Abstract
Objective
The aim of the project was to reduce the risk of patients using the estrogen only part of their hormone replacement therapy (HRT) inadvertently in Banstead PCN. Although understanding about the risk of unopposed estrogen is well understood by prescribers, there are numerous flash points where this exposure can occur which was highlighted by several cases encountered during a study period of 3 months.
Study design
Cases encountered revealed numerous reasons for this exposure which were split into three areas: Prescribing factors, dispensing checks and patient understanding.
Main outcome measures
Quality improvement suggestions were tailored to the factors involved. IT system changes to EMIS, our main computer software provider, were proposed to enable safer prescribing. Following discussion with key stakeholders, increased education for pharmacists was proposed alongside an alert sticker system at the dispensing end point. Patient understanding and education for all parties was delivered through various routes.
Results
The IT system alterations required are complex and still awaited. Funding was obtained and stickers distributed. The results from a re-audit from this intervention are awaited. Interim education measures at an individual level were meantime explored and the impact of them assessed. Patient education and the role of social media were explored. I produced a short video which was circulated to doctors with the plan to distribute via other clinician social media accounts.
Conclusions
A key discovery through this study is that many of the flash points identified can be difficult to detect and many are not measurable. The increasing number of HRT prescriptions, time pressures in primary care and the known risk from using unopposed estrogen of endometrial cancer means these changes are of potential great value.
Introduction
I provide Menopause Care in a well women clinic for my PCN. This covers five practices and roughly comprises 47,000 patients. This role has given me a broad perspective on HRT delivery across a wider area and the pitfalls encountered where safety may be compromised. Several cases where unopposed estrogen had been used were encountered and the reasons behind them explored. This was then used to bring about quality improvement to reduce their future occurrence.
Unopposed estrogen is a well-known factor for the development of endometrial hyperplasia1–6, a potential precursor for endometrial cancer. A literature search was carried out which demonstrated this clear and unequivocal link established back in the 1970s. Progestogen use has been shown to offset this risk6–8 and there are several different progestogens which can be used for this purpose. Increased media coverage of HRT in the last 2 years has resulted in prescriptions for HRT rising sharply as highlighted by our PCN figures: February 2022 10,083 HRT items, January 2023 14,336 HRT items. Patterns of prescribing have also changed over time towards mix and match HRT where estrogen is used separately to progestogen. Although there may be benefits to this approach, it also raises the possibility for user error. This comes on a background of rising cases of endometrial cancer and long current wait times in hysteroscopy clinics. Mix and match HRT is also associated with increased rates of unscheduled PV bleeding which is magnified by incorrect use. This puts pressure on 2-week rule clinics and increases pressure on secondary care.
I encountered several cases of inadvertent unopposed estrogen use over a 3-month period and resolved to improve safety by exploring the reasons behind them. I contacted our PCN practices who had all conducted unopposed estrogen audits in the recent past as they were aware of the issue and the importance of it. Other cases were also collected from stakeholder colleagues in the area who commonly prescribe HRT or have involvement in medicines safety.
