1. Normal and Abnormal Uterine Bleeding
UNC School of Medicine
Obstetrics and Gynecology Clerkship
Case Based Seminar Series

2. Objectives for Normal and Abnormal Bleeding
Define the normal menstrual cycle and describe its endocrinology and physiology
Define abnormal uterine bleeding
Describe the pathophysiology and identify etiologies of abnormal uterine bleeding
Discuss the steps in evaluation of abnormal uterine bleeding
Explain medical and surgical management options for patients with abnormal uterine bleeding
Counsel patients about management options for abnormal uterine bleeding

3. Normal Menstrual Cycle

4. Normal Menstrual Cycle
Basic functional components
Hypothalamic-pituitary unit
Ovaries
Uterus-endometrium

5. Normal Menstrual Cycle
Proliferative (Follicular) Phase: Days 1-13
Rise in FSH stimulates maturation of ovarian follicle
Follicles secrete estrogen as they mature
Estrogen stimulates proliferation of the endometrial lining
Endometrium reaches maximum thickness in late follicular phase
Level of estrogen peaks on day 12-13, stimulating LH surge on day 14
LH surge stimulates ovulation

6. Normal Menstrual Cycle
Secretory (Luteal) Phase: Days 14-28
After ovulation, FSH and LH cause follicle to transform into corpus luteum
Corpus luteum produces progesterone which maintains endometrial lining
Microvasculature becomes well-differentiated (spiral arterioles)
In absence of fertilization the corpus luteum involutes
Fall in progesterone triggers menstruation (endometrial sloughing)

7. Normal Menstrual Cycle
Normal parameters:
Cycle interval: 24 – 35 days
Menses: 4 – 7 days
Blood loss: 30 – 45 mL
Ovulatory bleeding is cyclic and predictable

8. Abnormal Uterine Bleeding: Definition
Bleeding that is outside the normal parameters of the menstrual cycle (volume, duration, or interval)
Abnormal Uterine Bleeding (AUB):
Polymenorrhea: regular cycle interval < 24 days
Oligomenorrhea: regular cycle interval > 40 days
Menorrhagia: regular blood loss > 80 mL or menses > 7 days
Metrorrhagia: irregular bleeding
Menometrorrhagia: heavy and irregular bleeding

9. AUB: Etiology Trauma Organic Dyscrasias Iatrogenic Systemic Other
Cervical laceration
Foreign body
Organic
Pregnancy complication
Uterine leiomyoma
Adenomyosis
Endometrial polyp
Endometrial hyperplasia
Malignancy (cervix, uterus)
Dyscrasias
Von Willebrand’s Disease
Thrombocytopenia
Iatrogenic
Exogenous estrogen
Intrauterine device (IUD)
Heparin, Coumadin
Systemic
Hepatic disease
Thyroid disease
Hyperprolactinemia
Renal failure
Other
Anovulation (DUB)

10. AUB: Evaluation History Pelvic Exam
Detailed menstrual history (volume, duration, intervals)
Symptoms associated with ovulation
e.g. breast tenderness, bloating, mood changes
Associated symptoms
e.g. dysmenorrhea, post-coital bleeding, galactorrhea, hirsutism
Weight changes
Medical history and medications
Pelvic Exam
Cervical and vaginal lesions
Size, shape of uterus

11. AUB: Evaluation Laboratory Diagnostic Procedures Urine pregnancy test
CBC with platelets
Coagulation studies
Thyroid studies (TSH, T4)
Prolactin
Diagnostic Procedures
Pap smear
Endometrial biopsy (EMB)
Transvaginal ultrasound
Hysteroscopy
Saline-infusion sonography (SIS)

12. AUB: Management (Medical)
Directed at treating the underlying pathology with relief of volume and duration of menses
Medical management
NSAID’s
Combination hormonal contraceptives (e.g. OCP’s, vaginal ring, patch)
Levonorgestrel IUD (Mirena)
GnRH agonists (e.g. Lupron)
Correct medical condition

