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Candace, a 49-year-old office administrator, comes to Abnormal uterine bleeding (AUB) is a condition that
see you for her annual periodic health examination. She affects approximately 30% of women during their repro-
reports that her periods are becoming more irregular ductive years.1 It is a considerable health care burden for
and unpredictable. Previously her menstrual cycle was women and has a definite effect on quality of life. Health
30 days, but during the past 6 months it has been 24 to care practitioners deal with this problem frequently.2
40 days. Her menses have been heavy since her second Abnormal uterine bleeding has various definitions
pregnancy 21 years ago and are getting worse. During and classifications. It can be loosely defined as a varia-
the first 2 days of her period she has to change a super- tion from the normal menstrual cycle. The variation can
size tampon and pad (used simultaneously) every 1 to 2 be in regularity, frequency, duration of flow, or amount
hours to prevent leaking onto her clothing; there is asso- of blood loss. Often the bleeding is heavy, which is
ciated mild cramping but no appreciable blood clots. Her excessive menstrual blood loss which interferes with
periods have become so bad that she often needs to take a womans physical, social, emotional and/or material
time off work during this time. She denies any spotting quality of life.3 The terms menorrhagia and metrorrhagia,
between periods or bleeding after coitus. She has occa- as well as other combinations, have become outdated.
sional hot flashes with no other menopausal symptoms. Abnormal uterine bleeding might be classified as pre-
Candace recently started taking 25 mg/d of hydro- menopausal, perimenopausal, or postmenopausal. In
chlorothiazide for essential hypertension. She has no premenopausal and perimenopausal women, AUB can
other medical conditions. For menstrual cramps she takes be further categorized as ovulatory and anovulatory.
325 mg of acetaminophen every 6 hours when needed and Ovulatory bleeding occurs at regular menstrual intervals
200 mg of ibuprofen once daily when needed. She has no and is typically associated with premenstrual symptoms
known allergies. Surgical history includes a tonsillectomy and painful periods. Anovulatory bleeding is more com-
as a child and tubal ligation. Her obstetric and gyneco- mon around menarche and menopause and is typified
logic history includes a monogamous relationship with her by heavy, irregular, and prolonged periods. There is a
husband and gravida 2, para 2both were spontaneous greater association of endometrial hyperplasia and can-
vaginal deliveries with no complications or postpartum cer with anovulatory bleeding in perimenopausal and
hemorrhage. Candace is a non-smoker and drinks alco- menopausal women.2
hol only occasionally. Her family history is remarkable for
hypertension in her mother; there is no family history of Causes and treatment goals
breast cancer or coagulopathies. Her mother had a hyster- There are many causes of AUB, including anatomic, sys-
ectomy at age 40 for fibroids. temic, and drug-related causes.4 Once investigations
Candaces physical examination reveals normal vital have determined the cause and ruled out premalignant
signs and a body mass index of 32 kg/m2. All physi- or malignant conditions, many of the treatment principles
cal examination findings are unremarkable except for are the same. A detailed chart about the causes of and
a bulky uterus found during bimanual examination. treatments for AUB is available from CFPlus.* The over-
Results of a recent Papanicolaou test were normal. all treatment goals for AUB include managing contributing
You perform an endometrial biopsy and order tests medical conditions, treating anemia if present, restoring
for complete blood count and thyroid-stimulating hor- predictability of bleeding or stopping menses, encouraging
mone levels, a urine test for chlamydia and gonorrhea, achievement of healthy body weight, and minimizing the
and a pelvic ultrasound. effect of abnormal bleeding on a womans daily activities.4
For our patient Candace, it is important to determine
her expectations regarding her condition in order to
This article is eligible for Mainpro-M1 develop a patient-centred management plan. Women
This article is eligible for Mainpro-M1 credits. To earn
credits.
credits, go To earn credits,and
to www.cfp.ca to www.cfp.ca
goclick andlink.
on the Mainpro click often do research about treatment options and have
on the Mainpro link.
La traduction en franais de cet article se trouve *The RxFiles chart on Abnormal Uterine Bleeding is avail-
www.cfp.ca dans la table des matires du numro daot 2015 able at www.cfp.ca. Go to the full text of this article and
la page e367. click on CFPlus in the menu at the top right-hand side of
the page.
