2. Mrs Smith 25 yr old banker
PC-
◦ heavy periods and mild pain, which now affects her job
HPC-
◦ since she started periods at 13
◦ Pain relieved by Ibuprophen
◦ Regular pad changes (20 per cycle)
◦ Some flooding
◦ Often tired
◦ Affecting quality of life
3. Increased menstrual blood loss ->80ml/cycle
15% of women have diagnosis.
Quality of life assessment
20. Lethaby A, Farquitiari C, Cooke I (2000)
AIM: To determine the effectiveness of antifibrinolytics in
achieving reduction in HMB
Selection: RCT – reproductive age. No PCB/IMB. 4 used.
21. Results: Antifibrinolytics compared to placebo
Significant reduction in mean blood loss
WMD -94.0 (CI -151.4 - -36.5)
Significant change in reduction of blood loss
-110.2 (CI -146.5— -73.8)
22. AF’s compared to:
Mefenamic acid WMD -73.0,
95% CI -123.4 to -22.6
Norethisterone - WMD -111.0,
95% CI -178.5 to -43.
Ethamsylate -WMD -100,
95% CI -143.9 to -56.1
23. Women preferred Tranexamic acid (wasn't significant)
– Flooding and sex life.
Conclusion – Antifibrinolytic therapy causes greater
reduction in objective measurements of HMB
compared to placebo and medical therapies
24. NSAIDs
Coulter A, Kelland J, Peto V, et al. 1995
Treating menorrhagia in primary care: An overview of
drug trials and a survey of prescribing
Concluded that NSAIDs work. They are not the most
effective but have a much better side-effect profile
25. NSAIDs
Mefenamic acid
(ten studies) reduction in MBL = 29.0%
[95% CI 27.9% to 30.2%];
Diclofenac
(two studies) reduction in MBL = 26.9%
[95% CI 23.3% to 30.6%];
Naproxen
(five studies) reduction in MBL = 26.4%
[95% CI 24.6% to 28.3%];
Ibuprofen
(three studies) reduction in MBL =16.2%
[95% CI 13.6% to 18.7%])
26. 2 RCT = no effect on menstrual bleeding, if
given during the luteal phase.
One small trial of 44 women supports
continuous progesterone between days 5-26.
MBL ↓83%
27. Treatment Reduction in
blood loss (%)
Source of
evidence
Additional comment
Levonorgestrel-releasing
intrauterine system
71–90 Several high-
quailty RCTs
Compared favourably with other treatments in head-to-head trials in terms
of effectiveness and patient satisfaction
Tranexamic acid 29–58 Several high-
quality RCTs
No long-term outcomes have been reported
Nonsteroidal anti-
inflammatory drugs
20–49 Several high-
quality RCTs
Mefenamic acid most effective, ibuprofen significantly less effective
Also effective treatment for menstrual pain
Combined oral contraceptive 43 One small RCT
(n = 45)
Other benefits including regulation of cycles and reduction in breast pain
High-dose oral
progestogen*
83 One small RCT
(n = 44)
Not as effective or preferred as the levonorgestrel-releasing intrauterine
system
Requires long-term use
Long-acting progestogen 22–47†
No direct evidence
from RCTs
Data extrapolated from large trials of women requiring long-term
contraception
Danazol About 50 Several high-
quality RCTs
Use limited by frequent, clinically significant adverse effects
Etamsylate About 13 Several high-
quality RCTs
Least effective treatment for menorrhagia
RCT = randomized controlled trial
* Use in both the follicular and luteal phases. Use in the luteal phase only is ineffective.
† Figure relates to the proportion of women with amenorrhoea after 1–2 years of use with depot medroxyprogesterone acetate.
Data from: [National Collaborating Centre for Women's and Children's Health, 2007]
28. Lethaby A, Sheppard S, Farquhar C, Cooke I 1999
Selection: RCT comparing endometrium techniques
(any) Vs Hysterectomy- 7 used.
