POGS CLINICAL PRACTICE GUIDELINES ON ABNORMAL ......© presentationgo.com 8 ABNORMAL UTERINE...

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POGS CLINICAL PRACTICE GUIDELINES ON ABNORMAL UTERINE BLEEDING (2017)

INA S. IRABON, MD, FPOGS, FPSRM, FPSGE

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• Philippine Obstetrical and Gynecological Society (POGS) Clinical Practice Guidelines on Abnormal Uterine Bleeding 2017.

REFERENCE



• Encompasses any significant deviation from normalfrequency, regularity, heaviness (volume or amount) andduration of menstrual bleeding.

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ABNORMAL UTERINE BLEEDINGDEFINITION

Frasier IS, et al. Hum Reprod 2007



• Excessive menstrual blood loss which interferes with awoman’s physical, emotional, social and material quality oflife, and which can occur alone or in combination with othersymptoms.

• Replaces the term “menorrhagia”

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HEAVY MENSTRUAL BLEEDINGDEFINITION

Philippine Obstetrical and Gynecological Society (POGS) Clinical Practice Guidelines on Abnormal Uterine Bleeding 2017.



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ABNORMAL UTERINE BLEEDING“PALM-COEIN” CLASSIFICATION




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ABNORMAL UTERINE BLEEDINGADENOMYOSIS

• Several hypothesis regarding adenomyosis and its association with AUB:

1. Increased endometrial surface2. Altered PGE/PGF2a balance3. Hampered myometrial contractility4. Abnormal myometrial angiogenesis associated with

fragile blood vessels




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ABNORMAL UTERINE BLEEDINGLEIOMYOMA

• AUB secondary to leiomyomas may be due to:1. Mechanical distortion leading to increase in endometrial

surface2. Bleeding from ulcerated endometrium overlying

submucous myoma3. Myomas interfering with normal uterine hemostasis or

compressing of the venous drainage at any site4. Dilatation of the venous plexuses draining the

endometrium




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Primary classification:AUB -L

Secondary classification Tertiary classification



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COAGULOPATHY (AUB-C)

• disorders of blood coagulation such as von Willebranddisease (most common), prothrombin deficiency, hemophilia, leukemia, severe sepsis, idiopathic thrombocytopenic purpura, and hypersplenism

• Other disorders that produce platelet deficiency, such as Chronic anticoagulation as a result of heparin, low-molecular-weight heparin, direct thrombin inhibitors, and direct factor Xa inhibitors

AUB-C

Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding; In Comprehensive Gynecology 7th edition, 2017;Lobo RA, GershensonDM, Lentz GM, ValeaFA editors; pp 621-633.



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OVULATORY DYSFUNCTION (AUB-O)

• Anovulatory bleeding is most common during the extremes of reproductive life: in the first few years after menarche and during perimenopause.

• What are the causes of anovulation? 1. extremes of reproductive life2. polycystic ovary syndrome (PCOS)3. hypothalamic dysfunction (related to weight loss,

severe exercise, stress, or drug use)4. abnormalities of other nonreproductive hormone

(thyroid hormone, prolactin, and cortisol)


AUB -O



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ENDOMETRIAL (AUB-E)• heavy menstrual bleeding in the absence of

other abnormalities are thought to have underlying disorders of the endometrium or are otherwise unclassified.

• In the past, this category has been called “ovulatory dysfunctional uterine bleeding.” • Low PGF2α/PGE à increase menstrual

blood loss

AUB-E




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IATROGENIC(AUB-I)• abnormal bleeding resulting from medications such as

hormonal preparations, including selective estrogen receptor modulators, and gonadotropic releasing hormone agonists and antagonists.

• combined and progesterone-only oral contraceptives may result in breakthrough bleeding (BTB).

• interactions between oral contraceptives and other medications, such as antibiotics and anticonvulsants may alter circulating levels of steroids, allowing follicular recruitment and increased endogenous levels of estrogen.

AUB-I




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NAUB-NOT OTHERWISE SPECIFIED (AUB-N)

• Abnormal bleeding not classified in the previous categories is considered AUB-N. • Examples of such conditions may include foreign

bodies or trauma. Treatment is tailored to the specific cause.

