Gynecologic Decision Making Based on Sonographic Findings

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Dortha Bruce
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1 Gynecologic Decision Making Based on Sonographic Findings Mindy Goldman, MD Department of Obstetrics & Gynecology & Vickie A. Feldstein, MD Department of Radiology University of California, San Francisco Abnormal Bleeding Leiomyomas & Myomectomy Endometrial Cancer Breast Cancer & Tamoxifen Ovarian Cancer Screening (Benign Ovarian Lesions) (Post Menopausal Ovarian Cysts) 1

2 Incidence of Abnormal Bleeding 30% of Gynecology visits related to abnormal bleeding 70% of all visits during peri- and post-menopause related to abnormal bleeding 1 in 20 pre-menopausal women have menstrual disorders each year Differential Diagnosis Hormonal Causes Anatomic Causes Infectious Neoplasia Systemic Disorders Coagulopathies Hormonal (= Anovulation) Physiologic Hyperandrogenic CNS Iatrogenic Adolescence PCOS Hyperprolactinemia Estrogen: HRT, OCP Peri-Menopause Congenital Adrenal Hyperplasia Stress Anorexia DMPA Norplant IUD Hypo/Hyper Thyroid Neuroleptics 2

3 Anatomic Causes Uterine Cervical Vaginal Fibroids Polyp Atrophy Polyps Trauma Trauma Adenomyosis Endometrial Atrophy Neoplastic Causes Uterine Cervical Ovarian Hyperplasia Dysplasia Hormone producing tumor Cancer Cancer Infectious Causes Uterine Cervical Vaginal PID Cervicitis Vaginitis (Trich) Endometritis 3

4 Non-Gynecologic Causes Coagulopathy Severe Liver Disease Renal Failure GI GU Evaluation Do a Pregnancy Test! Work-up of Bleeding in Pregnancy is completely different from Non-Pregnant state Includes: Ectopic Pregnancy Spontaneous Abortion Molar Pregnancy History Description of vaginal bleeding - spotting, light, heavy, clots Relationship to LMP intermenstrual, menorrhagia, menometrorrhagia Prior occurrences and treatments Medications including contraceptives, hormone replacement, prescription medications, herbs Any association with sexual activity 4

5 Bleeding Pattern History Intermenstrual or Post-coital: Cervical lesions, endometrial polyps, cervicitis, endometritis Menorrhagia: Fibroids, adenomyosis Menometrorrhagia: Anovulation, submucous myomas, adenomyosis, hyperplasia, carcinoma Physical Exam General: Observe skin color for pallor, bruises Vital Signs: Associated fever, tachycardia, orthostatic changes Abdomen: Any palpable masses, tenderness Pelvic: Any vaginal lesions, laceration, cervical discharge or polyp, prolapsing myoma, uterine enlargement, adnexal mass Rectal: stool guiac to ensure not rectal Endometrial Biopsy (EMB) vs. Endovaginal Ultrasound (EVUS) 5

under < 35-40 if obese or chronic anovulation Perform if persistent abnormal bleeding despite medical therapy Endovaginal Ultrasound Instead?

6 When to do an Endometrial Biopsy? Still considered gold standard Perform in all postmenopausal bleeding except if recent initiation of HRT Perform in age > with persistent irregular bleeding, typically 3 mos or more Consider under < if obese or chronic anovulation Perform if persistent abnormal bleeding despite medical therapy Endovaginal Ultrasound Instead? Measures thickness of endometrial stripe Can be useful if cervix stenotic and unable to obtain EMB Helpful for evaluating anatomic lesions like polyps or submucosal myomas may suggest need for sonohysterography Endovaginal Ultrasound Instead? * In PMP women with bleeding, if endometrial lining < 5mm, virtually rules out carcinoma Not useful in premenopausal women Not useful for women on Tamoxifen If negative result on both EMBx and EVUS but persistent bleeding ---> NEEDS further evaluation 6

7 S/P Endometrial Biopsy Secretory Endometrium Postmenstrual Endometrium 7

8 Hormonal Causes Other names: Anovulation, Dysfunctional Uterine Bleeding (DUB) No Anatomic Abnormality Tends to occur during adolescence and in perimenopause Majority of women treated for abnormal bleeding have no anatomic cause Perimenopause Anovulatory Bleeding Common 12% suddenly stop menstruating 18% have longer, heavier menses 70% have short, irregular menses Treatment: Anovulatory Bleeding Medical - NSAIDs Hormonal: OCPs, IUD HRT & Progestin only GnRH Agonist (Lupron) Surgical - Hysteroscopy with D&C Endometrial ablation Hysterectomy Uterine artery embolization 8

