Elaina Sexton, MD, MSc Obstetrics and Gynecology St. Vincent s Hospital. Objectives

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1 Elaina Sexton, MD, MSc Obstetrics and Gynecology St. Vincent s Hospital Objectives Definition of normal menstrual cycle and abnormal uterine bleeding (AUB) Evaluation of AUB Medical options for AUB Surgical options for AUB 1

Normal Menstrual Cycle Interval 28 +/- 7

cc (<80cc) 11 to 13 years 51 years 13 mg In

2 Normal Menstrual Cycle Interval 28 +/- 7 days (21-35) Duration Quantity Onset Age of Menopause Mean loss of iron/cycle 70% of blood loss 4 +/- 2 days (2-6) 40 cc +/- 20 cc (<80cc) 11 to 13 years 51 years 13 mg In first 2 days Hypothalamus Pituitary Ovary Uterus 2

3 Abnormal Uterine Bleeding Definitions Polymenorrhea: cycles < 21 days Oligomenorrhea: cycles > 35 days Menorrhagia: >80 cc of blood loss >7 days of bleeding Bleeding sufficient to cause anemia Hypomenorrha: <2 days of bleeding Metrorrhagia/Intermenstrual bleeding: bleeding at any other time than during the normal period Abnormal Uterine Bleeding Categories Pregnancy related Anovulatory Hormonal Ovulatory Anatomical Categories Estrogen breakthrough Too much Progestin breakthough Atrophic Estrogen withdrawal Atrophic Progestin withdrawal Normal response 3

4 Endometrial Development Estrogen Causes endometrial proliferation days 3 to 14 menstrual cycle From < 5 mm to 8 15 mm (total thickness) Progesterone Limits further endometrial growth (stabilizes) Induces: Secretory transformation Stromal edema Pseudo-decidualization Endometrial Development Endometrial Layers Functionalis: upper two thirds Proliferative, secretory and menstrual component Stratum spongiosum: edematous stroma with spiral arteries Stratum compactum: superficial layer Basalis: lower one third Regenerative layer Contains basal arteries from which spiral arteries grow 4

5 A Normal Period Progesterone Withdrawal After secretory withdrawal, progesterone withdrawal induces organized sloughing of functionalis layer down to the basalis layer Spiral and basal artery vasoconstriction and myometrial contraction limit bleeding Thrombin platelet plugs form Estrogen Rising estrogen levels cover up denuded basalislayer with new functionalis endometrium limiting bleeding Anovulatory Bleeding Estrogen breakthrough Growing follicle makes estradiol (E2) E2 thickens endometrium (can measure with ultrasound) No luteal progesterone to stabilize endometrium No progestin withdrawal to allow organized sloughing Endometrium outgrows blood supply and random segments detach at random intervals No spiral artery constriction so bleeding can be heavy Increased risk of hyperplasia/ca due to unopposed E2 5

6 Progestin Breakthrough Excess progestin causes thin, denuded friable endometrium that bleeds (need ultrasound) Frequent problem on OCPs and Depo provera Treatment is NOT to give more progestin! Switching to higher estrogen pill or adding exogenous estrogen works well Double dosing OCPs not effective (too much progestin) Systemic Diseases Ovulatory Bleeding Blood dyscrasias: Von Willebrand s(vwf) disease: most common dyscrasiain adolescents with uncontrolled bleeding Dx: vwf level, bleeding time Treat with desmopressin (DDAVP) or Factor VIII Factor deficiencies ITP Leukemia Endocrine Hypothyroidism (check TSH, prolactin) 6

7 Ovulatory Bleeding Anatomic Abnormalities GYN malignancies: cervix, endometrial, vagina, vulvar Leiomyomas Polyps Adenomyosis Infections, trauma, foreign bodies, urethral prolapse Blood tests Work up of AUB hcg: First test, ALWAYS, ALWAYS!!! TSH, Prolactin, Androgens CBC, iron, and coagulation studies, bleeding time, vwf, factor VIII Imaging: Ultrasound (sensitivity = 75%) Fibroids,polyps, adenomyosis EMT < 5mm reassuring for low risk of hyperplasia (post menopausal) Hysteroscopy 7

8 Endometrial Biopsy When to Biopsy? Age 35 years to menopause Any abnormal uterine bleeding Prolonged Younger than 35 Persistent AUB Bleeding in the setting of unopposed estrogen (obesity, chronic anovulation) Tamoxifen Lynch Syndrome Treatment Anovulatory Bleeding Cyclic Progestins OCPs Depo Provera GnRH Agonist Ovulatory Bleeding NSAIDs Antifibrinolytics Progestin IUD Reduction of Bleeding 30% 50% 60% 90% 20-50% 50% 80-90% 8

Medical Therapy- OCPs First approved for

US Less than 1% of women in Japan use the

9 Medical Therapy- OCPs First approved for use for contraception in the United States in 1960 Used by more than 100 women worldwide Used by 12 million women in the US Less than 1% of women in Japan use the pill while more than 1/3 of women in the UK use the pill 9

