1. ABNORMAL UTERINE BLEEDING
Cruz, Rivera, Tai, Veloso
ABNORMAL UTERINE BLEEDING

2. Menorrhagia - menses lasting longer than 7 days or exceeding 80 mL of blood loss
Metrorrhagia - intermenstrual bleeding.
menometrorrhagia.
hypomenorrhea - diminished flow or shortening of menses
Oligomenorrhea - interval longer than 35 days (normal 28 days ± 7 days)

3. withdrawal bleeding refers to the predictable bleeding that often results from abrupt progestin cessation.
Assessment: lack of correlation between patient perception of blood loss and objective measurement
passing clots more than 1.1 inches in diameter and changing pads more frequently than every 3 hours

4. FIGO Classification system for causes of abnormal uterine bleeding in nongravid women of reproductive age

6. P- Polyps Endometrial and endocervical
epithelial proliferations comprise a variable vascular, glandular, and fibromuscular and connective tissue
often asymptomatic, but generally accepted that at least some contribute to the genesis of AUB

7. A- Adenomyosis
presence of endometrial tissue within the uterine wall (myometrium)
Relationship unclear

8. L- Leiomyoma Benign fibromuscular tumors of the myometrium
submucosal lesions are the most likely to contribute to the genesis of AUB

9. M- Malignancy
Endometrial carcinoma is the most common invasive cancer of the female genital tract
Risks: obesity, diabetes, hypertension, infertility, unopposed estrogen stimulation

10. C- Coagulopathy Coagulation disorders Platelet deficiency
von Willebrand's disease
prothrombin deficiency
Platelet deficiency
leukemia, severe sepsis, idiopathic thrombocytopenic purpura, and hypersplenism, can also cause excessive bleeding.
. Claessens and Cowell reported that coagulation disorders are found in about 20% of adolescent females who require hospitalization for abnormal uterine bleeding. Coagulation defects are present in about one fourth of those whose hemoglobin levels fall below 10 g/100 mL, in one third of those who require transfusions, and in half of those whose severe menorrhagia occurred at the time of the first menstrual period. A more recent study by Falcone and associates indicated that a coagulation disorder was found in only 5% of adolescents hospitalized for heavy bleeding. Both studies indicate that the likelihood of a blood disorder in adolescents with heavy menses is sufficiently high so that they should all be evaluated to determine if a coagulopathy is present.

11. O – Ovulatory dysfunction
Unpredictable timing of bleeding and variable amount of flow

12. O - Ovulatory
absence of predictable cyclic progesterone production from the corpus luteum every 22– 35 days
later reproductive years: “luteal out-of- phase” events
Anovulatory dysfunctional uterine bleeding results from a disturbance of the normal hypothalamic-pituitary-ovarian axis and is particularly common at the extremes of the reproductive years. When ovulation does not occur, no progesterone is produced to stabilize the endometrium; thus, proliferative endometrium persists. Bleeding episodes become irregular, and amenorrhea, metrorrhagia, and menometrorrhagia are common. Bleeding from anovulatory dysfunctional uterine bleeding is thought to result from changes in prostaglandin concentration, increased endometrial responsiveness to vasodilating prostaglandins, and changes in endometrial vascular structure.
In ovulatory dysfunctional uterine bleeding, bleeding occurs cyclically, and menorrhagia is thought to originate from defects in the control mechanisms of menstruation. It is thought that, in women with ovulatory dysfunctional uterine bleeding, there is an increased rate of blood loss resulting from vasodilatation of the vessels supplying the endometrium due to decreased vascular tone, and prostaglandins have been strongly implicated. Therefore, these women lose blood at rates about 3 times faster than women with normal menses

13. O - Ovulatory Endocrinopathies
polycystic ovary syndrome, hypothyroidism, hyperprolactinemia, mental stress, obesity, anorexia, weight loss, or extreme exercise such as that associated with elite, athletic training).

