Current evidence suggests that transgender people have a higher risk of sexually transmitted infections (STIs) than general population, although most of the literature focuses on transwomen with HIV.
ObjectiveTo determine the prevalence of STDs diagnosed by serology in transgender population in our hospital and to analyze the impact of antiretroviral treatment on hormonal therapy.
MethodsWe design a cross-sectional study based on medical records of transgender people treated at the Transgender Care Unit of Cadiz from June 2022 to June 2023. Hepatitis, HIV and syphilis serology was requested from people between 16 and 65 years.
ResultsA total of 295 people were included, 48,14% transwomen (n = 142) and 51,86% transmen (n = 153), with an average age of 24,78 ± 9,2 years. It was detected 14 cases of HAV, 5 of syphilis, 3 of HBV and 3 of HCV. Prevalence of HIV was 3,73% (n = 11). Of the 9 transwomen with HIV infection, 3 of them required a change in antiretroviral medication and 2 cases required changes in the route of estrogen administration to achieve optimal plasma hormone levels.
ConclusionsWith the current model of care for transgender people in Andalusia, the prevalence of STDs detected in our sociocultural environment is low. Special attention should be paid to possible interactions between antiretroviral treatment and hormone therapy, especially in transwomen.
La evidencia actual sugiere que las personas trans presentan mayor riesgo de ITS que la población general, aunque la mayoría de la literatura se centra en mujeres trans con VIH.
ObjetivoDeterminar la prevalencia de las ITS diagnosticadas mediante serología en la población trans de nuestro medio y analizar el impacto del tratamiento antirretroviral sobre la terapia hormonal.
MétodosSe diseña un estudio transversal basado en las historias clínicas de la población trans atendida en la Unidad de Atención a Personas Trans de Cádiz desde junio de 2022 hasta junio de 2023. Se solicitó serología de VHA, VHB, VHC, VIH y sífilis a las personas entre 16 y 65 años.
ResultadosDe las 295 personas incluidas, el 48,14% eran mujeres trans (n = 142) y el 51,86% hombres trans (n = 153), con una edad media de 24,78 ± 9,2 años. Se detectaron 14 casos de VHA, 5 de sífilis, 3 de VHB y 3 de VHC. La prevalencia de VIH fue del 3,73% (n = 11). De las 9 mujeres trans con infección por VIH, 3 de ellas precisaron cambio de antirretroviral y 2 casos requirieron modificaciones en la vía de administración de estrógenos para conseguir niveles hormonales plasmáticos óptimos.
ConclusionesCon el modelo de atención a personas trans en Andalucía, en nuestro entorno sociocultural, la prevalencia de ITS detectada es baja. Se debe prestar especial atención a las posibles interacciones entre el tratamiento antirretroviral y la terapia hormonal, especialmente en mujeres trans.
The term transgender refers to those people who manifest a gender identity different from their sex assigned at birth. In recent years, healthcare for transgender people has grown exponentially, especially among adolescents and young adults, and many of them begin gender-affirming hormone therapy (GAHT) to adapt the secondary sex characteristics to the desired gender.1,2
In trans men, GAHT consists of the administration of intramuscular or transdermal testosterone, the main objective of which is to induce virilisation and suppress endogenous oestrogen production.3 In trans women, oral or transdermal oestrogens are combined to enhance secondary sexual characteristics associated with the female gender with anti-androgens to block testosterone production (which must be maintained until gonadectomy). The guidelines recommend 17-beta-estradiol as the oestrogen of choice due to its lower thrombotic risk. The most commonly used anti-androgens in our setting are gonadotropin-releasing hormone analogues and cyproterone acetate. Before GAHT, puberty blocking may be performed to slow the development of secondary sexual characteristics and provide more time to explore identity.4
Transgender people make up a diverse population, which, in many cases, is affected by a variety of negative health indicators, including sexually transmitted infections (STIs).5 However, there is little data available in Spain on this subject and the cohorts studied so far have a sociodemographic context that is different from Spain, such as the predominance of a private healthcare system, significant economic inequalities, more transactional sex practices or the need for a psychiatric assessment prior to hormone therapy, which may become a barrier to seeking medical care.6,7 Most of the studies focus on human immunodeficiency virus (HIV) infection in trans women, due to the perception that this subgroup has more risky sexual behaviours, similar to those of men who have sex with men,6 and on the possible interactions between GAHT and antiretroviral therapy (ART).8
Currently, the initial ART combinations recommended by the AIDS Study Group of the Spanish Society of Infectious Diseases and Clinical Microbiology are based on two nucleoside reverse transcriptase inhibitors and an integrase inhibitor, due to advantages related to their good tolerance, lower toxicity and a low risk of drug-drug interactions. In specific cases, nucleoside reverse transcriptase inhibitors are combined with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitors boosted with ritonavir or cobicistat, in which cases there is a higher risk of drug-drug interactions.9
Many antiretrovirals have inducing or inhibitory effects on the cytochrome P450 system and hormonal contraceptives are metabolised by this system, so they can alter oestrogen levels.10 Some transgender people self-medicate with drugs not recommended in the GAHT due to their high thrombotic risk, such as conjugated equine oestrogens and ethinyloestradiol, which is a common component of oral contraceptives.11
Our aim with this study was to determine the prevalence of the most common STIs in our setting which can be determined by serology in the transgender population and to analyse the impact of ART on hormone therapy in people infected with HIV.
