Can gender difference in prescription drug use be explained by gender-related morbidity?: a study on a Swedish population during 2006

Data was collected in 2006 from the total population aged 20 years or older in the Swedish county of Östergötland, which had about 400,000 residents in 2006. Östergötland is situated 200 km southwest of Stockholm and the age demographic matches that of the rest of Sweden [19]. Data on the population’s age, gender and diagnoses in both primary and secondary care was obtained from the Care Data Warehouse in Östergötland (CDWÖ), a register containing information on both public and private care. This register has been described previously [20]. The study was approved by the research ethics committee at Linköping University (approval numbers 147/05 and 29/06).

Multi-morbidity was calculated using the Johns Hopkins Adjusted Clinical Groups (ACG) Case-Mix System, a system based on the theory that multi-morbidity corresponds to a certain need for health care resources. This system is based on the patients’ diagnoses recorded during a defined period of time. The ethiology, duration, method of diagnosis, treatment and need of specialized care is considered for every one of the patients’ diagnoses. The ACG Case-Mix System has previously been described [21‐24]. Individuals without need of health care according to the ACG Case-Mix system are placed in Resource Utilization Band 0 (RUB 0) and individuals with a very high degree of need for health care resources are placed in RUB 5. For example, preventive interventions correspond to RUB 1, a single chronic diagnosis could correspond to RUB 3 and a certain combination of chronic diagnoses corresponds to RUB 4 or RUB 5.

The use (dichotomous variable) of prescription drug(s) in 2006 was the dependent variable. Information concerning the use of prescription drugs at the individual level was acquired from the Swedish Prescribed Drug Register, which is maintained by the National Board of Health and Welfare. This register collects information from the National Corporation of Swedish Pharmacies (Apoteket AB). In 2006 Apoteket AB had a monopoly on sales of prescription drugs and all prescription drugs were tracked through Apoteket AB.

The Anatomical Therapeutic Chemical (ATC) classification system was elaborated by the WHO to enable internationally comparable studies on prescription drugs. Active substances are classified in different groups according to the organ or system on which they act and their therapeutic, pharmacological and chemical properties. The drugs are divided into 14 main ATC groups and these groups are subsequently divided into five levels [25].

Over-the-counter drugs were not included in this study.

We used a report from the Swedish National Institute of Public Health to identify diseases that tend to afflict females more frequently [17]. In the report, the disability-adjusted life year (DALY) was used to measure the burden of disease. The DALY concept was elaborated by the WHO and the World Bank to measure the burden of disease in the population, taking into consideration both mortality and disability [26‐29]. The DALY is a time-based measure that combines years of life lost due to premature mortality and years spent living in states of less than full health. DALYs are the sum of life years lost due to premature mortality and years lived with disability, adjusted for severity. To put it simply, 1 DALY means one lost healthy year. In the report from the Swedish National Institute of Public Health, both major and minor gender differences were identified. To ensure that the prevalence of the disease and the difference between the genders were high enough to affect the results, we created two cut-off points. We selected diseases that had at least 7,500 DALYs in Sweden in 2006 for both genders combined and for which the difference between the genders was at least 20%, with a higher number of DALYs for females. Having identified the diseases that tend to afflict females to a higher extent, we identified the prescription drugs that are commonly used to treat these specific diseases (Table 1) according to Swedish National Guidelines [30, 31]. Anti-conception that is commonly used by healthy females as contraceptives is a special case. These prescription drugs are not considered to treat any disease but they may explain some of the difference in prescription drug treatment between the genders. Hence, these drugs were also identified as drugs causing a difference in prescription drug treatment between the genders.

The prescription drugs used to treat the diseases that afflict females to a higher extent, and anti-conception drugs, were excluded from the analysis using logistic regression. First, the prescription drugs were excluded one by one in subsequent univariate analyses. In the next step, the prescription drugs that caused a decrease in the gender difference, i.e. the prescription drugs that gave an odds ratio (OR) >0.45 [16] when excluded in the univariate analyses, were excluded. The OR represents the odds of having prescription drugs for males compared to females.

We used STATA version 12 (Stata Corporation, Texas, USA) for statistical analyses. Logistic regression was used to examine the odds of having prescription drugs in the study population, giving odds ratios (ORs and 95% confidence intervals (CIs). We generated three dichotomous models: Model 1 was adjusted for age and multi-morbidity; Model 2 was adjusted for age, multi-morbidity and relative ATC codes; and Model 3 was adjusted for age, multi-morbidity and ATC codes that gave an OR >0.45 when excluded in the univariate analyses.

Logistic regression gives us the odds ratio of having prescription drugs. For some diseases, it is highly likely to receive more than one prescription drug. For example in dementia, which afflicts females to a higher extent than males, there is a strong likelihood that the patient is using prescription drugs in addition to the prescription drug used to treat the dementia. The prescription drugs used to treat these diseases, for example dementia, were not excluded in this study.

Antidepressants

Benzodiazepines

Benzodiazepine-related drugs

Derivates of benzodiazepines

Hydroxyzine

Migraine drugs

Nitrofurantoin

Paracetamol

Propiomazine

Trimethoprim

Estrogens

Gestagens

Pivmecillinam

Thyroid hormones

Anti-conception drugs

Most of the diseases that females are afflicted with to a higher extent in the report from the Swedish National Institute of Public Health are diseases that may commonly be treated with only one prescription drug, i.e. hypothyroidism, cystitis and migraine. Even if we used Swedish guidelines when we identified the prescription drugs that are used to treat diseases that females are afflicted with to a higher extent [30, 31] there is a risk that the doctors do not follow guidelines. This could lead to both under- and overestimation of the results when prescription drugs with an indication for treatment of diseases that females are afflicted with to a higher extent are used for other purposes and vice versa.

As mentioned before, because of the logistic model for example dementia was not included among the diseases that affect females to a higher extent than males and consequently the prescription drugs used to treat dementia were not excluded from the study. This may have led to lower ORs and underestimation of the effect of gender-related morbidity on the gender difference in drug prescription.

The chosen cut-off point for the number of DALYs (7,500) may have been set too high and the chosen cut-off point for gender difference in DALYs (20%) may have been set too low. This may have led to underestimation of the effect of gender-related morbidity on the gender difference in drug prescription.

The classification of anti-conception drugs as prescription drugs may differ between different countries. In Sweden they are classified as prescription drugs and are included in all prescription drug statistics. The results of the present study cannot be generalised to countries where anti-conception drugs are not classified as prescription drugs.