AUB-N




DIAGNOSIS NOMENCLATURE:

• the acronym AUB is followed by the letters PALM-COEIN and a subscript 0 or 1 associated with each letter to indicate the absence or presence, respectively, of the abnormality. • Example #1: A patient with abnormal bleeding due

to a polyp :

AUB-P1A0L0M0-C0O0E0I0N0




DIAGNOSIS NOMENCLATURE:

•Example #2: A patient with abnormal bleeding that is both irregular and heavy may have endometrial hyperplasia due to anovulation.

AUB- P0A0L0M1- C0O1E0I0N0




DIAGNOSIS



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HEAVY MENSTRUAL BLEEDINGDIAGNOSIS: HISTORY AND PE

• A thorough and methodical history is necessary in the diagnosis of AUB

• Complete physical examination strongly advised on all patients to identify any structural pathology or systemic disease as the etiology for AUB




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HEAVY MENSTRUAL BLEEDINGDIAGNOSIS: BLOOD TESTS

1. Pregnancy should be excluded in women of reproductive age

2. An initial CBC with platelet count, PT, PTT are indicated for all adolescents with acute HMB including adult patients with positive screening history for bleeding disorder




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3. Coagulation tests should be considered in women with HMB since menarche, and/or have personal or family history suggestive of coagulopathy

*a disorder of hemostasis in pxs with HMB may be diagnosed in90% of cases based on the ff circumstances:

HMB since menarche

One of the following:Postpartum hemorrhagesurgical-related bleedingbleeding associated with dental work

Two or more of the followingBruising 1-2x/monthEpistaxis 1-2x/monthFrequent gum bleedingFH of bleeding symptoms




Part I I I GENERAL GYNECOLOGY626

DIAGNOSTIC APPROACH

When a woman presents with a complaint of abnormal bleed-ing, it is essential to take a thorough history regarding the frequency, duration, and amount of bleeding, as well as to inquire whether and when the menstrual pattern changed. This history is important for describing the menstrual abnor-mality as oligomenorrhea, polymenorrhea, heavy menstrual bleeding, or intermenstrual bleeding. History and physical examination provide clues about the diagnosis of ovulatory disorders and other systemic illnesses. Providing the woman with a calendar to record her bleeding episodes is a helpful way to characterize definitively the bleeding episodes. A num-ber of commercially available smart phone applications exist to track abnormal bleeding conveniently, although none of these have been validated. Symptoms present for the major-ity of the preceding 6 months are considered chronic, but symptoms lasting 3 months sufficiently indicate the need for investigation.

Because there is a poor correlation between a woman’s estimate of the amount of blood flow and the measured loss, as well as great variation in the amount of blood and fluid absorbed by different types of sanitary napkins and tampons (and by the same type in different women), objective criteria should be used to determine if menorrhagia (blood loss >80 mL) is present.

As direct measurement of MBL is not generally possible, indi-rect assessment by measurement of hemoglobin concentration, serum iron levels, and serum ferritin levels are useful. The serum ferritin level provides a valid indirect assessment of iron stores in the bone marrow. Additional useful laboratory tests include a sensitive β-hCG level determination and a sensitive TSH assay, as well as PRL. If PCOS is suspected, androgen level measure-ments may be considered but are not necessary.

For adolescent girls with heavy menstrual bleeding, as well as older women with the constellation of systemic disease, easy bruising and petechiae, a coagulation profile including platelet count, prothrombin time, von Willebrand factor, and

ristocetin cofactor should be obtained to rule out a coagula-tion defect. Once thought to be extremely rare as a cause for abnormal bleeding, studies have found a fairly high preva-lence of coagulation disorders in women presenting with heavy menstrual bleeding. Most abnormalities are platelet related. The single most common abnormality is a form of von Willebrand disease. It has been estimated that the preva-lence of von Willebrand disease, the most common of these bleeding disorders, is 11% in women with heavy menstrual bleeding (Dilley, 2001). von Willebrand factor is responsible for proper platelet adhesion and protects against coagulant factor degradation. History is essential before a comprehen-sive hematologic workup is undertaken. This includes a his-tory of menorrhagia, family history of bleeding, epistaxis, bruising, gum bleeding, postpartum hemorrhage, and surgi-cal bleeding. In the absence of these clues, a comprehensive workup is probably unnecessary at the outset but should be considered in cases refractory to treatment. A hematologist should be consulted to assist in confirming the diagnosis and to suggest possible treatment (Fig. 26.6).