14. E - Endometrial
predictable and cyclic menstrual bleeding, and particularly when no other definable causes are identified

15. E - Endometrial
deficiencies in local production of vasoconstrictors such as endothelin-1 and prostaglandin F2α; and/or,
accelerated lysis of endometrial clot because of excessive production of plasminogen activator
increased local production of prostaglandin E2 and prostacyclin (vasodilators)

16. E - Endometrial
deficiencies in the molecular mechanisms of endometrial repair secondary to:
endometrial inflammation or infection;
abnormalities in the local inflammatory response; or aberrations in endometrial vasculogenesis.

17. I - Iatrogenic Gonadal steroid therapy
breakthrough bleeding (BTB)
Systemically administered single-agent or combination gonadal steroids
impact the control of ovarian steroidogenesis via effects on the hypothalamus, pituitary, and/or ovary itself, and also exert a direct effect on the endometrium.
Breakthrough bleeding is most commonly caused by an excessively thick endometrium (uterine lining).
Breakthrough bleeding may also be caused by hormonal effects of ovulation.
Breakthrough bleeding is most common when a woman first begins taking oral contraceptives, or changes from one particular oral contraceptive to another, though it is possible for breakthrough bleeding to happen at any time. Smokers are especially prone to breakthrough bleeding while taking oral contraceptives; though many users experience breakthrough bleeding in the first three cycles of taking the pill, non-smokers tend to see the bleeding dissipate more quickly than smokers.
Breakthrough bleeding is likely due to hormonal fluctuations. The body is pre-programmed to make certain estrogen levels each day and the estrogen (and some additional hormones like FSH, LH and Progesterone) are responsible for regulating endometrium shedding. Therefore, when new levels of hormones enter the body through oral contraceptives, the body is provided with two ways to receive estrogen. These excess estrogen levels can cause pre-period bleeding (bleeding through). This should be regulated in several months.
According to Lange Gynecology and obstetrics, 8th edition, the most common side effect associated with OC use is breakthrough bleeding. It usually occurs during the first one or two cycles and resolves spontaneously. Another common problem is amenorrhea. Persistent break through bleeding and amenorrhea commonly reflect an atrophic endometrium, which means a thin and not developed endometrium.
Keep in mind that the usage of combined estrogen and progesterone eliminates the normal endogenous hormonal cycling and gradually produces atrophy of the endometrial glands. This is because the dosage of estrogen in the OCs pills is much lower than the quantity produced naturally by the ovaries. Higher quantities produced by the ovaries induce proliferation, but low levels supplied by the pills produce atrophy yet are sufficient to inhibit the endogenous secretion of the gonadotropins.
The exact chain of events that lead from an atrophic endometrium to the spotting between menses is not explained by the text. Yet it is indicated that this condition may be corrected by using a pill with a higher estrogen (which will stimulate further proliferation of the endometrium) or lower progestin content, which will reduce its stability.[2]
There are several mechanisms by which medical interventions or devices can cause or contribute to AUB (AUB-I). These include
medicated or inert intrauterine systems and pharmacologic agent
that directly impact the endometrium, interfere with blood coagulan mechanisms, or influence the systemic control of ovulation.

18. I - Iatrogenic Poor compliance Use of anticonvulsants and antibiotics
Cigarette smoking
It is likely that many episodes of unscheduled bleeding/BTB are
related to reduced circulating gonadal steroid levels secondary to
compliance issues such as missed, delayed, or erratic use of pills,
transdermal patches, or vaginal rings. With the resulting reduced
suppression of follicle-stimulating hormone production and subse-
quent development of follicles that produce endogenous estradiol,
additional and irregular stimulation of the endometrium may result in
BTB. In a pooled study of 7 trials, 35% ofwomenwith large follicles had
BTB [42]. Other potential causes of reduced levels of circulating
estrogens and progestins include the use of agents such as anticon-
vulsants and antibiotics (e.g. rifampin and griseofulvin) [43]. Cigarette
smoking can reduce levels of contraceptive steroids because of en-
hanced hepatic metabolism, which may explain the relatively high
incidence of BTB in smokers [44].

