A blog by Lynda Ware, Senior Fellow in General Practice with Cochrane UK, for non-medical readers, on Something done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes. choices for women with heavy periods.
A shocking newspaper article
In February 2016 a newspaper headline caught my eye:
‘Nepal’s bleeding shame: menstruating women banished to cattle sheds’
The article described a centuries-old custom, still practised in Nepal, of confining women to a cowshed or outbuilding during their period. This ingrained cultural practice called chaupadi (which translates as ‘untouchable being’) considers menstrual loss to be ‘impure’ and places severe restrictions on what women can eat, where they can go and with whom they can interact. The damage to women – both physical and psychological – is huge and efforts are being made to outlaw the behaviour.
A month before this piece was written, a Cochrane review was published looking at Surgery versus medical therapy for heavy menstrual bleeding. It occurred to me that this highlighted the very different world in which we live.
How heavy is heavy?
Now here’s the rub. What constitutes an unacceptably heavy period is very subjective. Medical wisdom defines heavy menstrual bleeding (or menorrhagia, to give it its medical name) as a loss of 80ml or more per menstrual cycle. When menstrual blood is measured (and it can be!) only about half of the women attending gynaecology clinics with a complaint of heavy periods are losing 80ml or more. A survey of menstruating women conducted in 2004 in the UK found that the self-reported The number of new occurrences of something in a population over a particular period of time, e.g. the number of cases of a disease in a country over one year. of menorrhagia was 25%. It is estimated that 5% of otherwise healthy women consult their GP complaining of heavy periods.
Heavy menstrual bleeding can significantly impair quality of life. It can of course cause anaemia and incurs a not insubstantial financial cost in terms of sanitary items and lost days at work if severe.
What is available to help?
A number of medical and surgical options are available to help lessen menstrual bleeding.
Initial treatment for menorrhagia, as recommended by NICE and the Royal College of Gynaecologists and Obstetricians, is usually medical and includes:
Levonorgesterel-intrauterine device (LNG-IUS). This is inserted into the womb and lasts for up to five years. It releases a low level of levonorgestrel (a progesterogenic hormone) which has the effect of suppressing the lining of the womb (endometrium). It has been reported to reduce menstrual loss by 94% in three months. It has the added advantage of being a highly effective contraceptive. However, it commonly causes irregular bleeding in the first few months of use and some women experience hormonal side effects such as weight gain and bloating.
Anti-fibrinolytic drugs such as tranexamic acid inhibit the breakdown of blood clots and can reduce bleeding by 40-50%. They are taken during menstruation and are usually well tolerated but can cause mild nausea and diarrhoea. Historically there has been some concern that they may increase the A way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of venous thromboembolic disease (ie blood clots in the legs or lungs).
Non-steroidal anti-inflammatory drugs (NSAIDs) such as mefenamic acid and naproxen can reduce bleeding by 33-55%. These drugs are also taken just at the time of menstruation. Side effects such as indigestion and diarrhoea are less likely to cause problems since the NSAIDs are only taken for a few days each cycle.
Progestogens such as norethisterone and medroxyprogesterone acetate are taken on a cyclical basis. They can be effective at reducing blood loss and at helping to regulate the menstrual cycle. Long term they are often unacceptable because of their side effects such as bloating, headache, breast tenderness and breakthrough bleeding. The contraceptive injection (eg Depo-Provera) may stop periods altogether but it is not licensed as a treatment for menorrhagia.
The combined oral contraceptive pill can often diminish menstrual loss although there is little Randomization is the process of randomly dividing into groups the people taking part in a trial. One group (the intervention group) will be given the intervention being tested (for example a drug, surgery, or exercise) and compared with a group which does not receive the intervention (the control group). evidence supporting this.
Danazol is a synthetic hormone and it is highly effective at reducing menstrual loss. However side effects such as weight gain, headache, nausea, tiredness and acne are common and can be severe.