If the woman has regular cycles, it is helpful to determine whether she is ovulating. However, if bleeding is very irregu-lar, it may be difficult to determine the phase of the cycle to document ovulatory function by means of serum progester-one level. Patients with chronic anovulation are at increased risk for endometrial hyperplasia and malignancy. If there is an enhanced risk for endometrial disease on the basis of history, endometrial sampling is indicated. Endometrial sampling is also recommended in patients with heavy menstrual bleeding over the age of 45 (NIH Clinical Excellence, 2007). Sampling is most often performed with a 3 mm Pipelle in the office, with little or no anesthesia. Sampling should include a measurement of the uterine length and subjective assessment of the quantity of tissue. When office endometrial biopsy is not possible or if the tissue sample is insufficient, dilation and curettage (D&C) should be performed under anesthesia. The sensitivity of endo-metrial biopsy was 68% when compared with hysterectomy specimens and was 78% when compared with D&C in one

Adults with HMB and h/o either

One of the following Two of the following

Testing

Figure 26.6 Diagnostic approach to adults with abnormal uterine bleeding due to coagulopathy. (Data from Kouides PA, Conard J, Peyvandi F, et al. Hemostasis and menstruation: appropriate investi-gation for underlying disorders of hemostasis in women with exces-sive menstrual bleeding. Fertil Steril. 2005;84[5]:1345-1351.)

10 100 1000

Menstrual blood loss (mL)

F 2α/

E ra

tio

r = –0.7P < .0005

10.0

5.0

2.5

0

–2.5

Figure 26.5 Correlation between ratio of endogenous concentra-tions of prostaglandin F2alpha and prostaglandin E and menstrual blood loss (MBL); normal secretory endometrium; persistent endo-metrium. (From Smith SK, Abel MH, Kelly RW, et al. The synthesis of prostaglandins from persistent proliferative endometrium. J Clin Endocrinol Metab. 1982;55[2]:284-289.)

Obstetrics & Gynecology Books Full




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4. Female hormone testing (E2, progesterone, LH, FSH, ) should not be routinely done on women with HMB

5. Thyroid screening should only be obtained in the presence of signs and/or symptoms of thyroid disease.




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HEAVY MENSTRUAL BLEEDINGDIAGNOSIS: IMAGING PROCEDURES

1. Ultrasound is the first line diagnostic tool for identifying structural abnormalities

2. Saline infusion sonography (SIS) is a useful tool in providing a more accurate evaluation of the uterus with intracavitary lesions.




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HEAVY MENSTRUAL BLEEDINGDIAGNOSIS: OTHERS

1. Hysteroscopy should be performed when the ultrasound results are inconclusive (eg to determine the exact location of a fibroid or the exact nature of an abnormality), or when focal lesions are seen within the endometrium

2. Outpatient endometrial biopsy should be the first line diagnostic tool to use when assessing women with HMB




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HEAVY MENSTRUAL BLEEDINGDIAGNOSIS: OTHERS

The following are indications for endometrial biopsy:

1. Age > 402. Risk factors for endometrial cancer3. Failure of medical treatment4. Breast cancer patients on tamoxifen with AUB




MANAGEMENT



TREATMENT• In the absence of an organic cause for excessive uterine bleeding, it is preferable to use medical instead of surgical treatment, especially if the woman desires to retain her uterus for future childbearing or will be undergoing natural menopause within a short time.

• the type of treatment depends on whether it is used to stop an acute heavy bleeding (acute AUB) episode or is given to reduce the amount of MBL in subsequent menstrual cycles (Chronic AUB)




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HEAVY MENSTRUAL BLEEDINGMEDICAL MANAGEMENT

Hormonal:1. Levonorgestrel-releasing intrauterine system (LNG-IUS)2. Combined oral contraceptives (COCs)3. Progestins4. Danazol and GnRH

Non-hormonal:1. Anti-fibrinolytic agents2. Nonsteroidal anti-inflammatory drugs (NSAIDs)




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1. LNG-IUS is an effective treatment for HMB compared to placebo, other medications, endometrial ablation and hysterectomy. Strong, ++

2. LNG-IUS and hysterectomy have similar patient satisfaction after treatment on 5-yr follow-up. Strong, ++++

3. COC is comparable to mefenamic acid, danazol and naproxen sodium Strong, +




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4. Estradiol valerate/dienogest (E2V/DNG) is more effective than placebo in reducing HMB. Strong, +++

