Management of menorrhagia

Management of Menorrhagia CLINICAL PRACTICE Management of Menorrhagia MINISTRY OF HEALTH MALAYSIA ACADEMY OF MEDICINE MALAYSIA GUIDELINES DEVELOPMENT AND OBJECTIVES
Guidelines Development
The work group for the development of these guidelines comprised Obstetricians and
Gynaecologists from various Ministry of Health and Ministry of Education facilities.
These guidelines were adapted from other international guidelines on management of
menorrhagia or heavy menstrual bleeding and modified to suit the local situation. These
include guidelines from New Zealand, Canada and the Royal College of Obstetrics and
Gynaecologists, UK. A systematic review of current evidence was carried out. Ranking
of evidence are based on a modified version of those used by the Catalonia Agency for
Health Technology Assessment (CAHTA) Spain; the classification of recommendation
was emulated from those used by the Scottish Intercollegiate Guidelines Network
(SIGN). The ranking of evidence is based on a modified version of that suggested by the
Catalonia Agency for Health Technology Assessment and Research (CAHTAR) Spain,
while the grading of recommendations in these guidelines emulates those used by the
Scottish Intercollegiate Guidelines Network (SIGN).The draft guidelines were posted on
both the Ministry of Health Malaysia and Academy of Medicine, Malaysia websites for
comment and feedback. These guidelines have also been presented to the Technical
Advisory Committee for Clinical Practice Guidelines and Health Technology Assessment
and Clinical Practice Guidelines Council, Ministry of Health Malaysia for review and
approval.

Objectives
The aim of this guideline is to aid doctors in general practice and gynaecologists in
clinical decision making, by providing well-balanced information on the management of
patients with menorrhagia.
Clinical Questions
The clinical questions for these guidelines are:
i.
How should the extent of heavy menstrual flow (menorrhagia) be assessed? How can menorrhagia be alleviated? How can patients with menorrhagia be treated successfully?
Target Population
These guidelines are developed to apply to women with menorrhagia.
Target Group
These guidelines are meant for all health care providers.
Management of Menorrhagia GUIDELINES COMMITTEE
Obstetrician & Gynaecologist Obstetrics & Gynaecology Obstetrician & Gynaecologist Obstetrics & Gynaecology Sultanah Aminah Hospital, Johor Bahru Datuk Dr Ghazali Ismail Obstetrician & Gynaecologist Obstetrics & Gynaecology Tengku Ampuan Afzan Hospital, Kuantan Assoc Prof Dr Ng Soon Pheng Obstetrician & Gynaecologist Obstetrics & Gynaecology University of Malaya Medical Centre Assoc Prof Dr Nik Mohamed Zaki Nik Mahmood Obstetrician & Gynaecologist Obstetrics & Gynaecology School of Medical Sciences, Health Campus, Science University of Malaysia Dr Shah Reza Johan Noor Consultant Obstetrician & Gynaecologist Obstetrics & Gynaecology School of Medical Sciences, Health Campus, Science University of Malaysia Dr Ahmad Zailan Hatta Obstetrician & Gynaecologist Obstetrics & Gynaecology University of Malaya Medical Centre Guidelines Coordinator
Ms Sin Lian Thye
Nursing Officer
Health Technology Assessment Unit
Ministry of Health Malaysia
Reviewed and edited by
Dr S Sivalal
Head, Health Technology Assessment Unit
Deputy Director
Medical Development Division
Ministry of Health Malaysia
We would like to express our deepest gratitude and appreciation to all those who had provided valuable input and feedback on the draft guidelines. Management of Menorrhagia LEVELS OF EVIDENCE SCALE
Strength of evidence Meta-analysis of RCT, Systematic review Large sample RCT Small sample RCT Non-randomised controlled prospective trial Non-randomised controlled prospective trial with Fair historical control Poor Case-control Non-controlled clinical series, descriptive studies Poor multi-centre Expert committees, consensus, case reports, (Adapted from Catalonian Agency for Health Technology Assessment & Research, [CAHTAR] Spain) GRADE OF RECOMMENDATIONS