MethodsDesign and study populationWe designed an observational, descriptive, cross-sectional study based on the medical records of the transgender population treated at the Unidad de Atención a Personas Trans (UAPT) [Transgender Person Care Unit] in Cádiz from June 2022 to June 2023 (both inclusive). Our UAPT, as a reference centre, covers a general population of 1,337,918 people.
In accordance with the current recommendations of the Ministry of Health at the time of the study, serology for hepatitis A, B and C viruses (HAV, HBV and HCV), HIV and syphilis was routinely performed at the first visit on people aged from 16 to 65 (both inclusive), and was repeated at subsequent visits in case of risky behaviours.
The study was approved by the Ethics Committee of the Hospital Universitario Puerta del Mar Portal de Ética de la Investigación Biomédica de Andalucía [PEIBA] [Andalusian Biomedical Research Ethics Portal] (PEIBA code 0474-N-22). The data were collected anonymously from medical records registered in the Diraya computer program. All the participants signed an informed consent form approved by the committee to allow the use of the data and, in the case of those under 18 years of age, it was signed by at least one of their parents (or legal guardian, if applicable).
Data collectionThe variables collected are detailed below:
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Sociodemographic: date of birth, gender assigned at birth (male or female), gender identity (trans man or trans woman) and ethnicity. As the non-binary population in our setting is not very representative, it was excluded from the analysis.
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Related to the transition process: prescription of puberty blockers and GAHT, age at which GAHT was started, sex hormone levels throughout treatment, request for psychological support, and type of gender-affirming surgery (GAS) performed.
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Related to STIs: serology results, age at diagnosis, and history of intravenous drug addiction. In cases of people with HIV infection, viral load, type of ART, and changes in hormone or antiretroviral therapy regimens were included.
For hepatitis A, IgG and IgM antibodies against HAV were determined (for the diagnosis of past infection or vaccination and acute infection respectively). For the diagnosis of hepatitis B, the HBV surface antigen was determined, and for hepatitis C, IgG antibodies against HCV and HCV viral load were determined by polymerase chain reaction(PCR) to confirm active infection. Two treponemal serologictests (chemiluminescence immunoassay and Treponema pallidum particle agglutination assay) were performed to detect T. pallidum-specific antibodies and one non-treponemal test (rapid plasma reagin test) to determine past or active syphilis infection. For HIV, antibodies and p24 antigen were detected simultaneously by ELISA, as well as the viral load by reverse transcriptase PCR.
Statistical analysisData were analysed with the statistical software SPSS® version 17.0 for Windows. We carried out an overall analysis of the data and an analysis by subgroups of reported gender identity (trans woman and trans man). Qualitative variables are expressed as percentages and compared using the Chi-square test or Fisher’s exact test where appropriate. The Kolmogorov-Smirnov test was performed to assess the normality of continuous variables. Quantitative variables are expressed as mean and standard deviation or median and interquartile range if the variable did not follow a normal distribution. We used the independent samples t-test to analyse parametric variables and the Mann-Whitney U test for non-parametric variables.