10 OCPs Inhibit follicular development and prevent ovulation Progesterone negative feedback decreases the release of GnRH by hypothalamus which decreases the release of FSH and LH Decreased FSH inhibits follicular development which leads to decreased levels of estradiol and lack of an LH surge which prevents ovulation Cervical mucus is thickened to inhibit sperm penetration Estrogen Better cycle control OCPs Reduction in breakthrough bleeding Stabilize endometrium Negative feedback on anterior pituitary inhibits secretion of FSH Helps prevents ovulation and inhibits follicular development 10

Contraindications: Smokers over age 35 Migraine with aura OCPs Known or suspected breast cancer Liver disease (cirrhosis) or liver tumor Blood clotting disorders Cardiovascular disease OCPs

11 Contraindications: Smokers over age 35 Migraine with aura OCPs Known or suspected breast cancer Liver disease (cirrhosis) or liver tumor Blood clotting disorders Cardiovascular disease OCPs Advantages: Cheap Improvement in dysmenorrhea, ovarian cysts, acne, endometriosis, and PCOS Decreases risk of ovarian cancer, endometrial cancer and colorectal cancer Decreases anemia due to menorrhagia Increased risk of DVT Pregnancy rate 2 to 8% because of skipping pills 11

12 Medical Therapy- DMPA Inhibits follicular development and prevents ovulation Decreases the pulse frequency GnRH by the hypothalmauswhich decreases the release of FSH and LH by the anterior pituitary Decreased levels of FSH prevent follicular development and therefore prevent an increase in estradiol levels Lack of estrogen positive feedback prevents LH surge Lack of LH surge prevents ovulation Advantages: DMPA Highly effective contraception Injection every 12 weeks NO estrogen so decreased risk of DVTs, stroke, and endometrial cancer Decreased incidence of primary dysmenorrhea, ovulation pain and ovarian cysts 12

13 DMPA Disadvantages: IM injection Irregular bleeding Progestin related side effects Alopecia Bone Loss Weight Gain Medical Therapy Cyclic Progestins Works as a medical curettage Medroxyprogesterone 10 mg PO q daily for 5 to 7 days Excellent for mid cycle bleeding, or when EMB demonstrates proliferative endometrium Must rule out atypiaor endometrial cancer before using 13

14 Cyclic Progestins Advantages: Helps with most mild bleeding Can be used in post menopausal women Progestin related side effects Does NOT work in acute bleeding Medical Therapy GnRH Agonist Synthetic peptide modeled after hypothalamus neurohormone GnRH Interacts with the GnRH receptor Works by initially increasing the release of gonadotropins followed by densensitizationand downregulation Leads to a hypogonadotropic state which resembles menopause Highly effective treatment for AUB Most women develop amenorrhea 14

15 Disadvantages: GnRH Agonists Rapid resumption of menses following discontinuation of medication Side effects include hot flashes, vaginal dryness, sleep disturbances, and mood swings Bone loss is the most serious side effect and limits therapy GnRH Agonists Commonly used as preoperative treatment for leiomyomas Can use add back therapy, estrogen mg and progesterone 2.5 mg in order to minimize the hypoestrogenic side effects 15

16 Medical Therapy- Antifibrinolytics Reduced menstrual flow 30 to 55% from baseline Approved in 2009 Inhibits multiple plasminogen binding sites, decreasing plasmin formation and fibrinolysis More effective than NSAIDs Less effective than IUD Only take during menses Contraindicated in women at risk for thrombosis Medical Therapy- NSAIDs Reduced volume of menstrual blood loss by 20 to 50% Mechanism of action is a reduction in the production of prostanglandinsynthesis in the endometrium which leads to vasoconstriction and reduced bleeding Less effective than IUD Several options including naproxen, ibuprofen, mefenamicacid 16

17 NSAIDs Advantages Cheap Reduction in dysmenorrhea Taken during menses only Disadvantages GI side effects including bleeding, ulcer Medical Therapy- Progestin IUD Reduces menstrual blood loss by 74 to 97% after one year of use (Mirena) Can be used by women with thrombophilia disorders FDA approved in 2009 for menorrhagia High local progestin concentration results in thinning of the endometrium Most effective medical treatment for menorrhagia 17

18 Progestin IUD Two doses available One contains 52mg of levonorgestrel with an intial release of 20 mcg/day (Mirena) Other contains 13.5 mg of levonorgestrelwith an initial release of 14 mcg/day (Skyla) Mirena IUD Progestin effect is mainly local Endometrial concentration of levonorgestrel is 1000 times higher than that obeserved with the subdermal implant Plasma concentration much lower Plasma concentration is enough to suppress ovulation in some patients 18

19 Mirena IUD Contraindications Uterine distortion anomalies, fibroids Active pelvic infection Known or suspected pregnancy Unexplained abnormal uterine bleeding Current breast cancer Menstrual Blood Loss in IUD Users Study Group Mean Blood Loss (ml) Control Copper T LNG-IUD 35 5o

