Use of Methenamine Hippurate in an Ageing Population: National Prescription Trends from Norway (2004–2020)

Introduction

Recurrent urinary tract infections (rUTIs), commonly defined as at least two within six months or at least three within 12 months, are a common condition.¹ They have been reported to affect up to 30% of women during their lifetime.² The sequelae are considerable, encompassing not only the physical and psychological burden on individual patients but also a significant socioeconomic impact at the population level.³

For patients where an underlying cause has been excluded, low-dose antibiotic prophylaxis represents a recognised management strategy.⁴ While it can have the desired therapeutic effect, this approach is associated with limitations. One major concern regarding prophylaxis is antibiotic resistance, a recognised global health challenge.⁵ A number of non-antibiotic alternatives do exist including methenamine hippurate. The latter is an antiseptic agent, which has bacteriostatic and bactericidal properties.⁶ This occurs as a result of the release of formaldehyde under acidic conditions in the urine.⁷ Methenamine hippurate has been in clinical use in the United States and worldwide for many years.⁸ While it is a commonly known agent to consider for use in this patient population and receives a recommendation from international guidelines, there is very little data, which reveals what proportion of the population use this medication, especially among males.⁹ There is value, from a public health perspective, in having such information in order to identify trends as well as evaluate equity and access. To this end, our aim was to catalogue the use of methenamine hippurate at a national level in Norway.

Materials and Methods

Data were obtained from the Norwegian Prescription Database (NorPD; Norwegian Institute of Public Health) for the period 2004–2020.¹⁰ NorPD provides a complete and centralised record of all prescriptions dispensed at pharmacies in Norway. The study period ended in 2020, as this was the most recent year for which complete data were available at the time of analysis. The medication was identified using the Anatomical Therapeutic Chemical (ATC) system and the following code: J01XX05. In Norway, methenamine hippurate is a prescription-only drug and cannot be purchased over the counter. It is also available on a special prescription for chronic conditions where the costs are subsidised by the government. All entries related to methenamine hippurate were eligible for inclusion and there were no exclusion criteria. Data was obtained on number of users (including per 1000 persons) as well as distribution according to age and sex. All data were aggregated, anonymised at source, and obtained from a publicly available database; therefore, ethical approval was not required. Descriptive analysis was performed with figures generated in R (R Foundation for Statistical Computing, Vienna, Austria).

Results

Overall Trends

Between 2004 and 2020, the number of individuals prescribed methenamine hippurate increased steadily, with an average annual increase of 5.3%. The number of unique users increased from 15,500 in 2004 to 35,134 in 2020. Across all age groups, the prevalence of use increased from 3.8 users per 1000 persons in 2004 to 6.5 per 1000 persons in 2020, representing a substantial increase over the study period.

Sex Distribution

Females accounted for the majority of methenamine hippurate users throughout the study period (Figure 1). Among women, prescription rates increased from 5.5 per 1000 persons in 2004 to 11.3 per 1000 persons in 2020. In contrast, male prescription rates increased modestly from 1.3 to 1.8 per 1000 persons during the same period. Although absolute use increased in both sexes, the relative proportion of male users declined from 18.8% in 2004 to 13.8% in 2020, reflecting a greater rise in prescribing among females.

Figure 1 Prescription rates of methenamine hippurate by sex, Norway, 2004–2020 (users per 1000 persons).

Age Distribution

Use of methenamine hippurate was strongly age-dependent. Individuals aged ≥80 years consistently represented the largest proportion of users, accounting for approximately 60% of all prescriptions throughout the study period. Prescription rates among children and younger adults remained low and stable, with individuals under 20 years accounting for less than 1% of users and those aged 20–39 years accounting for approximately 3%. In 2020, the highest prescription rates were observed among women aged >90 years, at 64.9 users per 1000 persons, compared with 25.8 per 1000 persons among men in the same age group (Figure 2). A similar age-dependent pattern was observed among men, with low prescription rates in younger age groups and a marked increase with advancing age.

Figure 2 Prescription rates of methenamine hippurate among women by age group.

Regional Variation

Prescription rates increased across all regions in Norway during the study period. However, substantial regional variation was observed. Higher prescribing rates were consistently noted in northern and more rural regions. In 2020, methenamine hippurate use was nearly twice as high in Nordland (8.1 users per 1000 persons) compared with Oslo (4.9 users per 1000 persons). This pattern remained consistent over time, despite overall increases in all regions.

Discussion

Despite being in clinical use for many decades, there are relatively few studies on the clinical use of methenamine hippurate in recent years. Findings from several systematic reviews and meta-analyses have generally concluded that it can confer a clinical benefit but consistently add caution based on the low volume of available evidence and heterogeneity of the included studies.⁶ However, there are two more recent studies that arguably serve to address elements of this knowledge gap. In 2022, Harding et al, reported findings from the ALTAR randomised trial, concluded methenamine hippurate to be non-inferior to daily low-dose antibiotics.¹¹ In 2025, findings from the ImpresU study were published.¹² The authors of this multicentre randomised trial found methenamine hippurate to reduce the frequency of rUTIs by 25% in older women. However, an increased risk of relapse was noted in the six months following discontinuation. The increase in prescribing among older women is likely multifactorial and may reflect greater awareness of guideline-driven practice, increased emphasis on antimicrobial stewardship, and demographic ageing of the population.

Methenamine hippurate is commonly considered as an option for females but our findings show that clinicians also use it for males as well. The prescription status for methenamine hippurate varies worldwide and so too do prescription costs. In the UK for example, it is possible for a pharmacist to issue the medication without a doctor’s prescription. Joshi et al, evaluated the costs of five different non-antimicrobials in the UK and reported vaginal oestrogen to be the cheapest for the user at £22.04 while D-mannose was the most costly at £158.4.¹³ Meanwhile, methenamine hippurate cost the user £100.44 for six months’ use. However, prescription costs and access differ between healthcare systems, and in Norway methenamine hippurate may be prescribed under the national reimbursement scheme (blå resept), resulting in a fixed patient cost. This may contribute to differences in utilisation patterns compared with countries such as the UK, where costs are more directly borne by patients. The final year of the study coincides with the COVID-19 pandemic, which may have influenced healthcare utilisation and prescribing patterns; however, the extent of this impact cannot be determined from the available data. There is limited evidence describing national prescribing trends of methenamine hippurate, which limits direct comparisons and underscores the relevance of the present study.

Several factors may contribute to the observed regional variation in prescribing, including differences in population demographics, access to healthcare, and variation in the uptake of non-antibiotic prophylactic strategies and clinical practice patterns.

There are a number of limitations to acknowledge in this study. Firstly, data were not available on discontinuation or adherence. Secondly, it was not possible to differentiate if medication had been prescribed in the setting of primary or secondary care. Notwithstanding these shortcomings, the centralised and national prescribing system provides a unique overview of the use of methenamine hippurate. To the authors’ knowledge, there are no other studies, which provide this kind of insight at a population level.

Conclusion

There has been a steady increase in the use of methenamine hippurate in the Norwegian population over the past two decades. Utilisation is highest among older females, while use among males has persisted but to a much lesser extent. This trend may reflect increased awareness of the burden of rUTIs, particularly among older women, as well as a shift towards non-antibiotic prophylaxis. However, it also highlights the need for further research to evaluate prescribing appropriateness, clinical effectiveness, and implications for antimicrobial stewardship.