Overcoming barriers to oral contraception in Italy an expert opinion to empower women

Abstract Oral contraceptives are among the most commonly used contraceptive methods. However, Italian women underused reliable hormonal contraceptives as compared with other European women. There is a need to streamline access to oral contraception, with expected benefits on emotional well-being of women and potential savings for health system in Italy. Indeed, women can only access to oral contraceptives through mandatory medical prescription. This is one of the most important barrier experienced by women. We hereby provide an expert opinion on the potential reclassification, extending pharmacy services to include responsible and appropriate use of POP, as an opportunity also in Italy to increase the use of safe and effective contraceptive methods.


Introduction
Contraception is widely used in Europe; in 2015, 90% of European women seeking to avoid pregnancies were using a contraceptive method [1].
A survey carried out in 2019 by the Italian National Statistics Institute (ISTAT) investigated the contraception mix used by Italian women [2]: the most frequently used method is the male condom (35%), while oral contraception is used only by roughly 20% of women, thus being one of the lowest rates in Europe and western countries.Nonetheless, Italian women still rely on less effective methods, such as withdrawal (18%), or do not use any contraceptive methods (23%) (2), a finding confirmed in other settings [3,4].
In Italy, women can only have access to the most effective contraceptive methods (e.g.oral contraceptives, intrauterine device and implants) through mandatory medical prescription, while less effective methods, including male condoms and behavioral-based methods (i.e.withdrawal and fertility awareness-based methods) are available without medical prescription.Access to oral contraception remains an issue having an impact on women decision to use it, with reported difficulties in seeing doctors to get the prescription [5].
In addition, unintended pregnancies in Italy are still frequent: a recent study carried out using a pregnancy risk model [6] highlighted that, with the current contraception mix used in Italy, almost a third of pregnancies are unintended.
The recent approval in the UK of a hormonal pill for sale in pharmacies without the need to see a doctor [7] has prompted renewed interest and enthusiasm in the subject.Among the different hormonal oral options, UK only reclassified a Progestogen-Only Pill (POP).At the time of the writing, also the US Food and Drug Administration is evaluating the reclassification from prescription to without mandatory medical prescription of a POP.A large coalition of prominent clinicians, researchers, and reproductive health, rights, and justice organizations has long focused on making POPs available without mandatory medical prescription, as POPs have few contraindications and would therefore be appropriate for a wide range of women.In addition, women and pharmacists are open to undertake oral contraception without mandatory medical prescription but with pharmacists as counselors, as reported in a recent survey carried out in Italy [5,8].
Therefore, with the aim of empowering women about a rational and safe use of oral contraceptives, overcoming the existing barriers to effective and inclusive family planning, we provided an expert opinion on the potential reclassification of POPs in Italy.

Material and methods
The present work is the result of an initiative carried out in Italy by seven multi-professional experts in the field of contraception and women health.The expert group included: a) three gynecologists (president or members of the Boards of the main Italian gynecological and contraception scientific societies); b) a territorial pharmacist (member of the national board of the main territorial professional association of pharmacists and president of a regional area); c) a general practitioner (secretary of one the most prominent scientific society of primary care physicians); d) two representatives of civic associations (involved in protecting the rights of citizens and in advocacy for women's health).
The working group convened in a digital meeting in November 2022 with the aim to review and discuss the current situation of oral contraception in Italy in terms of prescription and access, as compared to the international landscape.Following the expert meeting, the experts attended two further separated follow up meetings to agree upon which information include in the expert opinion starting from individual opinions regarding the potential role of reclassification as a mean of overcoming barriers in access to oral contraception in Italy.Insights on which kind of oral contraception options would be suitable for reclassification from prescription only to without mandatory prescription, in terms of safety and opportunities, were also discussed and agreed upon.
After the identification of POPs as a suitable option for reclassification, the working group considered how to facilitate the responsible and appropriate use of POPs containing desogestrel (DSG), known for their safety, without a mandatory medical prescription.
The discussion was carried out through a stepwise approach.Accordingly, each member of the working group provided her/ his opinion on the proposed topic.After a careful revision carried out by every member of the working group, the final expert opinion is reported in here.

Results and discussion
We present the results of the discussion of the working group on the following topics.Based on the state of the art, experts provided their opinions.

