NIHR Signal Treatments for reducing menopausal hot flushes are ranked for effectiveness

Published on 25 July 2017

A combination of oestrogen and progestogen via patches is the best treatment for menopause symptoms. Other options may be less beneficial, including tablets combining oestrogen and progestogen, and non-hormonal treatments, isoflavones and black cohosh, though they may have other benefits. There is no evidence to support the use of antidepressants.

Menopause affects women’s personal life and work life, but many don’t seek help from healthcare professionals. It is important to identify the most effective and safest treatment to help women in this transitional period.

This review compared treatment options for the short-term management of hot flushes and night sweats in women aged 45 years or older who had not had a hysterectomy. The results have informed the NICE guideline on diagnosis and management of menopause.

A notable limitation is the lack of evidence on short or long-term adverse effects, particularly for some of the non-drug treatments available.

Treatments for reducing menopausal hot flushes are ranked for effectiveness

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Why was this study needed?

Menopause usually occurs in women between 45 and 55 years old, with an average age of 51. About 1 in 100 women experience premature menopause before turning 40.

In 2016, a UK survey showed that women aged 45 to 65 years who had experienced menopause in the previous ten years experienced on average seven different symptoms, with 42% saying that symptoms were worse than expected. Despite the impact on home and work life, half of women reported not consulting a healthcare professional for management of symptoms.

It is important to identify the best treatment to manage menopause in order to decrease the impact it has on women’s lives. This systematic review and meta-analysis aimed to compare different interventions used to treat the most common “vasomotor” symptoms of menopause, hot flushes and night-sweats.

What did this study do?

This systematic review identified 47 randomised controlled trials including 8,326 women aged 45 years or older who had gone through natural menopause and not had a hysterectomy. Trials assessed 16 classes of treatments given for up to 26 weeks.

Most drugs were compared to placebo in the underlying studies. The authors conducted a network meta-analysis, which is a statistical technique used to estimate the effects of treatments with each other across the active arms of the included trials. The primary aim was to look at the frequency of vasomotor symptoms, adverse effects of treatment discontinuation and vaginal bleeding. Six months treatment was not long enough to quantify the frequency of rarer adverse effects.

Some analyses combined mixed populations of women with and without a uterus, as the authors found similar effects for both groups. The small number of studies, significant difference (heterogeneity) in results and lack of information on symptom severity may limit confidence in the indirect results or precise rankings.

What did it find?

  • Oestrogen and progestogen patches had the highest likelihood of being the best treatment for reducing the frequency of vasomotor symptoms. Patches were better than placebo (mean ratio [MR] 0.23, 95% credible intervals [CrI] 0.09 to 0.57) and also better than raloxifene, selective serotonin reuptake inhibitors (SSRIs) or serotonin–norepinephrine reuptake inhibitors (SNRIs), isoflavones and Chinese herbal medicine.
  • Oral oestrogen and progestogen tablets were no better than placebo (MR 0.52, 95% CrI 0.25 to 1.06), but neither were they significantly different from hormone patches (MR 2.23, 95% CrI 0.7 to 7.1). Estimates suggest that combination hormone tablets are better than placebo but poorer than treatment via patches.
  • Isoflavones and black cohosh were better than placebo (MR 0.62, 95% CrI 0.44 to 0.87 and MR 0.4, 95% CrI 0.17 to 0.9, respectively) but poorer than hormone patches and no different from hormone tablets.
  • Data on treatment discontinuation was available from 21 trials in 4,829 women. Women were less likely to discontinue combination oestrogen and progestogen than placebo (odds ratio [OR] 0.61, 95% CrI 0.37 to 0.99), and also less likely to discontinue conjugated oestrogen with bazedoxifene (OR 0.31, 95% CrI 0.1 to 1.00), though both links were of borderline statistical significance. Women taking tibolone and SSRIs/SNRIs were more likely to discontinue than women taking placebo.
  • There were not enough data to draw conclusions on the likelihood of vaginal bleeding with the different treatments.

What does current guidance say on this issue?

The NICE 2015 guideline on diagnosis and management of menopause recommends offering oestrogen and progestogen to women with a uterus for short-term management of vasomotor symptoms. NICE also recommend that before recommending isoflavones and black cohosh for vasomotor symptoms, practitioners should explain that evidence is limited, preparations may vary, safety is uncertain and there may be drug interactions.

The guideline recommends against the routine use of SSRIs, SNRIs and clonidine as first-line treatment.

What are the implications?

This study was conducted to shed light on the best treatment for short-term management of menopausal flushes. It was part of the development for the 2015 NICE guideline on menopause. It has confirmed the better efficacy of the combination of oestrogen with progestogen via patches compared to alternatives.

There is limited information on adverse effects. Separate publications will review treatment for women who have had a hysterectomy and for women at risk of, or with history of, breast cancer.