19. I - Iatrogenic Tricyclic antidepressants and phenothiazines
Use of anticoagulant drugs (e.g. warfarin, heparin and LMW heparin)
impact dopamine metabolism by reducing serotonin uptake. It is thought that the
resulting reduced inhibition of prolactin release causes prolactin-related disruption in the hypothalamic–pituitary–ovarian axis and
consequent disorders of ovulation, including anovulation. Conse-
quently, any agent that impacts serotonin uptake is a candidate for
causing ovulatory dysfunction and resulting amenorrhea or irregular
uterine bleeding

20. N – Not yet classified Chronic endometritis
Arteriovenous malformations
Myometrial Hypertrophy

21. Management

22. Medical treatment is preferred if there is no organic cause of AUB, especially if the woman wants to have more children or if she’s near menopause already
To cut or not to cut?

23. Medical Treatment Estrogen Progestogen NSAIDs
Anti-fibrinolytics agents
Danazol
Gonadotropin-releasing hormone (GnRH) agonists

24. Estrogen Used for acute management of AUB
Causes rapid endometrial growth
Preferred if endometrial lining is <5mm
Oral Conjugated Equine Estrogen (CEE)
10 mg/day, administered in 4 divided doses
May also promote platelet adhesiveness (Livio et.al)
Rapid growth occurs over the raw/ denuded tissue

25. Estrogen
IV Estrogen
Several hours needed to induce mitotic activity (DeVore, et.al)
No great advantage to oral estrogen
De Vore et al – more cessation of bleeding after the administration of a second two 25-mg CEE

26. Estrogen and Progestin
Estrogen + progestin (high dose) after bleeding has stopped
Most acute heavy bleeding episodes is due to anovulation
Progestin addition: Medroxyprogesterone acetate (MPS) 10mg OD
Estrogen and Progestin are given for 7-10 days then stopped

27. Estrogen and Progestin
OCPs that contain estrogen and progestin
Four tablets of an oral contraceptive containing 50 μg of estrogen q 24 h in divided doses
Not as effective as high doses of CEE

28. Progestogen
Slows down endometrial growth by organizing and supporting endometrial tissue
Organized slough to basalis layer stops bleeding quickly
Stimulates arachidonic acid formation in endometrium
Opposes effects of anovulation
Menometrorrhagia – MPA 10mg/day for 10 days monthly

29. Progesterone-releasing IUD
needs to be reinserted annually
rapid diffusion of progesterone through polysiloxone
Levonorgestrol-releasing intrauterine system (LNG-IUS)
duration of action: more than 5 years
Increases hemoglobin
Decreases dysmenorrhea
Reduces blood loss secondary to fibroids and adenomyosis
Good alternative to hysterectomy

30. NSAIDs Ideal for decreased endometrial bleeding NSAIDs blocks
Stop prostaglandin pathway
Allow thromboxane formation (for platelet aggregation)
NSAIDs blocks
Thromboxane formation
Prostaglandin pathway
More effective in ovulating women

31. Curretage
If bleeding does not cease within 24 hours  consider curretage
Invasive and fast
For volume-depleted and anemic patients
Thick endometrium ( >10-12 mm)
Anatomic problem

32. Antifibrinolytic Agents
Examples: ε-Aminocaproic acid (EACA), tranexamic acid (AMCA), and para-aminomethylbenzoic acid (PAMBA)
Study by Nilsson and Rybo
significant reduction in blood loss after treatment with EACA, AMCA, and oral contraceptives, and use of each of these agents resulted in about a 50% reduction in MBL
greatest reduction in blood loss with antifibrinolytic therapy occurred in women who exhibited the greatest MBL

33. Antifibrinolytic Agents
Preston et al
AMCA reduced MBL by 45%, but there was a 20% increase with norethindrone
side effects (in decreasing order of frequency): nausea, dizziness, diarrhea, headaches, abdominal pain, and allergic manifestations
*much more common with EACA than with AMCA