These include hysterectomy and conservative surgery in the form of endometrial resection or ablation.
Hysterectomy requires a general anaesthetic and a lengthy postoperative recovery period. It can be associated with postoperative complications, some of which may be serious.
Endometrial resection or ablation involves removing the lining of the womb by cutting it away or by destroying it, for example by contact with heat, cold or microwaves. These techniques are less invasive than hysterectomy and involve a shorter hospital stay, quicker recovery and fewer postoperative complications. Menstrual bleeding does not always cease completely and contraception should still be used. It has been reported that up to a third of women go on to have a hysterectomy after a previous ablation procedure.
Cochrane evidence on surgery vs medical treatment
This review from the Cochrane Gynaecology and Fertility Group set out to compare the The ability of an intervention (for example a drug, surgery, or exercise) to produce a desired effect, such as reduce symptoms., Refers to serious adverse effects, such as those that threaten life, require or prolong hospitalization, result in permanent disability, or cause birth defects. and acceptability of surgery versus medical therapy for heavy menstrual bleeding. It was published in January 2016 as an update to the original from 2010. Fifteen Clinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known. were included involving 1289 women, aged 30-50, all of whom had sought help for heavy periods.
How good was the evidence?
The The certainty (or quality) of evidence is the extent to which we can be confident that what the research tells us about a particular treatment effect is likely to be accurate. Concerns about factors such as bias can reduce the certainty of the evidence. Evidence may be of high certainty; moderate certainty; low certainty or very-low certainty. Cochrane has adopted the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) for assessing certainty (or quality) of evidence. Find out more here: https://training.cochrane.org/grade-approach varied from very low to moderate.
Some of the findings from the long-term studies were difficult to interpret since many women randomized to medical treatments went on to have surgery.
So what did the review find?
Surgery, especially hysterectomy, reduced menstrual loss more than medical treatment at one year. Oral medication did, however, suit a minority of women long term. There was no conclusive evidence of a difference in satisfaction between surgery and LNG-IUS. A high proportion of women initially treated with oral medication, conservative surgery or the LNG-IUS went on to require further A treatment, procedure or programme of health care that has the potential to change the course of events of a healthcare condition. Examples include a drug, surgery, exercise or counselling. . Hysterectomy, though the definitive treatment, was sometimes associated with serious side effects. Conservative surgery and the LNG-IUS appeared to be safe, acceptable and effective.
How might further research contribute?
A A trial conducted at several geographical sites. Trials are sometimes conducted among several collaborating institutions, rather than at a single institution - particularly when very large numbers of participants are needed. is under way in the Netherlands looking at an up-to-date method of endometrial ablation and comparing it to the LNG-IUS.
It has always seemed to me to be a design flaw in the grand scheme of things that women are destined to have periods for nearly forty years of their lives. Not very 21st century – surely we can do better?
For many the monthly cycle is a nuisance; for others it is a regular life changer causing disruption to everyday life. In Nepal it can mean rejection by society, sometimes with disastrous consequences. This review gives an insight into the choices available to some women.
An update – antifibrinolytics
Since writing this blog a further Cochrane Review has been published looking specifically at the role of antifibrinolytics for heavy menstrual bleeding. The updated review studied comparisons of antifibrinolytic drugs, mainly tranexamic acid, versus An intervention that appears to be the same as that which is being assessed but does not have the active component. For example, a placebo could be a tablet made of sugar, compared with a tablet containing a medicine./no treatment, the LGN-IUS, progestogens, and NSAIDs.
The authors concluded that antifibrinolytic treatment is probably effective in reducing menstrual blood loss when compared to placebo (moderate certainty evidence). What this means is that if 11% of women improve without treatment, 43% to 63% of women on antifibrinolytics will do so. There is low certainty evidence that antifibrinolytics are more effective than NSAIDs or cyclical progestogens. However, the most effective treatment is probably the LGN-IUS (moderate certainty evidence). The comparison with antifibrinolytics shows 85% of women improving with the LGN-IUS compared to 20% to 65% taking tranexamic acid.