9 Levonorgestrel IUD (Mirena) Low dose progestin acts locally > 80% reduction in blood loss, decreased cramping Prevents and treats hyperplasia May have irregular light bleeding during first 3 mos Use only in monogamous women Case #1 Suspect anovulatory cycles. US shows 9

hysterectomy 20-40% of women have symptomatic fibroids most commonly bleeding, pelvic pressure or pain ~50% of fibroids are

10 Anatomic Causes Non-Cancerous Uterine, Cervical, Vaginal: Fibroids Polyps Adenomyosis Trauma Atrophy Cancerous: Endometrial Cancer Less Common Cervical or Ovarian Cancer Fibroids - Leiomyomas Most common benign solid tumors in women & main indication for hysterectomy 20-40% of women have symptomatic fibroids most commonly bleeding, pelvic pressure or pain ~50% of fibroids are asymptomatic Increased incidence in African Americans Grow in response to hormonal stimulation (we think) and decrease in size after menopause 10

11 Bleeding: Usually menorrhagia Occasionally menometrorrhagia, if submucosal or intracavitary fibroids Pressure symptoms Dysmenorrhea or pelvic pain Fibroid Symptoms Case #2 Fibroids. US shows Transabdominal 11

Left Fundal Subserosal Submucosal Surgical Treatments for Fibroids

Myomectomy Hysteroscopic Laparoscopic Transabdominal Hysterectomy Uterine

Endometrial ablation Reduces but doesn t eliminate menses 15-30% need

12 Left Fundal Subserosal Submucosal Surgical Treatments for Fibroids Endometrial ablation - may be accompanied by hysteroscopic myomectomies Myomectomy Hysteroscopic Laparoscopic Transabdominal Hysterectomy Uterine artery embolization (UAE) Surgical Treatment Options Hysteroscopy with D&C Endometrial ablation Reduces but doesn t eliminate menses 15-30% need repeat ablation or hysterectomy in 5 years Can t be done in large uterine size, > 12 weeks 12

Hysteroscopic Myomectomy Works well with

myomas need at least 50% of myoma in endometrial

resolution of menorrhagia and pelvic pressure

hysterectomy 50% may recur within 5 years 20% may

available using morcellators but depends on number

13 Hysteroscopic Myomectomy Works well with intracavitary myomas less than 3 cm For submucosal myomas need at least 50% of myoma in endometrial cavity Submucosal Myoma by SHG Myomectomy 80% resolution of menorrhagia and pelvic pressure symptoms Similar complication rates and recovery as hysterectomy 50% may recur within 5 years 20% may need repeat surgery Laparoscopic myomectomy available using morcellators but depends on number of fibroids, size and location risks of uteroperitioneal fistulas and uterine dehiscence 13

14 Surgical Treatment Options Hysterectomy High patient satisfaction (90%) Improved quality of life, sexual satisfaction and decreased pain Increased long term risks of prolapse, urinary incontinence Surgical Treatment Options Uterine Artery Embolization Partially blocks blood supply to the uterine blood supply Most patients have significant decrease in symptoms and uterine size Requires hospitalization for pain control Unknown recurrence rate Long term consequences unknown > 2 weeks to return to full activities Uterine Artery Embolization Benefits: 30-50% decreased uterine size 75-90% bleeding improved % symptoms improved high patient satisfaction Risks: infection injury to uterus massive bleeding uterine necrosis 40% fever in 2 wks 5% expel fibroid through cervix significant pain ovarian failure? pregnancy 14

Other Anatomic Lesions Adenomyosis endometriosis of myometrium Try medical management with

specimen Polyps Cervical - often can be removed in office Endometrial removed via hysteroscopy

US shows Endometrial Cancer 4th most common cancer in women Most common gynecologic cancer

15 Other Anatomic Lesions Adenomyosis endometriosis of myometrium Try medical management with hormonal therapies contraceptives, HRT, Lupron May lead to hysterectomy diagnosis on pathology specimen Polyps Cervical - often can be removed in office Endometrial removed via hysteroscopy Case #3 Postmenopausal bleeding. US shows Endometrial Cancer 4th most common cancer in women Most common gynecologic cancer Median age at diagnosis 61, but 25% occur before menopause Main risk is increased circulating estrogen Tends to present in early stage Rare in absence of vaginal bleeding 15

endometrial cancer No data on safety or efficacy of SERMs Case #4 History of Breast CA on Tamoxifen.