34. Antifibrinolytic Agents
Produce a reduction in blood loss
Can be used by ovulating women with menorrhagia
Best combined with other agents like oral contraceptives for greater effect
Use limited by side effects
Mostly GI
Minimized by reducing dose and use to first 3 days of bleeding
Contraindications: Renal failure and pregnancy

35. Antifibrinolytic Agents
Ergot – Not recommended
Rarely effective
High incidence of side effects: nausea, vertigo, abdominal cramps
Nilsson and Rybo  no reduction in blood loss among 82 women with menorrhagia who were treated with methylergobase immaleate

36. Androgenic Steroids (Danazol)
MBL markedly reduced in studies from more than 200 mL to less than 25 mL with increased interval between bleeding episodes
Most common side effects: weight gain and acne (Reduction of dosage from 400 to 200 mg daily decreased the side effects but did not alter the reduction in blood loss)

37. Androgenic Steroids (Danazol)
Dockeray et al  Danazol was more effective in reducing MBL, 60% compared with 20% for mefenamic acid but side effects were more severe with Danazol and occurred in 75% of patients
Appears to be more effective than placebo, progestogens, oral contraceptives and NSAIDs. However, side effects were 7x greater as compared to NSAIDS and 4x more when compared with progestogens
Expensive with moderate side effects

38. GnRH Agonists
Possible to inhibit ovarian steroid production with GnRH agonists (not based on any large scale studies)
Due to expense and side effects, use for menorrhagia caused by ovulatory DUB  limited to women with severe MBL who fail to respond to other methods of medical management and wish to retain their childbearing capacity
Will help prevent bone loss if used with an estrogen and/or progestin (add-back therapy)

39. Dilatation and Curettage
Can be diagnostic and is therapeutic for immediate management of severe bleeding
Markedly excessive uterine bleeding with possible hypovolemia  quickest way to stop acute bleeding (Treatment of choice for hypovolemia from DUB)
Preferred to stop acute bleeding in women older than 35 (higher incidence of pathologic findings)

40. D&C Rarely curative for DUB
Temporary cure for chronic anovulation  removes hyperplastic endometrium but has no effect on underlying pathology
Not useful for ovulating women with menorrhagia
* Nilsson and Rybo  No difference or an in increase in MBL 1 month S/P D&C

41. D&C
Indications:
Acute bleeding that results in hypovolemia
Older women (Higher risk for endometrial neoplasia)
Otherwise: Medical therapy after ruling out organic disease via endometrial biopsy, sonohysteroscopy or diagnostic hysteroscopy

42. Endometrial Ablation
Laser photovaporization of the endometrium for menorrhagia
Minimum endometrial regeneration
Causes varying degrees of uterine contraction, scarring and adhesion formation but complications are minor and uncommon
Erian  56% amenorrhea, 38% reduced menses, 7% no reduction requiring 2nd treatment with good response
Cochrane database  preoperative GnRH agonists or danazol is beneficial
Photovaporization of the endometrium was performed by use of a neodymium-YAG laser with hysteroscopic visualization and fluid distention of the uterine cavity. Danazol, 800 mg/day, was ingested for 2 to 3 weeks before the procedure, and an additional 2 weeks of danazol treatment was given afterward
Fluid overload, infection, uterine perforation

43. Endometrial Ablation Laser photovaporization Nd-YAG laser (expensive)
Electrocautery by urologic resectoscope through a hysteroscope (Transcervical resection)
Magos et al  30% amenorrhea, 90% improvement in 1 treatment group

44. Endometrial Ablation
Thermal destruction via electrocautery through a ball-end electrode attached to a urologic resectoscope
Larger contact area, better fit into cornual area and easier contact with tissue as compared to loop electrode
Outpatient procedure with general anesthesia
Preop endometrial suppresion with at least 1 month danazol, GnRH analogues or progestin
Paskowitz  60% decreased bleeding
Easier to learn and equipment less expensive