At least one meta analysis, systematic review, or RCT, or evidence rated as A good and directly applicable to the target population
Evidence from well conducted clinical trials, directly applicable to the target B population, and demonstrating overall consistency of results; or evidence
extrapolated from meta analysis, systematic review, or RCT Evidence from expert committee reports, or opinions and /or clinical C experiences of respected authorities; indicates absence of directly applicable
clinical studies of good quality (Adapted from Scottish Intercollegiate Guidelines Network [SIGN])
Management of Menorrhagia TABLE OF CONTENTS
Guidelines Development and Objective Level of Evidence Scale & Grade of Recommendations ASSESSMENT AND INVESTIGATION Assessment of menstrual blood loss Pattern of menstrual blood loss Full Blood Count Thyroid function tests Assessment of endometrium 3.6.1. Ultrasound 3.6.2. Hysteroscopy and endometrial biopsy Non Steroidal Anti Inflammatory Drugs Combined oral contraceptive pills 4.1.4 Danazol Anti-fibrinolytic agents 4 Levonorgestrel intrauterine system 4.1.7 GnRH Medical versus surgical treatment Dilatation and curettage 5 Endometrial destruction 6 Hysterectomy 6 Appendix 1 : Comparison of different drugs used in medical treatment of heavy menstrual bleeding Appendix 2 : Comparison of the benefit and side effects of various drugs used in medical treatment of heavy menstrual bleeding Appendix 3: Choice of medical therapy for various conditions Appendix 4 : Decision analysis ranking on the use of medical therapy Appendix 5 :Recommended dosages of medical therapy Management of Menorrhagia 1. BACKGROUND

Menorrhagia, or heavy menstrual bleeding, is an important cause of ill health in women.
It is estimated that 9 to 30 percent of women of reproductive age suffer from
menorrhagia, the prevalence increasing with age, and peaking just prior to menopause
(Society of Obstetricians and Gynaecologists of Canada, 2001; level 9). Menorrhagia has
an impact on many women's lives, with one in twenty women aged 30 - 49 with
menorrhagia consulting their general practitioners each year. It has been found that once
referred to a gynaecologist, 60% of women with menorrhagia will have a hysterectomy
within five years, accounting for up to 75 percent of all hysterectomies performed
worldwide. (RCOG, 1998; 2001; level 9)
Apart from surgery, medical therapy, appears to be an attractive treatment option, there
being a wide variety of medication available to reduce heavy menstrual bleeding
including non-steroidal anti-inflammatory drugs, hormones, anti-fibrinolytics, and
intrauterine devices. However, there is considerable variation in practice, and uncertainty,
about the most appropriate therapy, due to age, desire to preserve fertility, co-existing
medical conditions, and patient preferences (RCOG, 1998; 2001; level 9).
2 DEFINITION

Menorrhagia can be defined as a complaint of heavy cyclical menstrual blood loss over
several consecutive menstrual cycles in a woman of reproductive years, or more
objectively, a total menstrual blood loss of more than 80 ml per menstruation (Hallberg et
al, 1966).
3
ASSESSMENT AND INVESTIGATION
Assessment of menstrual blood loss
There is poor correlation between a woman's perception of heavy menstrual bleeding and
menstrual blood loss of more than or equal to 80 ml/cycle, and between the amount of
sanitary pads used and the complaint of heavy bleeding (Hallberg et al, 1966; Janssen et
al, 1995; level 5).
The gold standard for measuring menstrual bleeding is the alkaline haematin test, which
is not freely available in most hospitals in Malaysia, since it is currently considered as an
investigative tool for research.
A simpler alternative to this is the pictorial blood loss assessment chart, that does not
involve collection of all used sanitary material. It has also been found to correspond well
with the alkaline haematin test (Katrina et al, 2001), and has been validated to be better
than the patient's verbal history alone (Higham et al, 1990; level 5; Janssen et al, 1995;
level 5).