Results – Significant advantage of Hysterectomy in the
improvement of HMB
(OR 0.04 (0.01-0.02) – at 1 yr
Satisfaction rates )OR 0.5 (0.3-0.8) compared with
ablation.
29. Repeat surgery OR 16.7 (5.8- 48.6)
Conclusion: Hysterectomy more effective at reducing
bleeding symptoms
Endometrial resection offers an alternative - short
term.
Nagele 1998 and Bourdez 2004 majority of women
would chose ablation over hysterectomy if success of
50%
.(Oxford clinical spec. Pg 253)
(ox. Textbook primary care 2005 vol 1 pg 868)
30% of women present with heavy periods at some point, but only half of these fulfil the criteria for menorrhagia.
HMB should be defined as excessive menstrual blood loss which interferes with the woman’s physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms. Any interventions should aim to improve quality of life measures.
Iron deficiency anaemia occurs in about two thirds of women with heavy menstrual bleeding [Lethaby and Farquhar, 2003; Duckitt and Collins, 2006].
Pcb - infection /lesion of cervix etc
Imb – common in women taking ocp, sign of more serious pathology .... Might want to do smear if due or do sooner if worried.
Painful sex- possibly infection . Need to ask whether pain superficial /.deep
Pain ful periods –
Pelvic pain – c ould be infection
Discharge – particularly a change – infection
All of these investigations when clinically indicated
Fbc in all case to access anaemia
if suggested by hx do thyroid and clotting
Pelvic u/s would be very helpful to identify uterine enlargement due to fibroids etc
If endometrinm identified as increased thickness – would suggest endometrial polyps or submucous fibroids
An endometrial biopsy should be performed on all women over 40 and under if risk factors or suspicious findings on u/s
The most effective way of excluding intrauterine pathology woud be a hysteroscopy
D.U.B is essentially a diagnosis of exclusion,and is essentially caused by dysfunction at an endometrial level, with no discerbable pelvic pathology present. It is responsible for between 40-60% of menorrhagia, accodring to Hickey et al in 2000. It may be caused by a combination of failure of small vessel clot stability and vasoconstriction.
The next most likely aetiology for menorrhagia results from pelvic pathologies. Fibroids is one of the most common pathologies of this subcategory, and studies have linked the site, size and number to the level of MBL (34 = nice)
Endometrial polyps are often linked to HMB in textbooks, but I could unearth no studies linking the two.
Adenomyosis and Endometriosis are also fairly common causes of HMB. Most people with endometriosis usually present with dysmenorrhoea, but several observational studies list HMB as a significant secondary symptom to this condition (53=nice)
Hypothyroidism is a condition linked in textbooks to HMB, but again there was no evidence base for this fact.
A more sinister condition that has been linked is endometrial carcinoma, where endometrial hyperplasia means that there is more cells to lose during the menstrual cycle.
One should also consider if any IUD is in situ, as this can sometimes disrupt the endometrium.
The last thing, that shouldn’t be forgotten is looking for abnormalities of clotting, such as Von willebrand Disease. Although this is rare, one cohort study comparing the prevelance of VWD in women with and without menorrhagia concluded that the OR for havein vWD in women with menorrhagia compared with women without menorrhagia was 8.6. (51=nice.)
Inta uterine levonergestrel-releasing systems (LNG-IUS).
This is basically a T-shaped bit of plasic, which has a membrane on the vertical stem with releases 20mg og levonorgstrel daily.
A contraceptive defice that is effective for 5 years.
It helps to reduce menstrual bleeding by preventing endometrial proliferaion, and the contraceptive effect is gained by causing the cervical mucus to thicken, and it prevents ovulation in some woemn.
The myrena coil was very quickly used as a treatment for menorrhagia after it’s introduction to the UK in 1995, however the evidence for it’s more general indications in Gynaecology was based more on case series as opposed to RCT. These have been done at a later date however, and do support its use in clinical practive.
There were 2 main reviews that I looked at to see the evidence base for this treatment
The first review I looked at is a cochrane review from 2005, looking at 10 RCT comparing the myrena coil to medical or surgical treatments.
