1. In the Name of God

2. Abnormal perimenopausal and Postmenopausal Bleeding F.Behnamfar GYNECOLOGY ONCOLOGY FELLOWSHIP KASHAN UNIVERSITY OF MEDICAL SCIENCES

3. Abnormal perimenopausal Bleeding ► After adolescence, menstrual cycle length normally is 21-35 days with fewer than seven days menstrual flow ► As a woman approaches menopause, cycle length becomes irregular as fewer cycles are ovulatory ► The avarage blood loss is 35cc per cycle, recurrent bleeding in excess of 80cc results in anemia ► Although pregnancy related bleeding should be considered, most frequent cause of irregular bleeding in reproductive age is hormonal

4. Anovulatory Uterine Bleeding Anovulatory Uterine Bleeding ► Anovulatory uterine bleeding (dysfunctional bleeding) is a result of estrogen breakthrough, endometrial growth without periodic shedding and breakdown of fragile endometrial tissue with irregular bleeding ► Episodes of amenorrhea followed by acute heavy bleeding ► Endogenous estradiol level is higher in perimenopausal women presenting with menorrhagia than those with normal cycle M.H.Moen Maturitas 47(2004)151-155 M.H.Moen Maturitas 47(2004)151-155

5. Differential Diagnosis ► Pregnancy related bleeding 50% of pregnancies in USA are unintended and these are more likely to occur among adolescents and women older than 40 ► Exogenous hormones Breakthrough bleeding during OCP use and other estrogen and progestin systems, progestin only regimens Clamydia Trachomatis infections more common in these individuals

6. Endocrine Causes Hypo and hyperthyroidism ► Graves disease 4-5 times more often in women than in men,especially perimenopausal. ► Can result in oligomenorrhea and elevated plasma estrogen Diabetes Mellitus ► Anovulatoin, obesity, insulin resistance,androgen excess, more immediate concern in older women of reproductive age ► Management with OCP or insulin sensitizing agents plus dietary exercise modification

7. Anatomic Causes Uterine leiomyomas ► 50% of all women 35 years and more ► Most common tumor of genital tract ► Asymptomatic in at least 50% of women ► Most common symptoms abnormal bleeding (30%) blaoting and pelvic discomfort Gupta Best Practice &Research Clinical Obs.Gyn 2008.1.008

8. Anatomic Causes Endometrial Polyps ► Intermenstrual,irregular bleeding menorrhagia and dysmenorrhea menorrhagia and dysmenorrhea ► Increasing incidence with age ► diagnosis based on visualization with hysteroscopy, sonohysterography or microscopic assessment of tissue obtained by biopsy ► 0.5% chance of malignancy

10. Anatomic Causes Cervical lesions ► endocervical polyps ► clamydia infection,herpes simplex ulceration,condylomata ► Cervical cancer, abnormal bleeding the most common symptom Abnormal intermenstrual or post coital bleeding ► Wide ectropion, nabothian cysts rarely cause bleeding

11. Coagulopathies and Hematologic disorders Excessive heavy menses ► Check CBC to detect anemia, leukemia,thrombocytopenia ► Abnormal liver function, decreased production of clotting factores ► von willebrand disease occuring in up to 1% of population,OCP increasing factor VIII and Desmopressin acetate may be necessary

12. Infectious Causes ► ► Women with cervicitis especially clamydial can experience AUB and PCB ► ► Endometritis may cause menorrhagia with dysmenorhea

13. Neoplasia ► Abnormal B is the most frequent symptom of invasive cervical cancer ► Biopsy of any obvious cervical lesion should be done ► Negative cytology results may be due to tumor necrosis ► Unoppsed estrogen(Obesity, anovulation,…) may cause variety of abnormalities from endometrial hyperplasia to cancer endometrial hyperplasia to cancer

14. Diagnosis ► Medical and gynecologic history ► Exclusion of pregnancy ► Consideration of possible malignancy ► Careful gynecologic examination ► Additional lab and imaging studies for: Women>35y Women>35y risk factors for STDs risk factors for STDs signs of androgen excess signs of androgen excess

15. Lab Studies ► ► CBC,hCG,PT,PTT,Platelet function

16. Imaging Studies ► Pelvic ultrasound if exam results is suboptimal or ovarian mass suspected, TVS particularly for obese women ► Measurement of endometrial strip thickness significantly less useful in premenopausal than post menopausal women than post menopausal women ► Sonohysterography especially helpful in visualizing intrauterine problems(polyp,myoma) Histologic evaluation is required to rule out malignancy