Management of Menorrhagia Pattern of menstrual blood loss
It has been noted that while 80-90 % of women with heavy menstrual bleeding have regular cycles, those with prolonged irregular and/or intermenstrual bleeding tend to have other intrauterine pathology (Dijkhuizen et al, 1996; level 5). On the other hand, for peri-menopausal women with delayed menstrual cycles, further investigation is only necessary if blood loss is excessive. 3.3 Pelvic
examination
An abdominal and pelvic examination to exclude obvious pelvic pathology, is advised in all patients. The Malaysian National Cervical Screening Programme has recommended a cervical smear be taken at the time of the pelvic examination, a pelvic ultrasound be carried out to confirm any abnormal finding, and subsequent referral to a gynaecologist as indicated. Full Blood Count
Since more than two thirds of women with menstrual blood loss greater than 80 ml per cycle have evidence of anaemia, a low haemoglobin reading is considered an objective indicator of heavy menstrual bleeding. However, a normal haemoglobin reading does not necessarily exclude heavy menstrual bleeding (Hallberg et al, 1966; Janssen et al, 1995; level 5). Since the signs and symptoms of anaemia do not correlate well with the haemoglobin level until the patient is moderately to severely anaemic, a full blood count would assist in determining the severity of menstrual blood loss. Thyroid function test
There is no evidence of heavy menstrual bleeding being associated with thyrotoxicosis,
but there is some evidence of association in hypothyroid patients (Krassas et al, 1994;
level 9; Attaran et al 1989). Hence, a routine thyroid function test is not recommended.
3.6
Assessment of endometrium
Endometrial pathology in pre-menopausal women with abnormal uterine bleeding is uncommon, with only 20% of cases of endometrial cancer occurring before menopause, mostly in women are aged between 40 – 50 years (Crissman et al, 1981; level 9; Jefrery et al, 1997; Mckenzie & Bibby, 1978, ). Endometrial hyperplasia is associated with obesity and age, being more common in women above 45 years of age, with a prevalence of hyperplasia of 2 – 7 % in pre-menopausal women (Dijkhuzen et al, 1996; level 5; Ash, Farrell & Flowerden, 1996; level 8; Crissman et al, 1981; level 9; Farquhar, 1998). It is a precursor of endometrial cancer, the likelihood of progression depending on the degree of hyperplasia (Ash, Farrell & Flowerden, 1996; level 8; Farquhar, 1998; Kurman, Kaminski & Norm, 1985; level 9 ; Terakawa, 1997; level 9; Hunter et al, 1994; level 9). Infertility and nulli-parity are also significantly associated with hyperplasia. Women who have received tamoxifen appear to be at increased risk of endometrial hyperplasia. However, 14% of the women diagnosed with endometrial hyperplasia had none of the above risk factors. Management of Menorrhagia The Royal College of Obstetricians and Gynaecologists recommends that women with heavy menstrual bleeding but with regular cycles, aged 40 years or less, need not have endometrial samples taken (RCOG, 1994; level 9). However, some authors suggest that women with irregular bleeding or other risk factors for hyperplasia, should have endometrial sampling irregardless of age (Ash, Farrell & Flowerden, 1996; level 9). The commonly used modes of endometrial assessment are ultrasound scan, endometrial biopsy or aspirate, hysteroscopy and dilatation and curettage (D&C). 3.6.1. Ultrasound
Ultrasonography is a primary diagnostic tool in evaluating women with abnormal vaginal
bleeding, being able to demonstrate anatomic findings not frequently detected in pelvic
examination. These include small ovarian cysts, leiomyoma, endometrial carcinoma, as
well as evaluation of the endometrium with respect to thickness, which would indirectly
reflect the endometrial histology, and hormonal status of patients (Okaro, 2003).
Transvaginal ultrasonography (TVS) is an accurate test for diagnosing endometrial hyperplasia when the endometrial thickness is 12 mm or more (Dijkhuizen et al, 1996; level 5; Vercellini et al, 1997; level 5). In women more than 40 years old and who failed medical treatment, 50% have an abnormal TVS (Nagele et al, 1996; level 5) 3.6.2. Hysteroscopy and endometrial biopsy Hysteroscopy allows for the examination of the whole endometrial cavity, lower segment and cervical canal, being able to detect small polyps or sub-mucous fibroids that have been missed by ultrasonography, endometrial biopsy or blind curettage. In women with irregular bleeding, polyps are present in about 25 % of cases and submucous fibroids are present in 15 – 18 % of cases (Fedele et al, 1991; level 5; Dijkhuizen et al, 1996; level 5). Hysteroscopy with biopsy is the best diagnostic test for intrauterine pathology with high specificity and sensitivity (Emanuel et al, 1995; level 5; Dijkhuizen et al, 1996; level 5). Hysteroscopy alone (without biopsy) is not very accurate in diagnosing endometrial hyperplasia and carcinoma (Widrich et al, 1996; level 9; Vercellini et al, 1997; level 5). The main purpose of an endometrial biopsy or aspirate is to exclude endometrial pathology like hyperplasia, endometrial disorders or malignancies. Endometrial biopsy is a simple, quick, safe, and convenient procedure, which can be performed on an ambulatory basis avoiding the need for anesthesia. Furthermore, the device is disposable and is less costly than the conventional D & C. Routine endometrial biopsy should not be an initial investigation for menorrhagia, being indicated only if menorrhagia persists or in the presence of risk factors (RCOG, 1998, level 9). Pipelle and Z sampler could be used as the first line endometrial device as they have been found to be more convenient to use compared to the Vabra aspirator (Bunkheila & Powell, 2002). While the sample adequacy rate was similar for these 3 devices, the Management of Menorrhagia Pipelle has been shown to be superior in the detection of atypical hyperplasia and
endometrial carcinoma (Dijkhuizen et al, 1996, level 5).