5. Cyclic progestogen given for 21 days for ovulatory bleeding results in a significant reduction in blood loss, although it is not superior over other medical therapies (NSAIDs, tranexamic acid, danazol and LNG-IUS) Strong, +++

6. Micronized progesterone is more effective than norethindrone in treating AUB Strong, ++++




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7. Danazol and GnRH agonist will reduce HMB and may be used in cases of failed medical treatment, or when such treatments are contraindicated Strong, ++++

8. Antifibrinolytic agents cause a greater reduction in HMB versus placebo or other medical treatments ( NSAIDs, oral progestogens) Strong, ++++

9. NSAIDs reduce HMB when compared with placebo, but are less effective than tranexamic acid, danazol, or LNG-IUS. Limited evidence show no difference in efficacy between NSAIDs and oral progestogens or COCs. Strong, ++




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HEAVY MENSTRUAL BLEEDINGSURGICAL MANAGEMENT

1. Dilatation and curettage is not recommended in the surgical management of HMB. Strong, +

2. Endometrial ablation may be offered as an initial treatment for HMB in women who are not desirous of future pregnancy, in the absence of any structural or histologic abnormality. Strong, +++

3. Women undergoing hysterectomy had better control of bleeding compared to oral medication or LNG-IUS. However it can cause serious complications and thus should not be used as first line treatment for HMB. Strong, ++++




mdedge.com/obgmanagement Vol. 30 No. 8 | August 2018 | OBG Management 39

FAST TRACK

Ulipristal acetate was well tolerated and superior to placebo in the rate of and time to amenorrhea in women with symptomatic leiomyomas

Ulipristal may be useful for managing AUB associated with uterine leiomyomasSimon JA, Catherino W, Segars JH, et al. Ulipristal

acetate for treatment of symptomatic uterine leiomyo-

mas: a randomized controlled trial. Obstet Gynecol.

2018;131(3):431–439.

Managing uterine leiomyomas is a common issue for gynecologists, as up to 70% of white women and more

than 80% of black women of reproductive age in the United States have leiomyomas.

Ulipristal acetate is an orally adminis-tered selective progesterone-receptor modu-lator that decreases bleeding and reduces leiomyoma size. Although trials conducted in Europe found ulipristal to be superior to pla-cebo and noninferior to leuprolide acetate in controlling bleeding and reducing leiomy-oma size, those initial trials were conducted in a predominantly white population.

Study assessed efficacy and safetySimon and colleagues recently conducted a randomized double-blind, placebo- controlled trial designed to assess the safety and efficacy of ulipristal in a more diverse population, such as patients in the United States. The 148 participants included in the

study were randomly assigned on a 1:1:1 basis to once-daily oral ulipristal 5 mg, ulipristal 10 mg, or placebo for 12 weeks, with a 12-week drug-free follow-up.

Amenorrhea achieved and quality of life improved The investigators found that ulipristal in 5-mg and 10-mg doses was well tolerated and supe-rior to placebo in both the rate of and the time to amenorrhea (the coprimary end points) in women with symptomatic leiomyomas. In women treated with ulipristal 5 mg, amenor-rhea was achieved in 25 of 53 (47.2%; 97.5% CI, 31.6–63.2), and of those treated with the 10-mg dose, 28 of 48 (58.3%; 97.5% CI, 41.2–74.1) achieved amenorrhea (P<.001 for both groups), compared with 1 of 56 (1.8%; 97.5% CI, 0.0–10.9) in the placebo group.

Ulipristal treatment also was shown to improve health-related quality of life, including physical and social activities. No patient discontinued ulipristal because of lack of efficacy, and 1 patient in the placebo group stopped taking the drug because of an adverse event. Estradiol levels were main-tained at midfollicular levels during ulipris-tal treatment, and endometrial biopsies did

Consider quality and cost in AUB treatment

AUB continues to be a significant issue for many women. As women’s health care providers, it is important that we deliver care with high value (Quality ÷ Cost). Therefore, consider these takeaway points:• The LNG-IUS consistently delivers high value by affecting both sides of this equation. We

should use it more.• Although we do not yet know what ulipristal acetate will cost in the United States, effective

medical treatments usually affect both sides of the Quality ÷ Cost equation, and new medications on the horizon are worth knowing about.

• Last, efficiency with office-based hysteroscopy is also an opportunity to increase value by improving biopsy and visualization quality.

O BG M anagem ent | August 2018 | Vol. 30 N o. 8 m dedge.com /obgm anagem ent



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