ResultsAll people between 16 and 65 years treated during the study period agreed to take part by signing the informed consent form. Of the 295 people included, 48.14% were trans women (n = 142) and the remaining 51.86%, trans men (n = 153), with an average age of 24.78 ± 9.2 years, with no significant differences between the two genders. Overall, 98.98% (n = 292) of the people were of Caucasian race. During the transition process, 11.86% (n = 35) requested psychological support. Only 3.05% (n = 9) started puberty blocking exclusively and 88.47% (261) were on GAHT. In terms of GAS, there were 25 mastectomies, 10 hysterectomies with double adnexectomy and one masculinising genioplasty in trans men, while in trans women, there were 15 mastoplasties, 2 orchiectomies, 13 feminising genitoplasties and one glottoplasty. Table 1 shows a summary of the characteristics of the population based on their gender identity.
Sociodemographic characteristics and care demands of the people treated.
| Trans women | Trans men | |
|---|---|---|
| (n = 142) | (n = 153) | |
| Mean agea | 25.69 ± 10.07 | 24.14 ± 8.06 |
| Ethnicityb | ||
| Caucasian | 139 (97.9) | 153 (100) |
| Asian | 1 (0.7) | 0 |
| Maghrebi | 1 (0.7) | 0 |
| Roma | 1 (0.7) | 0 |
| Psychological supportb | 22 (15.49) | 13 (8.50) |
| Puberty blockersb | 6 (4.23) | 3 (1.96) |
| GAHTb | 124 (87.32) | 137 (89.54) |
| Breast surgeryb | 15 (10.56) | 25 (16.34) |
| Genital surgeryb | 15 (10.56) | 11 (7.19) |
GAHT: gender-affirming hormone therapy. No statistically significant differences between the two groups were found for any of the variables. The non-binary population in our setting is not very representative, so it has been excluded from the study.
The prevalence of HIV was 3.73% (n = 11). Nine of the eleven were trans women. All were diagnosed prior to the study date and were on ART with an undetectable viral load. The prevalence of HAV was 4.75% (n = 14), HBV was 1.02% (n = 3) and HCV was 1.02% (n = 3). Of the total number of positive HAV serologies, 12.5% (n = 2) were due to vaccination and 87.5% (n = 14) due to previous infection. All cases of hepatitis B were chronic infections, but only the patient with HIV coinfection was on treatment. In terms of hepatitis C, two cases had positive antibodies with no viral load without prior treatment, which is interpreted as spontaneous cure, while the third case maintained a sustained viral response after 24 mo of treatment. The prevalence of syphilis was 1.69% (n = 5), all were trans women diagnosed and treated before the study and no reinfections were observed during the analysis period. A description of each STI case is shown in Table 2.
Description of the STI cases.
| GI | IVDA | HAV (age)* | HBV (age)* | HCV (age)* | Syphilis (age)* | HIV (age)* | GAHT (age)┼ | GAS | |
|---|---|---|---|---|---|---|---|---|---|
| Case 1 | TW | Former | − | − | − | + (31) | + (33) | Yes (38) | No |
| Case 2 | TW | No | − | − | − | − | + (42) | Yes | Genitoplasty/Mammoplasty |
| Case 3 | TW | Former | − | + | + | + (31) | + (26) | Yes (43) | No |
| Case 4 | TW | No | − | − | − | − | + (40) | Yes (18) | Orchiectomy |
| Case 5 | TW | No | − | − | − | − | + (21) | Yes (27) | Chondroplasty/Mammoplasty |
| Case 6 | TW | No | − | − | − | − | + | Yes | Genitoplasty |
| Case 7 | TW | No | − | − | − | − | + (19) | Yes (26) | Mammoplasty |
| Case 8 | TW | No | − | − | − | − | + (20) | Yes (29) | Mammoplasty |
| Case 9 | TW | No | − | − | − | + (36) | + (39) | Yes (41) | Orchiectomy |
| Case 10 | TM | Former | − | − | − | − | + (40) | Yes (44) | No |
| Case 11 | TM | Former | − | − | − | − | + (21) | Yes (43) | No |
| Case 12 | TM | No | + (20) | − | − | − | − | Yes (16) | Mastectomy |
| Case 13 | TW | No | + (18) | − | − | − | − | Yes (18) | No |
| Case 14 | TW | No | + (51) | − | − | + (51) | − | Yes (11) | Orchiectomy |
| Case 15 | TM | No | + (39) | + (39) | − | − | − | Yes (38) | No |
| Case 16 | TW | No | + (19) | − | − | − | − | Yes (19) | No |
| Case 17 | TW | No | + (23) | − | − | − | − | Yes (17) | No |
| Case 18 | TW | No | + (38) | − | − | − | − | Yes (24) | Mammoplasty |