4 MANAGEMENT

4.1 Medical
Treatment
4.1.1 Non Steroidal Anti-Inflammatory Drugs
Endometrial prostaglandins are elevated with excessive menstruation, and he non-
steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels through the
inhibition of the cyclo-oxygenase enzyme with reductions in menstrual blood loss of 25-
35% (Irvine &, Cameron, 1999; level 9). NSAIDs are found to be less effective than
tranexamic acid or danazol, but as effective as other medical treatments (Lethaby, Irvine
& Cameron, 2003; level 1), with the added advantage of relieving dysmenorrhoea (Fraser
et al, 1981; level 3)
4.1.2 Progestogens
Progestogens administered from the fifteenth day or from 19th - 26th day of the
menstrual cycle were significantly less effective in reducing menstrual blood loss when
compared to other medical therapies (Lethaby, Irvine & Cameron, 2003; level 1), and
found to be one of the least effective agents (Roy & Bhattacharya, 2004; level 5).
However, progestogen therapy administered for 21 days of the menstrual cycle results in
a significant reduction in menstrual blood loss, (Lethaby, 2003b; level 1), although they
have been found to be ineffective unless taken at high doses (Irvine & Cameron, 1999;
level 9).

4.1.3 Combined oral contraceptive pills
The combined oral contraceptive pill (OCP) in addition to providing contraception causes
a 50% reduction in menstrual blood loss by regular shedding of a thinner endometrium
nd by inhibiting ovulation (Irvine & Cameron, 1999, level 9). 4.1.4 Danazol Danazol is a synthetic steroid that suppresses oestrogen and progesterone receptors in the endometrium, leading to endometrial atrophy (thinning of the lining of the uterus) and reduced menstrual loss. It is an effective treatment for heavy menstrual bleeding. However, its side-effect profile, its lack of acceptability to women and the need for continuing treatment limits its use (Roy & Bhattacharya, 2004; level 5; Beaumont et al, 2003; level 1). 4.1.5 Anti-fibrinolytic agents Tranexamic acid, a synthetic derivative of the amino acid lysine, exerts an anti-fibrinolytic effect through reversible blockade on plasminogen, producing a 50% reduction in menstrual loss (Irvine & Cameron, 1999; level 9). Anti-fibrinolytic therapy causes a greater reduction in objective measurements of heavy menstrual bleeding compared to placebo or other medical therapies (Lethaby, Farquhar & Cooke 2003; level 1 Bonnar & Sheppard, 1996, level 1), and is not associated with an increase in side effects (Lethaby, Farquhar & Cooke, 2003; level 1, Lindoff, Rybo & Astedt, 1997; level 5). Management of Menorrhagia 4.1.6 Levonorgestrel intrauterine system
The levonorgestrel intrauterine system (LNG IUS) is a T shaped intrauterine device
releasing a steady amount of levonorgestrel (20µg /24 hours) from a steroid reservoir
around the vertical stem of the device. It reduces menstrual blood loss by 80% (Irvine &
Cameron, 1999; Level 9), and is found to be more effective than cyclical norethisterone,
with patients being more satisfied and willing to continue with treatment. However, these
patients experience more side effects such as inter-menstrual bleeding and breast
tenderness (Lethaby, 2003; level 1). Compared to transcervical resection of the
endometrium (TCRE), the LNG IUS produces smaller mean reduction in menstrual blood
loss, but there is no difference in the rate of satisfaction with treatment. LNG-IUS
appears equally beneficial in improving quality of life and may control bleeding as
effectively as conservative surgery over the long term (Marjoribanks, Lethaby, &
Farquhar, 2003; level 1).

