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Disorders of Menstruation Pathophysiology, Evaluation and Management

Disorders of Menstruation Pathophysiology, Evaluation and Management. Jennifer Mersereau, MD Division of Reproductive Endocrinology & Infertility Department of Obstetrics & Gynecology University of North Carolina March, 2009. Objectives. What defines abnormal menstruation?

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Disorders of Menstruation Pathophysiology, Evaluation and Management

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  1. Disorders of MenstruationPathophysiology, Evaluation and Management Jennifer Mersereau, MD Division of Reproductive Endocrinology & Infertility Department of Obstetrics & Gynecology University of North Carolina March, 2009

  2. Objectives • What defines abnormal menstruation? • Burden of disease • Differential diagnosis of abnormal menstruation patterns • Classification of abnormal menstruation • Evaluation • Treatment

  3. Physiology of Menstruation • Exact hormone levels  not crucial • Exact cycle day  not crucial • General sequence  crucial

  4. Progesterone Estrogen 2 4 6 8 10 12 14 16 18 20 22 24 26 28 Menses Ovulatory Cycles • Orderly proliferation • Synchronous, stable endometrial development • Lysosomal digestion, vasoconstriction & ischemia  desquamation, coagulation, hemostasis NORMAL MENSTRUAL BLEEDING IS SELF-LIMITED

  5. Menstrual CycleWhat is normal? Normal Menses Menometrorrhagia Abnormal Menorrhagia Polymenorrhea Oligomenorrhea Metrorrhagia

  6. Menstrual Cycle CharacteristicsAge Variations • Highest variation in early adolescent and perimenopausal years • Adolescent: long intervals for 5-7 years after menarche • Reproductive years: • Majority of cycles 25-28 days • Cycle length can change around age 40-42 until menopause Health, 1986; Belsey, 1997; Volman, 1977; Treolar, 1967; O’Connor, 2001; Taffe, 2002.

  7. Abnormal Menstruation: Burden of Disease • Most common reason for GYN visits • 600,000 hysterectomies each year • ¼ US women will have a hysterectomy by age 60 • 2nd most frequent surgery among reproductive-aged women • Annual cost of $5 billion • Most common conditions for hysterectomy: • Fibroids, endometriosis, prolapse • If < 30 years old, menstrual disturbances and dysplasia • Surveillance for Reproductive Health, Hysterectomy Surveillance—United States, 1994-1999.

  8. Evaluation of Abnormal Menstruation • Consider differential diagnosis • Target history to narrow differential • Exam • Labs • Imaging

  9. Evaluation of Abnormal MenstruationDifferential Diagnosis • Pregnancy complication! • Threatened or incomplete abortion • Ectopic pregnancy • Gestational trophoblastic disease • Retained products of conception • Benign anatomical lesion • Cervical or endometrial polyp • Leiomyoma • Adenomyosis • Malignancy • Cervical or uterine cancer (esp HIV + women)

  10. Trauma/foreign body Children Inflammatory conditions Endometritis Systemic illness Thyroid dysfunction Hyperprolactinemia Renal failure Hepatic dysfunction Bleeding disorder Thrombocytopenia Platelet function abnormalities von Willebrand’s disease Medications Steroidal Psychiatric Or….. Evaluation of Abnormal MenstruationDifferential Diagnosis

  11. Dysfunctional Uterine Bleeding • DUB is a diagnosis of exclusion! • DUB is: • Abnormal bleeding pattern, AND • NO ATTRIBUTABLE UNDERLYING ILLNESS OR PATHOLOGY • Causes: • Anovulation (90%) • Polycystic ovarian syndrome • Teenagers or peri-menopausal women • Rarely short follicular or luteal phase

  12. Evaluation of Abnormal MenstruationStep 1: History • Detailed menstrual history • Inter-menstrual intervals • Consistent, normal (q 24-35 days) • Variable • Character, volume • Duration • Normal (3-7 days) • Prolonged • Initial onset of symptoms

  13. Evaluation of Abnormal MenstruationStep 1: History • Other associated symptoms • Dysmenorrhea • Post-coital bleeding • Galactorrhea • Hirsutism • Fatigue, weight gain, constipation (thyroid) • Temporal associations w/ other events • Weight changes • Medication changes • Medical history & medications • GOAL OF HISTORY: • Does she ovulate? If not, DUB LIKELY! • What labs do you need to confirm you initial diagnosis?