Vol 61: august aot 2015 | Canadian Family Physician Le Mdecin de famille canadien 693
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spoken to friends and colleagues. Candace might be nonsteroidal anti-inflammatory drugs (NSAIDs), and
assuming that she will be offered a hysterectomy as her antifibrinolytics (Table 1).6
mother was in the past.
Hormonal therapy. Hormonal options available for the
Candaces investigation findings are normal. At the treatment of AUB include the levonorgestrel intrauterine
next visit, you review these findings and discuss treat- system (LNG-IUS), combined oral contraceptives (COCs),
ment options. depot medroxyprogesterone acetate (DMPA), and pro-
gestin-only pills.6 Hormonal options are generally the
Treatment options treatment of choice for AUB, as they assist in regulat-
Candace is in the perimenopausal category of AUB. ing the menstrual cycle and decrease the likelihood of
Because her investigation findings are normal, phar- unscheduled, prolonged, or heavy bleeding episodes.7
macologic treatment should be considered first line 5 More women experience adverse hormonal effects with
(Figure 1), and options include hormonal therapy, COCs than with the LNG-IUS owing to increased systemic
Perimenopausal AUB
YES
Tranexamic acid
YES
Contraindications to COCs* NSAIDs
Progestin-only
NO
contraceptives
(DMPA, LNG-IUS,
progestin-only pill)
Proceed with 3- to 6-mo trial of therapy based on
patient factors (all nonhormonal therapies can be
combined with hormonal therapies)
NO
AUBabnormal uterine bleeding, COCcombined oral contraceptive, DMPAdepot medroxyprogesterone acetate, HTNhypertension,
LNG-IUSlevonorgestrel intrauterine system, NSAIDnonsteroidal anti-inflammatory drug, VTEvenous thromboembolism.
*Contraindications to COCs include history of stroke or VTE, uncontrolled HTN, active liver disease, or history of breast cancer.
Adapted from Towriss.6
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absorption of the medication.8 These complaints include LNG-IUS include irregular bleeding or spotting (espe-
nausea, headache, breakthrough bleeding, fluid retention, cially in the first 3 to 6 months), cramping, and expul-
breast tenderness, and mood changes.7 sion of the device. A Cochrane meta-analysis review
Ideally, patients should use hormonal options for a trial comparing medical treatments with surgical treatments
period of 3 to 6 months to determine their effectiveness.4 (endometrial destruction and hysterectomy) revealed
Levonorgestrel intrauterine system: The LNG-IUS is that the LNG-IUS was less effective for reducing bleed-
designed to release 20 g/d of levonorgestrel for up ing but provided an equivalent improvement in quality
to 5 years.9 It has been shown to decrease menstrual of life.11 A low-dose LNG-IUS (6 g/d for 3 years) is now
blood loss by 86% at 3 months and 97% at 12 months, available in Canada; however, it is not officially indi-
with 20% to 80% of patients becoming amenorrheic cated for treatment of AUB.12
by 1 year.8,9 Dysmenorrhea and pelvic pain might also Combined oral contraceptives: Combined oral con-
improve. Evidence suggests that the LNG-IUS is the most traceptives are another available hormonal option.
reliable option in obese and overweight women.10 Some There is no evidence to suggest that one type of COC
of the most common complaints women have with the is more effective than another,6 but selecting a product
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with at least 30 g of ethinyl estradiol is recommended. nonhormonal options such as NSAIDs or antifibrinolyt-
Combined oral contraceptives decrease menstrual blood ics in order to optimally manage AUB.13 Antifibrinolytics
loss by 40% to 50% and improve dysmenorrhea.13 There provide symptomatic relief only, and NSAIDs are less
are many prescribing regimens described in the litera- effective than hormonal options. 6 Nonsteroidal anti-
ture, with the most aggressive being 1 tablet 3 times inflammatory drugs can increase bleeding in general;
daily until bleeding ceases, followed by tapering to once however, they cause a paradoxical reaction when treat-
daily continuously for 3 months before providing a pill- ing AUB. Nonsteroidal anti-inflammatory drugs decrease
free interval. However, starting with once-daily dosing total prostaglandin production to promote uterine vaso-
with or without the pill-free interval is also appropriate.5 constriction and actually decrease bleeding in AUB.6 In
The use of monophasic COCs in a continuous dosing most cases the benefit of using NSAIDs for AUB actually
regimen for up to 3 to 6 months has been demonstrated outweigh the risks. As there are no substantial differ-
to be effective in the treatment of AUB; however, there ences in the effectiveness of different NSAIDs,17 choice
is limited evidence to support the use of continuous tri- might be based on cost and tolerability.