4.1.7 GnRH
Gonadatrophin-releasing hormone (GnRH) agonists induce a reversible hypoestrogenic
state, reducing total uterine volume. They are highly effective, but their side-effects make
them suitable only for short-term use (Irvine & Cameron, 1999, level 9).GnRH agonists
may obviate emergency surgery in patients with high surgical risk (Vercellini, 1992; level
3).
4.2
Surgical Management
4.2.1 Medical versus surgical treatment Medical treatment for menorrhagia is not as effective as surgery despite improvement in control of bleeding. Oral medical therapy is associated with higher incidence of side effects, and approximately 60% of women who had medical treatment would require surgery by 2 years. Surgery has been found to reduce menstrual bleeding more than medical treatment at one year, although the majority of women prefer medical treatment (Marjoribanks, Lethaby & Farquhar, 2003; level 1). 4.2.2 Dilatation and curettage There is little evidence on the effectiveness of dilatation and curettage (D&C) for the relief of menorrhagia. It is not cost effective for the diagnosis of endometrial malignancy in women under 40 years since the prevalence of serious uterine conditions and endometrial cancer is low (Coulter et al, 1993; level 9). The potential benefits need to be weighed against the risks of anaesthesia and possible complications like uterine perforation and laceration of the cervix (MacKenzie & Bibby, 1978; level 9). Moreover, a significant proportion of endometrial lesions are not detected by D&C, (Vessey, Clarke, & MacKenzie, 1979) and its usefulness as a diagnostic tool has been repeatedly questioned. D&C may have a diagnostic role when endometrial biopsy is inconclusive and the symptoms persist or when the underlying pathology is suspect. Management of Menorrhagia 4.2.3 Endometrial destruction Endometrial destruction procedures are less invasive, more convenient and less expensive when no other gynecological condition is involved. It enables women to avoid major surgery and results in shorter hospital stay and convalescence. The various energy sources used to destroy the endometrium, are all comparable in terms of efficacy, and the re-operation rate ranges from 0 to 38.2%. The rate is higher in women under the age 35 years in studies where they have been observed for longer duration. The first-generation techniques involve lower costs than a hysterectomy, but the second-generation endometrial destruction techniques involve relatively high purchase and disposable supplies costs. However, these new techniques take less time to perform and have a lower incidence of intra-operative complications. The clinical impact of these two benefits has yet to be demonstrated (AETMIS, 2002; level 1). 4.2.4 Hysterectomy Hysterectomy is the most widely used treatment, and can be performed abdominally, vaginally or laparoscopically. The vaginal and laparoscopic approaches cause fewer complications and provide a shorter hospital stay and convalescence than abdominal hysterectomy. Although with hysterectomy there is a permanent cessation of menstrual flow resulting in a high level of satisfaction, it is a major invasive procedure incurring morbidity, mortality and costs with a risk of late complications as well. (AETMIS, 2002; level 1). Laparoscopic assisted vaginal hysterectomy is associated with longer operating times, and higher operating costs, but total costs are lower than abdominal hysterectomy. Management of Menorrhagia SUMMARY OF RECOMMENDATIONS

ASSESSMENT

1. Women should be encouraged to chart their menstrual blood loss using a pictorial
blood loss assessment chart (Grade B)
2. Women with erratic bleeding (regardless of loss) should be referred to a specialist as endometrial pathology is likely to be present (Grade B)

INVESTIGATION

1.
Perimenopausal women with less frequent menstrual cycles but with normal blood
loss, do not require further investigation as they are not at increased risk of
intrauterine pathology. (Grade C)
An abdominal and pelvic examination should be performed in women presenting
with heavy menstrual bleeding (Grade C).
Full blood count should be offered to all women presenting with heavy bleeding
(Grade A).
Women with heavy menstrual bleeding with severe anemia, should be referred to a
specialist for further assessment (Grade C).
Thyroid function test should not be routinely performed in women with heavy
menstrual bleeding unless they have signs or symptoms of hypothyroidism (Grade
C).
Transvaginal sonography, (TVS) if available, should be the first step in assessing
the endometrium (Grade B)
If the endometrial thickness on TVS is more than 12 mm an endometrial sampling
should be done (Grade A)
The chance of endometrial carcinoma in women less than 40 years is low and
endometrial biopsy is not warranted unless there are associated risk factors, or, if
symptoms are persistent or fail to respond to medical treatment (Grade B).