16 Endometrial Cancer Diagnosis: Endometrial Biopsy 90% sens, 100% spec False + due to small CAs arising in polyp or localized area of endometrium Treatment: Primarily surgical TAH / BSO recurrence rate 5 % Stop HRT no clear data on use in women with prior endometrial cancer No data on safety or efficacy of SERMs Case #4 History of Breast CA on Tamoxifen. US shows Hormonal Treatments of Breast Cancer Used to reduce systemic recurrences and overall breast cancer mortality in women with hormone receptor positive breast cancer 16

17 Hormonal Treatments of Breast Cancer Block production of estrogen Block action of estrogen Down-regulate the estrogen receptor SERMS: TAMOXIFEN, Raloxifene, Toremifene Estrogen Receptor Downregulators: Fulvestrant Aromatase Inhibitors: Anastrozole, Letrozole, Examestane Tamoxifen - Epidemiology Complex drug with estrogen and antiestrogen properties Originally made as contraceptive Suppressed mammary tumors in rats Has been the standard of care for hormone receptor + tumors regardless of age, menopausal status, LN status, or tumor size Tamoxifen as a Prevention for Breast Cancer Breast Cancer Prevention Trial showed 45% reduction in ER+ breast ca in high risk pts Approved for high risk women without breast ca in 1998 First drug approved by FDA for breast ca prevention 17

18 Tamoxifen - Biologic Effects Agonist and Antagonist effects Effects of Tamoxifen vary depending on hormonal environment Increased endometrial proliferation, hyperplasia, polyp formation & adenocarcinoma Tamoxifen & Premenopausal Women No significant estrogenic effects on endometrium - only rare reports of endometrial cancers Induces estrogen production and ovulation Case reports of ovarian cysts unclear incidence, reports as high as 40% Case reports of endometriomas Case reports of growth of uterine myomas Tamoxifen & Postmenopausal Women Acts as an agonist with estrogenic effects Case reports of growth of myomas Case reports of endometriosis & endometriomas Increased endometrial proliferation, hyperplasia polyp formation and adenocarcinoma 18

19 Tamoxifen & Endometrial Cancer Frequency of cancer dependent on endometrial surveillance: EVUS vs. EMBx and criteria for surveillance symptomatic vs. asymptomatic. RR 2-4 in RCT RR in the NSAPB trial was 2.53, seen in women > 50 95% of Endometrial Cancers present with Vaginal Bleeding No consensus regarding Endometrial Surveillance Tamoxifen Surveillance 2-4% fold increased risk of endometrial CA for women taking Tamoxifen for 5 years Tamoxifen users have higher rate of benign endometrial pathology polyps, thickening, cystic changes EVUS has high false positive rate Evaluation should only be done in women with abnormal bleeding EMBx not US Endometrial Surveillance - Ultrasound Increased endometrial thickness, irregular echoes, cystic changes in PMP women Increased Endometrial polyps and Hyperplasia Findings do not correlate with malignant histology 19

20 Endometrial Surveillance: US & Other Imaging Thickened endometrium can be atrophic. Mechanism may be enlargement of subendometrial glands Should not use endometrial thickness as an indicator for intervention, high false positive rate even with a cutoff of 10mm Sonohysterography and MRI not have not been found useful Tamoxifen What do we tell our patients? In general, the absolute decrease in breast cancer recurrence and contralateral breast ca from Tamoxifen is about 2X as large as the absolute increase in the incidence of endometrial cancer Case #5 Ovarian Surveillance, Higher Risk. US shows 20

Follow-up BRCA 1/2 and Cancer Autosomal dominant gene mutations that

melanoma, prostate, stomach, pancreas and colorectal cancer Mutation in

15-40% - Rates vary depending on penetrance Accounts for 2-3% of all

21 Follow-up BRCA 1/2 and Cancer Autosomal dominant gene mutations that increase risk of breast and ovarian cancers; leukemia, lymphoma, melanoma, prostate, stomach, pancreas and colorectal cancer Mutation in BRCA1/2 increases risk of breast cancer 60-85% and ovarian cancer by 15-40% - Rates vary depending on penetrance Accounts for 2-3% of all breast cancer and 9% of ovarian cancer Hereditary cancers occur at an earlier age than sporadic 21

BRCA 1/2 and Cancer More than 800 distinct mutations, polymorphisms and variants known for each gene Carrier Prevalence: General Population < 1% or 1 in 280 Ashkenazi Jewish 2.

22 BRCA 1/2 and Cancer More than 800 distinct mutations, polymorphisms and variants known for each gene Carrier Prevalence: General Population < 1% or 1 in 280 Ashkenazi Jewish 2.5% or 1 in 40 Genetic counseling and testing offered for personal or family history of breast cancer before age 50, ovarian cancer at any age, individual with both breast and ovarian cancer, or male breast cancer BRCA 1/2 and Cancer Management of carriers depends on age, reproductive plans and risk Surveillance and risk reducing strategies for Ovarian Cancer: Transvaginal sonography and serum CA125 every 6 mos beginning at age 35, although benefits not clearly established Possibly oral contraceptives Prophylactic salpingo-oophorectomy decreases risk of ovarian cancer by > 95% Benefits may decrease with age, occult malignancies found 15% of time Case #6 Abnormal bleeding. On Tamoxifen. US shows 22

23 Submucosal Myoma Endometrial Polyp 23

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