Abnormal Uterine Bleeding

Phases of Reproductive Cycle Follicular phase Ovulation Luteal phase Menses

Phases of Reproductive Cycle Follicular phase –Onset of menses to LH surge –14 days (varies) –Dominant follicle greatest number of granulosa cells and FSH receptors Ovulation Luteal phase

Phases of Reproductive Cycle Follicular phase Ovulation –30-36 hours after LH surge Luteal phase –LH surge to menses –14 days (constant)

Menses Involution of corpus luteum Decrease progesterone and estrogen cc of dark blood and endometrial tissue

How does Ovulation happen? Positive feedback to pituitary from estradiol LH surge Ovulation triggered Granulosa and theca cells now produce progesterone Oocyte expelled from follicle Follicle converts to corpus luteum

Luteal Phase Predominance of progesterone Abdominal bloating Fluid retention Mood and appetite changes

Phases of Reproductive Cycle Endometrium –Proliferative phase –Secretory phase

Abnormal uterine bleeding Change in frequency, duration and amount of menstrual bleeding

Definitions Normal menses Every 28 days +/- 7 days Mean duration is 4 days. More than 7 days is abnormal.

Average blood loss with menstruation is 35-50cc. 95% of women lose <60cc. Normal Menses

Definitions Menorrhagia: Prolonged bleeding > 7 days or > 80 cc occurring at regular intervals.

Frequency of AUB Menorrhagia occurs in 9-14% of healthy women. Most common Gyn disorder of reproductive age women

Definitions Metrorrhagia: Uterine bleeding occurring at irregular but frequent intervals.

Definitions Menometrorrhagia: Prolonged uterine bleeding occurring at irregular intervals.

Definitions Oligomenorrhea: Reduction in frequency of menses Between 35 days and 6 months.

Definitions Amenorrhea : Primary amenorrhea Secondary amenorrhea No menses for 3-6 months

Primary amenorrhea No menses by age 13 No secondary sexual development No menses by age 15 Secondary sexual development present

Definitions Menarche –average age years Menopause –average age 51.4 years Ovulatory cycles for over 30 years

Menstrual bleeding stops IF: Prostaglandins cause contractions and expulsion Endometrial healing and cessation of bleeding with increasing estrogen

Systemic Etiologies Coagulation defects –ITP –VonWillebrands

Routine screening for coagulation defects should be reserved for the young patient who has heavy flow with the onset of menstruation.

von Willebrands Disease is the most common inherited bleeding disorder with a frequency of 1/

Hypothyroidism can be associated with menorrhagia or metrorrhagia. The incidence has been reported to be %. Wilansky, et al., 1989

Most Common Causes of Reproductive Tract AUB Pre-menarchal –Foreign body Reproductive age –Gestational event Post-menopausal –Atrophy

Reproductive Tract Causes Gestational events Malignancies Benign –Atrophy –Leiomyoma –Polyps –Cervical lesions –Foreign body –Infections

Reproductive Tract Causes Gestational events –Abortions –Ectopic pregnancies –Trophoblastic disease –IUP

Reproductive Tract Causes Malignancies –Endometrial –Ovarian –Cervical

10% of women with postmenopausal bleeding will be diagnosed with endometrial cancer Karlsson, et al., 1995

FIGO System PALM-COEIN –Polyp –Adenomyosis –Leiomyoma –Malignancy and hyperplasia –Coagulopathy –Ovulatory disorders –Endometrium –Iatrogenic –Not classified

Classification of causes of AUB in reproductive years

Reproductive Tract Causes of Benign Origin Uterine Vaginal or labial lesions Cervical lesions Urethral lesions GI

Reproductive Tract Causes of Benign Origin Uterine –Pregnancy –Leiomyomas –Polyps –Hyperplasia –Carcinoma

Proposed Etiologies of Menorrhagia with Leiomyoma Increased vessel number Increased endometrial surface area Impeded uterine contraction with menstruation Clotting less efficient locally Wegienka, et al., 2003

Leiomyoma in any location is associated with increased risks of gushing or high pad/tampon use. Wegienka, et al., 2003

Reproductive Tract Causes of Benign Origin Uterine Vaginal or labial lesions –Carcinoma –Sarcoma –Adenosis –Lacerations –Foreign body

Reproductive Tract Causes of Benign Origin Uterine Vaginal or labial lesions Cervical lesions –Polyps –Condyloma –Cervicitis –Neoplasia

Causes of Benign Origin Uterine Vaginal or labial lesions Cervical lesions Urethral –Caruncle – Diverticulum GI –Hemorrhoids

Iatrogenic Causes of AUB Intra-uterine device Oral and injectable steroids Psychotropic drugs –MAOIs

With anovulation a corpus luteum is NOT produced and the ovary thereby fails to secrete progesterone. Physiology of Abnormal Uterine Bleeding

However, estrogen production continues, resulting in endometrial proliferation and subsequent AUB.