Amenorrhoea, as this forrest plot shows is far more likely to occur with the coil compared to medical treatment, with an odds ratio of 8.67 (CI 1.52-49.35) in favour of LNG-IUS.
The medical treatment in question was oral cyclical norethisterone given on days 5-26 of the menstrual cycle. There was also greater patient satisfaction in the myrena coil, compared to pharmaceutical treatment, with and after 6 months of treatment more women being treated with the myrena coil opted out of their planned hysterectomyes.
Lethaby AE, Cooke I, Rees M. Progesterone/progestogen releasing intrauterine systems for heavy menstrual bleeding. (Cochrane Review). In: Cochrane Database of Systematic Reviews, Issue 4, 2005. Oxford: Update Software.
Endometrial ablation was shown to be more effective in lowering MBL than the myrena IUD. The surgical group also had greater patient’s satisfatction , less progesterogenic side effects, but the quality of life reported at one year was similar between the two groups.
Economically, however, the IUS is a much cheaper short term option than the surgical options.
The other review that I saw mentioned wasn’t a meta analysis, and I couldn’t get access to it. They only included 5 RCT, and 5 case studies. The RCT reported decreased menstrual bleeding by using the IUS of between 71% and 96%
The duration of treatment was 8 cycles, each treatment was given for 2 cycles, then the effect on the bleeding was objectively measured. NOT blinded
NOT plaebo controlled
DIDN’t look at the advese outcomes of each of the medications.
This result showed a greater reduction that naproxen, but much less than danazol or mefenamic acid.
There are other benefits regarding this form of pharmacological management; it decreases breast pain, dysmenorrhoea, gives cycle control, and you also get contraception thrown in as an added bonus!
Tranexamic acid is a competitive inhibitor of plasminogen activation, so it acts as an antifibriolytic
Although it inhibits factors associated with blood clptting, it has no effect on coagulation within healthy blood vessels, as Swedish studies have revealed that there is no increase in risk from thrombosis by using these medications.
It’s method of action in HMB is thought to occur through it reducing fibrin breakdown in a pre-formed clot, as menstrual bleeding involve reversing the coagulation in clotted blood from spiral endometrial arterioles.
1.Confidence intervals were quite narrow at 47.9%-51.6%.
2. The second review’s compared tranexamic acid to placebo, and reported a deacrease in MBL of 93.96ml. This review’s confidence intervals, however are much wider; between -151.43 an -36ml, so although we can be less certain as to what the true reduction in MBL is, we are certain that the minimal reduction possible is 36ml.
3.
Coulter A, Kelland J, Peto V, et al. Treating menorrhagia in primary care: An overview of drug trials and a survey of prescribing practice. International Journal of Technology Assessment in Health Care 1995;11(3):456�71.
Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for heavy menstrual bleeding. (Cochrane Review). In: Cochrane Database of Systematic Reviews, Issue 4, 2004. Oxford: Update Software. 301. Wellington K, Wagstaff AJ. Tranexamic acid: a review of its use in the management of menorrhagia. Drugs 2003;63(13):1417�33.
Here is a forrest plot from the second review, which was a cochrane review that included 2 RCT. It shows that antifibrinolytics causes a greater reduction in objective measurement of HMB compared to a placebo. This reduction was also percieved by the study parcipitants, and was greater than the objectively measured reduction in menstrual bleeding compared to other medical therapies including NSAIDS, oral luteal phase progestagens and ethamsylate. There was, however no change in duration of days in which bleeding occurred, but there was no increased incidence of side effects compared to the placebo or the other medical treatments.
The third review concluded that giving 2 to 4.5g of oral tranexamic acid for 4-7 days per cycle caused a reduction of MBL by 34-59% in just 2-3 cycles.
However it also stated that around 12% of women on this treatment suffer adverse effects from the treatment (mostly GI related side effects.)
From all the research already done, only tranexamic acid has a sufficient evidence base to be used for the management of HMB.
