1. Abnormal Uterine Bleeding Akmal Abbasi, M.D.

2. Normal Menstrual Cycle Begins median age 12.4 years with 80% between the ages of 11 and 13.8 years and about 10% < 11 years Begins about 2.3 years after initiation of puberty with a range of 1-3 years Becomes regular after 2-2.5 years Occurs every 28 days with a range of 21 days to 42 days (3-6 weeks) Lasts for 3-5 days with a range of 2-7 days Results in average loss of 40 ml of blood per cycle with range of 25-70 ml Ovulatory cycles dependent on age of menarche.

3. Menstrual Irregularities A. Variations in frequency: 1. Polymenorrhea: Frequent regular or irregular bleeding at < 21-day intervals. (“I'm having too many periods.”) 2. Oligomenorrhea: Infrequent irregular bleeding of > 42-day intervals. (“My periods don't come often enough.”) 3. Primary amenorrhea: No menstrual flow by age 15.5 years

4. Menstrual Irregularities 4. Secondary amenorrhea: Absence of vaginal bleeding for > 3 months. (“I haven't had a period in months.”) 5. Irregular menses: Bleeding occurring with varying intervals at > 21-day intervals but < 42 days. (“My periods never come at the same time of the month.”)

5. Menstrual Irregularities B. Variations in amount and duration: 1. Metrorrhagia: Intermenstrual irregular bleeding between regular periods. (“I'm bleeding between my periods.”) Menorrhagia: Excessive amount and increased duration uterine bleeding occurring regularly. (“My periods are too long and too heavy and come too often.”) Dysfunctional uterine bleeding: Prolonged excessive menstrual bleeding associated with irregular periods usually due to anovulation in adolescence. (“I've been bleeding for 3 straight weeks.”)

6. Menstrual Irregularities C. Variations in amount: 1. Hypomenorrhea: Decreased menstrual flow occurring at regular intervals. (“My periods are too light.”) 2. Hypermenorrhea: Profuse menstrual flow of normal duration and occurring at regular intervals. (“My periods are too heavy.”)

7. Dysfunctional Uterine Bleeding (DUB) A. Definition 1. Lack of positive feedback response by the hypothalamic pituitary system to estrogen 2. Unopposed estrogen effect of the endometrium 3. No dominant follicle with uncontrolled growth and atresia of many follicles, resulting in fluctuation of circulating estrogens 4. Endometrial shedding dependent on amount of proliferative endometrium present 5. Without ovulation, imbalance of the ratio of prostaglandins (PGs) produced with the PGF 2 (vasoconstrictor) and PGE (vasodilator)

8. Dysfunctional Uterine Bleeding (DUB) B. Differential diagnosis 1. Immature hypothalamic pituitary gonadal axis 2. Drug use/abuse a. Prescribed b. Illegal or banned c. Tobacco 3. Chronic or systemic diseases

9. Dysfunctional Uterine Bleeding (DUB) 4. Endocrine disorders a. Anovulation b. Functional ovarian hyperandrogenism c. Thyroid disorders d. Excess adrenal androgen production e. Hyperprolactinemia 5. Premature ovarian failure 6. Adrenal or ovarian hormone-producing tumors

10. Evaluation of too frequent, too long, or too much bleeding menstrual irregularities.

11. Evaluation of too infrequent, too short, or too light bleeding menstrual irregularities.

12. Treatment Mild anemia: hematocrit (Hct) > 33% or hemoglobin (Hgb) > 11 gm/dl a. Acute treatment 1. Menstrual calendar 2. Iron supplementation 3. Consider: oral contraceptives (OCs) if patient is sexually active and desires contraception (standard once-daily dose) b. Long-term treatment 1. Monitor: Iron status (Hgb/Hct) 2. Follow up: 1-2 months

13. Treatment Moderate anemia: Hct 27-33% or Hgb 9- 11 gm/dl a. Acute treatment 1. Begin: OCs (30 μg EE monophasic) + antiemetics 2. Regimen: a. Two pills/day × 13-19 days b. Then withdraw bleed × 7 days

14. Treatment b. Long-term treatment 1. OCs cycle for 3 months. 2. Begin OCs one pill a day the Sunday after withdrawal bleeding begins. 3. Length of use dependent on resolution of anemia. Iron supplementation. 4. Monitor: Iron status 5. Follow up: 2-3 weeks and every 3 months

15. Treatment Severe anemia: Hct < 27% or Hgb < 9 gm/dl (or dropping). If Hgb < 7 gm/dl and actively bleeding, consider admission to hospital for conjugated estrogens, 25 mg IV every 4-6 hours IV × 24 hours while simultaneously beginning OCs. Blood transfusion may be indicated after hydration, when it becomes apparent anemia is more profound.