| Case 19 | TM | No | + (19) | + (19) | − | − | − | Yes (19) | No |
| Case 20 | TW | No | + (20) | − | − | − | − | Yes (16) | No |
| Case 21 | TW | Former | + (54) | − | − | − | − | Yes (44) | No |
| Case 22 | TW | No | + (21) | − | − | − | − | Yes (18) | No |
| Case 23 | TM | No | + (21) | − | − | − | − | Yes (19) | Mastectomy |
| Case 24 | TW | No | + (36) | − | − | − | − | Yes (36) | No |
| Case 25 | TM | No | + (26) | − | − | − | − | Yes (22) | Mastectomy |
| Case 26 | TW | Yes | − | − | + | − | − | Yes (35) | No |
| Case 27 | TW | No | − | − | + (33) | − | − | Yes (23) | Mammoplasty |
| Case 28 | TW | No | − | − | − | + (20) | − | No | No |
IVDA: intravenous drug addiction; GAS: gender-affirming surgery; TM: trans man; GI: genderidentity; TW: trans woman; GAHT: gender-affirming hormone therapy; HAV: hepatitis A virus; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus.
+Age at start of GAHT.
Of the trans men with HIV infection, one of them had started GAHT at another hospital, so we did not have analytical data. The second case was on treatment with elvitegravir/cobicistat/emtricitabine/tenofovir/alafenamide when starting intramuscular testosterone, achieving optimal levels of androgens (from 35 to 101 ng/dl) after six months of treatment.
Changes in plasma levels of oestradiol and testosterone in the trans women with HIV infection, and their changes in treatment, are shown in Table 3. Cases 1, 2, and 8, whose initial ART included a cobicistat-boosted integrase inhibitor, did not achieve optimal plasma oestrogen levels despite usingmaximum doses of oral oestradiol valerate. The change in ART regimen allowed adequate levels to be reached and the oestrogen dose to be reduced. Case 4 was on treatment with an NNRTI, but oestradiol patches were used from the start as GAHT due to a history of heterozygosity for factor V Leiden and oestrogen values remained within range during follow-up. In cases 5, 6 and 9, the initial ART included cobicistat and, after changing the route of oestrogen administration, optimal levels were achieved. Cases 3 and 7 reached the recommended hormonal ranges throughout follow-up without the need for changes in ART or GAHT.
Hormone levels and treatment adjustments in trans women with HIV infection.
| Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 | Case 7 | Case 8 | Case 9 | |
|---|---|---|---|---|---|---|---|---|---|
| Age at start of GAHT | 38 | – | 41 | 52 | 26 | – | 27 | 29 | 41 |
| Route of administration of oestrogens | Oral | Oral | Oral | Trans dermal | Oral | Oral | Oral | Oral | Oral |
| ART type | EVG/COBI/ FTC/TDx | EVG/COBI/ FTC/TDx | DTG/ABC/3TC | EFV/FTC/TDF | RPV + DRV/COBI | EVG/COBI/ FTC/TDx | FTC/RPV/TDF | EVG/COBI/FTC/TAF | EVG/COBI/TC/TDx |
| Viral load before GAHT | U | U | U | U | U | U | U | U | U |
| Baseline oestradiol (pg/ml)a | 28 | 8 | 5 | 39 | 29 | < 24 | 28 | 30 | 48 |
| Baseline testosterone (ng/dl)b | 781 | 257 | 197.7 | 501.9 | 876.85 | 183.7 | 477.6 | 155.17 | 499 |
| Viral load after GAHT | U | U | U | U | U | U | U | U | U |
| Oestradiol after 6 mo of GAHT (pg/ml)a | 25 | <24 | 54 | 56 | 18 | <24 | 30 | <24 | 8 |
| Testosterone after 6 mo of GAHT (ng/dl)b | 63 | 14.9 | 17.23 | 19.26 | 10.09 | 165.3 | 76 | 8.36 | 25.7 |
| Change in ART | Yes (DTG/ABC/3TC) | Yes (BIC/FTC/TAF) | No | No | No | No | No | Yes (BIC/FTC/TAF) | No |
| Switch to transdermal oestrogens | No | No | No | No | Yes | Yes | No | No | Yes |
| Viral load 6 mo after the change | U | U | – | – | U | U | – | U | U |
| Oestradiol 6 mo after the change (pg/ml)a | 65 | 67 | – | – | 49 | 50 | – | 48 | 55 |
| Testosterone 6 mo after the change (ng/dl)b | 42 | 15.27 | – | – | 16.7 | 130.8 | – | 6.37 | 15.27 |
3TC: lamivudine; ABC: abacavir; BIC: bictegravir; COBI: cobicistat; DRV: darunavir; DTG: dolutegravir; EFV: efavirenz; EVG: elvitegravir; FTC: emtricitabine; U: undetectable; RPV: rilpivirine; ART: antiretroviral therapy; TAF: tenofovir alafenamide; GART: gender-affirming hormone therapy; TDx: tenofovir disoproxil; TDF: tenofovir disoproxil fumarate.