Cases encountered in practice, flash points where unopposed estrogen occurs include: • Prior to an appointment, patient may have already tried estrogen only HRT in the form of a patch or gel borrowed from a friend or family member. In this context of absent medical counselling, they may fail to have realised the significance of the progestogen part of HRT and have not taken it alongside. This may be driven by the fact that estrogen makes them feel better whereas the progestogen can lead to side effects more commonly. Compliance is a known issue generally. • 52 mg Levonorgestrel IUD as progestogen in HRT-licensed use for 4 years and endorsed for 5 years in practice. This may differ from use in a contraception context which could be 8 years or longer if it was fitted in a patient over age 45. Use over 5 years has not been proven to provide sufficient protection from the effects on the endometrium from estrogen in HRT however. Patients may not appreciate this difference and refer to the original date on their card. • Date of fit of 52 mcg levonorgestrel IUD may not be recorded in the notes as could have been fitted by an external provider (such as family planning clinics with no obligation to write) and not coded or traceable in the patient record. Several cases encountered where this date had elapsed with no detection. • Length of duration of action means that original fit dates where a record is present are often many pages back in the notes and may not be looked for where repeat prescriptions are being issued when time is pressured. • Utrogestan is another form of progestogen in popular use however instructions in the patient leaflet can give rise to confusion as described by several patients. The reference to timing of taking it in relation to cycle point can leave patients feeling confused and more prone to using it incorrectly. Cycles are often irregular and commonly lengthy at this life stage. I encountered patients trying to time their pill taking to the occurrence of a bleed and using inadequate amounts of progestogen as a result. • Recent medication shortages of Utrogestan have also led to patients receiving only their estrogen at the pharmacy with limited counselling on the importance of the progestogen and hence limited intention to chase the progestogen part of it as they may be unaware of its significance. There is no traceability of this. • Sequential regimens are difficult to understand and several errors were encountered where patients had been using one capsule rather than two for part of the month. Menopause consultations are commonly complex with broad cover in terms of symptoms, risks and benefits of HRT. Practical prescribing issues may be given less focus where time is tight. • The impact on patients at this life stage from brain fog and poor concentration can also compound recall problems concerning safety and correct use of HRT.
These flashpoints could be split into three main sources: 1. Originating at the point of prescription, particularly repeat prescribing where the doctor and patient had no direct contact. 2. Lack of counselling at the end gate via the pharmacy teams. 3. Lack of patient awareness.
Method
To ensure each area was independently addressed, I approached each area separately.
Prescribing
Currently when we issue estrogen only HRT, an alert box will pop up on our computer screen.
This can be easily ignored however and most GPs are already aware of this fact. A more robust system is needed.
As a PCN, in an effort to improve safety, we are increasingly adding free text instructions alongside their HRT script which highlight this risk with hoped for improvements in compliance and understanding regarding safety. For example:
Evorel 50 mcg (Utrogestan as endometrial protection for example, or 52 mg levonorgestrel IUD fit date etc.)
This system, however, is dependent on an individual GP writing this in free text and it may not always be visible to the pharmacist or patient further down the line. To make future repeat issues more streamlined and clear, I met with EMIS (our IT system provider in Banstead) to see if we can alter the way we prescribe estrogen so that a box would autogenerate with a tick box system as follows:
Does the patient need progesterone for endometrial protection? Then select one of the following: • Utrogestan...could then autogenerate a script for this • MPA/other appropriate Progestogen-to type what this is • 52 mg Levonorgestrel IUD fitted. Date of fit. (Would always then appear for future reference) • No: Patient has had a hysterectomy (caveat: if severe endometriosis CCT advised) • Patient has had a subtotal hysterectomy and has completed a 3 months Progestogen challenge.
The GP can then select the appropriate box and this would appear adjacent to the estrogen for future reference for both GP, pharmacist and patient and will provide an at a glance check in place.
I also approached Ardens who produce many of our templates used in General Practice. Templates are increasingly used in primary care. They provide comprehensive suggested points of care to cover in a consultation in a specific care setting such as menopause. The bullet point design with the ability to tick the relevant box also saves the clinician considerable time in writing up notes and ensures all key information is covered with minimal omissions. They were able to add on a checklist question, ‘Patient has been counselled about the importance of the Progestogen’. This helps serve as a prompt to tell the patient and could be recordable afterwards. They have also subsequently been able to ensure a more visible levonorgestrel fit date appears once coded in the menopause template.
Besins who manufacture Utrogestan were also approached to ascertain whether their patient leaflet could be optimised. This was felt to be unlikely due to license restrictions and cost. They have since expressed an intention to explore this feasibility further.
