1. Petr Křepelka Menstrual cycle disorders

2. Diagnosis

3. MENSTRUATION Periodic desquamation of the endometrium The external hallmark of the menstrual cycle Just before menses the endometrium is infiltrated with leucocytes Prostaglandins are maximal in the endometrium just before menses Prostaglandins  constriction of the spiral arterioles  ischemia & desquamation Followed by arteriolar relaxation, bleeding & tissue breakdown

4. NORMAL MENSTRUAL CYCLE The mean duration of the MC Mean 28 days (only 15% of ♀) Range 21-35 The average duration of the MC 3-8 days The normal estimated blood loss? Approximately 30 ml Ovulation occurs Usually day 14 34 hrs after the onset of mid-cycle LH surge

5. Definition of normal menstruation Regularity Frequency - Cycle lenght Duration of menstrual flow Volume of menstrual flow

6. Describing normal uterine bleeding Regularity of menstruation –Regular –Iregular –Absent Frequency –Frequent –Normal –Infrequent

7. Describing normal uterine bleeding Duration of menstrual flow –Prolonged –Normal –Shortened Volume of menstrual flow –Heavy –Normal –Light

8. Nomenclature for normal menstraution Abnormal uterine bleeding FeatureNormalAbnormality 1Abnormality 2 RegularityRegular ±2;20d Iregular variation > 20d Absent FrequencyNormal q 24- 38d Frequent < 24d Infrequent >38d DurationNormal 4,5-8dProlonged > 8d Shortened <4,5d VolumeNormalHeavyLight

9. Abnorlam uterine bleeding Regularity of cycle –Iregular – metrorrhagia –Absent – amenorrhoea (primary, secondary) Frequency of cycle –Frequent - polymenorrhoea –Infrequent - oligomenorrhoea

10. Describing normal uterine bleeding Duration of menstrual flow –Prolonged – menorrhagia –Shortened - hypomenorrhoea Volume of menstrual flow –Heavy - hypermenorrhoea –Light - hypomenorrhoea

11. Classification of causes of abnormal uterine bleeding PolypCoagulopathy AdenomyosisOvulatory dysfunction LeiomyomaSubmucosalEndometrial OtherIatrogenic Malignancy&hyperpl asia Not classified

12. Myoma classification Submucosal0Pedunculated intracavitary 1>50% intracavitary 2≤50% intracavitary Other3Contacts endometrium, 0% intracavitary 4Intramural 5Subserosal ≥50% intramural 6Subserosal <50% intramural 7Subserosal pedunculated 8Other

13. Initial evaluation. For a diagnosis of chronic abnormal uterine bleeding (AUB), the initial assessment requires the patient to have experienced 1 or a combination of unpredictability, excessive duration, abnormal volume, or abnormal frequency of menses for at least the previous 3 months. Patients should undergo a structured history designed to determine ovulatory function, potential related medical disorders, medications, and lifestyle factors that might contribute to AUB. For those with heavy menstrual bleeding, the structured history should include the questions from Table 1. Understanding the future fertility desires of the patient will help to frame the discussion of therapy following appropriate investigation. Ancillary investigations should include a hemoglobin and/or a hematocrit assessment, appropriate tests for features that could contribute to an ovulatory disorder (thyroid function, prolactin, and serum androgens), and if the Table 1 -based structured history is positive for coagulopathy either referral to a hematologist or appropriate tests for von Willebrand disease. Reproduced, with permission, from Ref. [11]. Reproduced, with permission, from Ref. [11]. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age Munro, Malcolm G., International Journal of Gynecology & Obstetrics, Volume 113, Issue 1, 3-13 Copyright © 2011

14. Uterine evaluation. The uterine evaluation is, in part, guided by the history and other elements of the clinical situation, such as patient age, presence of an apparent chronic ovulatory disorder, or presence of other risk factors for endometrial hyperplasia or malignancy. For those at increased risk, endometrial biopsy is probably warranted. If there is a risk of structural anomaly, particularly if previous medical therapy has been unsuccessful, evaluation of the uterus should include imaging, at least with a “screening” transvaginal ultrasound (TVUS) examination. Unless the ultrasound image indicates a normal endometrial cavity, it will be necessary to use either or both hysteroscopy and saline infusion sonography (SIS) to determine whether target lesions are present. Such an approach is also desirable if endometrial sampling has not provided an adequate specimen. Uncommonly, these measures are inconclusive or, in the instance of virginal girls and women, not feasible outside of an anesthetized environment. In these instances, magnetic resonance imaging (MRI) may be of value, if available. Abbreviations: AUB, abnormal uterine bleeding; CA, carcinoma. Reproduced, with permission, from Ref. [11]. Reproduced, with permission, from Ref. [11]. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age Munro, Malcolm G., International Journal of Gynecology & Obstetrics, Volume 113, Issue 1, 3-13 Copyright © 2011

15. Menstrual cycle disorders Polymenorrhoea Oligomenorrhoea Hypomenorrhoea Amenorrhoea Menorrhagia Hypermenorrhoea Dysmenorrhoea Premenstrual syndrome

16. Polymenorrhoea vs. oligomenorrhoea

17. Hypermenorrhoea vs. menorrhagia

18. Dysmenorrhoea Painful menstruation Primary – occurs only in ovulatory cycles –High level of prostaglandines Secondary –Endometriosis –Pelvic inflammatory disease –Congenital abnormalities