There are insufficient Data is the information collected through research. to determine whether antifibrinolytics are associated with an increase in adverse events, in particular venous thromboembolism.
A further update (September 2019)
Since April 2018 five updated Cochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. have been published looking at the effectiveness and safety of different ways to reduce menstrual blood loss in women with heavy periods. Three reviews considered medical therapies and two summarised data on surgical techniques.
Combined oral contraceptives
An updated review on the use of combined oral contraceptives (COCP) concluded that there is moderate quality evidence suggesting that COCPs reduce unacceptable heavy periods and improve quality of life and haemoglobin levels when compared to placebo. However, they may be less effective than the levonorgestrel-releasing intrauterine system (LNG-IUS). There is insufficient evidence to determine how they compare with non-steroidal inflammatory agents (NSAIDs) or long course progestogens.
Another updated review considered the effectiveness of cyclical progestogens. The authors found that short courses of oral progestogen, taken for ten days per month, may be less effective than other medical treatments at making periods lighter. When taken for longer, from days 5 to 26 of the menstrual cycle, progestogens reduce menstrual loss but may still be inferior to tranexamic acid, COCPs and the LNG-IUS. The quality of evidence is low to very low.
Non-steroidal anti-inflammatory drugs (NSAIDs)
In September 2019 an updated review was published looking non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of heavy menstrual bleeding. There were no changes to the conclusions of the previous review that NSAIDs may be more effective than placebo at reducing heavy menstrual loss but less so than tranexamic acid, danazol and the LNG-IUS.
Two reviews published in 2019 looked at endometrial resection and ablation. One compared endometrial resection and ablation to hysterectomy. It concluded that endometrial resection and ablation techniques offer effective and possibly cheaper options to hysterectomy but that retreatment with additional surgery is sometimes needed (quality of evidence low to moderate). Hysterectomy is associated with longer operating times and a higher The speed or frequency of occurrence of an event, usually expressed with respect to time. For instance, a mortality rate might be the number of deaths per year, per 100,000 people. of surgical complications. For both surgical treatments, most women were happy with the results.
The other review compared different endometrial resection and ablation techniques. There are now three ‘generations’ of treatment. Evidence of very low to moderate quality indicates first and second generation techniques are similarly effective in reducing menstrual blood loss and most women in both groups expressed satisfaction with their treatment. Second generation methods appear to be safer in terms of some surgical complications such as lacerations to the cervix but both can result in uterine perforation. Second generation techniques are quicker and more likely to be performed under local rather than general anaesthetic. At present there are no data available assessing how third generation techniques compare.
A Cochrane review update on the effects of progestogen-releasing intrauterine systems on heavy menstrual bleeding (June 2020)
An update of a 1999 Cochrane review was published in June 2020 comparing the effectiveness and safety of progestogen-releasing intrauterine systems with other medical and surgical treatments for heavy menstrual bleeding.
Compared to norethisterone acetate, medroxyprogesterone acetate, oral contraceptive pills, mefanamic acid, tranexamic acid or usual medical treatment, levonorgestrel-releasing intrauterine systems (LNG-IUS) may lower menstrual loss and slightly improve quality of life. Comparing LNG-IUS to endometrial ablative methods, the evidence is inconsistent and the authors are uncertain whether there is a difference in bleeding Outcomes are measures of health (for example quality of life, pain, blood sugar levels) that can be used to assess the effectiveness and safety of a treatment or other intervention (for example a drug, surgery, or exercise). In research, the outcomes considered most important are ‘primary outcomes’ and those considered less important are ‘secondary outcomes’., satisfaction with treatment, quality of life or rate of failure. It is also uncertain whether LNG-IUS is better or worse than hysterectomy.
References may be found here.
Page last updated 08 July 2019