Dispensing
I offered teaching to raise awareness to local pharmacy teams; however, time restrictions by pharmacists meant this was not taken up. I then distributed posters to individual pharmacies within my PCN to raise awareness with a traffic light system style poster for an at a glance check. Despite receiving positive feedback from pharmacists, an audit revealed that patients were still not being asked/checked (see Appendix A). I then subsequently met with the CEO of community pharmacies in Surrey to explore solutions. She suggested affixing alert stickers to HRT at the dispensing point which would serve as a flag for highlighting increased risk. It is currently operational for several other medications where risk is raised such as lithium and methotrexate. The sticker would ensure a pharmacist with appropriate skills hands over the prescription bag to the patient and advises them accordingly. The sticker would prompt the check, ‘Are you using Progestogen for endometrial protection?’
Patient awareness
Recent high profile media and documentary coverage of menopause and HRT has highlighted the impact of social media for broad reach in terms of patient capture and attention. Internet content material can lead to adverse outcomes and misinformation but can potentially be utilised for benefit providing the source of information comes from trustworthy origins. I met with a menopause specialist colleague, Dr Fionnuala Barton who is active on social media and she suggested a campaign to raise awareness. Several social media content providers whose authorship was a doctor with menopause expertise were contacted. I also contacted several relevant organisations such as FSRH and BMS. Eve appeal who run a charity aimed at gynaecological cancer awareness were also contacted as a potentially interested party. They were very enthusiastic about the project and added that they had found patients understood little about important basic aspects such as, ‘what is HRT’ and ‘what is abnormal bleeding’. They initially proposed a week of education to launch in October to coincide with menopause awareness month. I also meantime produced an animation explainer video covering this topic which I hoped could be widely distributed.
Results
Prescribing
EMIS was approached initially by me and then as time progressed, other local stakeholders keen for quality improvement such as Nikki Smith, head of medicines safety for Surrey. It became apparent that the IT system changes proposed were complex and needed time to deliver a solution. However, the origin of many HRT prescribing errors could be resolved by this change and would have immediate broad reach as approx. 60% UK General Practice use EMIS. These changes are awaited to date.
Meantime, prescribing practice to include the risk and specific progestogen used (and fit date for levonorgestrel IUD) as free typed text was suggested for our PCN doctor colleagues at a locality update meeting then latterly at a meeting for clinical pharmacists working locally. This was done alongside teaching on HRT to raise awareness of this issue and other safety issues relating to HRT use. I also suggested we ensure the patient receives supplementary material on how to take the Utrogestan alongside their prescription for reference later. The PDF, ‘How to take your Utrogestan’ produced by Liverpool Hospital does this very clearly. I therefore included this in a menopause resource PDF alongside other helpful safety information that was saved to practice desktops and could be distributed to patients via an AccuRx text message.
Dispensing
The end gate check proved more difficult to change. The time restraints and pressure on pharmacies meant that opportunities for education were limited and the quick at a glance poster was not being utilised as demonstrated by my audit (88% of patients responding had not been advised about the significance of the progestogen). The audit was timed shortly following the poster distribution and timed to coincide with national stock shortages of Utrogestan when progestogen protection counselling was especially important.
A change to the system with the sticker use was therefore more likely to yield success as discussed with Neha Ramaiya, Senior Advisor for the Pharmaceutical Society who had seen this system successfully used in practice. There is currently no sticker system for HRT in practice and delivering this would require funding. Several pharma companies were approached to assist with this. Funding was agreed by Viatris for sticker use within Banstead PCN and the manufacture and distribution of stickers materialised. Since that time, Besins have also proposed a similar sticker system that they would organise in house with additional information and safety leaflets for patients with the potential for wide use-further confirmation is awaited. All parties where the project was discussed felt that education opportunities were key. Suggested modes of delivering this included: • Co-writing an e-bulletin for the ‘spotlight’ article sent to pharmacists quarterly in their Regulate Journal (published 23/10/23). • Writing a blog for the new Patient Safety Commissioner website (written and uploaded June 2023). • Update to local Clinical Pharmacists in our local PCN (delivered September 2023). • Contact with the Royal Pharmaceutical Society to produce education and resources. • Circulated reminders to local pharmacy colleagues about the poster plus the Liverpool Hospital leaflet described to raise awareness and increase the chance of patients being counselled appropriately. • The poster was discussed at a CCG prescribers meeting to obtain a ‘Surrey Heartlands’ badge for additional weight and attention and wider circulation. • It has also been shared for wider use on the PCWHF Facebook group.