45. Endometrial Ablation Thermal balloon
Does not require pretreatment regimens or hysteroscopy training
Local anesthesia
Meyer et al  Thermal balloon and rollerball – 80% return to normal bleeding
insert a latex balloon into the endometrial cavity, inject 5% dextrose in water into the balloon, heat the fluid to 87° C, and leave the heated filled balloon in the cavity for 8 minutes

46. Endometrial ablation
VestaBlate  new balloon device with a silicone inflatable electrode carrier
Hydrotherablator  heated free fluid system
Does not allow passage of fluid into fallopian tubes
May be used with endometrial distortions including fibroids
35% amenorrhea, 87% decreased blood flow
Novasure  3D bipolar device and generator with suction

47. Endometrial ablation Microwave, Cryoablation, Photodynamic therapy
Becoming more popular for women with menorrhagia without uterine lesions who are unresponsive to medical therapy
Alternative to hysterectomy (Less cost, mortality, days in hospital)
For women contraindicated for hysterectomy or those with ovulatory DUB who don’t want to take medication
Not for those who want to maintain their reproductive capacity

48. Endometrial ablation
Complications: fluid overload, uterine hemorrhage, uterine perforation, thermal damage to adjacent organs, and hematometria
When ablation extends too deep, opening up uterine vessels and exposing adjacent tissues to thermal injury

49. Endometrial ablation
Should be restricted to women with heavy MBL in the absence of organic distress
Should destroy all of the endometrium but only the superficial myometrium to reduce posttreatment problems
Suggested that the surgeon should perform 15 supervised procedures before being credentialed

50. Hysterectomy Decision should be made on an individual basis
For women with other indications for hysterectomy like leiomyomas or uterine prolapse
Only for persistent ovulatory DUB after all medical therapy has failed and with excessive amount of MBL by direct measurement or that causes abnormally low serum ferritin

51. Hysterectomy
Levonorgestrel releasing IUD (LNG-IUS) may be beneficial when hysterectomy/ablation are being considered
Uterine artery embolization  not effective unless fibroids cause excessive bleeding

52. Approach to Treatment
Depends on acute and chronic needs or short- term and long-term therapy

53. Acute bleeding Requires immediate cessation
Pharmacologic doses of estrogen or curettage (the latter to be used more liberally in older women with risk factors or in those who are hemodynamically compromised)
* not dependent on whether the patient is anovulatory or ovulatory
Estrogen will be temporarily helpful, even if there are abnormal anatomic findings, such as fibroids
If pathology is suspected  Curettage preferable

54. Acute bleeding
After the acute episode, it is imperative to know if the patient is bleeding from an anovulatory or ovulatory “dysfunctional” state
Majority of women: Anovulatory

55. Less significant bleeding
*Warrants treatment, but not necessitating the immediate cessation of blood loss
High doses of progestogen alone may be used (Popular practice but no good supporting data)

56. For Adolescents
10 mg of MPA for 10 days each month for at least 3 months should be prescribed with careful observation
Additional diagnostic studies to detect possible defects in the coagulation process, particularly if bleeding is severe

57. For women of reproductive age
Long-term therapy depends on whether she requires contraception, induction of ovulation, or treatment of DUB alone
DUB alone  oral contraceptive or MPA can be administered, monthly for at least 6 months, whereas oral contraceptives and clomiphene citrate are used for the other indications

58. For the perimenopausal
*Have lower amounts of circulating estrogen
Use of cyclic progestogen alone is frequently not curative
Abnormal bleeding is best treated by low-dose oral contraceptives
The cyclic use of CE (0.625–1.25 mg) given for 25 days, with 10 mg of MPA or another progestogen + CE from days 15 to 25 can also be used after ruling out abnormal endometrial histologic findings

59. Ovulatory women with menorrhagia
A challenge to treat chronically
No anatomic abnormalities  need long term therapy to reduce MBL
NSAIDs, progestins, oral contraceptives, danazol, and GnRH analogues are all useful
Combination of two or more of these agents is often required to obviate the need for endometrial ablation or hysterectomy