Download Abnormal Uterine Bleeding

Abnormal Uterine Bleeding:
Published on Cancer Network (http://www.cancernetwork.com)
Abnormal Uterine Bleeding:
May 01, 2005
By Jessica Miller, MD [1] and John R. Holman, MD, MPH [2]
Menstrual disorders are one of the most common complaints of women seen in primary care.
Abnormal uterine bleeding (AUB) is a broad term that encompasses bleeding at abnormal or
unexpected times or excessive flow at times of expected menses.
Menstrual disorders are one of the most common complaints of women seen in primary care.
Abnormal uterine bleeding (AUB) is a broad term that encompasses bleeding at abnormal or
unexpected times or excessive flow at times of expected menses.1 Excessive and unpredictable
cycles can cause iron deficiency anemia as well as psychological stress.
In this article, we review the principal causes of AUB, as well as approaches to evaluation and
treatment. Recommendations are made with reference to the strength of evidence (Box).
OVERVIEW
Normal menstruation occurs every 21 to 35 days and lasts approximately 4 to 6 days. Total blood
loss is approximately 30 mL. Menstrual flow that exceeds 80 mL is considered excessive, based on
the amount of blood loss that would produce anemia in a woman taking the recommended daily
allowance of iron.2
Table 1 -- Causes of
anovulation
Hypothalamic-pituitary immaturity
(adolescence)
Ovarian failure
Perimenopausal
Premature
Hyperandrogenic anovulation
Polycystic ovarian syndrome
Congenital adrenal hyperplasia
Androgen-producing tumors
Hypothalamic causes
Anorexia/bulimia
Strenuous exercise (endurance)
Hyperprolactinemia
Bradycardia
Hypothyroidism
Hyperthyroidism
Liver disease (estrogen metabolism
is impaired before coagulation is
affected)
Current obesity; previous obesity
with rapid weight loss
Medications
Metoclopramide
Ph
enot
hiazi
nes
Tri
cycli
c ant
idepr
essa
nts
Ciga
rette
smo
king
Page 1 of 7
Abnormal Uterine Bleeding:
Published on Cancer Network (http://www.cancernetwork.com)
Idiopathic
Despite many attempts to quantify blood loss, including pictorial charts and pad collection, the
assessment of abnormal uterine bleeding is primarily subjective.3 In one report, 14% of women with
menstrual blood loss of less than 20 mL reported heavy bleeding, while 41% of women with
menstrual loss of more than 80 mL described their bleeding as light to moderate.4 Of women who
report excessive menstrual flow, only half have measurable blood loss greater than 80 mL--the
formal criterion for excessive flow.5,6 Of women who meet this criterion, only two thirds have a
hemoglobin level below 12 g/dL and only 44% have low iron levels.4 Thus, not all women who meet
the criterion for excessive menstrual flow exhibit anemia and/or low iron levels.
Accurate diagnosis and effective medical management of women with AUB is critical. In one study,
10% of women scheduled for hysterectomy declined surgery when objective evidence showed that
their cycles were normal,6 and 14 of 17 women in a smaller study accepted reassurance and opted
not to have surgerywhen objective data showed that their blood loss was within the normal range
and posed no risk to their health.7 About 20% to 33% of women who undergo hysterectomies for
AUB have no anatomic abnormalities.8,9
Dysfunctional uterine bleeding (DUB) is a type of AUB that is not related to an anatomic condition,
systemic disease, or pregnancy.10 Many authors define DUB as occurring only with anovulatory
cycles; others consider ovulatory DUB to be a separate entity characterized by regular, predictable
cycles and excessive menstrual loss. Although the exact mechanism is unclear, ovulatory DUB is
thought to result from disruption of local hemostatic factors.11PREPUBERTAL GIRLS
Occasionally, newborn girls have a small amount of vaginal bleeding secondary to placental
estrogenic stimulation of the endometrium. This condition is self-limited; in the absence of trauma
and with a normal abdominal examination, only reassurance and follow-up are needed (strength of
recommendation [SOR] level C).1 After the newborn period, girls who present with vaginal bleeding
but without secondary sexual characteristics require a pelvic examination, occasionally under
anesthesia, to rule out a foreign body, vaginitis, genital trauma or, very rarely, malignancy (SOR
level C).1,12 In girls who manifest breast development or an unusual increase in height, an ovarian
source of estrogen should be ruled out with abdominal ultrasonography.1 An evaluation for
precocious puberty is recommended if a girl shows signs of pubertal development before age 8 years