It’s disadvantages include
Plasminogen activators are a group of enymes that cause fibinolysis. Women with HMB have increased levels of plasminogen activators in their endometrium compared with women who have normal menstrual loss.
Antifirinolytics are plaminogen activator inhibitors
AF vs placebo result basrd on tran acid vs placebo , based on 2 trials callender 1970 and edlund 1995
Preston 1995 and bonnar 1996
Plasminogen activators are a group of enymes that cause fibinolysis. Women with HMB have increased levels of plasminogen activators in their endometrium compared with women who have normal menstrual loss.
Antifirinolytics are plaminogen activator inhibitors
AF vs placebo result basrd on tran acid vs placebo , based on 2 trials callender 1970 and edlund 1995
Preston 1995 and bonnar 1996
Medical therapies included nsaids , progesterone and Etamsylate
Antifibrinolytic agentswere compared to only three othermedical (non-surgical) therapies:mefenamic acid, norethisterone administered
in the luteal phase and ethamsylate. In all instances, there was a significant reduction in mean blood loss (WMD -73.0, 95% CI -123.4
to -22.6; WMD -111.0, 95% CI -178.5 to -43.5; and WMD -100, 95% CI -143.9 to -56.1 respectively) and a strong, although nonsignificant
trend in favour of tranexamic acid in the participants’ perception of an improvement in menstrual blood loss.
Af vs luteal phase progestrone – 1x trial preston 1995 46pts
Af vs nsaids bonnar 1996 and andersch 1998 49pts
Af vs ethamsylate bonnar 1996 - significant difference in menstral blood loss after 3 months of rx between at and e groups.
Nice states reduction in blood loss of
t.Acid – 29-58%
Nsaids 20-49
Est 13%
Very often no differnece in subjective measures
Medical therapies included nsaids , progesterone and Etamsylate
Antifibrinolytic agentswere compared to only three othermedical (non-surgical) therapies:mefenamic acid, norethisterone administered
in the luteal phase and ethamsylate. In all instances, there was a significant reduction in mean blood loss (WMD -73.0, 95% CI -123.4
to -22.6; WMD -111.0, 95% CI -178.5 to -43.5; and WMD -100, 95% CI -143.9 to -56.1 respectively) and a strong, although nonsignificant
trend in favour of tranexamic acid in the participants’ perception of an improvement in menstrual blood loss.
Af vs luteal phase progestrone – 1x trial preston 1995 46pts
Af vs nsaids bonnar 1996 and andersch 1998 49pts
Af vs ethamsylate bonnar 1996 - significant difference in menstral blood loss after 3 months of rx between at and e groups.
Nice states reduction in blood loss of
t.Acid – 29-58%
Nsaids 20-49
Est 13%
Very often no differnece in subjective measures
Progesterone is a physiological hormone produced during the luteal phase of the menstrual cycle. It is responsible for secretory transformation of the endometrium and bleeding occurs after endogenous levels of estrogen and progesterone fall (fertilisation not having occurred). Progesterone is not available in oral formulation in the UK although vaginal preparations are available. A variety of oral synthetic progestogens are in clinical use. They vary in their potency and adverse effect profiles. The mechanisms by which oral progestogens reduce MBL are not fully understood
Lethaby A, Irvine G, Cameron I. Cyclical progestogens for heavy menstrual bleeding. (Cochrane Review). In: Cochrane Database of Systematic Reviews, Issue 4, 2004. Oxford: Update Software.
Endometrial techniques – basically destroying the endometrium by laser, thermal/microwave ablation. Obviously dont grantee amennorohea as hystect does . Sides effects of ablation – hemmoarrage, infection, uterine perforation
Hstrec was one of the most commonly performed operations in uk – the over all life time risk for one was 20% - 93/94
Hystrectomy pts – increased energy, pain and general health improved.
Duration surgery shorter , less infections less hospital and recovery time for ablation/tcre compared to surgery – however more likely to need more intervention