Oral contraception in Italy: current situation
Contraception use rates in Italy are lower than in other Western countries, as highlighted by several sources: according to the Italian National Statistics Institute [2], 23% of women between 18 and 49 years old do not use any contraceptive method, despite being sexually active.Another source indicated a contraceptive prevalence rate (CPR), i.e. the proportion of sexually active women using any contraceptive method, of 69.4%, while the modern CPR (mCPR) was of 66.5% [9].Among the most frequently used contraceptive methods, there are condoms (about 35%) and coitus interruptus (about 18%), that are unreliable contraceptive methods, characterized by high failure rates [10], whereas oral contraception is about 20% [2].
In Italy, promotion of 'Responsible Parenthood' , which includes education on the most effective means to avoid an unintended pregnancy, is appointed to counseling centers, established under the Law n. 405 in 1975 as a mean to support health protection of the women and their children.
However, appropriate information on contraception is still lacking [11].Indeed, the 'Studio Nazionale Fertilità' [12] reported that 84% of girls and 89% of boys interviewed mainly gathered information related to sexual and reproductive health in internet, without any supervision by healthcare professionals.In addition, 76% of adolescent girls and 68% of boys declared that they have never been in a counseling center; 26% of adolescents use withdrawal as preferred method of contraception, and 11% rely on standard days.Within the study, 10% declared that they did not use any contraceptive method.Recent data indicated that peer communication and experiences served as influential factors in the use of emergency contraception (EC) over-the-counter (OTC), potentially reducing appropriate understanding of efficacy and safety in Italy [13].
Moreover, the rate of unintended pregnancies correlates with the low contraception rate: in a multicenter study based on cross-sectional data from maternity clinics located in 6 different Italian regions [14], 35.5% of pregnant women reported that they had mistimed or did not intend their pregnancy.Another recent study estimated the number of unintended pregnancies, considering the prevalence of the contraceptive methods used by Italian women, resulting in nearly 1/3 of women experiencing an unplanned pregnancy in one year [6].
Unplanned pregnancy intention is supposed to be an indicator of increased risk for some poor birth and maternal outcomes and should be considered in interventions aimed at improving the health of the mother and child [15].
The working group agreed that in italy contraception in general, and oral contraception in particular, remains less used than in other countries.
considering the above-mentioned information regarding unintended pregnancies and their poorer outcomes for women and their babies, the panel agreed there is a need in italy to streamline access to safe and effective contraception, such as oral contraception.
This would help to reduce the use of emergency contraception and the decision of voluntary terminating pregnancies, with expected benefits on emotional well-being of women and potential savings for health system in italy

Barriers to oral contraception in Italy: the prescription issue
Barriers to accessing contraceptive information and methods include legal restrictions, health care provider (HCP) attitudes, and healthcare systems [16].In details, among the factors making it difficult for women to seek information or access oral contraception openly there are cultural and religious beliefs leading to moralistic attitudes.Other factors include lack of comprehensive sexual education, misconceptions about risk and benefits of different birth control methods, and challenges in finding a healthcare provider who can prescribe oral contraception and provide adequate information about its use, due to lack of capillary healthcare facilities and financial constraints.
Addressing these barriers involves comprehensive sexual education, improved access to healthcare services, reduction of financial constraints, and promotion of an open conversations about contraception.
In Italy, while there is a wide range of contraceptive methods, options available without a prescription are limited to the least effective methods, including male condoms, some spermicides, female condoms, and behavioral-based methods (i.e.withdrawal and fertility awareness-based methods).Interestingly, these methods available without prescription are among the most frequently used by Italian women [2,17].
In contrast, women can only access by prescription all the contraceptive methods classified as 'effective' (e.g.oral contraceptives) and 'most' effective (i.e.male and female sterilization, intrauterine devices and implants).
The Italian Pharmaceutical Agency has classified oral contraceptives in the 'C' category, which makes them in charge of women, in addition to requiring medical prescription.Some Italian Regions have decided to provide oral contraceptives free of charge; however, this possibility, where available, is reserved to small subgroups of the eligible population, i.e. young women (until 26 years of age), women that underwent an abortion in the previous two years and women with income exemptions [18].
The ability to access affordable, safe and effective contraceptives is an essential element of the right to reproductive health [19].Unfortunately, the requirement to have a prescription for hormonal oral contraceptives can be a barrier to access, preventing many people from easily obtaining birth control means.
Women cited as barriers for not using oral contraceptives the cost of contraceptives, the need to see a doctor, undergo a gynecological examination, and long waits for appointments [5].Among the youngest women, reasons for not using oral contraception currently appear linked to the need of seeing a doctor.These requirements represent a barrier not only to initiating use of effective contraceptive methods, but also to continuing their consistent use once started [20][21][22].
In the last decade, major medical organizations have expressed support for moving oral contraceptives to OTC, or dispensing oral contraceptives without mandatory medical prescription, with the aim of eliminating barriers to access to oral contraceptives for regular use and expressed support for the dispensing of oral contraceptives without a medical prescription [23].
The working group agreed that prescription is one of the barriers that women experience when initiating or continuing the use of oral contraception.Thus, in the opinion of the experts, prescription, even in the limited cases in which it is free of charge, is a factor that reduces the rate of use of oral contraception in italy

