman's monthly cycle. Every month, your body prepares for pregnancy. If no pregnancy occurs, the uterus, or womb, sheds its lining. The menstrual blood is partly blood and partly tissue from inside the uterus. It passes out of the body through the vagina." MedlinePlus: A service of the U.S. National Library of Medicine National Institutes of Health

5. The Normal Menstrual Period
Blood loss < 80 ml (average ml)
Duration of flow 2-7 days (average 4 days)
Cycle length days (average 29 days)
(28 days +/- 7 days}

6. Phases of the Menstrual Cycle Reproductive Cycle
Follicular
Begins with Menses ends with luteinizing (LH) hormone surge
Ovulation (30-36 hours)
Begins with LH surge and ends with ovulation
Luteal (14 days)
Begins with the end of the LH surge and ends with onset of menses
The duration of the Luteal Phase is relatively day length. Both Follicular and Luteal phases are approximately 14 days. Therefore, the fluctuation in cycle length vary on the length of the follicular phase. Menstrual irregularities are more common at the extremes of reproductive age women.
Beckman, et al., Obstetrics & Gynecology, 7th ed., p. 337

7. The Normal Menstrual Cycle Another Way of looking at it
Visually, one can see the ebb and rise of gonadotropins as well as the ovarian steroid hormones. Also remember that the endometrium is going through changes due to these ovarian hormones. The phases of endometrial changes are menstrual, proliferative and secretory.
M. Manting; DUB LECTURE 2008

8. Phases of the Menstrual Cycle Endometrium
Proliferative
Begins with menses and ends at ovulation
Secretory
Begins at ovulation and ends with menses

9. The Normal Menstrual Cycle Another Way of looking at it
Visually, one can see the ebb and rise of gonadotropins as well as the ovarian steroid hormones. Also remember that the endometrium is going through changes due to these ovarian hormones. The phases of endometrial changes are menstrual, proliferative and secretory.
M. Manting; DUB LECTURE 2008

10. Regulation: Hypothalamic Pituitary Axis
Hypothalamus is the pulse generator mediated through GnRH
GnRH cannot be directly measured
Negative Feedback
The negative feedback loop could have its own hour of lecture, but there are some basic principals that need to be basic knowledge. With the Hypothalamus secreting GnRH, the anterior pituitary. The anterior pituitary produces LH & FSH. These two gonadotropins act respectively on the theca cells and granulosa cells to produce estrogen. Most progesterone comes from peripheral conversion, but some comes from the graafian follicle. The E2 & P along with inhibin increase to inhibit GnRH, creating the negative feedback loop.

11. Abnormal Uterine Bleeding (AUB)
Definition:
Any change in menstrual period
Flow
Duration
Frequency
Bleeding between cycles
Prevalence:
20 million office visits/year
25% of visits to gynecologists

12. Old Terminology Dysmenorrhea: Pelvic pain with menses
Menorrhagia
Metrorrhagia
Menometrorrhagia
Polymenorrhea
Dysmenorrhea
Amenorrhea
Oligomenorrhea
Hypomenorrhea
Menorrhagia – bleeding at normal intervals but with heavy flow (> 80 cc) and/or long duration
(> 7 days)
Metrorrhagia – irregular bleeding between menstrual periods
Menometrorrhagia – bleeding at irregular intervals with heavy flow and/or long duration
Polymenorrhea – bleeding at intervals < 21 days
Oligomenorrhea: > 35 day cyles
Hypomenorrhea: scanty flow
Dysmenorrhea: Pelvic pain with menses
Amenorrhea: 3 months without menses if previously regular or 6 months if irregular
Oligomenorrhea: >35 days between menses
Hypomenorrhea: <2 days light menses

13. New Terminology Heavy Menstrual Bleeding Intermenstrual Bleeding Acute
Chronic
Intermenstrual Bleeding

14. History for AUB Onset Quantity : Spotting or heavy
daily or intermittent
Duration

15. History for AUB Associated Symptoms Pain Fever/chills Dysmenorrhea
Menstrual Changes
Timing
Flow (clots)
Frequency
Fever/chills
Changes in hair/ body
Bruising/bleeding
Rectal/urethral bleeding
Nausea/vomiting