Traditionally, a higher risk of STI infection has been reported in transgender people than in the general population, especially in trans women, according to data from the Centers for Disease Control and Prevention.12 Associated risk factors include isolation and social stigma, risky sexual behaviour, low use of barrier methods, co-infection with other STIs, intravenous drug use, and difficulty accessing medical care.6,13 The current healthcare model in Andalusia, characterised by greater accessibility thanks to decentralisation, support during the transition process and supervision of the GAHT by a multidisciplinary team, probably contributes to the fact that the prevalence of STIs in our setting is lower than that reported to date in the international literature, although it is true that future studies would need to delve deeper into the risk factors described to see how they affect our cohort.
Worldwide, the STI screening rate among the transgender community varies widely. In a US study, 80.5% of respondents reported having had at least one STI test, particularly transgender people who were older, with a stable partner, had known HIV-positive serological status, or who had received pre-exposure prophylaxis (PrEP).14 In contrast, a recent Iranian study concluded that 87% of trans women hadnever undergone any type of early detection test.7 The transgender community’s mistrust and suspicion of healthcare professionals, discrimination against the group, and insufficient healthcare coverage are some reasons that explain the disparity in data between different countries.
At the national level, the latest consensus document from the Ministry of Health published in 2024 advises screening for HIV, syphilis, viral hepatitis, Neisseria gonorrhoeae and Chlamydia trachomatis for all transgender people, considering them a vulnerable group for acquiring STIs.15 In the previous consensus of 2014, in force while we were conducting our study, only viral serology was recommended initially.16
Most research on STIs in transgender people has focused on HIV and, to a lesser extent on other infections such as chlamydia, gonorrhoea and syphilis.17,18 In the transgender population worldwide, the reported prevalence of HBV infection is 11% and of HCV, 9%.19 In our population, the number of cases barely reached 1% for either HBV or HCV. These significantly lower rates are partly due to the inclusion of the HBV vaccine in the vaccination programme since 200020 and recent advances in the treatment of HCV infections.21
In the case of HAV, although its main route of transmission is faecal-oral through the consumption of contaminated food, sexual practices involving anal-oral contact are another common form of transmission. Excluding positive serologies due to vaccination, in our cohort, the prevalence of HAV infection was 4.75%, although we were not able to determine the route of infection. The only review on this subject does not report cases of HAV in the transgender population.22 On the other hand, our data reported on the prevalence of syphilis are similar to those of the Callander Australian cohort23 and do not differ significantly from that of cis homosexual and bisexual men.22
According to a 2013 multi-centre systematic review, the prevalence of HIV in trans women worldwide is estimated to be around 19.1%,24 lower in studies based on self-reported health and higher in those where infection is confirmed by laboratory techniques. In trans men, there are far fewer studies and they report a prevalence of between 2% and 4%.23,25 In our UAPT, nine trans women and two trans men with HIV infection have been treated, which is equivalent to 6.33% of the total number of trans women and 1.31% of all the trans men in the cohort. Although these figures are higher than the current prevalence of HIV in Spain, estimated at 0.3% for the general population,26 they are notably lower than those described in cohorts of trans people from other countries, possibly because they are a younger population with better sexual health education, in addition to having better accessibility to the public health system, in contrast to the private American model. In Spain we do not have STI studies in the transgender population with which to compare the data obtained in our study.