The case of POPs: eligibility criteria
After agreeing upon the prescription as a barrier for the use of oral contraception, the working group debated if there is an option, among the currently available oral contraception pills, that would be safe and effective to dispense without mandatory medical prescription.
The two types of available oral contraceptives are the Combined Oral Contraceptive (COCs) containing an estrogen and a progestin, and the Progestogen-only Pills (POPs) [24].POPs differ from COCs as being estrogen-free, with a lower concentration of progestogens [25].
Compared to COC, POPs have few contraindications overall.Therefore, they would be appropriate for a wide range of women, as only 0.6-1.6% of them have contraindications [26,27].
POPs can be proposed as the best choice for an oral contraception without the requirement of a medical prescription, thus increasing accessibility for individuals encountering barriers to getting a prescription [28].
Medical Eligibility Criteria (MEC) for oral contraception have been developed by three international organizations: the World Health Organization [29], the Centers for Disease Control and Prevention (CDC) [30] and the UK Faculty of Sexual and Reproductive Health [31], which published guidelines targeted to POPs.
The WHO document, published in 2009 [29] defined the conditions for which initiation of contraceptives use would be graded as Category 3 or 4, indicating that the risks outweigh the benefits of use, or that use poses an unacceptable health risk, respectively.The only absolute contraindication (MEC 4) was current breast cancer.Category 3 conditions (relative contraindication) for initiation of POPs are: According to the CDC MEC [30], the only one condition representing an absolute contraindication (category 4) to the POP is breast cancer diagnosed more recently than in the past 5 years.
In addition, MEC 3 conditions (relative contraindication) for initiation of POPs are: Consistently, the FSRH 2022 guidelines highlighted that breast cancer, arterial thromboembolism that occurred during use of a POP, decompensated cirrhosis and hepatocellular tumors are MEC3 or MEC4 conditions that contraindicates the use of all POPs [31].
As far as effectiveness and efficacy rates, the typical use failure rate of POPs has been estimated at 9% in the prescription setting, meaning 9% of women experience an unintended pregnancy during the first year of typical use [10].Other authors [28] recently reported that the median method failure rate of POPs is 0.97%, as compared to 0.30%, that is the rate of pregnancy among perfect users of COCs.As stated, these 'findings can help ensure that policymakers, reproductive health advocates, and the general public have the necessary information, backed by clinical evidence, to make decisions about an OTC POP product' .In facts, women using no contraceptives over the course of a year have an 85% chance of experiencing an unintended pregnancy [10].In addition, all current contraceptive methods available without mandatory prescription have higher typical use failure rates, ranging from 18% (male condoms) to 22% (coitus interruptus) [10].
Moving to individual moieties, desogestrel (DSG) 75 µg tablets is a well-known medicinal product, with an established favorable efficacy and safety profile.There is now more than 25 years post-authorization experience with DSG 75 µg tablets, as the reference medicinal product (i.e.Cerazette) was initially approved in 1997 under prescription, with first generic available since 2007 in various European countries, and several generic products on the market.Today, DSG is considered as the most commonly used POP in Europe [32].
In addition, the pill-taking regimen is simple and fixed, without a hormone-free interval, and fertility returns promptly upon discontinuation [33].
in the opinion of the working group, among oral contraceptive options and in consideration of their long-term data on safety and effectiveness profile, PoPs are a suitable option to be dispensed without mandatory prescription in italy.among PoPs, the experts agreed upon the fact that there is no clinical reason why dSG 75 µg tablets should still require a mandatory medical prescription