phasic COCs.14 Transdermal patches or a vaginal ring,
used continuously or in a cyclic fashion, are also appro- Surgical treatment. Surgical treatment is not consid-
priate options for AUB treatment; however, limited evi- ered first line in Candaces case owing to its invasive
dence is available for this indication. When prescribing, nature. Additionally, she has not failed medical therapy
it is important to review all of a patients potential risks yet, has no contraindications to drug treatment, and she
of thromboembolism (Table 1).6 is not anemic.5 It is worth noting that approximately 50%
Our patient Candace does not have any contraindica- of women who receive drug therapy eventually choose
tions to COCs, but she should be educated about signs surgical therapy owing to refractory bleeding or a desire
and symptoms of venous thromboembolism if this is her for definitive treatment.18,19
treatment of choice.
Depot medroxyprogesterone acetate:Intramuscular You share with Candace that younger patients with AUB
administration of a 150-mg dose of DMPA every 12 often prefer COCs and NSAIDs but that perimenopausal
weeks is a suitable option for the management of AUB. women usually prefer the LNG-IUS.20-22 You also explain
Although there are no trials assessing the effective- to her that the LNG-IUS is the most reliable hormonal
ness and safety of DMPA in AUB, it has been shown to choice considering her increased body mass index.
decrease menstrual blood loss by 60% to 70%, with most Candace feels cautious about the LNG-IUS (despite
women becoming amenorrheic at 1 year15 when using the fact the endometrial biopsy was well tolerated) and
it for contraception. It can also cause irregular break- decides to try a COC. You prescribe a 30-g ethinyl
through bleeding, breast tenderness, nausea, mood estradiol formulation and plan for a follow-up visit to
symptoms, and weight gain. Additionally, DMPA has review this treatment in 3 months time. You also pre-
been shown to cause a small decrease in bone mineral scribe 1000 mg of naproxen to take the day before men-
density, about 1.5%,16 which is reversible upon discon- ses, then 500 mg twice daily for 3 to 5 days to both help
tinuation. Depot medroxyprogesterone acetate could with symptoms and decrease bleeding.
be considered for Candace at 49 years of age, but if However, 2 months later Candace returns telling you
she chooses this option she should be educated about that her periods are lighter but lasting 9 days, which she
appropriate diet and exercise to assist with bone health. finds unacceptable. She would like to revisit other treat-
Progestin-only pills: Progestin-only pills are another ment options.
hormonal option available for the treatment of AUB. A
10-mg daily dose of medroxyprogesterone acetate from Candace might achieve better control of her flow if
cycle days 5 to 26 (21 days) or a 100-mg daily dose of she continues the initial COC for a few more months.
micronized progesterone from days 14 to 28 (luteal phase) Changing the COC formulation to one with a higher
achieved menstrual regularity in only 50% of women.15 estrogen component or to another type of progestogen
Luteal phase progestin alone is usually not effective for might be helpful.20 There is no evidence as to which
heavy menstrual bleeding. The long-cycle dosing (21 days) works best.6
has been shown to decrease heavy menstrual bleeding, but
hormonal adverse effects limit its practicality. Complicated Candace tells you that a friend at work has had good
prescribing regimens such as cyclic dosing can often lead success with the LNG-IUS and she would like to try
to nonadherence. Low-dose norethindrone (ie, 0.35 mg/d) this. You mention that the up-front cost is approximately
has not been studied for the management of AUB. $350, but that overall it is a cost-effective option at $70
a year. You insert the device without complication. You
Nonsteroidal anti-inflammatory drugs and antifibrinol- follow up with Candace in the clinic 3 months later. She
ytics. All of the hormonal options can be combined with is very pleased with the LNG-IUS. After having some
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