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Are more men seeking help for erectile dysfunction? A time trend analysis

Background: Sildenafil and tadalafil are recommended first line treatment for Erectile Dysfunction (ED). Sildenafil was legally reclassified to a ‘pharmacy’ medicine in the United Kingdom in 2018. Aim: To assess the prescribing patterns and costs associated with prescribing of ED drugs in England and to investigate the link between prescribing and deprivation, regional demography and legal reclassification. Design and setting: Analyses of publicly available government data from various sources pertaining to primary care prescribing and demographics in England was conducted. Methods: Prescribing and cost data for the last 10 years (2009-2019) were extracted and adjusted for inflation, male populations and regional deprivation. Results: Between 2009 and 2019 the rate of prescribing, measured as the number of items per 1000 men, increased by 110%. In 2019, the rate of prescribing of ED medicines in the most deprived areas was 21.0% higher than the rate observed in least deprived areas. The Northern regions of England had approximately 50% higher rate of prescribing compared to London. A 0.5% annual increase in the number of prescription items was observed between 2018 and 2019, compared to 5.0% increase observed from 2017 to 2018. Conclusion: The two-fold increase in the rate of primary care prescriptions in the last 10 years suggests that more men are being screened for or seeking help for ED. Higher rate of prescribing offers opportunity for monitoring of linked risk factors such as diabetes mellitus, dyslipidaemia, and vascular disorders in deprived populations. Reclassification of sildenafil had a modest impact on prescribing practices.


Introduction
Erectile dysfunction (ED), 'the persistent inability to achieve or maintain an erection that is sufficient to permit satisfactory sexual performance', can affect the physical, emotional and psychosocial health of the sufferer. 1 ED can have both organic and psychogenic origin and can be a risk marker for underlying cardiovascular diseases (CVDs) and mental health conditions that may warrant further evaluation and treatment. 2,3 Medications such as antihypertensives, antidepressants and antipsychotics can also lead to ED through their mechanisms of action. 2  The global prevalence of ED has been estimated to range from 3% to 76.5%. 4 A significant number of patients are known to suffer in isolation and do not seek help. Therefore, prevalence data are likely to be an under-estimate. 5 It is common for men with ED to experience anxiety, depression, relationship difficulties and a lack of sexual confidence. 2,3 These factors often lead to poorer quality of life for the sufferer, their partner and family. A c c e p t e d M a n u s c r i p t -B J G P O -b j g p o p e n 2 0 X 1 0 1 1 4 5 online pharmacies to supply the drug to the patients without the need of a prescription. 6 MHRA in the UK make decisions to alter the legal status of medicines from 'prescription only' medicines to 'Pharmacy' or 'General Sales List' categories (table 1). 7,8 The decision to reclassify such medicines are primarily based on safety data. 7 Such reclassifications are often expected to reduce the volume of prescribing and costs from the perspective of the NHS as patients are required to pay the price of the medicines at the point of purchase.
A cardiovascular risk assessment by a pharmacist in the community pharmacy is prerequisite to pharmacy supply of sildenafil. 9 Such risk assessment is undertaken using a series of questions asked to the patients before a supply can be made. Sildenafil is still available on National Health Services (NHS) prescription as well along with the tadalafil, vardenafil and avanafil.
There is a lack of research in relation to presentation and management of ED in primary care, particularly in the United Kingdom (UK). To date, no longitudinal research has looked into the prescribing patterns and costs of PDE-5Is in English primary care settings. Given the association of ED with cardiovascular diseases (CVD) including diabetes, vascular disorders as well as mental health conditions, 2,3,10 Understanding any link that exist between deprivation and ED drugs prescribing trend will enable targeted interventions to manage comorbidities and reduce health inequality.
The primary aim of this study was to investigate the trend in quantity and cost of prescribing

Ethical consideration
This study represents secondary analysis of the information retrieved from publicly available anonymised datasets and does not warrant formal ethical approval.

Study Design
A secondary analysis of routinely collected data on the prescribing and dispensing of two ED drugs, sildenafil and tadalafil, within the NHS England primary care settings between January 2009 and November 2019, was conducted. This time period includes switches from patented medicines to generic drugs for both tadalafil and sildenafil as well as the reclassification of sildenafil to 'pharmacy only' medicine in March 2018.

Data Collection
Prescribing datasets were extracted from NHS Digital sources including OpenPrescribing.net 11 and Prescription Cost Analysis (PCA). 12 These included data on the number of items prescribed, cost of prescribing and prescribing patterns within specific clinical commissioning groups (CCGs) for both drugs. Data were adjusted for inflation using Bank of England inflation calculator based on ONS composite price index. 13 Data were also adjusted for male population estimates for each year. 14 All data were extracted, independently checked for accuracies and analysed using Microsoft Excel and SPSS V21.

