Normal and AbnormalUterine Bleeding

UNC School of MedicineObstetrics and Gynecology Clerkship

Case Based Seminar Series

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

Normal Menstrual Cycle

Basic functional components Hypothalamic-pituitary unit Ovaries Uterus-endometrium

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

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)

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

Normal Menstrual Cycle

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

Abnormal Uterine Bleeding: Definition

Iatrogenic Exogenous estrogen Intrauterine device (IUD) Heparin, Coumadin

Systemic Hepatic disease Thyroid disease Hyperprolactinemia Renal failure

Other Anovulation (DUB)

AUB: Etiology

Trauma Cervical laceration Foreign body

Organic Pregnancy complication Uterine leiomyoma Adenomyosis Endometrial polyp Endometrial hyperplasia Malignancy (cervix, uterus)

Dyscrasias Von Willebrand’s Disease Thrombocytopenia

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

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)

AUB: Evaluation

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

AUB: Management (Medical)

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)

AUB: Management (Surgical)

Abnormal uterine bleeding with no attributable underlying illness or pathology Diagnosis of exclusion! Must exclude all other causes of AUB

Dysfunctional Uterine Bleeding: Definition

Anovulation Polycystic ovary syndrome (PCOS) Obesity Adrenal hyperplasia Luteal phase defect (rare)

DUB: Etiology

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)

DUB: PCOS

DUB: Etiology

22 44 66 88 1010 28281212 1414 1616 1818 24242020 2222 2626

Menses

Estrogen

Progesterone

Ovulatory Cycle

DUB/Anovulation

Estrogen

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)

DUB: Evaluation

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

DUB: Management (Medical)

Management of Moderate Menometrorrhagia1. 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

2. 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

3. Mirena IUD

DUB: Management (Medical)

Patients who do not respond to medical therapy Patients who do not desire future pregnancies

Management: Endometrial ablation Hysterectomy

DUB: Management (Surgical)

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.

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).