PGE 2 vasodilation PGF 2 α vasoconstriction Progesterone is necessary to increase arachidonic acid, the precursor to PGF 2 α. With decreased progesterone there is a decreased PGF 2 α/PGE 2 ratio.

Evaluation and Work-up: Early Reproductive Years/Adolescent Thorough history Screen for eating disorder Labs: –CBC, PT, PTT,FSH, TSH, hCG

Evaluation and Work-up: Women of Reproductive Age hCG, LH/FSH, CBC, TSH Cervical cultures U/S Hysteroscopy EMB

Evaluation and Work-up: Post-menopausal Women Transvaginal U/S EMB (endometrial biopsy)

60% atrophy Causes of Postmenopausal Bleeding

An endometrial cancer is diagnosed in approximately 10% of women with PMB.¹ PMB (postmenopausal bleeding) incurs a 64-fold increased risk for developing endometrial CA.²

Not a single case of endometrial CA was missed when a <4mm cut-off for the endometrial stripe was used in their 10 year follow- up study. Specificity 60%, PPV 25%, NPV 100% PPV- positive predictive value. NPV- negative predictive value

EMB Complications rare. Rate of perforation 1-2/1,000. Infection and bleeding rarer.

EMB Sensitivity 90-95% Easy to perform Numerous sampling devices available

Incidence of Endometrial Cancer in Premenopausal Women 2.3/100,000 in year old 6.1/100,000 in year old 36/100,000 in year old

Therefore, based upon age alone, an EMB to exclude malignancy is indicated in any woman > 35 years of age with AUB. ACOG Practice Bulletin #14, March 2000

Endometrial Cancer Most common genital tract malignancy. Incidence 1 in 50! 4 th most common malignancy after breast, bowel, and lung. 34,000 new cases annually > 6,000 deaths annually

Endometrial Cancer Risk Factors Nulliparity: 2-3 times Diabetes: 2.8 times Unopposed estrogen: 4-8 times Weight gain –20 to 50 pounds: 3 times –Greater than 50 lbs: 10 times!

AUB Management Options: Progesterone Estrogen OCPs NSAIDs Surgical

Progestins: Mechanisms of Action Inhibit endometrial growth –Inhibit synthesis of estrogen receptors –Promote conversion of estradiol estrone –Inhibit LH Organized slough to basalis layer Stimulate arachidonic acid formation

Management: Progesterone Cyclooxygenase Pathway Arachidonic Acid Prostaglandins PGF 2 α* ThromboxaneProstacyclin *Net result is increased PGF2α/PGE ratio

Progestational Agents Cyclic Provera mg daily for days Continuous Provera 2.5-5mg daily DepoProvera ® 150mg IM every 3 months Levonorgestrel IUD (5 years)

Endometrial Hyperplasia *EMB path report simple hypersplasia WITHOUT atypia. *Progesterone therapy Provera® 5-10 mg daily Mirena IUD *Repeat EMB in 3-6 months

Management acute Bleeding: Estrogen IV Estrogen 25mg q6 hours OR Premarin ® 1.25mg, 2 tabs QID

AUB Management: NSAIDs Arachidonic Acid Prostaglandins ThromboxaneProstacyclin* cyclic endoperoxides are inhibited X *Causes vasodilation and inhibits platelet aggregation

Surgical Options: Endometrial Ablation Hysterectomy

NovaSureThermaChoice

Summary Think coagulation defect in the menarchal adolescent patient with severe menorrhagia Gestational events are the single most likely cause of AUB in reproductive age women 35 yrs and older with AUB EMB If Rx estrogen be sure to screen for contraindications Levonorgestrel IUD is excellent means to control AUB

Summary Most common cause of AUB in post-menopausal women is atrophy TVS is an excellent screening tool for the evaluation of PMB Women with recurrent PMB require definitive F/U Endometrial CA risk factors: age, obesity, unopposed estrogen, DM, and BP

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