1. Normal & Abnormal Uterine Bleeding
Suzanne Bush, MD, FACOG
Clinical Associate Professor
FSU College of Medicine

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. Case One
16 year old G0P0 presents because she is concerned about her periods being irregular. She describes her cycles as coming the 18th of one month & the 16th the next month. She never knows when it is coming.
How would you counsel this patient?

4. How would you counsel this patient?
Oral combined contraception pills will regulate her cycles
She needs to do 3 months of a menstrual diary using an App on her smartphone
She probably has a luteal phase defect and needs progesterone days
She has normal cycles and needs reassurance.

5. 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.

6. 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 lasts 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

7. 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}

8. Phases of the Menstrual Cycle Reproductive Cycle
Follicular (variable)
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

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

10. Case Two
A 25 year old G0P0 just moved to the area and desires a pregnancy. She has irregular menses. She was told by her previous doctor that she has polycystic ovarian syndrome (PCOS) and does not ovulate. She has results of a day 21 endometrial biopsy that shows “Secretory Endometrium.” What can you tell this patient?

11. What can you tell this patient?
The biopsy confirms anovulation
The biopsy was done on the wrong day
The biopsy confirms ovulation.
This patient does not have PCOS

12. Phases of the Reproductive Cycle Phases of the Endometrium
Compare
Phases of the Reproductive Cycle
Phases of the Endometrium
Follicular
Ovulatory
Luteal
Proliferative
Secretory

13. 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. Of note, one can’t have secretory endometrium without ovulation.
M. Manting; DUB LECTURE 2008

14. Regulation: Hypothalamic Pituitary Axis
Hypothalamus is the pulse generator mediated through GnRH
GnRH cannot be directly measured
Negative Feedback Loop
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.

15. Regulation of The Ovary 2 Cell Theory
Theca Cell
Granulosa Cell
The negative feedback loop relies on the 2 Cell Theory of estrogen formation from the interaction of the theca and granulosa cells

16. 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

17. 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

18. New Terminology Heavy Menstrual Bleeding Intermenstrual Bleeding
Acute
Chronic
Intermenstrual Bleeding
Munro MG, FIGO Classification of AUB 2011

19. Clinical dimensions of menstruation and the menstrual cycle
Descriptive terms
Normal limits (5th to 95th percentiles)
Frequency of menses (days)
Frequent
<24
Normal
24–38
Infrequent
>38
Regularity of menses (cycle to cycle variation over 12 months)
Absent No
Regular
2–20 days
Irregular
>20 days
Duration of flow (days)
Prolonged
>8.0 days
4.5–8.0 days
Shortened
<4.5 days
Volume of monthly blood loss (mL)
Heavy
>80
5–80
Light
<5

20. History for AUB Ask lots of questions! HPI Onset Quantity :
Spotting or heavy
daily or intermittent
Duration
The history for AUB is an opportunity for your inner sleuth skills to shine. Ask lots of questions. Number of pads or tampons? What size pad or tampon? Are they soaked or partially soiled? Clots? What size? Do soil your sheets? Do you take a change of clothes to work or school?

21. History for AUB Gender Specific Associated Symptoms Menstrual
Contraception
Gynecologic
Obstetric
Sexual
Genital Infections
Associated Symptoms
Pain
Nausea
Fatigue
Headache
Mastalgia

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

23. Case Three
48 year old G2P2, S/P Bilateral Tubal Ligation 14 years ago, referred from her primary care office with RLQ pain of 3 months duration. LMP 5 weeks ago has had many years of irregular menses thought to be menopause transition.
Ultrasound shows an 8 cm adnexal cyst with CA 125 normal.

24. The next step is: Get her on the schedule for surgery MRI
Order Follicle Stimulating hormone(FSH)
Urine Pregnancy Test
Estradiol

25. Never forget pregnancy Assumption can lead to death
Age is not an issue!
Prove it!
Assumption can lead to death

26. 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.

27. 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

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

29. 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)

30. Case Four
42 year old G3P3 who is in your civic group presents with heavy, cyclic uterine bleeding. You note spider angioma across her chest & down her arms. She has a slightly protuberant abdomen. Her husband had a vasectomy 7 years ago, and her pregnancy test is negative.

31. The best next step in evaluating her heavy uterine bleeding:
Fasting Blood Glucose
Thyroid Stimulating Hormone
Liver Function Test
Follicle Stimulating Hormone
Estradiol

32. What FIGO nomenclature would you use to label her AUB?
AUB-C
AUB-O
AUB-E
AUB-I
AUB-N

33. 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.

34. Differential Diagnosis of AUB Post-Menopausal Menarche Reproductive
Pre-menarche
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.

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

36. Acute * Sub-Acute * Chronic
EVALUATION OF AUB
Pregnant?
Evaluate for complications
IUP, SAB, Ectopic
Structural (PALM)
VS.
Non-Structural (COEIN) NO
YES
Acute * Sub-Acute * Chronic

37. AUB Evaluation Initial Assessment History & Physical Laboratory
Vital Signs
Shock Signs
Laboratory
Pregnancy Test
Complete Blood Count
Evaluation of the Uterus & Endometrium
Endometrial Biopsy
Transvaginal &/or abdominal Ultrasound (TVS/AUS)
Saline Sono-hysteroscopy (SIS)
Hysteroscopy
General impression of the patient is your first clue. Is she pale, tachycardic, Hypotensive? Is there a positive sock sign?

38. 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).

39. 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

40. Evaluation Hysteroscopy MRI Precisely localizes sub-mucosal fibroids
MRI is not superior to TVS & SIS in overall diagnostic potential
Dueholm M, et al. Fertil Steril. 2001;76(2):350357
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.

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

42. Medical Management Iron Parenteral estrogens Anti-fibrinolytics
Anti-prostiglandin
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.

43. Minimally Invasive Surgery
Surgical Approach
Minimally Invasive Surgery
Major Surgery
Intrauterine Device (IUD) with progesterone
Dilation & Curettage
Endometrial Ablation
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)
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.

44. Final Case
32 year old G2P2002 presents to the ER with 10 day history of heavy uterine bleeding. She is pale and appears frightened. Pulse is 120, BP is 90/60. Hemoglobin is 6, Hematocrit is 18. Pregnancy test is negative.
How do you manage this patient?
Acute, sub-acute, or chronic?

45. The Best Next Step? Oxygen & IV Fluids Type and Cross 2 units of blood
Order a pelvic ultrasound
Order TSH, CBC, Coagulation panel
IV Conjugated Equine Estrogen
Consent for surgery

46. Management Chronic, Stable AUB Acute AUB Combined Oral Contraception
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 D&C
Combined Oral Contraception
AUB-O progestin therapy
Levonorgestrel IUD
Endometrial sampling is indicated prior to starting hormones in older women
Medical failures have the surgical options
Start with ABC’s in an Acute Blood Loss case. Use clinical judgment to for the most likely etiology to begin treatment.

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

48. 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