16. Gender Specific History
Menstrual
Contraception
Gynecologic
Obstetric
Sexual
Genital Infections

17. Other Important Details
Family History
Anyone else?
Von Willebrand's
PCOS
Nutrition and exercise
Weight changes
Exercise habits
diet
Chronic conditions
Liver disease
Kidney disease
Anemia
Drugs /medications
Psychiatric medications
Thyroid Disorders
Blood thinners

18. Differential Diagnosis Of AUB
Structural: PALM-COEIN
(Non Gravid Women)
Life Cycles: Pre-menarche Menarche
Reproductive
Post-Menopause
Anatomic: “Bottoms Up”
This is an introduction into how to organize your medical information. Once the organization of the differential is determined, apply it clinically in an organized fashion.
PALM-COEIN was published in FIGO 2011 and adopted by ACOG. Sometimes more than one strategy is used to develop a differential diagnosis.

19. Pregnancy P PROVE IT! Never Forget Pregnancy Age is Not An Issue!
Assumptions can
lead to death

20. PALM-COEIN
FIGO Classification System (PALM-COEIN) for causes of AUB in non gravid women of reproductive age
Structural vs. Non-Structural
Developed to create a universally accepted nomenclature

21. PALM Structural Causes
P- Polyp (AUB-P) A- Adenomyosis (AUB-A) L- Leiomyoma (AUB-L) Submucosal myoma (AUB-LSM) Other myoma (AUB-LO) M- Malignancy & hyperplasia (AUB-M)

22. COEIN Non-Structural Causes
C- Coagulopathy (AUB-C) O-Ovulatory dysfunction (AUB-O) E- Endometrial (AUB-E) I- Iatrogenic (AUB-I) N- Not yet classified (AUB-N

23. AUB-O Abnormal Uterine Bleeding with ovulatory dysfunction
Heavy, irregular bleeding

24. Causes of Anovulation:
Physiologic
Adolescence
Menopause Transition
Lactation
Pregnancy

25. Causes of Anovulation Pathologic
Hyperandrogenic anovulation (e.g., PCOS, CAH, or androgen-producing tumors)
Hypothalamic dysfunction
Hyperprolactinemia
Thyroid disease
Pituitary disease
Premature ovarian failure
Iatrogenic (Chemo)
Medications

26. Iatrogenic I IUD related Post-instrumentation Post medical abortion
Infection
Endometritis
Cervicitis
Ascending/PID
Hematogenously (TB)
Clinical findings may be very subtle. Very thorough, gender specific history is absolutely necessary to find the clues that illuminate the diagnosis. Think about how differently a clinical vs. sub-clinical infection might present.

27. Liver Disease
Patients known to have liver disease manifest additional symptomatology because of abnormal hepatic function.
Evaluate patients for spider angioma, palmar erythema, splenomegaly, ascites, jaundice, and asterixis.

28. Coagulation Disorders
Rule out
von Willebrand's
in any girl who
requires
transfusion for excessive
bleeding
when first
starting periods

29. Bleeding from ther SitesGI
Neoplasia or hemorrhoids GU
Urethral caruncle or diverticulum
Renal lithiasis or hemorrhagic cystitis
GYN
Labia, cervix, or vagina
Trauma, infection, or
neoplasia
Remember
Hemoccult
& Urinalysis

30. Differential Diagnosis of AUB: Life Cycles
Pre-Menarche
Menarche
Reproductive
Postmenopausal

31. Etiology of AUB Life Cycles Approach
E2 withdrawal
@birth
Foreign Body
Sarcoma
Ovarian Tumor
Trauma
Coagulation
Defects
Hypothalamic
Immaturity
Psychogenic
Pregnancy
Anovulation
Endogenous
Exogenous
Anatomic
Carcinoma
Vaginal Atrophy
E2 Replacement
Post-Menopausal
Menarche
Reproductive
Premenarchal
In all ages one must consider foreign body. Anatomic = uterine lyomas, polyps, muellerian anomalies, etc. Sarcoma Botryoides is a very aggressive almost uniformly fatal pediatric cancer.