  14. Evaluation of Abnormal Menstruation • Ovulation - does she or doesn’t she? • Menstrual history • Basal body temperature (BBT) monitoring (biphasic) • Ovulation predictor kits • Timed serum progesterone (> 3 ng/ml) • Ultrasound • Implications: if ovulatory… • Search for an anatomical/pathological cause

  15. Endocervical Polyps Squamous Cell Carcinoma of Cervix Evaluation of Abnormal MenstruationStep 2: Exam • Weight • Thyroid exam • Signs of other illnesses • Signs of hyperandrogenism • Hirsutism • Acne • Pelvic exam • Cervical and vaginal lesions • Size, shape of uterus

  16. Evaluation of Abnormal MenstruationStep 3: Laboratory Tests • All patients: screen for • Pregnancy (history or urine hcg) • Thyroid disorder (TSH) • Anemia, thrombocytopenia (CBC) • Select patients: • Hyperprolactinemia (PRL) • Bleeding disorders (coagulation panel, vWF) • Chemistry (AST, ALT, Creatinine) • Endometrial biopsy????

  17. Evaluation of Abnormal MenstruationEndometrial Biopsy • Risk of endometrial carcinoma: • Age 30-34: 2.3/10,000 • Age 35-39: 6.1/10,000 • Age 40-49: 36.2/10,000 • Duration of time exposed to unopposed estrogen is more important than age • Possible results: proliferative, secretory, hyperplasia, atypia, carcinoma, acute or chronic endometritis Ash, J Reprod Med, 1996.; ACOG Practice Bulletin 14, 2000.

  18. Chronic endometritis Adenocarcinoma Endometrial Hyperplasia Endometrial Biopsy

  19. Regular cycles • volume • duration Regular cycles intermenstrual bleeding Abnormal bleeding, evidence of ovulation Failed medical management RULE OUT ANATOMIC LESION Evaluation of Abnormal MenstruationStep 4: Imaging Who needs imaging?

  20. Evaluation of Abnormal MenstruationStep 4: Imaging • Ultrasound can help diagnosis: • Fibroids • Polyps • Adenomyosis • Endometrial stripe • < 5 mm, denuded, atrophic • 5-12 mm, normal • > 12 mm, thick, biopsy! • Hydrosonogram: increases sensitivity to detect endometrial lesions, 70%  90% • Hysteroscopy Becker, 2002.

  21. Uterine ImagingUltrasound Normal endometrium Late proliferative or luteal phase Thin endometrium Early proliferative phase or atrophy

  22. Uterine Imaging Routine Ultrasound Saline Sonogram Endometrial polyp Submucous myoma

  23. Hyperplasia Polyps Atrophy Myoma Adenocarcinoma Uterine ImagingHysteroscopy

  24. DUB Restore growth, development and shedding of a stable endometrium Prevent development of hyperplasia or neoplasia Bleeding from Specific Cause Treatment of Abnormal Menstruation What is the diagnosis?

  25. Progesterone Estrogen Estrogen 2 4 6 8 10 12 14 16 18 20 22 24 26 28 Ovulatory Cycle DUB/Anovulation Menses Cycle Physiology

  26. Treatment: DUB Rx Progestin Rx Progestin Endogenous estrogen 1 5 9 21 25 1 5 9 21 25 13 17 13 17 Calendar Day Option 1: Cyclic Progestins Progestins: 1. Medroxyprogesterone (MPA) 10mg qd 2. Norethindrone acetate 5 mg qd

  27. Treatment: DUB Rx Cyclic OCP Rx Cyclic OCP Progestin Progestin Estrogen Estrogen Endogenous estrogen 1 5 9 21 25 1 5 9 21 25 13 17 13 17 Pill Cycle Day Option 2: Oral Contraceptives

  28. Treatment of Anovulation with Acute, Heavy Bleeding • Hemodynamically stable?? • IVF, CBC, transfusion • D&C • Strongly consider biopsy • Ultrasound • Treatment – High dose OCP taper

  29. Treatment of AnovulationMaintenance Therapy • Goal: Restore regular menstrual bleeding patterns • Prevent endometrial cancer!! • Failed management = further workup

  30. Treatment: Anovulatory BleedingPreventing Endometrial Hyperplasia & Neoplasia Kurman et al, Cancer, 1985

  31. ATYPIA Present Absent Fertility desired? No Yes Megace 40-80mg x 3-6 months Re-biopsy Hysterectomy Cyclic progestins or OCPS Rebiopsy if abnormal bleeding occurs Treatment: AnovulationPreventing Endometrial Neoplasia

  32. DUB Bleeding from Specific Cause Treat underlying cause Decrease volume and duration of menses Treatment of Abnormal Menstruation What is the diagnosis?

