Emed.chris-barton.com

Treatment of Menorrhagia
BARBARA S. APGAR, MD, MS, AMANDA H. KAUFMAN, MD, UCHE GEORGE-NWOGU, MD, and
ANNE KITTENDORF, MD, University of Michigan Medical Center, Ann Arbor, Michigan
Menorrhagia is defined as excessive uterine bleeding occurring at regular intervals or prolonged uterine bleeding lasting
more than seven days. The classic definition of menorrhagia (i.e., greater than 80 mL of blood loss per cycle) is rarely
used clinically. Women describe the loss or reduction of daily activities as more important than the actual volume of
bleeding. Routine testing of all women with menorrhagia for inherited coagulation disorders is unnecessary. Saline
infusion sonohysteroscopy detects intracavitary abnormalities such as endometrial polyps or uterine leiomyoma and
is less expensive and invasive than hysteroscopy. Endometrial biopsy is effective for diagnosing precancerous lesions
and adenocarcinoma but not for intracavitary lesions. Except for continuous progestin, medical therapies are limited.
The levonorgestrel-releasing intrauterine device is an effective therapy for women who want to preserve fertility and
avoid surgery. Surgical therapies include endometrial ablation methods that preserve the uterus; and hysterectomy,
which results in high satisfaction rates but with potential surgical morbidity. Overall, hysterectomy and endometrial
ablation result in the greatest satisfaction rates if future childbearing is not desired. Treatment of menorrhagia results
in substantial improvement in quality of life. (Am Fam Physician 2007;75:1813-9,1820. Copyright 2007 American
Academy of Family Physicians.)
▲ Patient information:
A handout on menorrha-gia, written by the authors of this article, is provided on page 1820.
The term “abnormal uterine bleed- very heavy, 25 percent had losses of less than ing” encompasses noncyclic and 35 mL per cycle, and 25 percent of those cyclic bleeding. Anovulatory who rated their periods as heavy had losses bleeding is the most common type of more than 82 mL.6 Physicians may be of noncyclic uterine bleeding. Menorrhagia unable to judge volume from patient history is defined as excessive cyclic uterine bleeding or may consider measurements unimport-that occurs at regular intervals over several ant in deciding treatment.5 Pictorial blood cycles, or prolonged bleeding that lasts for loss assessment charts may not accurately more than seven days.1 Anovulatory bleeding reflect the hygiene products used.5 Addi-and menorrhagia, although often grouped tionally, women change hygiene products at together in discussions of treatment, do not a varied frequency whether saturation has have the same etiology or require the same occurred or not. Therefore, the criterion of diagnostic testing.
loss of more than 80 mL is of doubtful clini- Average menstrual blood loss is between cal significance.4 30 and 40 mL per cycle.2 An early popula- tion-based study concluded that the upper strongly with blood loss volume include the limit of normal menstrual blood loss was rate of change of sanitary protection during between 60 and 80 mL, with the upper limit full flow, and the total number of pads and subsequently adopted as the classic defini- tampons used.6 Other associations include tion of menorrhagia.3,4 A greater prevalence the size of clots and the number of clots of impaired iron status was noted with a loss greater than about 1 inch in diameter. A low of more than 60 mL.3 There are shortcom- ferritin level correctly predicts 60 percent of ings to this volume definition because actual women with periods with measured losses blood loss is largely subjective and difficult of more than 80 mL; therefore, a loss of to quantify objectively.
In 34 percent of women, the subjective ately well by a model that includes ferritin complaint of “heavy periods” appears to cor- levels, clot size, and the rate of pad change relate with a significantly higher quantified during full flow.6average blood loss.5 Some women, however, do not consider heavy menstrual flow to be ceived increase in the volume of menstrual abnormal. Of women who rated their flow as bleeding are reported more often as severe Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright 2007 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests.