13. AUB: Management (Surgical)
Surgical management
Endometrial ablation
D&C - IF clinically indicated
Myomectomy – IF leiomyomata and fertility desired
Hysteroscopic resection – IF polyp, submucous myoma
Hysterectomy (TAH, TVH, or TLH)

14. Dysfunctional Uterine Bleeding: Definition
Abnormal uterine bleeding with no attributable underlying illness or pathology
Diagnosis of exclusion!
Must exclude all other causes of AUB

15. DUB: Etiology Anovulation Polycystic ovary syndrome (PCOS) Obesity
Adrenal hyperplasia
Luteal phase defect (rare)

16. DUB: PCOS Polycystic ovary syndrome (PCOS)
Increased circulating androgens aromatize to estrone (E1)
Constant, noncyclic, unopposed level of estrogen stimulates growth and development of the endometrium
Estrogen provides feedback to pituitary, resulting in low FSH and high LH
Static levels of LH trigger chronic anovulation
Without ovulation, progesterone-induced changes do not occur
Endometrium outgrows blood supply and sloughs at irregular times in unpredictable amounts (usually frequent and heavy)

17. DUB: Etiology DUB/Anovulation Ovulatory Cycle Progesterone Estrogen2 4 6 8 10 28 12 14 16 18 24 20 22 26
Menses
Estrogen
Progesterone
Ovulatory Cycle

18. DUB: Evaluation Pelvic Exam Laboratory evaluation Procedures
Cervical and vaginal lesions
Size, shape of uterus
Laboratory evaluation
Urine pregnancy test
CBC with platelets
Coagulation studies
Thyroid studies (TSH, T4)
DHEAS and testosterone, if symptoms of hirsutism
Prolactin
Procedures
Endometrial biopsy (R/O neoplasia)
Transvaginal ultrasound (R/O anatomic lesions)

19. DUB: Management (Medical)
Massive Intractable Bleeding
Conjugated Estrogens 25 mg IV
Continued Management after Massive Bleeding
Conjugated Estrogens 2.5 mg po daily x 25 days
Medroxyprogesterone acetate 10 mg for the last 10 days
Allow 5-7 days for withdrawal bleed
Administer Mirena IUD

20. DUB: Management (Medical)
Management of Moderate Menometrorrhagia
Estrogen-Progestin Combination
Conjugated Estrogen 1.25 mg po daily x 25 days + Medroxyprogesterone acetate 10 mg po for last 10 days
OCP x 21 days, with 7 day withdrawal
Cyclic Progestin
Medroxyprogesterone acetate 10 mg po daily x days ea. month
Norethindrone acetate 5 mg po daily x days ea. month
5 – 7 days menstrual withdrawal should follow cessation ea. month
Mirena IUD

21. DUB: Management (Surgical)
Patients who do not respond to medical therapy
Patients who do not desire future pregnancies
Management:
Endometrial ablation
Hysterectomy

22. Bottom Line Concepts
Abnormal menstruation is one of the most common problems dealt with in the gynecologic clinic.
Understanding of the physiology and endocrinology of the menstrual cycle is imperative in a thorough evaluation and management of AUB.
It is important to rule out unsuspected pregnancies and endometrial cancer in the evaluation of AUB.
Irregular bleeding that is unrelated to anatomic lesions of the uterus is referred to as dysfunctional uterine bleeding (DUB/anovulatory).
Before DUB can be diagnosed, anatomic causes including neoplasia should be excluded.
The primary goal of treatment of DUB is to ensure regular shedding of the endometrium and consequent regulation of menses.
In AUB from other causes it is important to correct underlying pathology and decrease volume and duration of menses.

23. References and Resources
APGO Medical Student Educational Objectives, 9th edition, (2009), Educational Topic 45 (p96-97).
Beckman & Ling: Obstetrics and Gynecology, 6th edition, (2010), Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William NP Herbert, Douglas W Laube, Roger P Smith. Chapter 35 (p ).
Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 33 (p ).