(SOR level D).13ADOLESCENTS
AUB is the most frequent cause of urgent admission to the hospital among adolescent girls.3 By far
the most common cause of AUB in this age group is anovulation attributable to immaturity of the
hypothalamic-pituitary axis. However, other causes of heavy bleeding--including complications of
pregnancy and bleeding disorders--must be considered. Up to 80% of adolescents are anovulatory
for the first year after menarche, and about 50% of adolescents are anovulatory for the first 2 years
of menses.10,14 Persistence of anovulation beyond 2 to 3 years of menarche warrants further
investigation (SOR level C).1
Although anovulatory cycles are normal during the onset of menarche, most adolescents do not
experience excessive bleeding. The incidence of bleeding disorders among adolescents evaluated for
excessive bleeding is about 12% to 33%.6,15 One report found that 25% of adolescents who present
with a hemoglobin level of less than 10 g/dL had an underlying coagulation disorder.15 Another study
demonstrated that 13% of women of all ages who presented with menorrhagia had bleeding
disorders.16
Because the prevalence of bleeding disorders in adolescents is significant, screening with
coagulation studies (such as prothrombin time or partial thromboplastin time) and a platelet count is
warranted (SOR level B). Adolescents with significant menstrual blood loss--defined as a hemoglobin
level of less than 10 g/dL or bleeding that warrants hospitalization--should also have a ristocetin
cofactor assay of von Willebrand factor before hormone therapy is initiated (SOR level B).17,18
WOMEN OF REPRODUCTIVE AGE AND OLDER WOMEN
After pregnancy is ruled out, a detailed history of a patient's menstrual cycles is critical. Determine
the cycle length and bleeding duration, and attempt to quantify the amount of flow. Women often
describe their cycles as "irregular" whether they are experiencing intermenstrual bleeding or
menometrorrhagia.
Intermenstrual bleeding. This is a pattern of unpredictable, usually light, bleeding or spotting
between regular cycles. If a patient has a history of intermenstrual bleeding, ask about postcoital
bleeding, which may occur in the setting of cervicitis, polyps, or other cervical or vaginal lesions.
Page 2 of 7
Abnormal Uterine Bleeding:
Published on Cancer Network (http://www.cancernetwork.com)
Recurrent spotting at day 14 in a normal ovulatory cycle occurs in some women as the estrogen
level dips; in the absence of other risk factors, only reassurance is required (SOR level D).3
Table 2
Contraceptive modalities, including inertintrauterine devices (IUDs), progesterone-only
contraceptives, and combination oral contraceptive pills (OCPs), frequently cause intermenstrual
bleeding. Even one missed pill can cause breakthrough bleeding. An increased
progesterone-to-estrogen ratio can result in thinning and denudation of the endometrial lining.
Breakthrough bleeding has become more common with the use of lower doses of estrogen. However,
even in OCPs that contain higher doses, bleeding can occur as a result of the saturation of estrogen
receptors by progesterone, which greatly reduces the concentration of estrogen.19
The physical examination of a patient with intermenstrual bleeding includes a thorough inspection of
the perineal area to detect other possible causes of bleeding, including urinary or GI sources. The
speculum examination, in which all surfaces of the vaginal walls are viewed, also focuses on
identification of specific sites of potential blood loss. A cervix that is friable because of inflammation
is a frequent source of intermenstrual spotting. Therefore, in addition to cervical cultures and a
Papanicolaou smear, consider a potassium hydroxide evaluation and a saline wet slide preparation.
Depending on the patient's age and other risk factors, endometrial cavity evaluation for focal
hyperplasia or cancer may be warranted.
Metrorrhagia/menometrorrhagia. These conditions imply anovulation. In the absence of
ovulation, unopposed estrogen causes proliferation of the endometrium, which eventually outgrows
its structural support and sloughs.3 Therefore, women with anovulatory cycles often have episodes of
amenorrhea or very light cycles interspersed with very heavy bleeding.
Determine the length of anovulation, and obtain a detailed history to determine whether a secondary
cause of anovulation (Table 1) might be present. Findings such as acanthosis nigricans, obesity,
striae, hirsutism, and acne may support androgenic causes.