Hysteroscopy with biopsy is indicated for women with erratic menstrual bleeding,
failed medical therapy, or transvaginal ultrasound suggestive of intrauterine
pathology (Grade B)
10. Hysteroscopy with biopsy is indicated in women with menorrhagia if aged more than 40 (Grade B)
Management of Menorrhagia MEDICAL TREATMENT
NSAIDs are effective for reducing heavy menstrual bleeding (Grade A)
Progestogens given in the luteal phase of the menstrual cycle are not effective in
reducing regular heavy menstrual bleeding (Grade A)
Treatment with progesterone for 21 days (days 5-25) is effective in reducing
menstrual blood loss (Grade A)
Oral contraceptives can be used to reduce heavy menstrual bleeding (Grade A)
Danazol is effective for reducing heavy menstrual bleeding but side effects limit it
use (Grade A)
Tranexamic acid is effective for reducing heavy menstrual bleeding (Grade A)
The levonorgestrel releasing intrauterine system is effective in reducing heavy
menstrual bleeding (Grade A)
GnRH agonists are highly effective but used for short term only (Grade A)

SURGICAL MANAGEMENT
1.
Surgical option is more effective in treatment of menorrhagia compared to medical
therapy. LNG-IUS is a reasonable alternative to surgical therapy provided patients
are aware of possible need for further surgical treatment later (Grade B)
While D&C may have a diagnostic role, it is not effective therapy for women with
menorrhagia (Grade C)
Endometrial destruction procedure provides an alternative treatment option to
hysterectomy (Grade A)
Vaginal hysterectomy is the most cost-effective mode of hysterectomy (Grade B)
Management of Menorrhagia ALOGRITHM OF MANAGEMENT OF MENORRHAGIA
Women complaining of heavy menstrual bleeding Full history and physical examination Assess severity of Refer for further Treat anaemia & asses risk of hyperplasia Low risk group & -bodyweight > 90kg unexplained menstrual -other risk factors Assess endometrium - endometrial biopsy if ET - 12mm or TVS not available -Levonogestrel intrauterine device -Tranexamic acid - NSAID -Norethisterone -Oral contraceptive pill Treatment Successful If abnormal endometrium Management of Menorrhagia REFERNCES
Agence d'évaluation des technologies et des modes d'intervention en santé (AETMIS). Endometrial ablation techniques in the treatment of dysfunctional uterine bleeding. Report prepared by Chantale Lessard and Alicia Framarin. (AETMIS 02-04 RF). Montréal: AETMIS, 2002, xxxi-166 p. Ash SJ, Farrell SA, Flowerden G. (1996) Endometrial biopsy in DUB. J Reprod Med, 41, pp 892-896 Attaran M., Boes C, Weber AM, Gidwani G. (1997) Evaluation of adolescents with abnormal uterine bleeding. 1997 Beaumont H, Augood C, Duckitt K, Lethaby A (2003) Danazol for heavy menstrual bleeding Cochrane Database Syst Rev. (2):CD001501 Bonnar J, Sheppard BL. (1996) Treatment of menorrhagia during menstruation: randomised controlled trial of ethamsylate, mefenamic acid, and tranexamic acid. BMJ; 313, pp 579-582. Bunkheila AK, Powell MC. (2002) Menorrhgia and DUB. Current Obst & Gynecol , 12, pp 328-333 Crissman JD, Azoury RS, Barnes AE, Schellhas HF. (1981) Endometrial carcinoma in woman 40 years of age or younger. Obstet Gynecol, 57, pp 699-704 Coulter A, Klassen A, MacKenzie IZ, McPherson K. (1993) Diagnostic dilatation and curettage: is it used appropriately? BMJ; 306, pp 236-239. Dijkhuizen FP, Brolmann HA, Potters AE, Bongers MY, Bongers MY, Heinz AP (1996). The accuracy of transvaginal ultrasonography in the diagnosis of endomendometrial thicknessrial abnormalities. Obstendometrial thickness Gynaecol ,87, pp345-349 10. Emanuel MH, Verdel MJ, Wamsteker K, Lannes FB. (1995) A prospective comparison of transvaginal ultrasonography and diagnostic hysteroscopy in the evaluation of patients with abnormal uterine bleeding. Am J Obstet Gynecol, 172, pp 547-552 11. Farquhar CML endometrial thickness by A, Sowter M, Verry J, Baranyai J. (1998) An evaluation of risk factors for endometrial hyperplasia in premenopausal women with abnormal menstrual bleeding ,1998. 