Italy's National Bioethics Committee (CNB) updated its stance on the use of puberty blockers to treat gender dysphoria. The November 2024 guidance states that puberty blockers should only be provided after mental health interventions failed, and only in the context of proper research trials. The CNB's key recommendations are:
- Puberty blocker prescriptions for gender dysphoria should occur only after the documented failure of psychotherapy or psychiatric interventions.
- All clinical assessments must be multidisciplinary, and decisions thoroughly documented.
- Clinical trials should follow the double-blind, randomized, controlled model, ensuring robust data.
- Use of puberty blockers outside clinical trials for this indication must adhere to the same rigorous criteria, with all data transmitted to a national registry.
The 2024 guidance was issued in response to the questions raised by the Ministry of Health on December 22, 2023 regarding the ethics of puberty blockers for gender dysphoria, "particularly considering the sensitivity of the issue, which concerns minors who are going through a decisive stage of their development, and concerns their awareness in giving their consent to this pathway." The CNB noted that the potential benefits of puberty blockers for the treatment of gender dysphoria in adolescents must be weighed against "elements of uncertainty... including the paucity of safety and efficacy studies and insufficient follow-up data of treated cases." The CNB also noted that the balance of benefits and harms of puberty blockers continues to be hotly debated in the international community, with differing outcomes by country:
"The use of tryptorelin [puberty blockers] was discontinued or limited in the United Kingdom, Sweden, Finland, and Norway, while other countries did not see fit to drastically reduce its use, e.g., Canada, the Netherlands, Belgium, Switzerland. In general, all these countries used or still use this drug consistently with the 'Dutch protocol,' but often, in practice, in ways that are heterogeneous among themselves and with respect to Italy, also in view of the different organization and articulation of National Health Systems."
The CNB held a series of hearings inviting a number of scientific societies in Italy, including the Italian Society of Obstetrics and Gynecology (SIGO); Italian Psychoanalytic Society (SPI); Italian Society of Pediatrics (SIP); Italian Society of Gender, Identity and Health (SIGIS); Italian Society of Pediatric Endocrinology and Diabetology (SIEDP); Italian Society of Andrology and Medicine of Sexuality (SIAMS); Italian Society of Neuropsychiatry; of Childhood and Adolescence (SINPIA); and Italian Society of Behavioral and Cognitive Therapy (SITCC). The CNB noted a plurality of views expressed, which reflect the state of international debates. Based on the information gathered in the hearing, the CNB concluded that there is "insufficiency of scientific data on the use of puberty blockers," noting that the research conducted to date is "inadequate to the objective."
The CNB recommended that Italy fund high-quality trials that evaluate a wide range of outcomes, from psychological and cognitive to those related to physical development. Leaving the precise trial design to experts in experimental research, the CNB reminded the community that, from a methodological point of view, in order for a drug to be licensed for use, it has to be subjected to a double-blind randomized controlled trial (RTC). The CNB recognized the difficulty of "blinding" in the context of puberty blockers, but believes that there are feasible designs that can accommodate this concern. Further, the CNB strongly recommended a systematic review of existing evidence as well as relevant existing observational data in the Italian context. The CNB called out the need to analyze the outcomes by sex. The CNB also recommended that any trial of puberty blockers should take place only after psychotherapy and psychiatric care have not proven effective.
The CNB opinion was approved by a large majority of those present, with four of the non-voting members joining, and was accompanied by one dissenting note, one abstention note, and two explanations of vote. The machine translation of the summary of the CNB opinion is reproduced below, with the original documents in Italian, and the machine-translated versions attached below.
"The answer to the question posed by the Ministry of Health concerns strictly and solely the use of the drug in the context indicated by the question.
As a result of expert hearings and the evaluation of available literature, the CNB highlighted, in general, the insufficiency of scientific data on the use of puberty blockers and the need to strengthen them. Consequently, the CNB stresses the need for the Ministry of Health to take charge of funding independent clinical studies aimed at obtaining decisive data on the efficacy and risks of drug administration, of higher quality than those already carried out, which do not appear adequate to the objective.
From an ethical perspective, regarding trial design, the CNB recalls that the gold standard for clinical trials for drug approval is a double-blind, randomized controlled clinical trial. The CNB recommends that clinical evaluations should be multidisciplinary, and the prescription of tryptorelin should only occur following a finding of ineffectiveness of a psychotherapeutic/psychological, and possibly psychiatric, course. The decision-making process should always be thoroughly documented in all its steps.
Given the uncertainty about the risk-benefit ratio of tryptorelin puberty blockade, the CNB would like to see prescriptions only within the scope of trials sponsored by the Ministry of Health.
Even where administrations occur outside of trials, that is, in the case of denial of consent or as a result of specific clinical evaluations by the physician that should always be documented, the CNB recommends that the same criteria indicated for trials be followed, and that in any case all data always be submitted to a dedicated registry. This is also in light of the fact that, at the moment, data on the use of tryptorelin reported by the regions (i.e., on its use during the period 2019-2023) are lacking and fragmentary.
The opinion was approved by a large majority of those present, with 4 of the non-voting members joining, and was accompanied by one dissenting note, one abstention note, and two explanations of vote, one of which was signed by 15 members, and the other by 7."