Women's Health III: Abnormal Uterine Bleeding

What does Varney have to say about abnormal uterine bleeding?

When a woman's menstrual cycle varies from it's typical characteristics it may indeed be irregular; but it is not necessarily a cause for alarm or an indication of pathology. Though some presentations always require prompt investigations (e.g. postmenopausal bleeding), occasional variations in menstrual cycles are normal and may be due to changes in routine like travel or moves, nutrition, exercise, illness, emotional, stress or other unknown causes. Not every menstrual change warrants immediate further investigation.

You are caring for a 47 year old woman who presents to the office reporting 3 episodes in the last 6 months where she had "two periods" in a month and in some of the episodes the bleeding lasted two weeks. She is generally well, has no chronic medical problems and takes no medications. What is the most appropriate next step? a) Endometrial biopsy b) Transvaginal ultrasound c) Hysteroscopy with biopsy if indicated d) Offer medical management of bleeding and advise further testing is indicated if abnormal bleeding persists

a) Endometrial biopsy

You are caring for a 57 year old postmenopausal woman who had an episode of light vaginal bleeding that lasted 4 days. She is just 2 years postmenopausal and has a history of PCOS and obesity. Which of the following is the BEST immediate plan for this patient? a) Endometrial biopsy, with reflex to transvaginal ultrasound if biopsy is normal b) Transvaginal ultrasound and referral for biopsy if endometrial thickness is >5 mm c) Sonohysterography d) Referral to gynecologic oncology

a) Endometrial biopsy, with reflex to transvaginal ultrasound if biopsy is normal

What is the mainstay of AUB treatment?

Hormones! Progestin only therapies include: - LNG-IUC - Medoxyprogesterone acetate (pill) - Depot medoxyprogesterone acetate (injection) - Megestrol acetate - Norethindrone acetate Combined contraceptives include: - Oral pills (not one formulation over another) - Transdermal patches - Vaginal ring - Cyclic or continuous use

Why are we concerned about anovulation?

If you are not ovulating you are not getting that source of progestin. If you don't have a source of progestin you get chronic, unopposed estrogen stimulation of the endometrial lining and you get a thickened, unstable endometrium. People with chronic anovulation are at risk later in life for developing endometrial hyperplasia and cancer - Ex. Obesity, PCOS

What did the systematic review by Matteson et al. (2013) find about AUB treatment?

Included RCTs, goal was to look at AUB-E and AUB-O but there was not enough available data to make recommendations for AUB-O In terms of reducing blood loss: Remember there might be other factors to consider - Found LNG-IUC, combined OCPs, extended cycle progestins, tranexamic acid, and NSAIDs were all effective treatments - LNG-IUC, combined OCPs and antifibrinolytics were all superior to luteal phase progestins - LNG-IUC superior to OCPs and NSAIDS - Antifibrinolytics superior to NSAIDs

Irregular menstrual bleeding= >___ days of variation in 1 year

Irregular menstrual bleeding= >*20* days of variation in 1 year

Our goals as providers are: *PRIMARY:* Rule out the can't misses, in the case of AUB that is usually pregnancy and cancer. Prevent complication from acute bleeding. *SECONDARY:* Look for underlying cause of abnormal bleeding, such as ovulatory dysfunction, myoma or polyps. Treatment goals are to regulate menses, minimize blood loss, improve quality of life, and protect the endometrium from future hyperplasia/cancer.

Just a fact

Talk to me about the pathophys of a "normal" menstrual cycle

Menses= The shedding of the endometrium which occurs because progesterone decreases as the corpus luteum shrivels up Regular ovulation= regular period

Of all the PALM-COEIN terms, which two do we care about the most?

Most important: AUB-E and AUB-O *O= ovulatory problem*--> irregular bleeding most common, not going to be on a cyclic schedule *E= endometrial related*--> regular but heaving bleeding

What else can cause anovulation besides PCOS?