12. Fedele L, Bianchi S, Dorta M, Brioschi D, Zanotti F, Vercellini P. (1991) Transvaginal ultrasonography versus hysteroscopy in the diagnosis of uterine submucous myomas. Obstet Gynecol , 77, pp 745-748 13. Guidelines for the management of abnormal menstrual bleeding - Society of Obstetricians and Gynaecologists of Canada, 2001Canada 14. Hallberg L, Hogdahl A, Nilsson L, Rybo G (1966). Menstrual blood loss- a population study: variation at different ages and attempts to define normality. Acta Obstetricia Gynecologica Scandinavica, 45, pp 320-351 15. Higham JM, O'Brien PMS, Shaw RW. (1990) Assessment of menstrual blood loss using a pictorial chart. Br. J Obstet Gynaecol, 97, pp734-9 16. Hunter JE, Tritz DE, Howell MG, DePriest PD, Gallion HH, Andrews SJ et al, (1994) The prognostic and therapeutic implications of cytologic atypia in patients with endometrial hyperplasia. Gynecol Oncol, 55, pp 66 – 71 17. Irvine GA, Cameron IT. (1999) Medical management of dysfunctional uterine bleeding Baillieres Best Pract Res Clin Obstet Gynaeco;13(2), Jun, pp189-202 Management of Menorrhagia 18. Janssen CA, Scholten PC, Heintz AP. (1995) A simple visual assessment technique to discriminate bendometrial thicknessween menorrhagia and normal menstrual blood loss. Obstendometrial thicknessrics & Gynecology, 85, pp 977-982 19. Jefrery JD, Taylor R, Robertson DI, Stuart GC. (1997) Endometrial carcinoma occurring in patients under the age of 45 years. Am. J Obstet Gynaecol, 261, pp 485-489 20. Katrina MW, Paul WD, Tracy JW, O'Brien PMS. (2001) DEendometrial thickness determination of total menstrual blood loss. Fertility & Sterility,76,(1), pp125-131 21. Krassas GE, Pontikides N, Kaltsas T, Papdopolou P, Batrinos M. (1994) Menstrual disturbances in thyrotoxicosis. Clin Endocrinol, 40 pp 641-644 22. Kurman RJ, Kaminski PF, Norm HJ. (1985) The behaviour of endometrial hyperplasia. A long-term study of untreated hyperplasia in 170 patients. Cancer, 56, pp 403-412 23. Lethaby AE, Cooke I, Rees M. (2000) Progesterone/progestogen releasing intrauterine systems versus either placebo or any other medication for heavy menstrual bleeding. Cochrane Database Syst Rev. (2):CD002126. 24. (2000) Antifibrinolytics for heavy menstrual bleeding. Cochrane Database Syst Rev.(4):CD000249 25. Lethaby A, Augood C, Duckitt K (2003a) Nonsteroidal anti-inflammatory drugs for heavy menstrual bleeding. Cochrane Database Syst Rev. (1): CD000400. 26. Lethaby A, Irvine G, Cameron I (2003b) Cyclical progestogens for heavy menstrual bleeding. Cochrane Systematic Review 1 28. Marjoribanks J, Lethaby A, Farquhar C. (2003) Surgery versus medical therapy for heavy menstrual bleeding. Cochrane Database Syst Rev. (2):CD003855. 29. MacKenzie IZ, Bibby JG. (1978) Critical assessment of dilatation and curettage of 1029 women. Lancet, 2: 566-568. 30. Nagele F, O'Connor H, Davies A, Badeery A, Mohamed H, Magos A. (1996) 2500 Outpatient diagnostic hysteroscopies. Obstet Gynecol, 88, pp 87-92 31. National Health Committee New Zealand (1998) Guidelines for the management of heavy menstrual bleeding, May 32. Okaro E. (2003) The role of ultrasond in the management of menorrhagia. Review Gynecol Practice,3, pp 16-25 33. RCOG Evidence-based clinical guideline number 1 : The initial management of menorrhagia, 1998. 