1. Menstrual Disorders Geetha Kamath, M.D. Dept. of Medicine West Virginia University

2. Definition Normal menstrual cycle involves hypothalamus- pituitary-ovary and uterus and is 28 days Normal menstrual cycle involves hypothalamus- pituitary-ovary and uterus and is 28 days Vaginal bleeding is abnormal (Abnormal Uterine Bleeding--AUB) when: Vaginal bleeding is abnormal (Abnormal Uterine Bleeding--AUB) when: Volume is excessive or Volume is excessive or Occurs at times other than expected, including during pregnancy or menopause Occurs at times other than expected, including during pregnancy or menopause Known as dysfunctional uterine bleeding (DUB) when organic causes are excluded Known as dysfunctional uterine bleeding (DUB) when organic causes are excluded

3. AUB Duration >7 days or Duration >7 days or Flow >80ml/cycle or Flow >80ml/cycle or Occurs more frequently than 21 days or Occurs more frequently than 21 days or Occurs more than 90 days apart or Occurs more than 90 days apart or Intermenstrual or postcoital bleeding Intermenstrual or postcoital bleeding

4. Terminology Menorrhagia: excessive flow Menorrhagia: excessive flow Menometrorrhagia: excessive volume Menometrorrhagia: excessive volume Oligomenorrhea: scanty flow Oligomenorrhea: scanty flow Dysmenorrhea: painful menstrual cycles Dysmenorrhea: painful menstrual cycles

5. Causes of Menstrual Disorders Structural Structural Pregnancy associated Pregnancy associated Hormonal and endocrine Hormonal and endocrine Hematologic and coagulation disorders Hematologic and coagulation disorders Other Other

6. Causes--structural Endometrial polyps Endometrial polyps Endometrial hyperplasia Endometrial hyperplasia Endometritis Endometritis Fibroids Fibroids Intrauterine devices Intrauterine devices Uterine arterio-venous malformation (AVM) Uterine arterio-venous malformation (AVM) Uterine sarcoma Uterine sarcoma

7. Pregnancy related Implantational bleeding Implantational bleeding Ectopic pregnancy Ectopic pregnancy Spontaneous abortion [incomplete, missed, septic, threatened] Spontaneous abortion [incomplete, missed, septic, threatened] Therapeutic abortion Therapeutic abortion Gestational trophoblastic disease Gestational trophoblastic disease

8. Hormonal and Endocrine causes Anovulatory (including polycystic ovary syndrome) Anovulatory (including polycystic ovary syndrome) Ovarian cyst Ovarian cyst Estrogen-producing ovarian tumor Estrogen-producing ovarian tumor Perimenopause Perimenopause Hormonal contraceptives Hormonal contraceptives Hormone Replacement Therapy Hormone Replacement Therapy Hypothyroidism Hypothyroidism

9. Hematologic Von Willebrand’s disease (most common inherited bleeding disorder with frequency 1/800-1000) Von Willebrand’s disease (most common inherited bleeding disorder with frequency 1/800-1000) Hemophilia Hemophilia Thrombocytopenia Thrombocytopenia Hematologic malignancies (leukemia) Hematologic malignancies (leukemia) Liver disease Liver disease

10. Other DUB (dysfunctional uterine bleeding): non-organic causes, either ovulatory or anovulatory DUB (dysfunctional uterine bleeding): non-organic causes, either ovulatory or anovulatory Fallopian tube cancer Fallopian tube cancer Trauma Trauma Foreign body Foreign body Cervical bleeding--mets, cervicitis, cervical cancer Cervical bleeding--mets, cervicitis, cervical cancer Vaginitis--atrophic, cancer of vagina Vaginitis--atrophic, cancer of vagina Endometrial cancer (10% of post-menopausal bleeding) Endometrial cancer (10% of post-menopausal bleeding)

11. Evaluation of Abnormal Uterine Bleeding (AUB) Acute Acute History suggestive of: Pregnancy and related complications Pregnancy and related complications Recent and Heavy bleeding Recent and Heavy bleeding Pelvic pain Pelvic pain Medications contributing to above Medications contributing to above Chronic History: Long standing abnormal menstrual history Symptoms of anemia, hypothyroidism, perimenopause Personal or family history of excessive bleeding

12. AUB Examination Assess vitals/hemodynamic stability Assess vitals/hemodynamic stability Look for features of anemia (pallor, tachycardia, syncope) Look for features of anemia (pallor, tachycardia, syncope) Look for features of hypothyroidism Look for features of hypothyroidism Look for metabolic syndrome (obesity, hirsutism, acne) Look for metabolic syndrome (obesity, hirsutism, acne) Pelvic exam for structural abnormalities: fibroids, pregnancy, active bleeding—uterine vs. cervical bleeding Pelvic exam for structural abnormalities: fibroids, pregnancy, active bleeding—uterine vs. cervical bleeding