Menorrhagia
SORT: KEY RECOMMENDATIONS FOR PRACTICE
Physicians should prescribe oral progestin therapy for 21 continuous days (days 5 to 26 of the menstrual cycle) to reduce menstrual blood loss.
medical treatment of menorrhagia, but patient satisfaction is higher with the levonorgestrel-releasing intrauterine device.
The levonorgestrel-releasing intrauterine device is an effective long-term option for menorrhagia if future childbearing is desired.
Physicians should prescribe hysterectomy for patients in whom no further childbearing is desired.
For patients who wish to avoid major surgery and in whom childbearing is completed, endometrial ablation is a reasonable and effective alternative to hysterectomy.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 1754 or http://www.aafp.org/afpsort.xml. problems by women with menorrhagia than is absolute hysterectomy for the sole indication of menorrhagia.14 blood loss.4 Patient distress may be related more to dis- A more stringent meta-analysis concluded that there are ruptions in work, sexual activity, or quality of life than inadequate data to justify routine testing for all women menstrual volume alone. These perceptions are impor- with menorrhagia.13 Generally, if the patient has von tant, because the amount of blood loss alone is not linked Willebrand’s disease, it is already known at the time of to a decision to proceed with hysterectomy. A woman’s evaluation.
perception of blood loss and the disruption that it causes ACOG does not recommend a complete blood count, are the key determinants of subsequent treatment.7 thyroid function test, or prolactin test for women with menorrhagia.1 Evidence-based guidelines from the Royal Risk Factors
College of Obstetricians and Gynaecologists, however, Established risk factors for menorrhagia include increased recommend these tests, although thyroid function and age,8 premenopausal leiomyomata,9 and endometrial bleeding disorders should be evaluated only if other his-polyps.10 Parity, body mass index, and smoking are not torical or clinical features suggest specific conditions.15risk factors.8 For some women, a cause of menorrhagia ACOG lists menstrual irregularity as a risk factor for endometrial cancer,16 and it is reasonable to exclude Abnormalities of platelet function, such as von Wille- cancer in adult women with persistent menorrhagia.15 brand’s disease, appear to be more prevalent in women This is particularly true in cases where it is difficult with menorrhagia than in the general population.1,11 The to determine whether the menorrhagia is caused by prevalence of von Willebrand’s disease in women with anatomic causes, such as fibroids or polyps, or is a func-menorrhagia varies from 5 to 24 percent.12 There are no tion of abnormal uterine bleeding. An exception is in data suggesting that a lower quality of life occurs more adolescents, in whom endometrial cancer is rare and commonly in women with menorrhagia and von Wille- in whom most abnormal uterine bleeding is a result of brand’s disease than in those with menorrhagia alone.13 physiologic anovulation. Invasive diagnostic modalities include endometrial biopsy, transvaginal ultrasonog- Diagnostic Testing
raphy, saline infusion sonohysteroscopy, and hysteros- The American College of Obstetricians and Gynecolo- copy1 (Table 117-21). Although abnormal uterine bleeding gists (ACOG) recommends testing for von Willebrand’s in adolescents is usually physiologic, reproductive-age disease in adolescents with severe menorrhagia, in adult women with menorrhagia require evaluation for a spe-women with menorrhagia, and in women undergoing cific cause.1 1814  American Family Physician
Volume 75, Number 12 ◆ June 15, 2007 Menorrhagia
The detection rate of endometrial cancer using endo- abnormalities in premenopausal women than transvagi- metrial biopsy is 91 percent, with a 2 percent false-positive nal ultrasonography if the goal is to avoid expensive and rate in premenopausal women,17 making it an accurate invasive hysteroscopy.20,21,24diagnostic test for women with abnormal uterine bleed-ing.18 Greater sensitivity (97 percent) and negative pre- Treatment of Menorrhagia
dictive value (94 percent) can be achieved by combining Menorrhagia can result in severe anemia. Of 115 women endometrial biopsy with saline infusion sonohystero- with physician-diagnosed menorrhagia, 58 percent reported scopy.19 Saline infusion sonohysteroscopy incorporates a history of anemia, for which 89 percent received treat-real-time ultrasonography with static images during infu- ment.11 Additionally, 4 percent had received transfusion. sion of sterile saline into the uterus.22 If bleeding persists Treatment of menorrhagia results in substantial improve-
despite a negative endometrial biopsy or saline infusion ment in quality of life.25
sonohysteroscopy, hysteroscopy (sensitivity 86 percent,
specificity 99 percent) should be considered despite the MEDICAl ThERAPIES
cost and invasive nature of the procedure.23
The treatment of choice for anovulatory bleeding is The most common anatomic causes of menstrual dis- medical therapy with oral contraceptive pills or proges- orders in premenopausal women are uterine polyps and togens.1 High-quality comparative evidence on which to submucous fibroids.20 Transvaginal ultrasonography base therapy for menorrhagia, however, is limited.