Citation and Funding

Sarri G, Pedder H, Dias S, et al. Vasomotor symptoms due to natural menopause; systematic review and network meta-analysis (NMA) of treatment effects from the NICE Menopause Guideline. BJOG. 2017. [Epub ahead of print].

This work was undertaken in part by authors (GS, HP, YG) from the National Guideline Alliance (formerly the National Collaborating Centre for Women and Children’s Health) which received funding from the National Institute for Health and Care Excellence. The views expressed in this publication are those of the authors and not necessarily those of the Institute. SD received support from the Centre for Clinical Practice (NICE), with funding from the NICE Clinical Guidelines Technical Support Unit, University of Bristol and from the Medical Research Council (MRC Grant MR/M005232/1).

Bibliography

BMS. Are women suffering in silence? New BMS survey puts spotlight on significant impact of menopause. Marlow: British Menopause Society; 2016.

Griffiths A, MacLennan SJ, Hassard J. Menopause and work: an electronic survey of employees' attitudes in the UK. Maturitas. 2013;76(2):155-9.

NHS Choices. Menopause. London: Department of Health; 2015.

NICE. Menopause: diagnosis and management. NG23. London: National Institute for Health and Clinical Excellence; 2015.

Why was this study needed?

Menopause usually occurs in women between 45 and 55 years old, with an average age of 51. About 1 in 100 women experience premature menopause before turning 40.

In 2016, a UK survey showed that women aged 45 to 65 years who had experienced menopause in the previous ten years experienced on average seven different symptoms, with 42% saying that symptoms were worse than expected. Despite the impact on home and work life, half of women reported not consulting a healthcare professional for management of symptoms.

It is important to identify the best treatment to manage menopause in order to decrease the impact it has on women’s lives. This systematic review and meta-analysis aimed to compare different interventions used to treat the most common “vasomotor” symptoms of menopause, hot flushes and night-sweats.

What did this study do?

This systematic review identified 47 randomised controlled trials including 8,326 women aged 45 years or older who had gone through natural menopause and not had a hysterectomy. Trials assessed 16 classes of treatments given for up to 26 weeks.

Most drugs were compared to placebo in the underlying studies. The authors conducted a network meta-analysis, which is a statistical technique used to estimate the effects of treatments with each other across the active arms of the included trials. The primary aim was to look at the frequency of vasomotor symptoms, adverse effects of treatment discontinuation and vaginal bleeding. Six months treatment was not long enough to quantify the frequency of rarer adverse effects.

Some analyses combined mixed populations of women with and without a uterus, as the authors found similar effects for both groups. The small number of studies, significant difference (heterogeneity) in results and lack of information on symptom severity may limit confidence in the indirect results or precise rankings.

What did it find?

  • Oestrogen and progestogen patches had the highest likelihood of being the best treatment for reducing the frequency of vasomotor symptoms. Patches were better than placebo (mean ratio [MR] 0.23, 95% credible intervals [CrI] 0.09 to 0.57) and also better than raloxifene, selective serotonin reuptake inhibitors (SSRIs) or serotonin–norepinephrine reuptake inhibitors (SNRIs), isoflavones and Chinese herbal medicine.
  • Oral oestrogen and progestogen tablets were no better than placebo (MR 0.52, 95% CrI 0.25 to 1.06), but neither were they significantly different from hormone patches (MR 2.23, 95% CrI 0.7 to 7.1). Estimates suggest that combination hormone tablets are better than placebo but poorer than treatment via patches.
  • Isoflavones and black cohosh were better than placebo (MR 0.62, 95% CrI 0.44 to 0.87 and MR 0.4, 95% CrI 0.17 to 0.9, respectively) but poorer than hormone patches and no different from hormone tablets.
  • Data on treatment discontinuation was available from 21 trials in 4,829 women. Women were less likely to discontinue combination oestrogen and progestogen than placebo (odds ratio [OR] 0.61, 95% CrI 0.37 to 0.99), and also less likely to discontinue conjugated oestrogen with bazedoxifene (OR 0.31, 95% CrI 0.1 to 1.00), though both links were of borderline statistical significance. Women taking tibolone and SSRIs/SNRIs were more likely to discontinue than women taking placebo.
  • There were not enough data to draw conclusions on the likelihood of vaginal bleeding with the different treatments.

What does current guidance say on this issue?

The NICE 2015 guideline on diagnosis and management of menopause recommends offering oestrogen and progestogen to women with a uterus for short-term management of vasomotor symptoms. NICE also recommend that before recommending isoflavones and black cohosh for vasomotor symptoms, practitioners should explain that evidence is limited, preparations may vary, safety is uncertain and there may be drug interactions.

The guideline recommends against the routine use of SSRIs, SNRIs and clonidine as first-line treatment.

What are the implications?