Other conditions that interfere with HPO axis: - Athletes - Eating disorders

Define: Abnormal uterine bleeding

Overarching term used to describe any departure from normal menstruation from a normal menstrual cycle Old terminologies that should be discarded: - Menorrhagia, metrorrhagia, and most other terms of Greek or Latin origin - The term 'Dysfunctional uterine bleeding' --> Previously the catch all term when other diagnosis were excluded. Now we can further classify these by the mechanism responsible

What's the sitch with people on OCPs getting their period? Is it medically necessary?

Regular ovulation= regular period --> According to this definition, no one on birth control should get a period! - People who created OCPs wanted patients to still "feel like a woman" - There is no medical benefit of having a period while on OCPs --> Important to explain this to patients

You are caring for a 29-year-old sexually active woman who presents to the office reporting 10 days of heavy vaginal bleeding. At one point she bled through her clothes but now is changing her pad about ever 2 hours. She states in the last year her menses have been on time but are increasingly heavy and crampy. She has no prior episodes of bleeding like this. She is otherwise well with a negative review of symptoms. No medications or PMH. She recently had a negative STI screen. Her office pregnancy test is negative and vital signs are normal. What is the best combination of studies to order? a) H/H, TSH and coagulation studies b) H/H, TSH and transvaginal ultrasound c) Preoperative labs as patient is a good candidate for D&C referral d) No further evaluation is indicated at this time

b) H/H, TSH and transvaginal ultrasound

____-____% of female bodied individuals with anovulatory cycles in the reproductive years have underlying PCOS

*6-10%* of female bodied individuals with anovulatory cycles in the reproductive years have underlying PCOS

What are surgical options for treating AUB?

*Hysterectomy*- definitive *D&C* - May be used as diagnostic tool/treatment intervention by some OB/GYNs but the evidence suggests more appropriate diagnostic tools and treatments *Endometrial Ablation* - Effective but not definitive- not uncommon to need future hysterectomy, particularly in younger women - ACOG PB cites a study that showed it was not better than LNG-IUC - Must have completed childbearing - can lead to complications - Can impair future ability to evaluate the uterine cavity/endometrium - Have been cases of endometrial cancer diagnosed after procedure

What are some times you'd get an endometrial biopsy instead of an ultrasound?

- Any women with post menopausal bleeding - Any women over the age of 45 with persistent AUB and younger women with persistent AUB and risk factors for hyperplasia or cancer (Loren would go as young as 35) - Women with atypical endometrial cells found on pap test - Women with AUB who are taking tamoxifen - To evaluate unscheduled bleeding in women on HRT

What's on your differential for heavy or irregular bleeding in pts ages 13-18?

- Birth control (stopping/starting, adherence) - STIs - Pregnancy - PCOS - Eating disorders/ other causes of anovulatory bleeding - Anovulation that is normal at beginning of menses - *Bleeding disorders* (Only age group where we are considering coagulation because this is when it will present)

What's on your differential for heavy or irregular bleeding in pts ages 19-39?

- Birth control (stopping/starting, adherence) - STIs - Pregnancy - PCOS - Eating disorders/ other causes of anovulatory bleeding - Anovulation that is normal at beginning of menses - *Fibroids* (More common in 2nd half of life) - *Thyroid abnormalities* (Always order a TSH, especially if it has been abnormal for multiple cycles)

What's on your differential for heavy or irregular bleeding in pts ages 40 to menopause?

- Birth control (stopping/starting, adherence) - STIs - Pregnancy - PCOS - Eating disorders/ other causes of anovulatory bleeding - Anovulation that is normal at beginning of menses - Fibroids - Thyroid abnormalities - *Endometrial hyperplasia/ cancer*

What do FIGO and ACOG have to say about when endometrial biopsy should be first line?

- FIGO recommends biopsy as first line in women with 'enhanced risk of hyperplasia or neoplasia or both' - ACOG supports FIGO - ACOG recommends it as first line in women > 45 years old - ACOG recommends it in women <45 who have a history of unopposed estrogen exposure (such as women with PCOS or obesity) as well as in women with failed medical mgmt or persistent AUB - Loren has never done a biopsy in patients <30

When are endometrial biopsy samples good and when might they miss things? Essentially what are the pros and cons of endometrial biopsies?