(sensitivity 60 percent, specificity 93 percent) and endo- Oral progestogens are the most commonly prescribed metrial biopsy are less effective than saline infusion sono- therapy for menorrhagia.26 When administered solely in hysteroscopy for diagnosing intracavitary abnormalities. the luteal phase, they are significantly less effective than Saline infusion sonohysteroscopy is more accurate for the levonorgestrel-releasing intrauterine device (IUD; detecting uterine fibroids (sensitivity 87 percent, speci- Mirena).26 Oral progestin therapy for 21 continuous ficity 92 percent) than for endometrial polyps (sensitivity days (days 5 to 26 of the menstrual cycle) effectively 86 percent, specificity 81 percent); therefore, a negative reduces menstrual blood loss, but patient satisfaction is test does not rule out intracavitary abnormalities.23 It is higher with the levonorgestrel-releasing IUD. This regi-unknown if structural lesions missed on saline infusion men has the strongest role in the short-term treatment sonohysteroscopy are diagnosed more efficiently with of menorrhagia.26hysteroscopy.21 Saline infusion sonohysteroscopy is a There is insufficient evidence to assess the effective- more effective initial diagnostic test for intracavitary ness of monthly oral contraceptive pills for reducing Table 1. Endometrial Evaluation for Women with Menorrhagia
To rule out neoplasia in adult women; office procedure, well tolerated, anesthesia and cervical dilation usual y not required; limitations include cervical stenosis and insufficient samples if endometrial atrophy present Less effective than saline infusion sonohysteroscopy for identification of intracavitary abnormalities Sterile isotonic fluid is infused into the uterus under continuous visualization of the endometrial surface with transvaginal Highest cost; may require cervical dilation; does not reduce hysterectomy rate despite absence of intracavitary pathology; used as the preferred method over other procedures Information from references 17 through 21. June 15, 2007 ◆ Volume 75, Number 12 American Family Physician  1815
Menorrhagia
menorrhagia.2 Although continuous-use oral Table 2. Endometrial Ablation Methods
contraceptive pills and injectable progestins reduce bleeding episodes over an extended First-generation methods* (amenorrhea rate)
period,27 there have been no specific studies Transcervical resection of endometrium (26 to 40 percent) the effectiveness of nonsteroidal anti-inflam- Second-generation methods (amenorrhea rate)
matory drugs,28 danazol,29 or the antifibrino- Laser intrauterine thermotherapy (71 percent) lytic agent tranexamic acid (Cyklokapron)30 Microwave ablation† (Microsulis‡; 61 percent) in reducing menorrhagia, because the stud- ies are small and underpowered to detect a Although used as a contraceptive, the levo- norgestrel-releasing IUD produces signifi- Radiofrequency ablation (Novasure‡; 41 percent) cant reductions in menstrual blood loss. This IUD has not been compared with placebo or *—Satisfaction rates with first-generation methods are 80 percent or greater; subse-quent hysterectomies are performed on 2 to 21 percent of patients. no treatment.31 One small trial compared †—Can be used for patients with uterine polyps, irregularly-shaped uterus, or moder- it with oral progestin administered on days 5 to 26 of the menstrual cycle and showed ‡—Approved by the U.S. Food and Drug Administration. the IUD to be significantly more effective in §—Contraindications include previous cesarean delivery and uterine wall thickness of less than 8 mm. reducing menstrual blood loss.31 There were Information from references 7, 35, and 36. more short-term adverse effects in the IUD group, but a significantly greater number of Table 3. Comparison of Medical and Surgical Therapies for Menorrhagia