17. Endometrial Sampling ► Should be performed to evaluate abnormal bleeding in women who are at risk for endometrial polyps,hyperplasia or carcinoma ► Sampling is mandatory in evaluation of anovulatory bleeding in women older than 35-40 years, in younger women who are obese and in those with history of prolonged anovulation

20. Endometrial Sampling ► D&C has been replaced largely by office endometrial biopsy ► Studies have showed comparable ability to detect anomalies ► D&C for cervical stenosis, suspected polyp, persistent AUB ► Hysteroscopy may be done in office or operating room

21. Management ► In most cases medical therapy is effective and should be attempted before surgical management ► In women with anovulatory bleeding and failed medical therapy endometrial ablation is an efficient alternative to hysterectomy ► In women with liomyomas,hysterectomy is a definitive cure (Alternatives :UAE, Myomectomy)

22. None surgical management ► NSAIDS (30-50% decrease in menstrual flow) ► Antifibrinolytics, Tranexamic acid (FDA not approved) ► Levonorgestrel IUDs, significant reduce in blood loss(80-90%), improved quality of life, may be comparable to hysterectomy

23. Hormonal Management ► Treatment of choice for anovulatory bleeding, LD OCP for premenopausals If healthy nonsmoker, and no major cardiovascular risk factor If healthy nonsmoker, and no major cardiovascular risk factor Benefits of menstrual regulation in such women often overrides potential risks If estrogen use contraindicated,Progestins oral, parenteral can be used

24. Hormonal Management ► ► Cyclic oral medroxyprogestrone acetate ► ► Depot formulations of medroxyprogestrone acetate ► ► Parenteral /intrauterine delivery of progestins ► ► Danazol,rarely for ongoing management of AUB ► ► GnRH agonists

25. Surgical Therapy ► Should be reserved for situations in which medical therapy fails or is contraindicated ► D&C,diagnostic technique, questionable as a therapeutic modality ► Variety of techniques of endometrial ablation or resection to hysterectomy ► Myoma:hysteroscopic resection,laparoscopic myomectomy,Uterine artry embolization,MR guided ultrasonographic ablation myomectomy,Uterine artry embolization,MR guided ultrasonographic ablation Choice of Procedures: Cause, patient preference, Physicians experience and skills In the absence of preexisting psycopathology,indicated but elective hysterectomy have few if any sequelae

26. Abnormal Bleeding in Postmenopuasal Age Group ► Exogenous estrogens 30% ► Athrophic vaginitis,endometritis 30% ► Endometrial cancer 15% ► Endometrial/cervical Polyps 10% ► Endometrial Hyperplasia 5% ► Miscellaneous 10%

28. Benign Disorders ► Women who are taking HRT during menopause,endometrial sampling is indicated for any unexpected bleeding that occurs with hormone therapy ► A significant change in withdrawal bleeding or breakthrough bleeding ► Other benign causes: polyps,athrophic vaginitis ► Postmenopausal women may attempt to minimize the extent of problem In the absence of HRT any bleeding after menopause should prompt evaluation with endometrial sampling

29. Neoplasia ► At least one forth of postmanopausal women with bleeding have a neoplastic lesion ► Endometrial polyps are more likely to be malignant in postmenopausals ► In the study by Antunes in women over 60y,5.3 times more prevalence of malignancy in polyps ► Cervical malignancy grossly visible lesion biopsy, Colposcopy biopsy for abnormal pap results Maturitas 2007 415-421 Maturitas 2007 415-421

30. Diagnosis Cervical endometrial and ovarian malignancy should be ruled out ► Pelvic examination (local lesions,Pap test) ► Pelvic ultrasound and in particular vaginal ultrasound ► Endometrial sampling essential ► Initial biopsy done in the office is more cost effective than D&C ► An endometrial thickness of less than 6 mm essentially excludes malignancy

31. Management ► Athrophic vaginitis,topical or systemic steroid ► Polyps,removal ► Benign hyperplasia of endometrium is resolved with D&C or progestin therapy,repeat biopsy is needed,repeat biopsy is needed Hysterectomy for those who do not respond and for atypical hyperplasia Progestin therapy for atypical hyperplasia only if poor candidates for hysterectomy

32. Thank You