- Highest accuracy is when a good sample is obtained and abnormality is global as they only sample a small percentage of the endometrial surface - If cancer occupies <50% of cavity or is limited to a polyp it can be missed by biopsy - *Better for ruling in than ruling out disease* --> Thus they are not the endpoint - further evaluation is need for persistent symptoms, when sample is insufficient or non-diagnostic - If negative, you can be assured but not fully reassured. Could be a focal area that was missed via biopsy - *Good for diagnosing hyperplasia and cancer only*

In order to assess for endometrial hyperplasia or endometrial cancer, we need to evaluate the uterus. How did this used to be done and what do we use now?

- Historically D&C was gold standard --> "blind" D&C no longer has evidence-based role in evaluating/managing AUB - 1990s- in office "blind" endometrial biopsy gains widespread popularity - Extensive research in the last 2 decades on ultrasound and now has clearly established role - Beyond ultrasound, studies look at role of sonohysterography and hysteroscopy *Two major options today: Ultrasound or biopsy*

Some stats we hopefully don't need to know about endometrial hyperplasia: - In the absence of therapy ____-____% will progress to cancer over a 13 year period - Most likely to progress to cancer are those with atypia who are not treated - Less than ____% without atypia progress - 30% with atypia progress and up to _____% women with atypia have concurrent adenocarcinoma

- In the absence of therapy *2-23%* will progress to cancer over a 13 year period - Most likely to progress to cancer are those with atypia who are not treated - Less than *5%* without atypia progress - 30% with atypia progress and up to *50%* women with atypia have concurrent adenocarcinoma

Talk to me about risk of endometrial cancer in relation to age/ menopause status

- Mean age of diagnosis is 60, primarily a postmenopausal disease - Incidence of Endometrial hyperplasia in premenopausal women reported to be 2-10% - 10-20% cases of endometrial cancer occur before menopause, but most of these women are between ages 40 and 50. *Less than 2% endometrial cancer occurs in women before 45* - When seen in younger women, it is usually in women with significant risk factors

What are some risk factors for endometrial hyperplasia and endometrial cancer?

- Obesity - PCOS/Chronic Anovulation (Up to 3 fold risk. These women are at risk at a younger age) - Estrogen Therapy - Tamoxifen - HNPCC (Lynch Syndrome) - Diabetes - Hypertension - History of infertility and nulliparity - *Age*

When in the evaluation process can abnormal uterine bleeding be treated?

- Perhaps right away in patients at very low risk for hyperplasia, neoplasia, or structural abnormality such as adolescents • Your approach will be different for patients presenting with acute versus chronic abnormal bleeding - Patients with AUB over 45 and younger pts w/risk factors should have complete diagnostic evaluation before starting therapy

4-24% of pts with post-menopausal bleeding will have cancer--> this means 75% of them don't have cancer. Reassuring, but need to rule out cancer What else can cause postmenopausal bleeding besides cancer?

- Polyps - Infection - Atrophy (everything atrophies i.e. not just the vulva)

What's the research out there on the sensitivity of an endometrial biopsy?

- Some studies show as high at 96% sensitivity for cancer, slightly lower for atypical hyperplasia (81)% - ACOG PB cites a meta-analysis showing a sensitivity of 68-78% and a sampling failure rate of 0-54% (due to range in quality of the sample) - In a systematic review, in 1013 subjects 3 endometrial cancers were missed in women with normal sufficient biopsy and another in an insufficient sample

What is a transvaginal ultrasound good at finding?

- Structural issues (fibroids etc.) - Measuring thickness of endometrium - Ovarian cysts and masses - Polyps (so so, not great) --> polyps are almost always benign. They are soft and collapse easily so can be difficult to see

What are some of the factors that dictate the treatment plan for AUB?