Seeking low intervention, contraception, preserves fertility; high patient satisfaction; endometrial transcervical resection or bal oon ablation $ = least expensive; $$$$ = most expensive; IUD = intrauterine device. *—No medical therapy, including the levonorgestrel IUD, is U.S. Food and Drug Administration approved for treatment of menorrhagia. Information from references 2, 7, 25, 27 through 31, and 37. 1816  American Family Physician
Volume 75, Number 12 ◆ June 15, 2007 Menorrhagia
women were satisfied and willing to continue with the thinning with gonadotropin-releasing hormone analogues IUD compared with the progestin (77 versus 22 percent, or danazol improves technical performance and results in respectively).31 higher rates of postoperative amenorrhea.34 Ablation methods (transcervical resection and balloon Clearly, selection of women is important. Women ablation) resulted in greater reductions of mean men- must have completed childbearing and have a benign strual blood loss and higher amenorrhea rates than the cause for their menorrhagia.35 First- and second-gen-levonorgestrel-releasing IUD,30 but the satisfaction rates eration methods are effective in reducing average blood were similar despite more adverse effects with the IUD.29 loss. Complication rates for both are low, and satisfac- When the levonorgestrel-releasing IUD and hysterec- tion is high.7,15 Studies evaluating the effectiveness of tomy were compared, there was no difference in quality of endometrial ablation have been performed primarily on life or satisfaction rates, but the surgery was more expen- women with menorrhagia, not on anovulatory women.1 sive at one and five years after surgery.31 About 70 percent The first-generation procedures (endometrial resection of women continued with the IUD at 12 months.32 More and rollerball or laser ablation) are performed through than 64 percent of women using the levonorgestrel-releas- a hysteroscope after uterine infusion of a distension ing IUD as a bridge to a previously scheduled hysterec- medium to improve visualization.35,36 Although consid- tomy for menorrhagia cancelled their surgery.33 ered the standard for endometrial ablation, the first-gen-eration procedures take more time to perform, require SuRgICAl ThERAPIES
regional or general anesthesia, and are technically more Minimally invasive methods of endometrial destruction difficult than second-generation methods.7 There is a 4 have been evaluated as alternatives to hysterectomy in percent risk of fluid overload with first-generation proce-women with menorrhagia. The procedures are divided dures,37 making them unsuitable for women with cardiac into first- and second-generation methods depending on or renal disease.35whether a hysteroscope is used. Preoperative endometrial Second-generation methods are performed “blind” (without a hysteroscope), usually in the outpatient setting under local anesthesia, and require minimal Table 3. Comparison of Medical and Surgical Therapies for Menorrhagia
cervical dilation.35,36 These methods include cryoabla-tion, thermal balloon ablation, radiofrequency ablation, microwave ablation, and diode laser thermotherapy.