Any complaint of AUB warrants a thorough pelvic examination. Cultures for Neisseria gonorrhoeae
and Chlamydia and a recent cervical smear are also required. However, perineal, vaginal, and
cervical lesions and inflammation are unlikely to cause the pattern of bleeding observed with
anovulatory cycles.
Question the patient to confirm the absence of ovulatory symptoms, such as premenstrual
discomfort, breast tenderness, mood changes, and bloating. Obtain a 21-day progesterone level if
ovulation cannot be determined by history.20
Other recommended laboratory studies include tests for pregnancy, thyroid-stimulating hormone,
and fasting serum prolactin (SOR level B). Only one third of women with hyperprolactinemia have
galactorrhea, and subclinical hypothyroidism and hyperthyroidism may both cause abnormal
bleeding.18 Obtain a hematocrit or hemoglobin level if bleeding is excessive. Testing for androgenic
causes with a luteinizing hormone (LH) tofollicle-stimulating hormone (FSH) ratio and free
testosterone may be indicated by the history.21 A low FSH level may also indicate a hypothalamic
cause, and elevated levels of both LH and FSH may indicate ovarian failure.21 Endometrial cavity
evaluation is sometimes warranted, especially if the patient has received long-standing unopposed
estrogen therapy.
Menorrhagia. In women who are found to be ovulatory by history or laboratory testing, attempt to
determine the extent of menstrual loss, possibly with use of pictorial charts.7 Heavy ovulatory
bleeding is less common than anovulatory bleeding and indicates impaired hemostasis either
locally--as in the setting of submucosal fibroids or ovulatory DUB--or from a systemic coagulopathy.12
A history of alcoholism or liver disease, easy bruising or bleeding, heavy menses since menarche, or
a family history of bleeding disorders may prompt further workup for coagulopathy. If the patient has
undergone major surgery without excessive bleeding, a hereditary coagulation disorder is unlikely.22
Note any extensive bruising or ecchymosis. Submucosal fibroids cannot be ruled out by examination
and are the only fibroids thought to interfere with local hemostasis. Ultrasonography is therefore
recommended to document uterine anatomy (SOR level B). Hemoglobin or hematocrit level and a
urinary human chorionic gonadotropin test are the only universally recommended laboratory studies.
Other tests may be considered depending on the history. One report found that in women aged 30 to
49 years with menorrhagia, the incidence of an inherited bleeding disorder was 17%. This suggests
that coagulation studies may be warranted in women with documented menorrhagia in the absence
Page 3 of 7
Abnormal Uterine Bleeding:
Published on Cancer Network (http://www.cancernetwork.com)
of anatomic pathology (SOR level C).23
Perimenopausal and postmenopausal bleeding. Vaginal bleeding after menopause in a woman
who is not taking hormone replacement therapy or 12 months after the initiation of hormone
replacement therapy warrants a complete assessment to rule out anatomic pathology. A thorough
pelvic examination, including cervical smear, should be followed by an evaluation of the uterine
cavity (SOR level B).
Endometrial cancer is the fourth most common cause of malignancy in women; most cases occur in
postmenopausal women.24 An endometrial tissue evaluation is indicated in postmenopausal women
with vaginal bleeding to rule out hyperplasia and cancer. Pipelle endometrial sampling is as accurate
as dilation and curettage and is easily performed in the office.25 However, Pipelle sampling is
nondiagnostic in 2% to 38% of cases, is uncomfortable, and often misses focal hyperplasia or
polyps.24
A large meta-analysis demonstrated that transvaginal ultrasonography (TVUS) showing a thin
endometrial stripe (5 mm or less) has negative predictive value comparable to that of endometrial
Pipelle sampling (96% vs 97.5%) and is an acceptable alternative (SOR level A).24 Moreover, other
pathologic conditions, such as atypical or focal hyperplasia and polyps, may be detected with
TVUS.24 The specificity of TVUS decreases to 77% in women using hormone replacement therapy.