13. AUB Lab Studies Serum HCG to rule out pregnancy Serum HCG to rule out pregnancy CBC and iron studies to assess severity of anemia CBC and iron studies to assess severity of anemia TSH for thyroid disorders TSH for thyroid disorders Coagulation studies (PT, PTT, platelet count, VWF) (primarily for adolescents) Coagulation studies (PT, PTT, platelet count, VWF) (primarily for adolescents) Transvaginal ultrasound to look for fibroids and other masses/lesions Transvaginal ultrasound to look for fibroids and other masses/lesions Endometrial biopsy to rule out endometrial cancer in perimenopausal and chronic anovulatory cycles (primarily for women >35 years with AUB and postmenopausal women) Endometrial biopsy to rule out endometrial cancer in perimenopausal and chronic anovulatory cycles (primarily for women >35 years with AUB and postmenopausal women) Sonohysterography is useful in diagnosis of anatomical lesions which might even be missed with transvaginal ultrasound Sonohysterography is useful in diagnosis of anatomical lesions which might even be missed with transvaginal ultrasound

14. Treatment of Chronic Menorrhagia for Most Causes (including DUB)  Combined hormonal contraceptives (cyclical or continuous)  DMPA (depot medroxyprogesterone)  IUD (Intrauterine devices)

15. Treatment options continued After excluding coagulopathy, pregnancy, or malignancy: Progestins Progestins Estrogens including oral contraceptives Estrogens including oral contraceptives Cyclic NSAIDS Cyclic NSAIDS Dilatation and curettage (surgical) Dilatation and curettage (surgical) Endometrial ablation (surgical) Endometrial ablation (surgical) Hysteroscopic endometrial resection (surgical) Hysteroscopic endometrial resection (surgical)

16. Treatment for Fibroids Surgical: Hysterectomy/myomectomy, uterine artery ablation Surgical: Hysterectomy/myomectomy, uterine artery ablation Medical: Suppression of gonadotropins (danazol and leuprolide) Medical: Suppression of gonadotropins (danazol and leuprolide)

17. Treatment: progestins Inhibits endometrial growth by inhibiting synthesis of estrogen receptors, promotes conversion of estradiol to estrone, inhibits LH Inhibits endometrial growth by inhibiting synthesis of estrogen receptors, promotes conversion of estradiol to estrone, inhibits LH Organized slough to basalis layer Organized slough to basalis layer Stimulates arachidonic acid production Stimulates arachidonic acid production Progestins preferred for those women with anovulatory AUB Progestins preferred for those women with anovulatory AUB

18. Progestational Agents Cyclic medroxyprogesterone 2.5-10mg daily for 10-14 days Cyclic medroxyprogesterone 2.5-10mg daily for 10-14 days Continuous medroxyprogesterone 2.5-5mg daily Continuous medroxyprogesterone 2.5-5mg daily DMPA 150 mg IM every 3 months DMPA 150 mg IM every 3 months Levonorgestrel IUD (5 years) Levonorgestrel IUD (5 years)

19. Estrogens Conjugated estrogens given IV every 6 hours effective in controlling heavy bleeding followed by oral estrogen Conjugated estrogens given IV every 6 hours effective in controlling heavy bleeding followed by oral estrogen For less severe bleeding, oral conjugated estrogens 1.25 mg, 2 tabs qid--until bleeding stops For less severe bleeding, oral conjugated estrogens 1.25 mg, 2 tabs qid--until bleeding stops

20. NSAIDS Cyclooxygenase pathway is blocked Cyclooxygenase pathway is blocked Arachidonic acid conversion from prostaglandins to thromboxane and prostacyclin (which promotes bleeding by causing vasodilation and platelet aggregation) is blocked Arachidonic acid conversion from prostaglandins to thromboxane and prostacyclin (which promotes bleeding by causing vasodilation and platelet aggregation) is blocked

21. Clinical Highlights Most common cause of AUB in reproductive age is pregnancy related--so initial evaluation must include pregnancy test. Most common cause of AUB in reproductive age is pregnancy related--so initial evaluation must include pregnancy test. Pregnancy must be ruled out before initiating invasive testes or medical therapy Pregnancy must be ruled out before initiating invasive testes or medical therapy

22. Clinical Highlights Endometrial biopsy is recommended for post menopausal women Endometrial biopsy is recommended for post menopausal womenOr Younger women with history of chronic anovulation >35 years of age Younger women with history of chronic anovulation >35 years of age

23. Clinical Highlights Uterine cancer and endometrial hyperplasia must be ruled out before medical therapy is initiated in postmenopausal/perimenopausal bleeding Uterine cancer and endometrial hyperplasia must be ruled out before medical therapy is initiated in postmenopausal/perimenopausal bleeding NSAIDS may reduce menstrual flow by 20-60% in women with chronic menorrhagia NSAIDS may reduce menstrual flow by 20-60% in women with chronic menorrhagia Coagulopathy workup must be initiated in menorrhagia in adolescents Coagulopathy workup must be initiated in menorrhagia in adolescents

24. References ACOG Practice Bulletin #14, 2000 ACOG Practice Bulletin #14, 2000 American Journal Obstetrics and Gynecol 2005;193:1361 American Journal Obstetrics and Gynecol 2005;193:1361 Clinical Obstetrics & Gynecology 50(2):324-353, June 2007 Clinical Obstetrics & Gynecology 50(2):324-353, June 2007 Comprehensive Gynecology, 4 th edition Comprehensive Gynecology, 4 th edition Harrison’s Principles of Internal Medicine, 14 th edition Harrison’s Principles of Internal Medicine, 14 th edition Karlsson, et al, 1995 Karlsson, et al, 1995