A Cochrane review of 13 trials comparing first- and second-generation methods found no differences in satisfaction rates at one, three, and five years.7 There were also no significant differences for outcomes of inability to work, amenorrhea rates, or requirements for any additional surgery or hysterectomy. All second- generation methods required significantly less operating time and use of general anesthesia than first-genera- tion techniques.7 There were, however, more reports of Seeking low intervention, contraception, equipment failure with the second-generation tech- preserves fertility; high patient satisfaction; Hysterectomy is a definitive treatment for menorrha- gia, but there is risk of surgical morbidity and the eco- nomic cost is high.15,37 Although endometrial resection procedures result in faster return to normal activities than hysterectomy, they are associated with a reinter- vention rate of up to 22 percent, so the cost difference between hysterectomy and endometrial resection nar-rows over time.37 There are no randomized controlled $ = least expensive; $$$$ = most expensive; IUD = intrauterine device. trials comparing various surgical methods with hyster- *—No medical therapy, including the levonorgestrel IUD, is U.S. Food and Drug Administration approved for treatment of menorrhagia. Information from references 2, 7, 25, 27 through 31, and 37. Table 32,7,25,27-31,37 compares medical and surgical options for treatment of menorrhagia.
June 15, 2007 ◆ Volume 75, Number 12 American Family Physician  1817
Menorrhagia
Clinical Decisions About Treatment
She received her medical degree from the University of Ibadan in Nigeria, It is important to ask women about the amount of men- and completed a family medicine residency at New York University Medical School at St. Joseph Hospital in New York City.
strual bleeding and level of fertility they will accept before any treatment recommendations are made.38 When women ANNE KITTENDORF, MD, is a lecturer of family medicine at the University of Michigan Medical Center. She received her medical degree and com- with menorrhagia were offered an interview and informa- pleted a family medicine residency at the University of Michigan.
tion packet describing treatment options and outcomes, they were more satisfied with their role in decision mak- Address correspondence to Barbara Apgar, MD, MS, 883 Sciomeadow Dr., Ann Arbor, MI 48103 (e-mail: [email protected]). Reprints are ing and less likely to undergo hysterectomy.39 Although not available from the authors. amenorrhea as a primary end point is easily measured, it Author disclosure: Nothing to disclose.
is not required for improved quality of life and patient sat-isfaction.40 Lifestyle and amenorrhea outcomes correlate poorly and should not be considered interchangeable.6 REFERENCES
Women who tolerate menstrual bleeding and wish to 1. ACOG Committee on Practice Bul etins—Gynecology. ACOG practice maintain fertility can try medical therapy with continu- bul etin: management of anovulatory bleeding. Int J Gynaecol Obstet ous progestin on days 5 to 26 of the menstrual cycle.15 The levonorgestrel-releasing IUD is an effective long- 2. Iyer V, Farquhar C, Jepson R. Oral contraceptive pil s for heavy men- strual bleeding. Cochrane Database Syst Rev 2000;(2):CD000154.
term option if future childbearing is desired.33 This IUD 3. Hal berg L, Hogdahl AM, Nilsson L, Rybo G. Menstrual blood loss—a is more effective than continuous progestin in reducing population study. Variation at different ages and attempts to define menorrhagia but is significantly less effective than endo- normality. Acta Obstet Gynecol Scand 1966;45:320-51.
metrial transcervical resection or balloon ablation.31 4. Warner PE, Critchley HO, Lumsden MA, Campbel -Brown M, Douglas A, Murray GD. Menorrhagia II: is the 80-mL blood loss criterion useful When medical and transcervical resection (ablation) in management of complaint of menorrhagia? Am J Obstet Gynecol therapy for menorrhagia were compared, women pre- ferred endometrial resection.41 Women who continued 5. Wyatt KM, Dimmock PW, Walker TJ, O’Brien PM. Determination of total medical therapy had lower quality of life and menstrual menstrual blood loss. Fertil Steril 2001;76:125-31.
outcomes than women undergoing resection. There 6. Warner PE, Critchley HO, Lumsden MA, Campbel -Brown M, Douglas A, Murray GD. Menorrhagia I: measured blood loss, clinical features, were significantly fewer secondary treatments in the and outcome in women with heavy periods: a survey with fol ow-up data. Am J Obstet Gynecol 2004;190:1216-23.