16. Treatment a. Acute treatment--If not actively bleeding, Hgb is between 7 and 9 gm/dl, and orthostatics as measured by heart rate and blood pressure are negative, initial treatment may be limited to two pills a day for the next 2- 3 weeks, followed by a withdrawal bleed. 1. Begin: OCs (30 μg EE monophasic) + antiemetics a. 4 pills/day × 4 days b. 3 pills/day × 4 days c. 2 pills/day × 13-19 days d. Withdrawal bleeding × 7 days

17. Treatment b.Long-term treatment 1. Cycle with OCs, one pill a day starting the Sunday after withdrawal bleeding begins 2. Length of OC use dependent on resolution of anemia. Iron supplementation. 3. Monitor: Iron status 4. Follow up: 2-3 weeks and every 3 months

18. Primary Amenorrhea--causes Müllerian fusion abnormalities 1. Second most common cause of primary amenorrhea 2. Absence or hypoplasia of vagina—imperforate, transverse uterus normal → rudimentary 3. Female (46XX) 4. Growth and development normal; normal hair distribution and breast development and growth

19. Primary Amenorrhea--causes 5. 10-33% have urinary tract abnormalities a. Ectopic kidney b. Renal agenesis c. Horseshoe kidney d. Abnormal collecting system 6. 3-5% with spine abnormalities and rarely limb abnormalities 7. VACTERL complex (vertebral, anal, cardiac, tracheoesophageal, renal, limb abnormalities)

20. Primary Amenorrhea--causes Androgen insensitivity 1. Third most common cause of primary amenorrhea 2. Male pseudohermaphrodite (46XY) 3. Maternal X-linked recessive gene responsible for androgen intracellular receptor 4. Prepubertal presentation may be inguinal hernias; 50% at puberty 5. Growth and development normal; taller height

21. Primary Amenorrhea--causes 6. Large breasts with small nipples, pale areolas 7. Blind vaginal pouch with no uterus; presence of antimüllerian hormone 8. Absent to sparse body hair 9. 5% malignant gonad tumors; remove at 16-18 years 10. May have renal abnormalities

22. Evaluation of primary amenorrhea.

23. Secondary Amenorrhea--causes Hypothalamus Abnormalities of height/weight and nutrition Exercise Stress Infiltrative disease (craniopharyngioma, sarcoidosis, histiocytosis)

24. Secondary Amenorrhea--causes Pituitary Prolactin-secreting pituitary tumor Empty sella syndrome Sheehan syndrome ACTH-secreting pituitary tumors(Cushing disease)

25. Secondary Amenorrhea--causes Ovary Premature ovarian failure Polycystic ovarian disease Ovarian tumors Uterus Asherman syndrome Other Late-onset adrenal hyperplasia Hypothyroidism or hyperthyroidism

26. Work-up for diagnosis of secondary amenorrhea

27. Primary and Secondary Dysmenorrhea Primary dysmenorrhea: Painful menses with no identifiable pelvic pathology a. Overall prevalence: 50-90% b. Mild (27%) c. Moderate (41%) d. Severe (23%) Secondary dysmenorrhea: painful menses resulting from pelvic pathology

28. Differential Diagnosis of Secondary Dysmenorrhea Reproductive organs: Endometriosis Genital tract malformations and/or obstruction Mittelschmerz Ovarian cyst Pelvic inflammatory disease (acute or chronic) Pelvic serositis Postoperative adhesions

29. Differential Diagnosis of Secondary Dysmenorrhea Gastrointestinal: Constipation Irritable bowel Food intolerance Infections Inflammatory bowel disease

30. Differential Diagnosis of Secondary Dysmenorrhea Urinary tract Infection Congenital/acquired obstruction Musculoskeletal Disc disease/malalignment Inflammation Neoplasms Stress fractures (pubis, vertebral body) Psychosomatic

31. Treatment Medications for the Treatment of Primary Dysmenorrhea include: Aspirin Acetaminophen Ibuprofen Ketoprofen Naproxen Naproxen sodium Rofecoxib

32. Evaluation for Dysmenorrhea.