19. Premenstrual syndrome Complex of physical and emotional symptoms that occur cyclic before menstruation Therapy - symptomatic

20. THERAPY

21. Polymenorrhoea Polymenorrhoe – cycle < 21 days Therapy –Progestines during luteal phase of cycle (normoestrogenic disorders) –Progestines+estrogenes (hypoestrogenic disorders)

22. Oligomenorrhoe Oligomenorrhoe – cycle > 35 days Therapy -No therapy (normoestrogenic disorders) –Progestines during luteal phase of cycle (normoestrogenic disorders) –Progestines+estrogenes (hypoestrogenic disorders) –Induction of ovulation (infertility)

23. Primary amenorrhoe Therapy - casual –Progestines+estrogenes (hypoestrogenic disorders)

24. Secondary amenorrhoe Therapy – normoprolactinemic and normoestrogenic –Progestogenes –Ovulation induction

25. Heavy or prolonged uterine bleeding Menoragia Hypermenorhea DUB =dysfunctional uterine bleeding AUB = abnormal uterine bleeding

26. 26 Dysfunctional uterine bleeding - therapy Observation    DG   Pharmacological    Spont.normalization       Recurrence     D & C   Failure        - Surgical - Endometrial ablation/destruction / Hysterectomy

27. Pharmacological therapy of DUB Hormonal –Estrogens (E) –Progestins (P) –E/P –Danazol –GnRh - a –SERM Non-hormonal –Nonsteroidal antirevmatics –Mefenamic acid –Ethamsylate –Antifibrinolytics EAC Tranexamic acid

28. 28 Pharmacological therapy of DUB Individual Age-specific Treatment outcome and side effects are unpredictable Side effects are common Economic efficiency Need for surgical treatment is often

29. Estrogens –CEE - 2.5 mg p.o. a 6 h. or 25 mg i.v. a 4 h. for 48 h. Progestins –MPA 10 mg/d for 10-12 d. –NES 10-15 mg/d 10 d. –LNG-IUS 29 Pharmacological therapy of DUB

30. E/P –Combined orla contraception Acute DUB - 70-140 μg/d Prevention – usual pattern, long cycle pattern, continual –Adolescent gynecology acute DUB Progesterone 10 mg/ Estradioldipropionate 2 mg i.m. 30 Pharmacological therapy of DUB

31. Danazol 200-400 mg/d –not available in Czech Republic GnRH agonists –goserelin (Zoladex Depot 3,75 mg) –tryptorelin (Decapeptyl Depot 4,12 mg, Dipherelin 4,39 mg) –leuprorelin (Lucrin Depot 3,75 mg) 31 Pharmacological therapy of DUB

32. Nonsteroidal antirevmatics –Naproxen (Aleve tbl.220 mg, Apo-naproxen tbl. 250 mg, Nalgesin tbl. 270 mg) –Mefenamic acid (Nimesulid tbl. 100 mg) Antifibrinolytics –Tranexamic acid (Exacyl p.o. tbl. 500 mg, oral solution 10ml/1000 mg a venous injection 5 ml/500mg) 32 Pharmacological therapy of DUB

33. Effectiveness of pharmacotherapy Hormonal –Progestins - 21 day cycle 30-90% –Combined oral contraception 43% –Danazol 50-80% –LNG IUS 74-97% –DMPA 50-66% –GnRH agonists >90% Non-hormonal –Non-steroidal antirevmatics 20-50% ? –Tranexamic acid 47- 54% –Etamsylate 13%?

34. Surgical therapy of DUB Endometrial ablation – hysteroscopical –Roller ball ablation (25-60%) –Transcervical resection (26-40%) –Laser ablation (37%) 34

35. Surgical therapy of DUB Endometrial ablation – non- hysteroscopical methods –RFEA – Radio Frequency Endometrial Ablation (41%) –TBEA – Thermal Balloon Endometrial Ablation (48%) –MWEA – Microwave Endometrial Ablation (61%) 35

36. Surgical therapy of DUB Vaginal hysterectomy LAVH – laparoscopically assisted vaginal hysterectomy Abdominal hysterectomy (minilaparotomy) 36

37. Surgical therapy of DUB - controversies Dilatation+curettage –Diagnostic procedure Endometrial - Resection/ablation –Many costly methods –Many failures selhání Hysterectomy –Invazive –Operational risks –Expensive –Suitable for women over 40 37

38. Hypomenorrhoe Posttraumatic – Aschermanns syndrome Therapy –Hysteroskopy – lysis of adhaesions – IUD - estrogens

39. Dysmenorrhea - therapy Secondary dysmenorrhoea – causative Primary dysmenorrhoea – combined hormonal contraception effectivity – 90% Progestogens contraception – long acting LNG-IUS Non-steroidal anti-inflammatory drugs (NSAIDs) –2-3 days before menstrual bleeding –Continue to the 2.day of bleeding

40. Premenstrual syndrome - therapy Diet regime – restriction of coffein, alcohol, salt, glycids Aerobic exercise Psychological consultation

41. Premenstrual syndrome - therapy Symptomatic treatment according to prevailing syndrome Combined oral contraception (drospirenon) Agnus castus Non-steroidal anti-inflammatory drugs SIRS - fluoxetin

42. …thank you for your attention