A re-audit is proposed once the sticker system is operational and established.
A reply from the MHRA revealed that whilst pharmacists check dispensing against prescriptions, they do not necessarily check the appropriateness of the prescription itself which may in part explain why this end gate check can be a source of unopposed estrogen use as described. Patient awareness is therefore key.
Patient awareness
The concept of a campaign which would deliver a simultaneous and widely delivered message from numerous respected contacts was promising. However, producing agreed content for this was more complex. Many replies from social media colleagues were largely positive and in support, including Eve appeal (a gynaecological cancer charity) who initially hoped to help produce the content. Time and budget restrictions prevented this from happening.
Eve appeal expressed concern that many patients they had contact with through their organisation had profound gaps in understanding on HRT basics such as, ‘what is HRT’ and ‘how it works’. I then produced a short (1 min 40 s) and simple video using the animation software ‘Doodly’ to help address this gap. I initially asked for feedback from menopause speciality colleagues at Guy’s Hospital and also a friend who has a respected Science communicator role in cancer care. Following their feedback, adjustments to the video were made. It has subsequently been circulated for use: • Locality GP’s in the ‘menopause resources’ attachment to send to patients via text message alongside other helpful information. • PCWHF Facebook Group used by over 4000 clinicians with an interest in women’s health to share with their patients. • It has also been ‘posted’ on Instagram by menopause specialist doctor colleague, Dr Fionnuala Barton, ‘themenopausemedic’ with 18.4k ‘followers’. • ‘Retweeted’ by Carolyn Harris MP on Twitter. • Posted on the PSC website alongside the blog. • A link to the video was sent out via the Regulate article mentioned.
Discussion
The project revealed several areas for quality improvement and highlighted the numerous reasons that exposure to unopposed estrogen may occur in practice. These findings were also echoed by other key women’s health spokespersons involved with UK professional bodies such as BMS, PCWHF and the RCGP who all supported the project following a presentation of it at the Clinical reference Group committee. There is additional concern about the use of higher than recommended doses of estrogen being used on occasion currently which added further importance to this issue. A key concern involved is the traceability of many of these occurrences which may limit wider funding appeals for broader change at a national level as discussed with NHS England safety representatives.
However, change is underway with our improved National safety alert system to ensure these instances are documented. Reporting of both patient and doctor is now possible which should in time mean that traditionally poorly traceable events will come to light and a clearer picture of current hazards is possible.
Improved guidance is also awaited with a proposed new consensus document around managing unscheduled bleeding which also provide further clarity around appropriate doses of progestogens.
Pilot projects at a local level which demonstrate quality improvement can also springboard change more widely and so the future proposed audit results are awaited.
Education is crucial at delivering change and methods of providing this need to be tailored to the audience for whom it is required taking into account increasingly tight time restrictions placed on many healthcare workers. Supplementary material for later reference is key alongside quick and accessible clear information. The internet has provided a platform for facilitating this.
Footnotes
Acknowledgements
Nikki Smith, Kajal Haghmordi, Deborah Bruce, Janice Rymer, Henrietta Hughes OBE, Kerry Seelhof, Julia Powell, Neha Ramaiya, Jenny Grant, Priyanka Amin and Dr Fionnuala Barton.
Contributorship
My own work except for literature search and support from Advanced certificate supervisor colleagues. Additional contributions from Dr Fionnuala Barton regarding social media contacts.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