Regulatory scenario: from scientific endorsers to UK decision
In the recent past, several scientific-technical societies have positioned themselves in favor of the reclassification of oral contraceptives regular use, with the aim to improve access to women seeking contraception.Among them: The American College of Obstetricians and Gynecologists [38].
The World Health Organization (WHO) Guide on Self-Care Interventions for Health and Well-being published on 13 July 2021 and revised in 2022 [39] recommended 'self-care interventions as ways to improve people's contraceptive options and their choices of place to access these' .Among these self-care interventions, the OTC availability of oral contraception is included.
One strategy for removing barriers to contraception is a pharmacy access model, wherein pharmacists can directly provide contraception to patients after a brief consultation [40].While this model still requires interaction with a health care provider, pharmacies are capillary points of access that can be easily reached by women seeking contraception.
In this direction, the WHO Academy has launched a learning program on the counseling and prescribing of contraception in pharmacies [41].
In addition, several countries have already taken decisive actions in order to facilitate the access to oral contraceptives for regular use:

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In New Zealand, in 2017 the Medicines and Medical Devices Safety Authority (Medsafe) accepted a recommendation by the Medicine Classifications Committee (MCC) to change the classification of selected oral contraceptives (containing desogestrel, ethinylestradiol, levonorgestrel and norethisterone) from 'prescription' to 'restricted' medicines, allowing them to be sold OTC after a consultation with a pharmacist [42].

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In four Canadian provinces (AB, SK, QC, and NS), pharmacists can prescribe birth control to varying degrees, and there is strong support across the country for pharmacists to be another access point for renewing and prescribing oral contraceptives.A large majority of women believe this would result in better access to birth control.Therefore, Canadian Pharmacy Association (CPhA) issued a call 'for equity across the country when it comes to allowing pharmacists to practice their expertise to full extent in order to improve access to primary health care services' [43].

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In the Netherlands, since 1997, oral contraceptives can be supplied in pharmacies, after an initial prescription and without a repeat prescription [44].Data from the Netherlands demonstrate that long-term continuation of hormonal contraception without ongoing counseling from a prescriber does not have detrimental effects on women, their well-being, and the society.
The most recent regulatory decision on availability of oral contraception without a mandatory medical prescription was in the United Kingdom.Indeed, the UK Medicines and Healthcare products Agency approved the reclassification of DSG 75 µg from Prescription to Pharmacy status in July 2021 [7].
The decision, that makes DSG available without medical prescription under the supervision of a pharmacist, was made considering the advice of the CHM and following the outcome of a public consultation [45].
The Licensing authority recognized that pharmacy availability of DSG 75 µg without a prescription will enable women to access oral contraception from a pharmacist and that DSG-containing oral contraception will still be available on prescription from GPs and family planning services.Therefore, women will choose between which setting they use.
In the opinion of the Licensing Authority, pharmacists have the expertise to advice women on whether DSG is an appropriate and safe oral contraceptive pill for them to use and to give women the information they need to make informed choice [45].
The availability of POPs without mandatory medical prescription would contribute to reducing the overload of medical consultations, directing the medical efforts toward more relevant clinical needs.
This announcement was considered a huge win for women and girls who will no longer face unnecessary barriers when accessing this type of contraception.
In addition, in a recent survey, Italian women have shown a widespread support to access to oral contraceptives without prescription, reporting convenience as the main reason why females would be likely to use oral contraceptives in this setting [5,8].
The working group considered how many scientific societies have positioned themselves in favor of the reclassification of oral contraception from prescription to without mandatory prescription worldwide, with some countries that already offer some oral contraceptive pills without mandatory prescription.The opinion of the experts was that this reclassification, already operated in some countries, could be an opportunity also in italy to increase the use of safe and effective contraceptive methods.Thus, the italian medical authorities could take advantage from UK and other countries experience to guide strategies in the field of contraception also in italy