  33. Empty Sac Ectopic Treatment Complications of Pregnancy • Ectopic pregnancy • Salpingostomy • Salpingectomy • Methotrexate • Threatened abortion • Observation • Incomplete/inevitable abortion • Curettage

  34. Indirect cause of bleeding Twice as common in HIV+ patients Doxycycline 100mg bid x 10 days Treatment Chronic endometritis Kerr-Layton et al, Infect Dis Obstet Gynecol, 1998

  35. Medical treatment OCPs: decrease volume/duration of menses NSAIDS GnRH agonists Surgical treatment Myomectomy Hysterectomy Treatment Leiomyomas

  36. Treatment Small Submucous Myomas, Polyps 1 2 3 Hysteroscopic Resection

  37. Treatment Prolapsing, Large Myomas Abdominal or Laparscopic Myomectomy Vaginal Myomectomy

  38. Treatment Multiple Myomas Completed Childbearing Abdominal Hysterectomy

  39. Treatment: Ovulatory Patient with Unexplained Menorrhagia • Medical Options • NSAIDS: 20-40% decrease • OCPs: 40% decrease • Levonorgestrel IUD: 75-95% decrease • Excellent option with chronic illnesses • Women highly satisfied • GnRH agonists • Surgical Options • Endometrial ablation • Hysterectomy Hall, Br J Obstet Gynecol, 1987; Fraser, Aust NZ J Obstet Gynecol, 1995; Cochrane Database Syst Rev, 2002.

  40. Outflow obstruction, Mullerian abnormalities Androgen insensitivity syndrome – 46 XY Ovarian failure Turners syndrome, 45 XO Autoimmune Cancer treatments Other causes Asherman’s syndrome Premature ovarian failure Pituitary lesion Most common = prolactinoma Sheehan’s syndrome Hypothalamic hypogonadism Other causes Absence of Menstruation Primary Amenorrhea Secondary Amenorrhea

  41. <8 years old GnRH-dependent Idiopathic – most common CNS abnormality GnRH-independent Ovarian cyst/tumor McCune Albright syndrome Treatment: Surgery when appropriate GnRH agonist See primary amenorrhea Abnormal Puberty Precocious Puberty Delayed Puberty

  42. Conclusions • Abnormal menstruation is extremely common • Most common cause of a sudden change in bleeding patterns is a complication of pregnancy! • Careful menstrual history • Use labs and imaging to support your clinical suspicions • Anovulatory bleeding: goal is to restore normal menstrual patterns • Bleeding from other causes: correct underlying pathology and decrease volume/duration of menses

  43. Questions?

  44. Examples of Effects of Exogenous Progestin in Ovulatory Cycles Ovulation Provera C Provera B Provera A Endogenous Progesterone Follicular Phase 14 Luteal Phase 28

  45. Treatment: Anovulatory BleedingPreventing Endometrial Hyperplasia & Neoplasia Simple Hyperplasia Complex Hyperplasia Complex Atypical Hyperplasia

  46. Menstrual CycleDefinitions of Abnormalities • Irregular intervals • Oligomenorrhea, > 35 days • Polymenorrhea, < 24 days • Excess amount and/or duration • Menorrhagia • Irregular interval • Metrorrhagia • Irregular interval and amount/duration • Menometrorrhagia

  47. Uterine ImagingUltrasound Submucous myoma Intramural myoma Adenomyosis

  48. ADD: (4/7) • Info about PCOS vs. hypo-hypo. • Look up DUB (is it almost always PCOS??) • More about HIV?

  49. Progestin Rx OCP (monophasic) bid X 7d, qd X 7-14d Estrogen Endogenous Estrogen Menses Treatment: Acute bleedingHigh dose OCP ‘Taper’

  50. Rx Progestin Rx Estrogen (CEE 1.25-2.5 mg/d or micronized estradiol 2.0 mg/d, q4h prn; CEE 25 mg i.v. q4h prn) Endogenous Estrogen Menses Treatment: Atrophic EndometriumSequential Estrogen and Progestin

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