34. Roy SN, Bhattacharya S (2004) Benefits and risks of pharmacological agents used for the treatment of menorrhagia. Drug Saf, 27(2), pp75-90 35. Terakawa N, Kigawa J, Takendometrial thicknessani Y, Yoshikawa, Yajima A, Noda K. (1997) The behaviour of endometrial hyperplasia: A prospective study. J Obstet Gynaecol Res, 28, pp 223-230 36. Vercellini P, Cortesi I, Oldani S, Moschssta M, De Giorgi O, Crosignani PG. (1997) The role of transvaginal ultrasonography and outpatient diagnostic Management of Menorrhagia hysteroscopy in the evaluation of patients with menorrhagia. Human Reprod, 12, pp 1768-1771 37. Vessey M, Clarke J, MacKenzie I. (1979) Dilatation and curettage in young women. Health Bull, 39: 59-62. 38. Wildrich T, Bradley LD, Mitchinson AR, Collin RL.(1996)Comparison of saline infusion sonography with office hysteroscopy for the evaluation of the endometrium. Am. J Obstet Gynecol,174, pp 1327-1334 Management of Menorrhagia Appendix 1
COMPARISON OF DIFFERENCE DRUG USE IN MEDICAL TREATMENT OF HEAVY MENSTRUAL BLEEDING Comparative table of medical therapy for the treatment of heavy menstrual bleeding Drug Mean reduction in blood Women benefiting – proportion with MBL<80ml/cycle (%) Oral progesterone (days 5-25) Tranexamic acid Oral progesterone (luteal phase) (Guidelines for the management of heavy menstrual bleeding -New Zealand, 1998) Management of Menorrhagia Appendix 2
COMPARISON THE BENEFIT AND SIDE EFFECT OF VARIOUS DRUG USE IN MEDICAL THERAPY OF HEAVY MENSTRUAL BLEEDING Comparative table of medical therapy for the treatment of heavy menstrual bleeding Drug Specific benefits Adverse benefits Menstrual cramps Oral progesterone Bloating, moody, PMS, Nausea, diarrhoea Nausea, diarrhoea, OC Contraception Nausea, breast tenderness, Relieve dysmenorrhoea Weight gain, acne, hot flushes, bloating, moody, PMS (Guidelines for the management of heavy menstrual bleeding -New Zealand, 1998) Management of Menorrhagia APPENDIX 3
CHOICE OF MEDICAL THERAPY FOR VARIOUS CONDITIONS The choice of medical therapy will be dependent on the individual patient requirements Contraception LNG Dysmenorrhoea LNG Unable to tolerate hormones NSAIDs Tranexamic acid LNG IUS Trying to conceive NSAIDs Tranexamic acid Progestogen followed by clomiphene* Cyclic progestogens Perimenopausal women* Cyclic progestogens pre surgery with severe anaemia** Some women who have completed their family may decline medical therapy and choose surgery as a first option Note * Clinical management guidelines for management of an ovulatory bleeding (ACOG, 2000) Vercellini P on Gonadotropin releasing hormone agonist treatment for severe
menorrhagia in patients with contraindications to surgery, Eur J Obstet Gynecol
Reprod Biol. 1992 Jun 16; 45(1):70-2)
(Guidelines for the management of heavy menstrual bleeding -New Zealand, 1998) Management of Menorrhagia Appendix 4
DECISION ANALYSIS RANKING ON THE USE OF MEDICAL THERAPY
Medical Therapy* Ranking according to decision analysis** NSAIDs 2 OC 3 Norethisterone D5-25 15mg daily Danazol 4 (Guidelines for the management of heavy menstrual bleeding -New Zealand, 1998) - more than one therapy can be considered - based on efficacy , side effect profile and acceptability to women over 12 Management of Menorrhagia Appendix 5
RECOMMENDED DOSE OF MEDICAL THERAPY
1g every 6 hours for the first 4 days NSAIDs D1- D5 or until cessation of Mefenemic acid 500mg TDS OC containing 30ug ethinyloestradiol Progestogens D5-25 Norethisterone 15mg daily or Medoxyprogesterone 30mg daily 100-200mg daily for 3 months (Guidelines for the management of abnormal menstrual bleeding -Canada)

Source: http://www.sgh-og.com/wp-content/uploads/2014/03/2004-cpg-management-of-menorrhagia.pdf