The false-negative rate of TVUS (8%) also compares favorably with that of Pipelle sampling (5% to
15%), which suggests that neither test excludes endometrial cancer with complete certainty.24,26
Therefore, if an identifiable source of bleeding is not found in a postmenopausal woman, referral to a
gynecologist for possible hysteroscopy or saline infusion sonohysterography is warranted (SOR level
B).26,27
Although abnormal bleeding in perimenopausal women is often attributable to anovulatory cycles,
10% to 20% of cases of endometrial cancer occur in premenopausal women.28 How to identify
women who are at risk for endometrial cancer or hyperplasia is still a subject of debate. Most
clinicians use age as a criterion for evaluating the uterine cavity. However, the incidence of
endometrial cancer is 2% to 5% in women younger than 40 years.29
Risk stratification based on factors other than age may therefore be appropriate.30 Risks include
long-standing anovulation, obesity, nulliparity, diabetes mellitus, hypertension, tamoxifen therapy,
and a family history of colon cancer.28,29,30 Weight of more than 90 kg was shown to have the highest
predictive value for endometrial hyperplasia or carcinoma; it correlated better than age older than
45 years in one study.28 Another study showed irregular cycles to be a better predictor of
hyperplasia on biopsy than age.31 Consider endometrial cavity evaluation at an earlier age in obese
women and in those with anovulatory cycles (SOR level B).18,28 Larger studies are needed to
determine whether women older than 40 years who have AUB and no other risk factors can be
managed with watchful waiting.
Recent studies have shown that a thin endometrial stripe on ultrasonography is also sufficient to
exclude hyperplasia or cancer in premenopausal women.31 Initial screening with TVUS on day 4 to 6
of a woman's cycle decreases the need for endometrial biopsy by 65%. This method reduces costs
and detects focal abnormalities that may have been missed by biopsy (SOR level B).31 Moreover, it
better distinguishes premenopausal women whose lesions require more focal hysteroscopic
sampling from those with globally thickened endometrial tissue, who are more appropriate
candidates for Pipelle sampling.31MEDICAL MANAGEMENT
Options for medical management of AUB include OCPs and other hormone therapies, as well as
NSAIDs.
OCPs. These are the most widely prescribed agents for AUB in the United States; they are effective
for both menorrhagia and metromenorrhagia. However, there is little high-quality evidence to
support their use. One small trial showed that a monophasic OCP was equivalent to NSAIDs and
low-dose danazol for menorrhagia.32 A more recent randomized controlled trial showed that a
triphasic preparation containing 35 µg of estrogen reduced blood loss in DUB more effectively than
placebo.33 OCPs are considered first-line treatment in anovulatory cycles for women who also desire
contraception (SOR level B).34 No evidence supports the superiority of monophasic over triphasic
agents.
OCPs are also widely used for acute bleeding in hemodynamically stable women who have an
acceptable hematocrit or as a way to add progesterone in women whose acute bleeding has already
been stabilized by estrogen, although only anecdotal evidence supports their use in this setting. The
typical regimen is estrogen, 35 µg bid to q6h, for 5 to 7 days (SOR level D).34
NSAIDs. In a Cochrane meta-analysis, 5 of 7 randomized controlled trials showed that NSAIDs were
an effective treatment for menorrhagia (SOR level B).35 However, a trial that compared NSAIDs with
Page 4 of 7
Abnormal Uterine Bleeding:
Published on Cancer Network (http://www.cancernetwork.com)
other treatments showed that both danazol and tranexamic acid (an antifibrinolytic) were more
effective for menorrhagia.36,37 There are few studies that compare combination OCPs with NSAIDs,
and there is no evidence that any one NSAID is superior to another. NSAIDs are a readily available
treatment option for menorrhagia--especially in the case of desired fertility--when used during
menses or with concurrent dysmenorrhea (SOR level B).