Responsible and appropriate use of POPs without prescription in Italy: considerations on the pharmacy role
The informed and responsible access to POPs without mandatory medical prescription should be balanced with women safety.Not only the drug must be safe, but also the person should be able to use it without the help of a clinician.In this sense, pharmacists can play an important role.
During the COVID-19 pandemic in Italy, both hospital and community pharmacists have shown a key 'counsellor' role for citizens and patients [46].Indeed, under the pressure of the COVID-19 emergency, pharmacies have given a boost to the concept of 'Pharmacy of Services' , in support of the healthcare system [47] thus making a transition from compounding and dispensing of pharmaceutical agents to distribution of services connected with the protection of health.
Sexual reproductive health is an important need that should be addressed in the community by healthcare professionals, and especially by pharmacists, as they serve as first-line responders to patients.They play a crucial role in the community to counsel and empower patients by providing information and delivering self-care interventions to maximize health benefits [48].Thus, dispensing DSG 75 µg without mandatory prescription would reinforce the role of pharmacists within the national health system in Italy, according to the concept of 'Pharmacy of Services' .
In facts, can already dispense emergency contraception without medical prescription, providing suggestions and acting as counselors to women requesting EC.Therefore, in the light of the emerging concept of 'pharmacies of services' , pharmacies can represent a real opportunity for increasing access to contraception.Indeed, community pharmacists can play a relevant role in advising women on whether DSG is an appropriate and safe oral contraceptive pill for them to use and to give women the information they need to make informed choices [49,50].
Community pharmacies are conveniently located.As of December 2022, in Italy there are over 19,900 pharmacies employing 67,000 pharmacists.The number of pharmacies, among which the vast majority are private, has been constantly growing [50].The density of pharmacies per inhabitant in Italy (one for every 2,977 inhabitants) is higher than the European average (one for every 3,245 inhabitants), confirming the great capillarity of the Italian pharmacies [50].
Moreover, a recent survey explored Italian pharmacists' attitude toward dispensing oral contraceptives without mandatory medical prescription [5,8]: the vast majority of Italian pharmacists showed a favorable position regarding dispensing oral contraception without prescription, already acting as counselor to women coming to obtain it, at least twice a week.
The working group agreed that extending pharmacy services to include provision of PoPs, alongside ec, would lower barriers to access, enabling more women to bridge between methods of contraception, safely and on their own terms.Furthermore, the experts highlighted how community pharmacies can alleviate ongoing pressure on the national Health Service.
However, the experts suggested the need of appropriate updating of knowledge, development of dispensing protocols and establishment of communication channels between the different levels of care, considering how access to effective and safe contraception as PoPs is relevant as much as the responsible and appropriate use of these medicinal products

Expert opinion
In order to evaluate if current evidence supports the safe use of POPs in the majority of women, a group of designated experts was enrolled to discuss about this novel paradigm of contraception.In particular, gynecologists, civic organizations, a pharmacist, and a general practitioner attended the expert meeting.
Based on the current evidence, in the light of all the considerations above mentioned, the experts supported the following recommendations and conclusions:

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Medical prescription is often considered a barrier in the provision of effective and safe contraception.

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It is important for women to start an effective contraception based on their own informed choices.• Since more than 20 years, progestin-only contraceptive pills containing desogestrel (DSG) have being considered effective and safe for most women.Therefore, DSG can be selected for an improved access without mandatory prescription.

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In Italy, pharmacists are able to have a 'counsellor' role, according to the new and recognized concept of 'Pharmacy of Services' .

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As recognized for the UK, even in Italy pharmacists could have the expertise to advice women on whether DSG is an appropriate and safe oral contraceptive pill for them to use and to give women the information they need to make informed choice.

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This would potentially reduce the rate of unintended pregnancies, which have been reported to result in poorer outcomes for women and their babies, along with the use of emergency contraceptives and the decision of voluntary termination of pregnancy, with expected benefits on emotional well-being of women and potential savings for health system in Italy.• However, the availability of POPs without medical prescription after a consultation with a pharmacist will require appropriate updating of knowledge, the establishment of an appropriate welcoming of the women in pharmacies' premises and the development of dispensing protocols considering communication channels between the different levels of care.• Improved access to effective and safe contraception as POP is relevant as much as the responsible and appropriate use of these medicinal products.