When randomized to continue cyclic progestin for 7. Lethaby A, Hickey M, Garry R. Endometrial destruction techniques for heavy menstrual bleeding. Cochrane Database Syst Rev 2005;(4): refractory abnormal uterine bleeding or hysterectomy, hysterectomy was shown to be superior for symptom 8. Janssen CA, Scholten PC, Heintz AP. Menorrhagia—a search for epide-improvement and may be the optimal choice for women miological risk markers. Maturitas 1997;28:19-25.
who give high priority to resolving bothersome symptoms 9. Wegienka G, Baird DD, Hertz-Picciotto I, Harlow SD, Steege JF, Hall MC, of menorrhagia and pain.42 et al. Self-reported heavy bleeding associated with uterine leiomyo-mata. Obstet Gynecol 2003;101:431-7.
Hysterectomy is a well-suited option for women who 10. DeWaay DJ, Syrop CH, Nygaard IE, Davis WA, Van Voorhis BJ. Natural his- do not desire further childbearing or menstrual bleeding tory of uterine polyps and leiomyomata. Obstet Gynecol 2002;100:3-7.
and are willing to assume the risk of surgery.43 However, 11. Philipp CS, Faiz A, Dowling N, Dil ey A, Michaels LA, Ayers C, et al. if there is a desire to avoid major surgery, and childbear- Age and prevalence of bleeding disorders in women with menorrhagia. Obstet Gynecol 2005;105:61-6.
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13. James A, Matcher DB, Myers ER. Testing for von Wil ebrand disease in The Authors
women with menorrhagia: a systematic review. Obstet Gynecol 2004; 104:381-8.
BARBARA S. APGAR, MD, MS, is a professor of family medicine at the 14. ACOG Committee on Gynecologic Practice. Committee Opinion: No. University of Michigan Medical Center, Ann Arbor. She received her 263, December 2001. Von Wil ebrand’s disease in gynecologic practice. medical degree and completed a family medicine residency at Texas Tech Health Sciences Center in Lubbock. Dr. Apgar is also an associate editor 15. Royal Col ege of Obstetricians and Gynaecologists. National evi- for American Family Physician.
dence-based clinical guidelines: the management of menorrhagia in AMANDA H. KAUFMAN, MD, is a lecturer of family medicine at the secondary care. Accessed January 23, 2007, at: http://www.rcog.org.
University of Michigan Medical Center. She received her medical degree and completed a family medicine residency at the University of Michigan.
16. American Col ege of Obstetricians and Gynecologists. ACOG practice bul etin, clinical management guidelines for obstetrician-gynecologists, UCHE GEORGE-NWOGU, MD, is an instructor and assistant residency No. 65, August 2005. Management of endometrial cancer. Obstet director of family medicine at the University of Michigan Medical Center. 1818  American Family Physician
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17. Dijkhuizen FP, Mol BW, Brolmann HA, Heintz AP. The accuracy of for heavy menstrual bleeding. Cochrane Database Syst Rev 2005;(4): endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer 2000;89:1765-72.
32. Hurskainen R, Teperi J, Rissanen P, Aalto AM, Grenman S, Kivela A, 18. Clark TJ, Mann CH, Shah N, Khan KS, Song F, Gupta JK. Accuracy of et al. Clinical outcomes and costs with the levonorgestrel-releasing outpatient endometrial biopsy in the diagnosis of endometrial cancer: intrauterine system or hysterectomy for treatment of menorrhagia: a systematic quantitative review. BJOG 2002;109:313-21.
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19. Mihm LM, Quick VA, Brumfield JA, Connors AF Jr, Finnerty JJ. The 33. Lahteenmaki P, Haukkamaa M, Puolakka J, Ri konen U, Sainio S, Suvisaari accuracy of endometrial biopsy and saline sonohysterography in the J, et al. Open randomised study of use of levonorgestrel releasing intra- determination of the cause of abnormal uterine bleeding. Am J Obstet uterine system as alternative to hysterectomy. BMJ 1998;316:1122-6.