20 Severe bleeding Estrogen If hemodynamicallystable, first line therapy is high dose oral estrogen, Premarin 2.5 mg four times daily An alternative regimen is high dose oral contraceptives (containing 30 to 35 mcg ethinylestradiol) taken two to four times daily Severe bleeding related to anovulation can be treated with high dose progestins (thickened endometrium) Medical Therapy Attributes NSAIDs OCs DMPA LNG-IUD Efficacy 20 to 25% 50% 60% 90% Dosing Changein Bleeding Pattern 3 x daily during menses Modest blood loss Daily 3 months 5 years Modest blood loss Reduction in blood loss to amenorrhea Reduction in bloodloss to amenorrhea Side Effects GI Hormonally related Contraceptive Effects 1 year pregnancy rate None Moderatelyto highly effective Hormonally related Highly effective Occasional hormonal Highly effective N/A 5% 0.3% 0.1% 20

21 Uterine Artery Embolization Indicated for premenopausal women with symptoms related to fibroids who wish to retain their uterus, avoid prolonged medical therapy and avoid surgery Performed under local anesthesia Catheter passed into distal portion of one of the uterine arteries under fluroscopicguidance followed by infusion of the embolizing agent Long term outcomes show reduction of 85 to 95% in bleeding Uterine Artery Embolization Performed by interventional radiologists Not recommended for patients who desire future fertility 2% complication rates (including deaths from infections due to infarcting, degenerating fibroids) 80 to 90% success rate 21

22 Uterine Artery Embolization Surgical Treatments Hysteroscopy Myomectomy Hysterectomy Endometrial Ablation 22

pregnancy loss Infertility Dysmenorrhea Fibroids

multiple fibroids are not likely to benefit from

23 Hysteroscopic Myomectomy Performed for intracavitary fibroids Indications: AUB Recurrent pregnancy loss Infertility Dysmenorrhea Fibroids should be less than 3 cm in size Patients with multiple fibroids are not likely to benefit from this procedure Success rate 75 to 90% Hysteroscopic Resection 23

24 Endometrial Ablation Surgical destruction of the endometrial lining Technologies approved in the United States: Bipolar radiofrequency (Novasure) Hot liquid filled balloon (Thermachoice) Cryotherapy(Her Option) Circulation Hot Water (Hydro Thermaablation) Microwave (Microwave Endometrial Ablation) Endometrial Ablation Contraindications: Desire to preserve fertility Endometrial hyperplasia or cancer Uterine anomalies Myometrial thinning following uterine surgery Postmenopausal women Active pelvic infection Presence of fibroids controversial 24

25 Endometrial Ablation- Novasure Three dimensional bipolar mesh that delivers radiofrequency current Advantages: Reduction in uterine bleeding very high at 5 years (98%) Low rates of hysterectomy following procedure Disadvantage: Cannot be used in women with irregular shaped uterine cavities Endometrial Ablation- Hydro ThermalAblator Hysteroscopicsheath is inserted into the uterine cavity under direct visualization Heated isotonic saline is administered through the sheath Advantages: Can be used in women with intracavitary lesions Done under direct visualization Disadvantages: Postoperative pain higher Reports of vaginal and perineal burns 25

26 Hysterectomy Most commonly performed gynecological procedure Prevalence decreasing due to availability of less invasive therapies Methods: Abdominal Vaginal Laparoscopic Robotic Assisted Hysterectomy Cochrane Review 2006, Review of 3 approaches to hysterectomy for benign gynecological disease Laparoscopic hysterectomy compared to Abdominal Hysterectomy Shorter hospitalization Quicker return to normal activities Fewer infections Less blood loss Longer operating time More urinary tract injuries 26

27 Hysterectomy Vaginal hysterectomy compared to Abdominal hysterectomy Shorter hospitalization Quicker return to normal activities Fewer infections Laparoscopic hysterctomycompared to vaginal hysterectomy Similar outcomes Robotic Assisted Advantages: Superior 3D visual input Hysterectomy Minimally invasive approach for procedures that would otherwise require laparotomy Mechanical freedom Shorter hospital stay More rapid post operative recovery Ability to operate in obese patients 27

Hysterectomy Robotic Assisted Disadvantages: COST Increased operating room time Steep learning curve for the surgeon Lack of tactile feedback Conclusions Abnormal uterine bleeding can have many

28 Hysterectomy Robotic Assisted Disadvantages: COST Increased operating room time Steep learning curve for the surgeon Lack of tactile feedback Conclusions Abnormal uterine bleeding can have many different etiologies including hormonal or structural Careful evaluation of the cause should be performed including physical exam, labs and imaging studies Many different treatment options, both medical and surgical to fit the patient s needs 28

29 Questions?? 29

Frequency of menses. Duration of menses 3 days to 7 days. Flow/amount of menses Average blood loss with menstruation is 60-80cc.

Frequency of menses. Duration of menses 3 days to 7 days. Flow/amount of menses Average blood loss with menstruation is 60-80cc. Frequency of menses 24 days (0.5%) to 35 days (0.9%) Age 25, 40% are between 25 and 28 days Age 25-35, 60% are between 25 and 28 days Teens and women over 40 s cycles may be longer apart Duration of menses