To the best of our knowledge, this is the first study exploring gender difference in drug use and carried out on the entire Italian population. Our findings showed substantial differences between men and women in terms of prevalence of drug prescriptions. The volume of drugs belonging to the pharmacological groups in the study which were dispensed in Italy in 2012 was 19 billion DDD corresponding to 888.4 DDD/1000 inhabitants daily. Antibiotics and anti-asthmatics were the most used drugs in Italian children and adolescents for both males and females. These results were consistent with another national drug use study in which antibiotics were widely prescribed in pediatric outpatients with both quantitative and qualitative marked territorial differences .
Our results highlighted that some differences between males and females, stratified by pharmacological groups, are expected. In all age groups, women had a higher prescription prevalence for most pharmacological groups. More particularly, approximately 5% of women received at least one prescription for calcium and drugs for bone structure and this value was higher than that for men (0.4%). It comes as no surprise since the use of antiosteoporosis drugs is a mainly a female issue worldwide [19, 20]. Apart from the greater risk older women run of developing osteoporosis owing to the more extensive loss of bone mineral density [21, 22], the crucial impact of gender may also reflect the greater likelihood of women to obtain a relative drug or supplement with or without prescription.
Another relevant result of our study regarded thyroid preparations. Italian women used these drugs more than men, and the reason is probably to be found in the epidemiological development of thyroid disease [23, 24]. Hoffman F et al.  showed that, in Germany, thyroid diseases affect women almost 5 times more frequently than men.
In 2012, Italian women took more antidepressants then men (9.7% women vs 4.5% men). Major depression affects both sexes, but more women than men are likely to be diagnosed with depression in any given year [3, 25]. The prevalence of depression is estimated to be 11.2% in the Italian population, with women using more drugs than men (women 7.8% men vs 3.6%). Women are twice as likely to use antidepressant drugs compared to men.
In addition, such as other international studies, Italian women were undertreated as regards cardiovascular drugs (including antilipidemicemic agents, beta- blockers and related medication and angiotensin – converting enzyme inhibitors). ACE inhibitors primarily used for the treatment of heart failure and hypertension, were more commonly used in Italian men. In this context, in 1991 Bernardine Healy called attention to the discriminatory behavior of cardiologists towards women with under-diagnosed and under-treated ischaemic heart disease (IHD) in a publication in the New England Journal of Medicine entitled “Yentl syndrome” . This disparity between men and women regarding healthcare management appeared to depend largely upon multiple factors related to the patient, to consequences of the disease and to the physician’s assessment of patient risk. Over time, the term ‘Yentl Syndrome’ has come to be used in medicine to define the possibility that diagnostic and therapeutic strategies are not offered in a similar manner to both men and women (or that women are discriminated against). In 2011, Merz CN  suggested that the Yentl syndrome is alive and well 10 years later [28, 29]. With regard to this, two new studies demonstrating the medical under-treatment of women, including lower rates of aspirin and ACE inhibitor use in stable women compared to men and lower rates of ACE inhibitor, b-blocker, and statin medication in women with acute coronary syndrome compared to men became available.
It was clear that women in Italy used more drugs then men, and this result is consistent with other drug use statistics. According to data published by the National Agency for Medicines, Italian women have more contact with the healthcare system which may provide them with an opportunity for detecting disease and receiving prescriptions. Women have a higher life expectancy at birth than men (79.4 years men vs. 84.5 years women), suffer from chronic degenerative diseases associated with aging more than men (35.3% men vs 40.0% women), benefit more from the health services and, in the age group between 15 and 64 years in Italy, show a level of drug exposure 8% higher than that of men. Moreover, the fact that most of the preclinical and clinical studies are conducted on male animals and men (gender blindness) and then the results of these studies are then shifted onto women gives rise to most cases of inappropriate therapy. In literature, several papers have highlighted that belonging to one gender rather than to the other represents a risk factor as regards the development of adverse drug reactions (ADR). In fact, female patients have a 1.5 to 1.7 fold greater risk of developing an ADR compared to male patients . In Italy, the data of the National Network of Pharmacovigilance show a greater number (59% in 2011) of spontaneous reports of adverse drug reactions (ADR) in women in all age groups starting from the second year of life. ADRs in women are more numerous and even more serious than in men and lead to a higher number of hospital admissions (about 60% of hospitalizations for ADR regard women) . In contrast with this evidence, a typical antipsychotic prescribed with dementia, psychosis or attention-deficit hyperactivity disorder (ADHD) shows a greater risk of provoking ADRs in male patients than in women .
The main strength of this study is the coverage of all dispensed prescription drugs reimbursed by the National Health Service to the entire Italian population. Another strength is the data source of the study which provides a more accurate picture of actual drug use stratified by gender.
The most important limitation of this study is the lack of clinical information on patients in order to assess the reason behind the observed differences. It is important to emphasise that gender differences may only be hypothesised from these data. Moreover, data on out of pocket drugs were excluded. We only had information on the third level ATC, but, in reality, this is not a severe limit since we can identify the pharmacological group by means of the ATC III.
Despite the limitations detailed above, the results of this study made it possible to formulate some thoughts of interest to public health. They represent a starting point for informing health care workers of the importance of gender differences in order for them to provide the best possible health care. In this context, behavourial and preventive interventions would be necessary to reduce the gender disparity. Moreover, the doctor-pharmacist-patient relationship should be characterized by dialogue as an opportunity for education management therapies.