The rate of adherence to ART in transgender people is usually lower than that of the cis population (59% vs 82%, respectively) according to the study by Melendez et al., leading to viral loads up to three times higher and a low rate of viral suppression.27 One explanation for the low adherence to ART may be fear that it interferes with the hormone therapy.28 Knowledge of the potential interactions between ART and GAHT is essential for a comprehensive approach to transgender people, although it has to be said that most of the evidence comes from cis women on combination hormonal contraception.
In 2019, the iFACT study reported no alterations in plasma oestrogen levels in trans women on oral or transdermal oestradiol therapy taking emtricitabine/tenofovir disoproxil fumarate as PrEP, although the tenofovir concentration was reduced by 13%.29 However, in cis women using oral contraceptives, a decrease has been reported in exogenous oestrogen levels due to the interaction with ART which included boosters (ritonavir or cobicistat) or an NNRTI (efavirenz or nevirapine).30
It is worth highlighting the Leinung et al. article on a series of cases of trans women with HIV infection on antiretroviral regimens that included an NNRTI (efavirenz). In the first case, optimal oestradiol levels were found after changing ART; in the second, reference values were reached simply by changing the route of administration of oestrogen from oral to transdermal; and the third was already on initial treatment with transdermal oestrogen, maintaining serum oestradiol levels within range during follow-up.31
In our cohort, a total of six trans women were initially treated with an ART regimen that included cobicistat and none achieved optimal plasma oestrogen levels after six months of GAHT. Guided by the evidence in the literature, the treatment regimen was readjusted; in three of them the ART was changed (avoiding cobicistat, ritonavir or an NNRTI) and in the remaining three, the oestrogen administration route was changed from oral to transdermal. Six months after the change, all the women had oestrogen levels in the desired range. Based on these results, we propose conducting studies to determine whether, instead of requiring a change in ART to achieve effective results, as has been suggested up to now, it would be enough to change the administration route of the hormone therapy and so avoid first-pass metabolism in the liver through cytochrome P450.
Regarding trans men, there are no data in the literature pointing to an interaction between testosterone and ART and the only case described in our cohort achieved adequate testosterone levels six months after starting GAHT.
In summary, this study addresses for the first time in Spain the prevalence of STIs in the transgender population under a healthcare model that stands out for its accessibility and multidisciplinary care, unlike many of the other cohorts reported to date, which are framed in a sociocultural context characterised by the lack of public health strategies guaranteeing equitable access to medical care. However, it is not without limitations, as the reported results refer to data from a single centre and there was a limited sample size, so they cannot be extrapolated to the general population. It should be noted that our work refers to the transgender population seen in a gender identity unit, so we do not have data on those who do not require medical care. Broad population-based studies are needed to confirm the reported trends and to delve deeper into the transmission routes of the STIs and potential risk factors, in order to establish prevention strategies, separate from those for HIV. Furthermore, because of the design of the study, we did not analyse gonococcal and chlamydia infections, as both require specific samples to be taken. In future work, it would be interesting to include bacterial STsI and forms of genderidentity more removed from classic binarism.
ConclusionsIn our setting, with the current healthcare model in Andalusia, the prevalence of STIs in the transgender population reported in our UAPT is not as high as that reported by previous studies. It is necessary to create comprehensive care programmes for transgender people which, in addition to addressing GAHT, provide interventions to promote sexual health, provide preventive counselling for STIs and offer screening in accordance with current recommendations. Finally, it is important to highlight the essential nature of multidisciplinary monitoring for transgender people with HIV to manage potential drug-drug interactions and adverse effects, especially when they receive ART which includes an NNRTI or boosters such as cobicistat or ritonavir.
Ethical considerationsThe study was approved by the Ethics Committee of the Hospital Universitario Puerta del Mar University Hospital (ethical approval code PEIBA 0474-N-22). The authors declare that they have followed the protocols established by the Ethics Committee for accessing data from medical records for the purposes of this publication, which is intended for research and dissemination to the scientific community.
FundingNone.
The authors declare that they have no conflicts of interest.