NSAIDs are also an option for first-line treatment of women who have breakthrough bleeding
associated with OCPs (SOR level D) or bleeding associated with copper or other inert IUDs (SOR level
C).10,34 Women with anovulatory cycles are unlikely to respond to NSAIDs.4
Antifibrinolytics. A number of randomized controlled trials show that tranexamic acid is a more
effective treatment of menorrhagia than NSAIDs and cyclic progestins (SOR Level A).4
Antifibrinolytics decrease blood loss by 40% to 60% and are taken only 4 days per month.38 Strong
evidence supports the safety of antifibrinolytics; a large Scandinavian trial that followed 238,000
women for 19 years dispelled the notion of a theoretical increased risk of thromboembolic disease,
even in high-risk women.39,40
Although tranexamic acid is the mainstay of treatment of menorrhagia in the rest of the world, it is
not available in the United States. This option would be particularly appealing for women who desire
fertility. No randomized controlled trials have compared antifibrinolytics with OCPs. Women with
anovulatory cycles are unlikely to benefit from antifibrinolytics.34
Clomiphene citrate. There is no evidence from randomized controlled trials to support the
effectiveness of this agent for AUB. However, it is recommended by the American College of
Obstetrics and Gynecology and other groups as an option for women with idiopathic anovulatory
bleeding who desire fertility (SOR level C).4,11,19
Estrogens. High-dose estrogens are the most widely used treatment for acute AUB. However, only
one randomized controlled trial exists that shows intravenous estrogen to be superior to placebo
(cessation of bleeding in 71% of women, compared with 38% in the placebo group).41 Nevertheless,
conjugated equine estrogens, 25 mg q4h IV for a maximum of 24 hours, are considered first-line
treatment for acute AUB, even when bleeding is attributable to presumed anovulatory cycles and
excess estrogen (SOR level B).4,18 Once acute bleeding has subsided, progestins are usually added,
either alone or in a combination OCP. Because nausea and vomiting are common side effects of
high-dose estrogen treatment, antiemetics are often required.
Oral estrogens are also used to rebuild a denuded endometrium attributable to excess progesterone.
One week of supplemental estrogen (ethinyl estradiol, 20 µg/d) may alleviate OCP-induced
breakthrough bleeding that persists for 3 months. Other options include conjugated estrogens, 0.625
to 1.25 mg/d, and estradiol, 0.5 to 1 mg/d for 1 to 2 weeks. This therapy is therefore recommended
as an alternative to NSAIDs as first-line treatment in bleeding caused by OCPs (SOR level C).10
Progestins. A Cochrane meta-analysis showed that cyclic oral progestins were less effective than
tranexamic acid, danazol, or a progesterone-impregnated IUD for menorrhagia.35 There are no trials
that have compared these agents with placebo. However, cyclic oral progestins taken approximately
10 days per month are effective in decreasing menstrual loss attributable to unopposed estrogen in
at least 50% of anovulatory women (SOR level B).42
Continuous local progestins. Progesterone-impregnated IUDs are a promising tool in the
management of AUB. Several high-quality randomized trials have shown that results obtained with
the IUD are highly satisfactory43-45 and, in some cases, superior to those obtained with medical and
surgical treatments (SOR level B).44,45 Reported reductions in bleeding ranged from 79% to 94%.43,45
In one small study, 64% of women scheduled for hysterectomy for menorrhagia canceled their
surgery because of satisfaction with the IUD, compared with only 14.3% treated with other
modalities.45
Women are often more satisfied with the IUD than other similarly effective medical therapies. In one
study, 76% of women who were given an IUD wanted to continue with it, compared with only 22% of
those who were given progesterone, despite similar reductions in blood flow.46 Another small
randomized trial showed that satisfactory results were obtained with the progesterone IUD,
compared with hysteroscopic endometrial resection.43 Neither the progesterone-impregnated IUD
nor continuous local progestins have been evaluated in anovulatory women.
Androgens. Danazol, an androgenic compound often prescribed by gynecologists, is an effective
treatment for menorrhagia.34 However, because of masculinizing side effects, only half of women in
one study were willing to continue the medication.36
Gonadotropin-releasing hormone agonists. These agents are occasionally used as a
temporizing treatment for menorrhagia secondary to uterine fibroids. They are also used as an
alternative to parenteral estrogen in acute severe bleeding; however, there are no studies
Page 5 of 7
Abnormal Uterine Bleeding:
Published on Cancer Network (http://www.cancernetwork.com)
supporting this approach, and heavy bleeding often develops 1 to 2 weeks after use.34
Antiprogestational agents. There may be an important role for these agents in reducing fibroid
growth. In one small study, the antiprogestin RU-486, 50 mg/d, stopped bleeding attributable to
uterine fibroids; it produced amenorrhea and a 50% reduction in fibroid size.47 More large-scale
studies are required to confirm these results. However, the use of this agent as an abortifacient may
make availability and further research challenging.
References: REFERENCES:
1. Shwayder JM. Pathophysiology of abnormal uterine bleeding. Obstet Gynecol Clin North Am.
2000;27: 219-234.
