Evidence
Surveillance decision
We will update the NICE guideline on menopause.
The update will cover managing urogenital atrophy and the long-term benefits and risks of hormone replacement therapy (HRT).
Reasons for the decision
We initially consulted on the proposal to not update the guideline. At that time, the identified new evidence was broadly in line with the guideline or showed inconsistent effects across studies so there was no clear indicator for proposing an update.
We also identified new evidence on treating vulvar and vaginal atrophy. Ospemifene is licensed in the UK for treating moderate to severe symptomatic vulvar and vaginal atrophy in women who are not candidates for vaginal oestrogen. Prasterone is licensed in the UK for treating vulvar and vaginal atrophy in postmenopausal women having moderate to severe symptoms.
The cost of prasterone is comparable with available intravaginal oestrogen pessaries, and although ospemifene is more expensive, its use is restricted to a smaller group of women for whom intravaginal oestrogen is not suitable. Therefore, we did not expect these treatments to have a substantial impact on NHS resources. This led to our initial proposal to not update this section of the guideline.
During consultation, a new study on the risk of breast cancer associated with HRT was published, accompanied by a Medicines and Healthcare products Regulatory Agency (MHRA) Drug Safety Update based on the results of the study. This was the main reason for changing the conclusion to recommend an update to the guideline.
This new study performed detailed and complex analyses. The results cannot be easily compared directly with the risk data considered when developing the guideline. The new study data on risk of breast cancer was reported over different treatment and follow-up periods than are detailed currently in the guideline.
For up to 5 years' use of HRT and follow up of 5 years to 10 years, the risks of breast cancer reported in the new study were similar to those detailed in the guideline. However, the MHRA Drug Safety Update highlighted that 'some excess risk of breast cancer with systemic HRT persists for more than 10 years after stopping; the total increased risk of breast cancer associated with HRT is therefore higher than previous estimates'. The MHRA Drug Safety Update, based on the results of the new study, therefore suggests that risk data in the guideline, particularly for people who have stopped taking HRT, are out of date and an update is necessary.
However, the new study conducted a case-control analysis of individual participant data from 568,859 women. The review protocols from the guideline excluded this study design. Many of the studies informing the paper were excluded from the guideline. Similarly, many of the studies informing the guideline were excluded from the paper dataset. Additionally, in surveillance we identified 10 new cohort studies that measured the effects of HRT on breast cancer, only 1 of which was included in the new study. Notably, 1 analysis of more than 1 million women (Brusselaers et al. 2018) was not included in the new study.
Across all identified studies there are inconsistencies in the direction and size of effects of different types and durations of HRT on rates of breast cancer. For example, the size of the effects of HRT on breast cancer reported in Brusselaers et al. 2018 (more than 1 million women) were consistently smaller than the effects reported in the new study (more than half a million women).
Therefore, we will update the section of the guideline on the long-term risks and benefits of HRT. While the update is in process, we will remove the risk table for breast cancer and cross-refer to the MHRA risk table until the update publishes.
However, if the update process results in the inclusion of case-control studies for breast cancer, then all other risks and benefits of HRT should be reconsidered using the same revised methods.
Additionally, we decided that the section on urogenital atrophy should be updated to include ospemifene and prasterone. Stakeholder feedback indicated a desire for these drugs to be considered in an update and changes in the benefits and risk profiling of HRT may lead to changes in acceptability of HRT to women and therefore increase the prominence of other interventions for treatment of menopausal symptoms.
Other sections of the guideline
New evidence for other treatments for short-term menopausal symptoms was identified, including drug treatments, psychological treatments, and alternative medicine and complementary therapies. However, the evidence for these treatments did not indicate a need to update the guideline at this time because each intervention was usually assessed in a single small trial, which was deemed insufficient to change existing recommendations.
We identified 1 study for each of the sections on diagnosing perimenopause and menopause and diagnosing and managing premature ovarian insufficiency, but neither study indicated an update was necessary.
For further details and a summary of all evidence identified in surveillance, see appendix A.
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