Summary
The aim of this study was to investigate the trend in prescribing of drugs for ED in primary care settings in England and to assess the impact of deprivation, regional demography and legal reclassification of sildenafil on prescribing practices of ED drugs.
There was a persistent increase in the rate of prescribing for treatment of ED in men Data showed that reclassification of sildenafil to a pharmacy medicine from 'prescription only medicine' had modest impact on the trend of prescribing. It could be assumed that the reclassification of sildenafil would lead to a decrease in the number of items prescribed as people would be able to get their medicine directly from the pharmacy instead of needing to go to the doctors and wait for an appointment. It is important to note, however, that the pharmacy version of sildenafil costs approximately £20 for a pack of 4 tablets (as of April 2020) whereas the generic sildenafil prescriptions from a general practitioner only costs £9 for the same number of tablets. The higher cost of pharmacy version of the medicine compared to the prescription cost may dissuade patients from using pharmacy for accessing sildenafil. In addition, confidentiality and privacy have been cited as barriers to utilisation of sexual health services from pharmacy. 17 The lack of long term monitoring and follow up in pharmacy settings may also discourage many patients from accessing the pharmacy version of sildenafil.

Comparison with existing literature
There is a lack of literature on the prescribing and management of ED in primary care.
Previous studies have reported that many men do not seek help with sexual problems to avoid perceived embarrassment for themselves and their doctors. 18,19 The observed increasing trend in the rate of prescriptions may have been contributed by various factors.
These include inclusion of ED assessment for diabetic men in the Quality and Outcomes

Implications for research and practice
The data suggests that more men are seeking help or being assessed for ED in primary care. The increased presentations and hence prescribing for EDs allows further opportunities to screen for the associated risk factors for ED. These include CVDs such as hypertension, coronary artery disease, peripheral vasculopathy; endocrine disorders such as diabetes, metabolic syndrome and hyperthyroidisim; as well as assessment of psychogenic risk factors and medication induced ED. 2 Prescribers should be aware of wider organic and psychogenic nature and linked risk factors of ED including diabetes, vascular disorders and mental health conditions. Cause of ED needs to be established before treatment can commence and patients should be referred to specialist clinics where appropriate.
Guidelines recommend that a physical examination including genitourinary, endocrine, vascular and neurological systems reveal any unsuspected diagnoses such as Peyronie's disease, pre-malignant or malignant genital lesions, prostatic enlargement or 9 A c c e p t e d M a n u s c r i p t -B J G P O -b j g p o p e n 2 0 X 1 0 1 1 4 5 irregularity/nodularity, or signs and symptoms suggesting hypogonadism are needed. 2,3 It is however, unclear how often are patients screened for the red flag symptoms. Long term safety outcomes of PDE5 inhibitors are not understood. Prescribers should therefore reassess the continuous use of these drugs on a periodic basis. 22,23 Reclassification to allow 'pharmacy only' supply of drugs to free up general practitioner time and resources have faced successes and barriers in the past. [24][25][26] For example, reclassification of drugs such as chloramphenicol eye products, mild steroids and antifungal products have been positively received by patients, general practitioners and pharmacists.
However, reclassified pharmacy version of simvastatin was not adopted in practice to the same extent. 24 Research on community pharmacist and patient perspectives on the need, supply and aspects of risk assessments and referrals are warranted. General practitioners and patient experiences of access of sildenafil from pharmacy also need to be further explored.

Strengths and Limitations
This project included data from very large routinely collected datasets covering all primary care prescriptions in England. Deprivation data was based on CCG level and individual practice level variations were not accounted for. This study only included NHS prescriptions data and private prescriptions are not accounted for. We only included two PDE-5Is, sildenafil and tadalafil as our observation suggested that the rest of the PED-5Is accounted for negligible volume of prescribing and hence did not impact on the trend analysis. Similarly, community and online pharmacy sales of over-the-counter sildenafil was not included in the trend analysis. Some patients may avoid perceived embarrassment and confidentiality issues in face-to-face clinical consultations in primary care and community pharmacy 17 by accessing medicines through online sources. We did not include other available treatments for ED including vacuum pump treatment and psychosexual therapies in our study. In addition, prevalence data of ED over time were considered for this study. The segmented regression for different policy changes (e.g. Sildenafil patent expiry in June 2013, Tadalafil patent expiry in November 2017 and reclassification of Sildenafil from prescription medicine to pharmacy medicine in March 2018) could not be performed due to i) absence of monthly prescribing and spending (access was restricted to annual level for historical data prior to 2015) data and ii) inadequate time-points before and after different policy changes needed to conduct segmented regression analysis. 27

Conclusions
Results of this study suggest that more men are being screened for or seeking help with ED.

Pharmacy (P) General Sale List (GSL)
Available only under a prescription from a medical or a non-medical prescriber such as doctors, dentists or a healthcare professional with an independent prescribing qualification and authority Available under the supervision of a pharmacist from a pharmacy registered with General Pharmaceutical Council (GPhC) Available in general retail outlets such as supermarkets.