This study was conducted to shed light on the best treatment for short-term management of menopausal flushes. It was part of the development for the 2015 NICE guideline on menopause. It has confirmed the better efficacy of the combination of oestrogen with progestogen via patches compared to alternatives.

There is limited information on adverse effects. Separate publications will review treatment for women who have had a hysterectomy and for women at risk of, or with history of, breast cancer.

Citation and Funding

Sarri G, Pedder H, Dias S, et al. Vasomotor symptoms due to natural menopause; systematic review and network meta-analysis (NMA) of treatment effects from the NICE Menopause Guideline. BJOG. 2017. [Epub ahead of print].

This work was undertaken in part by authors (GS, HP, YG) from the National Guideline Alliance (formerly the National Collaborating Centre for Women and Children’s Health) which received funding from the National Institute for Health and Care Excellence. The views expressed in this publication are those of the authors and not necessarily those of the Institute. SD received support from the Centre for Clinical Practice (NICE), with funding from the NICE Clinical Guidelines Technical Support Unit, University of Bristol and from the Medical Research Council (MRC Grant MR/M005232/1).

Bibliography

BMS. Are women suffering in silence? New BMS survey puts spotlight on significant impact of menopause. Marlow: British Menopause Society; 2016.

Griffiths A, MacLennan SJ, Hassard J. Menopause and work: an electronic survey of employees' attitudes in the UK. Maturitas. 2013;76(2):155-9.

NHS Choices. Menopause. London: Department of Health; 2015.

NICE. Menopause: diagnosis and management. NG23. London: National Institute for Health and Clinical Excellence; 2015.

Vasomotor symptoms due to natural menopause; systematic review and network meta-analysis (NMA) of treatment effects from the NICE Menopause Guideline

Published on 10 March 2017

Sarri, G.,Pedder, H.,Dias, S.,Guo, Y.,Lumsden, M. A.

Bjog , 2017

BACKGROUND: Vasomotor symptoms (VMS) are the hallmarks of menopause, occurring in approximately 75% of postmenopausal women in the UK and are severe in 25%. OBJECTIVES: To identify which treatments are most clinically effective for the relief of VMS for non-hysterectomized women in natural menopause. SEARCH STRATEGY: English publications in MEDLINE, Embase and The Cochrane Library up to 13th January 2015 were searched. SELECTION CRITERIA: Randomized trials (RCTs) of treatments for women with a uterus for the outcomes of frequency of VMS (up to 26 weeks), vaginal bleeding and discontinuation. DATA COLLECTION AND ANALYSIS: Bayesian network meta-analysis (NMA) using mean ratios (MRs) and odd ratios (ORs). MAIN RESULTS: Across the three networks, 47 RCTs of 16 treatment classes (N=8326 women) were included. When compared to placebo, transdermal oestradiol and progestogen (O+P) had the highest probability of being the most effective treatment for VMS relief (69.8%) (MR: 0.23 [95%CrI (0.09, 0.57)] whereas oral O+P was ranked lower than transdermal O+P, although oral and transdermal O+P were no different for this outcome (MR: 2.23 [95%CrI (0.7, 7.1)]. Isoflavones and black cohosh were more effective than placebo, though not significantly better than O+P. Not only were SSRIs or SNRIs found ineffective in relieving VMS but they also had significantly higher odds of discontinuation than placebo. Limited data were available for bleeding therefore no conclusions could be made. CONCLUSIONS: For non-hysterectomized women, transdermal O+P was the most effective treatment for VMS relief. This article is protected by copyright. All rights reserved.

The first sign that a woman is approaching menopause is a change in the normal patterns of her periods. Natural menopause is usually defined by the absence of menstruation for 12 consecutive months. Menopause symptoms usually last around four years but women can experience them for longer. The most common symptoms are hot flushes and night sweats. Others include difficulty sleeping, headaches, more noticeable heartbeats, sexual problems, mood changes and reduced concentration and memory.

Network meta-analyses use advanced statistical methods and sometimes report credible intervals (CrI), which summarise the level of certainty of the results. This study reports 95% CrI, which means there is a 95% probability that the true value lies in the interval.

Expert commentary

Menopausal symptoms (flushing, night sweats) are a problem for many women. NICE updated its recommendations in 2015. Hormone replacement therapy is the standard treatment (with concerns about breast cancer/cardiovascular risk). Non-hormonal treatments are suggested but have a poor evidence base.

This network meta-analysis reinforces that hormonal treatments (trans-dermal followed by oral) are the most effective. Non-hormonal treatments (e.g. isoflavones/black cohosh) are less effective, and antidepressants are not effective in relieving vasomotor symptoms. The study does not address long term safety. This study should help clinicians help women to make an informed choice. 

Dr Melvyn Jones, Senior Lecturer, Department of Primary Care & Population Sciences, UCL

Categories

  •   Gynaecological disorders, Medicines