34. Sowter MC, Lethaby A, Singla AA. Pre-operative endometrial thinning 20. Dijkhuizen FP, Mol BW, Bongers MY, Brolmann HA, Heintz AP. Cost- agents before endometrial destruction for heavy menstrual bleeding. effectiveness of transvaginal sonography and saline infused sonogra- Cochrane Database Syst Rev 2002;(3):CD001124.
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37. Lethaby A, Shepperd S, Cooke I, Farquhar C. Endometrial resection and 22. Breitkopf D, Goldstein SR, Seeds JW, for the ACOG Committee on ablation versus hysterectomy for heavy menstrual bleeding. Cochrane Gynecologic Practice. ACOG technology assessment in obstetrics and Database Syst Rev 1999;(2):CD000329.
gynecology, No. 3, September 2003. Saline infusion sonohysterogra- 38. Bourdrez P, Bongers MY, Mol BW. Treatment of dysfunctional uterine phy. Obstet Gynecol 2003;102:659-62.
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39. Kennedy AD, Sculpher MJ, Coulter A, Dwyer N, Rees M, Abrams KR, 24. de Vries LD, Dijkhuizen FP, Mol BW, Brolman HA, Moret E, Heintz AP. et al. Effects of decision aids for menorrhagia on treatment choices, Comparison of transvaginal sonography, saline infusion sonography, and health outcomes, and costs: a randomized control ed trial [Published hysteroscopy in premenopausal women with abnormal uterine bleeding. correction appears in JAMA 2003;289:703]. JAMA 2002;288:2701-8.
40. Abbott JA, Hawe J, Garry R. Quality of life should be considered the 25. Hurskainen R, Teperi J, Rissanen P, Aalto AM, Grenman S, Kivela A, primary outcome for measuring success of endometrial ablation. J Am et al. Quality of life and cost-effectiveness of levonorgestrel-releasing Assoc Gynecol Laparosc 2003;10:491-5.
intrauterine system versus hysterectomy for treatment of menorrhagia: 41. Cooper KG, Jack SA, Parkin DE, Grant AM. Five-year fol ow up of a randomised trial. Lancet 2001;357:273-7.
women randomised to medical management or transcervical resection 26. Lethaby A, Irvine G, Cameron I. Cyclical progestogens for heavy men- of the endometrium for heavy menstrual loss: clinical and quality of life strual bleeding. Cochrane Database Syst Rev 1998;(4):CD001016.
27. Mil er L, Hughes JP. Continuous combination oral contraceptive pil s 42. Learman LA, Summitt RL Jr, Varner RE, Richter HE, Lin F, Ireland CC, to eliminate withdrawal bleeding: a randomized trial. Obstet Gynecol et al. Hysterectomy versus expanded medical treatment for abnormal uterine bleeding: clinical outcomes in the medicine or surgery trial. 28. Lethaby A, Augood C, Duckitt K. Nonsteroidal anti-inflammatory drugs Obstet Gynecol 2004;103(5 pt 1):824-33.
for heavy menstrual bleeding. Cochrane Database Syst Rev 1998;(3): 43. Kuppermann M, Varner RE, Summitt RL Jr, Learman LA, Ireland C, Vittinghoff E, et al., for the Ms Research Group. Effect of hysterec- 29. Beaumont H, Augood C, Duckitt K, Lethaby A. Danazol for heavy men- tomy vs medical treatment on health-related quality of life and sexual strual bleeding. Cochrane Database Syst Rev 2002;(2):CD001017.
functioning: the medicine or surgery (Ms) randomized trial. JAMA 30. Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for heavy menstrual bleeding. Cochrane Databse Syst Rev 2000;(4):CD000249.
44. Abbott J. Immediate endometrial resection for menorrhagia was more 31. Lethaby AE, Cooke I, Rees M. Progesterone/progestogen releasing effective in the long term than initial medical management [Commen- intrauterine systems versus either placebo or any other medication tary]. Evidence-based Obstet Gynecol 2002;4:126-7.
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