32. Differential Diagnosis of AUB: Structural
“Bottoms Up”
Vulva
Vagina
Cervix
Ovary
Brain
Contiguous Anatomy GU GI
Non-Pelvic Etiology
Endogenous
Iatrogenic

33. PHYSICAL EXAM: INSPECTION IS IMPORTANT
Vulvar
Infections
HPV
Atrophy
Benign Lesions
Cancerous lesions
Dermatologic Causes
PHYSICAL EXAM: INSPECTION IS IMPORTANT

34. Vagina Malignancy : Infections Foreign bodies Laceration/trauma
Carcinoma
Sarcoma
Infections
Foreign bodies
Diaphragm, Pessary
Tampon
other
Laceration/trauma
Atrophic changes
Granulomatous tissue
formed after surgery
post hysterectomy
Physical Exam: Inspection is important

35. Cervix Neoplasia Cervical Eversion (Ectropion) Infection Cancer Polyps
Myomas
Cervical Eversion (Ectropion)
Infection
Cervicitis
Condyloma Acuminata
IMPORTANT:
Visualize the Cervix!

36. until proven otherwise PHYSICAL EXAM: Bimanual Exam checks enlargement
Postmenopausal
Bleeding
is considered
endometrial cancer
until proven otherwise
Uterus
Myomas
Polyps
Endometrial Hyperplasia
Endometrial Carcinoma
Atrophy
Postmenopausal
bleeding
is evaluated
by an
Endometrial
biopsy
Most PMB
Is due to
Atrophy
PHYSICAL EXAM: Bimanual Exam checks enlargement

37. Ovary
Anovulation
PCOS
Menopause Transition

38. Pathophysiology Etiologies Of AUB
Estrogen Withdrawal
Estrogen Breakthrough
Progesterone Withdrawal
Pathophysiology:
Estrogen Withdrawal: Sudden withdrawal of estrogen will cause the uterus to bleed, either iatrogenic (bilateral oophorectomy) or endogenous (natural drop of estradiol at mid cycle ovulation).
Estrogen Breakthrough: During an anovulatory cycle, the corpus luteum fails to form, which causes failure of normal cyclical progesterone secretion. This results in continuous unopposed production of estradiol, stimulating overgrowth of the endometrium. Without progesterone, the endometrium proliferates and eventually outgrows its blood supply, leading to necrosis. The end result is overproduction of uterine blood flow. There is not universal simultaneous change with and orderly progression of cyclic events involving formation of rigid, compact glandular structure, vasomotor rhythmicity, vasoconstriction, structural collapse and clotting.
Progesterone Withdrawal: Sudden decrease in the progesterone levels in a female which is iatrogenic (a progesterone only oral contraceptive). The endometrium Atrophies and ulcerates due to lack of estrogen and is prone to bleeding
Clinical Management of Abnormal Uterine Bleeding:
APGO Educational Series, May 2002, p. 8.

39. Initial Assessment of AUB
Acute
Sub-Acute
Chronic
Initial evaluation should be directed at assessing patient's volume status and degree of anemia.

40. Initial Assessment of AUB
History & Physical
Vital Signs
Shock Signs
Laboratory
Pregnancy Test
Complete Blood Count
General impression of the patient is your first clue. Is she pale, tachycardic, Hypotensive? Is there a positive sock sign?

41. EVALUATION OF AUB Pregnant? Evaluate for complications
IUP, SAB, Ectopic
Structural (PALM)
VS.
Non-Structural (COEIN)
YES NO

42. Evaluation of AUB Evaluation of the Endometrium Endometrial Biopsy
Pregnancy test
Endometrial Biopsy
Transvaginal &/or abdominal Ultrasound (TVS/AUS)
Saline Sono-hysterocopy (SIS)
Hysteroscopy
Evaluation of the Uterus
TVS
SIS

43. Endometrial Biopsy (EMB)
Evaluation of the Endometrium
Pipelle
Endometrial Biopsy is sensitive 98-99% in diagnosing cancer, but it misses 50% of benign diagnosis (i.e., polyps, fibroids, endometritis).

44. Transvaginal Ultrasound
To assess for thickened endometrium
In 92% of abnormal endometrial biopsies, ultrasound showed >5mm endometrium
In 96% of endometrial cancer by biopsy result, ultrasound showed >5mm endometrium
Therefore, ultrasound measured endometrium <5mm is likely benign uterine condition

45. TVS & SIS
SIS is superior to TVS alone fo evaluating the uterine cavity. Sterile saline is infused into the endometrial cavity during real-time ultrasound. The saline provides contrast to clearly define endometrial abnormalities.
TVS
SIS

46. Hysteroscopy
Hysteroscopy, which may been done as an office procedure, allows for direct visualization of the endometrial cavity. For many years it was considered the gold standard for evaluation of the endometrial cavity. More recently, studies have shown hysteroscopy is less sensitive in detecting endometrial hyperplasia.