2. Munro MG. Abnormal uterine bleeding in the reproductive years. Part II--medical management. J
Am Assoc Gynecol Laparascop. 2000;7:17-34.
3. Quint EH, Smith YR. Abnormal uterine bleeding in adolescents. J Midwifery Womens Health.
2003;48: 186-191.
4. Hallberg L, Hogdahl A, Nilsson L, Rybo G. Menstrual blood loss--a population study. Acta Obstet
Gynecol Scand. 1966;45:320.
5. Higham JM, O'Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial
chart. Br J Obstet Gynaecol. 1990;97:734-739.
6. Gannon MJ, Day P, Hammadieh N, Johnson N. A new method for measuring menstrual blood loss
and its use in screening women before endometrial ablation. Br J Obstet Gynaecol.
1996;103:1029-1033.
7. Rees MC. Role of menstrual blood loss measurements in management of complaints of excessive
menstrual bleeding. Br J Obstet Gynaecol. 1991;98: 327-328.
8. Stabinsky SA, Einstein M, Breen JL. Modern treatments of menorrhagia attributable to
dysfunctional uterine bleeding. Obstet Gynecol Surv. 1999;54: 61-72.
9. Bradley LD, Ke RW, Smith RP, Strickland JL. Clinical Management of Abnormal Uterine
Bleeding. APGO Educational Series on Women's Health Issues. Crofton, Md: Association of
Professors of Gynecology and Obstetrics; 2002.
10. Oriel KA, Schrager S. Abnormal uterine bleeding. Am Fam Physician. 1999;60:1371-1382.
11. Munro MG. Abnormal uterine bleeding in the reproductive years, part 1: pathogenesis and
clinical investigation. J Am Assoc Gynecol Laparosc. 1999;6: 393-416.
12. Hill NC, Oppenheimer LW, Morton KE. The aetiology of vaginal bleeding in children. A 20-year
review. Br J Obstet Gynaecol. 1996;96:467-470.
13. Carpenter SE, Rock J. Pediatric and Adolescent Gynecology. New York: Raven Press; 1992:153.
14. Neinstein LS. Menstrual problems in adolescents. Med Clin North Am. 1990;74:1181-1203.
15. Claessens EA, Cowell CA. Acute adolescent menorrhagia. Am J Obstet Gynecol. 1981;139:1981.
16. Woo YL, White B, Corbally R, et al. Von Willebrand's disease: an important cause of
dysfunctional uterine bleeding. Blood Coagul Fibrinolysis. 2002;13: 89-93.
17. American College of Obstetrics and Gynecology. Management of Anovulatory Bleeding.
Washington, DC: ACOG; 2000.
18. ACOG Committee Opinion. Von Willebrand's disease in gynecologic practice. American
College of Obstetrics and Gynecology Committee on gynecologic practice. Int J Gynaecol
Obstet. 2002;76:336-337.
19. Schrager S. Abnormal uterine bleeding associated with hormonal contraception. Am Family
Physician. 2002;65:2073-2080.
20. Herbst AL. Comprehensive Gynecology. 2nd ed. St Louis: Mosby Year Book; 1992:1194-1195.
21. Munro MG. Dysfunctional uterine bleeding: advances in diagnosis and treatment. Curr Opin
Obstet Gynecol. 2001;13:475-489.
22. Lusher JM. Screening and diagnosis of coagulation disorders. Am J Obstet Gynecol. 1996;175:
778-783.
23. Kadir RA, Economides DL, Sabin CA, et al. Frequency of inherited bleeding disorders in women
with menorrhagia. Lancet. 1998;351:485-489.
24. Smith-Bindman R, Kerlikowske K, Feldstein VA, et al. Endovaginal ultrasound to exclude
endometrial cancer and other endometrial abnormalities. JAMA. 1998;280:1510-1517.
25. Stovall TG, Photopulos GJ, Poston WM, et al. Pipelle endometrial sampling in patients with known
endometrial carcinoma. Obstet Gynecol. 1991;77: 954-956.
26. O'Connell LP, Fries MH, Zeringue E, Brehm W. Triage of abnormal postmenopausal
bleeding: a comparison of endometrial biopsy and transvaginal sonohysterography versus fractional
Page 6 of 7
Abnormal Uterine Bleeding:
Published on Cancer Network (http://www.cancernetwork.com)
curettage with hysteroscopy. Am J Obstet Gynecol. 1998;178: 956-961.