- The cause of abnormal bleeding - The severity of the bleeding - Patient's desire for contraception and future fertility - Perimenopause status - Existing health conditions - does the patient have cautions or contraindications to hormonal therapy? - What is patient's past experience with hormonal therapy?

What are some nonhormonal options for AUB treatment?

- Weight loss --> Does work to return patients to ovulation - NSAIDs -->Will lighten bleeding but does not help it become more consistent - Tranexamic Acid

What are some times you'd get an ultrasound instead of a biopsy?

- Women with an enlarged uterus or pelvic mass on exam - Women with AUB who are young and without risk factors for hyperplasia or cancer --> *Especially if they have failed medical management*. Women more likely to have a structural abnormality (e.g menses are regular but heavy or painful) - As triage in postmenopausal women to look at thickness of endometrium - When endometrial biopsy is insufficient or can't be obtained - If a woman is having AUB and is pregnant - Persistent bleeding after normal endometrial biopsy

Amenorrhea= menstrual bleeding absent for a ____ day period or greater

Amenorrhea= menstrual bleeding absent for a *90* day period or greater

When is anovulation "normal?"

Anovulation is "normal" at the "extremes" of the reproductive years --> The first 2-3 years after menarche in and in the years leading to menopause (Varney describes many people as seeing cycle changes 4-8 years before menopause)

So if people on OCPs aren't ovulating why aren't we concerned about that?

Because of the progestin component--> unopposed estrogen is the problem

What patterns of abnormal bleeding are suspicious for hyperplasia or cancer?

Bleeding that is *more suspicious* for endometrial cancer is characterized by the following: non-cyclic (anovulatory); unpredictable; and abnormal pattern persisting for at least 3 months Bleeding that is *less suspicious* tends to be cyclic (ovulatory, monthly) but may be longer or heavier than normal. It is often due to a structural abnormality rather than anovulation *Postmenopausal bleeding is always suspicious* --> must do a work up

What's one of the drawbacks of transvaginal ultrasounds?

Endometrial thickness changes through the cycle and there is no upper limit of what is not ok--> *measuring endometrial thickness in premenopausal women does not work*. Only works in postmenopausal women

True or false: ACOG says AUB-O is an endocrine problem that should be managed medically and surgical therapy is rarely indicated though there are exceptions

True

True or false: Heavy menstrual bleeding can be regular or irregular

True

What does Loren have to say about the usefulness of PALM-COEIN in practice?

Used to help classify, but not used on a day to day basis in clinic In Loren's practice, the place to start is: - Pregnancy - Infection - Hormonal contraception related bleeding - These are the most common causes of an acute change in bleeding in the GYN setting - It does highlight the many benign causes (polyps, fibroids, anovulation) of AUB while also highlighting a major "can't miss":

Frequent menstrual bleeding= more than ____ episodes in a ____ day period

Frequent menstrual bleeding= more than *4* episodes in a *90* day period

If an exam asks you about a first line imaging test in a GYN setting, you always pick...

Transvaginal pelvic ultrasound! You will see mention of times where SIS, hysteroscopy, or MRI are mentioned as tools for better visualization or characterization but they are not primary tests (you will generally not be ordering these, they should be left to the specialists you refer patients to)

You are caring for a 24-year-old sexually active woman reporting irregular menses. On further questioning it appears she has about 5-6 days of moderate bleeding that occurs every 4-6 weeks. She has no pain and no other abnormal bleeding. She is well and has no chronic medical problems. She has never been on birth control, has no other complaints today, and reports she is healthy and takes no medications. She is up to date with well woman care. After a basic in office evaluation, what would be the next best step? a) Recommend transvaginal ultrasound before offering therapy b) Recommend endometrial biopsy before offering therapy c) Offer hormonal management of bleeding if desired today and follow up depending on further bleeding d) Have patient keep a bleeding diary for three months before offering further evaluation

c) Offer hormonal management of bleeding if desired today and follow up depending on further bleeding