47. MRI Precisely localizes sub-mucosal fibroids
MRI is not superior to TVS & SIS in overall diagnostic potential
MRI is used primarily to determine whether a patient is a candidate for Selective Uterine Artery Embolization (EUA).
Dueholm M, et al. Fertil Steril. 2001;76(2):350357

48. Treatment of AUB Observation Medical Minimally invasive surgery
Major surgery

49. Medical Management Iron Parenteral estrogens Anti-fibrinolytics
Progestins
Estrogen + progestins (OCP)
Parenteral estrogens
Androgens
GnRH agonists
Anti-progestational agents
For older, stable (hematocrit 25-35%) patients with a known history of DUB, iron deficiency anemia, and moderate amount of prolonged bleeding, administer a combination of high-doses estrogen and synthetic progesterone oral contraceptives (e.g., Ortho-Novum 1/50 qid 7 d) to arrest bleeding. Oral contraceptives may aggravate an already suppressed hypothalamic-ovarian axis in young postmenarcheal patients; therefore, use it in patients with an established menstrual history. Exclude pregnancy prior to initiating therapy. Modicon 21 (ethinyl estradiol, norethindrone) Ortho-Novum 1/35 (ethinyl estradiol, norethindrone) Ortho-Novum 1/50 (mestranol, norethindrone) Levlen 21,28 (ethinyl estradiol, levonorgestrel) Lo/Ovral (ethinyl estradiol, norgestrel) Ortho-Cept 21 (ethinyl estradiol, desogestrel) Demulen 1/30,50 (ethinyl estradiol, ethynodiol diacetate) These can be started safely in the ED after the severe acute bleeding episode is curtailed with IV estrogen and pregnancy has been ruled out.

50. Minimally Invasive Surgery
Intrauterine Device (IUD) with progesterone
Dilation & Curettage
Endometrial Ablation
Progesterone containing IUD reduces bleeding in most women with the added benefit of providing contraception as well. 95% are satisfied with the reduction in bleeding.
D & C is only 70% effective in controlling bleeding.
Endometrial Ablation is comparable to progesterone IUD in controlling AUB. The smaller the uterus the better the result.

51. Major Surgery Myomectomy Total Abdominal Hysterectomy (TAH)
Total Vaginal Hysterectomy (TVH)
Laparoscopic Hysterectomy
LSH (laparoscopic supra-cervical)
TLH (total laparoscopic)
LAVH (laparoscopically assisted vaginal hysterectomy)
Robotic (TLH or LSH)
Total hysterectomy refers to the removal of the cervix with the uterine fundus. Supra-cervical Hysterectomy may be done abdominally or laparoscopic. Note that a hysterectomy can be done as minimally invasive. All hysterectomies may or may not include removal of the ovaries.

52. Management of Acute AUB
Can be a life-threatening emergency
Monitor Vital signs, Start oxygen
IV fluids (wide bore IV catheter)
Type and Cross 2-4 units of blood
IV Estrogen
IM Progesterone
NSAIDS (Anti-prostaglandins vs. Anti-fibrinolytics)
Emergency Dilatation and Curettage (D&C)
Start with ABC’s. Use clinical judgment to for the most likely etiology to begin treatment.

53. Treatment in Chronic, Stable AUB
High dose OCP’s to slow the bleeding
Anovulatory Bleeding can be treated with progesterone alone
Endometrial sampling is indicated prior to starting hormones in older women

54. Clinical Pearls PROVE IT! Never Forget Pregnancy! Age is Not an Issue!
Assumptions Can
Lead to Death!

55. References ACOG Practice Bulletin No. 136, July 2013
Beckmann, et al., Obstetrics & Gynecology, 7th ed., Chapters 37, 39
Clinical Management of Abnormal Uterine Bleeding: APGO Educational Series, May 2002
Dueholm M, et al. Fertil Steril. 2001;76(2):350357
Fritz, MA, Speroff et al, Clinical and Gynecologic Endocrinology and Infertility,
8th ed
Manting M., AUB Lecture 2008
Munro, MG, et al, FIGO Classification System (PALM-COEIN) for causes of AUB in non gravid women of reproductive age. Int J Gynaecol Obstet 2011; 113:3-13