27.Albers JR, Hull SK, Wesley RM. Abnormal uterine bleeding. Am Fam Physician. 2004;69:
1915-1926.
28. Farquhar CM, Lethaby A, Sowter M, Baranyai J. An evaluation of risk factors for endometrial
hyperplasia in premenopausal women with abnormal menstrual bleeding. Am J Obstet Gynecol.
1999;181: 525-529.
29. Dunn TS, Stamm CA, Delorit M, Goldberg G. Clinical pathway for evaluating women with
abnor-mal uterine bleeding. J Reprod Med. 2001;46:831-834.
30. Ash SJ, Farrell SA, Glowerdew GD. Endometrial biopsy in DUB. J Reprod Med. 1996;41:892-896.
31. Goldstein SR, Zeltser I, Horan CK, et al. Ultrasonography-based triage for perimenopausal
patients with abnormal uterine bleeding. Am J Obstet Gynecol. 1997;177:102-108.
32. Fraser IS, McGarron G. Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in
women with a complaint of menorrhagia. Aust N Z J Obstet Gynaecol. 1991;31:66-70.
33. Davis A, Godwin A, Lippman J, et al. Triphasic norgestimate-ethinyl estradiol for treating
dysfunctional uterine bleeding. Obstet Gynecol. 2000;96: 913-920.
34. Munro MG. Medical management of abnormal uterine bleeding. Obstet Gynecol Clin North Am.
2000;27:287-304.
35. Lethaby A, Augood C, Duckitt K. Nonsteroidal anti-inflammatory drugs for heavy menstrual
bleeding. Cochrane Database Syst Rev. 2002;(2):CD001017.
36. Dockeray CJ, Sheppard BL, Bonnar J. Comparison between mefenamic acid and danazol in the
treatment of established menorrhagia. Br J Obstet Gynaecol. 1989;96:840-844.
37. Andersch B, Milsom I, Rybo G. An objective evaluation of flurbiprofen and tranexamic acid in the
treatment of idiopathic menorrhagia. Acta Obstet Gynecol Scand. 1988;67:645-648.
38. Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for heavy menstrual bleeding. Cochrane
Database Syst Rev. 2000;(4):CD000249.
39. Rybo G. Tranexamic acid therapy effective treatment in heavy menstrual bleeding. Clinical
update on safety. Ther Adv. 1991;4:1-8.
40. Lindoff C, Rybo G, Astedt B. Treatment with tranexamic acid during pregnancy, and the risk of
thrombo-embolic complications. Thromb Haemost. 1993;70:238-240.
41. DeVore GR, Owens O, Kase N. Use of intravenous premarin in the treatment of dysfunctional
uterine bleeding--a double-blind randomized control study. Obstet Gynecol. 1982;59:285-291.
42. Fraser IS. Treatment of ovulatory and anovulatory dysfunctional uterine bleeding with oral
progestogens. Aust N Z J Obstet Gynaecol. 1990;30: 353-356.
43. Crosignani PG, Vercellini P, Mosconi P, et al. Levonorgestrel-releasing intrauterine device versus
hysteroscopic endometrial resection in the treatment of dysfunctional uterine bleeding. Obstet
Gynecol. 1997;90:257-263.
44. Barrington JW, Bowen-Simpkins P. The levonorgestrel intrauterine system in the management of
menorrhagia. Br J Obstet Gynaecol. 1997;104: 614-616.
45. Lahteenmaki P, Haukkamaa M, Puolakka J, et al. Open randomised study of use of levonorgestrel
releasing intrauterine system as alternative to hysterectomy. BMJ. 1998;316:1122-1126.
46. Irvine GA, Campbell-Brown MB, Lumsden MA, et al. Randomised comparative trial of the
levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia. Br J
Obstet Gynaecol. 1998;105:592-598.
47. Murphy AA, Kettel LM, Morales AJ, et al. Regression of uterine leiomyomata in response to the
antiprogesterone RU 486. J Clin Endocrinol Metab. 1993;76:513-517.
Source URL: http://www.cancernetwork.com/articles/abnormal-uterine-bleeding
Links:
[1] http://www.cancernetwork.com/authors/jessica-miller-md
[2] http://www.cancernetwork.com/authors/john-r-holman-md-mph
Page 7 of 7