Normal and Abnormal Uterine Bleeding

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

10. AUB: Evaluation • History • 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 • 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, submucousmyoma • 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. Progesterone Estrogen Estrogen 2 4 6 8 10 12 14 16 18 20 22 24 26 28 DUB/Anovulation Menses DUB: Etiology Ovulatory Cycle

18. DUB: Evaluation • Pelvic Exam • 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 10-15 days ea. month • Norethindrone acetate 5 mg po daily x 10-15 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 (p315-319). • 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 (p368-370).