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Regret after Gender-affirmation Surgery: A Systematic Review and Meta-analysis of Prevalence

Supplemental Digital Content is available in the text.


INTRODUCTION
Discordance or misalignment between gender identity and sex assigned at birth can translate into disproportionate discomfort, configuring the definition of gender dysphoria. [1][2][3] This population has increased risk of psychiatric conditions, including depression, substance abuse disorders, self-injury, and suicide, compared with cis-gender individuals. 4,5 Approximately 0.6% of adults in the United States identify themselves as transgenders. 6 Despite advocacy to promote and increase awareness of the human rights of transgender and gender non-binary (TGNB) individuals, discrimination continue to afflict the daily life of these individuals. 4,7 Gender-affirmation care plays an important role in tackling gender dysphoria. 5,[8][9][10] Gender-affirmation surgeries (GAS) aim to align the patients' appearance with their gender identity and help achieve personal comfort with one-self, which will help decrease psychological distress. 5,10 These interventions should be addressed by a multidisciplinary team, including psychiatrists, psychologists, endocrinologists, physical therapists, and surgeons. 1,9 The number of GAS has consistently increased during the last years. In the United States, from 2017 to 2018, the number of GAS increased to 15.3%. 8,11 , 12 Significant improvement in the quality of life, body image/satisfaction, and overall psychiatric functioning in patients who underwent GAS has been well documented. 5 , [13][14][15][16][17][18][19] However, despite this, there is a minor population that experiences regret, occasionally leading to de-transition surgeries. 20 Both regret and de-transition may add an important burden of physical, social, and mental distress, which raises concerns about the appropriateness and effectiveness of these procedures in selected patients. Special attention should be paid in identifying and recognizing the prevalence and factors associated with regret. In the present study, we hypothesized that the prevalence of regret is less than the last estimation by Pfafflin in 1993, due to improvements in standard of care, patient selection, surgical techniques, and gender confirmation care. Therefore, the aim of this study was to evaluate the prevalence of regret and assess associated factors in TGNB patients 13-years-old or older who underwent GAS. 20

Search Methodology
Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a comprehensive research of several databases from each database's inception to May 11, 2020, for studies in both English and Spanish languages, was conducted. 21

Study Selection
Search results were exported from the database into XML format and then uploaded to Covidence. 22 The study selection was performed in a 2-stage screening process. The first step was conducted by 2 screeners (V.P.B. and S.S.B.), who reviewed titles and abstracts and selected those of relevance to the research question. Then, the same 2 screeners reviewed full text of the remaining articles and selected those eligible according to the inclusion and exclusion criteria (Fig. 1). If disagreements were encountered, a third reviewer (O.J.M.) moderated a discussion, and a joint decision between the 3 reviewers was made for a final determination. Inclusion criteria were all the articles that included patients aged 13 years or more who underwent GAS and report regret or de-transition rates, and observational or interventional studies in English or Spanish language. Exclusion criteria were letter to the editors, case series with <10 patients, case reports correspondences, and animal studies.

Data Extraction/Synthesis
After selecting the articles, we assessed study characteristics. We identified year of publication, country in which the study was conducted, population size, and number of transmasculine and transfemenine patients with their respective mean age (expressed with SD, range, or interquartile range if included in the study). In addition, we extracted information of the method of data collection (interviews versus questionnaires), number of regrets following GAS, as well as the type of surgery, time of followup, and de-transition procedures. We classified the type of regret based on the patient's reasons for regret if they were mentioned in the studies. We used the Pfäfflin and Kuiper and Cohen-Kettenis classifications of regret (Table 1). 20,23

Quality Assessment
To assess the risk of bias within each study, the National Institute of Health (NIH) quality assessment tool was used. 24 This tool ranks each article as "good," "fair," or "poor," and with this, we categorized each article into "low risk," "moderate risk," or "high risk" of bias, respectively.

Outcomes
Our primary outcome of interest was the prevalence of regret of transgender patients who underwent any type of GAS. Secondary outcomes of interest were discriminating the prevalence of regrets by type gender transition (transfemenine and transmasculine), and type of surgery.

Data Analysis and Synthesis
The binominal data were analyzed, and the pooled prevalence of regret was estimated using proportion meta-analysis with Stata Software/IC (version 16.1). 25 Given the heterogeneity between studies, we conducted a logistic-normal-random-effect model. The study-specific proportions with 95% exact CIs and overall pooled estimates with 95% Wald CIs with Freeman-Turkey double arcsine transformation were used. The effect size and percentage of weight were presented for each individual study. 25,26 To evaluate heterogeneity, I 2 statistics was used. If P < 0.05 or I 2 > 50%, significant heterogeneity was considered. A univariate meta-regression analysis was performed to assess the significance in country of origin, tools of measurement, and quality of the studies.
To assess publication bias, we used funnel plot graphic and the Egger test. If this test showed us no statistical significance (P > 0.05), we assumed that the publication bias had a low impact on the results of our metanalysis. To assess the impact of the publication bias on our missing studies, we used the trim-and-fill method.
A sensitivity analysis was conducted to assess the influence of certain characteristics in the magnitude and precision of the overall prevalence of regret. The following characteristics were excluded: <10 participants included, and the presence of a high risk of bias.  Pfäfflin, 1993 Minor Feeling of regret secondary to surgical complications or social problems. Major "True" regret. Feeling of dysphoria secondary to the new appearance, or desires of pursuing a de-transition surgery.

Kuiper and
Cohen-Kettenis, 1998 Clear regret Patients openly express their regret and have role reversal either by undergoing de-transition surgery or returning to their former gender role.

Regret uncertain
Patients don't have role reversal, but freely express their regret by never considering doing GAS or pass through the same preoperative scenario again. They are truly disappointed with the results of GAS. Also, they don't consider the new gender role so difficult and might consider a second GAS. Regret Patients have role reversal but don't express their feelings of regret. Some might state that they are happy about their decision and consider themselves as transgender. However, they live as their former gender role for practical and social reasons. Regret assumed by others Don't have role reversal and don't express feelings of regret but have unfavorable social circumstances or psychological disturbances that raise concerns to relatives, clinicians, and others that patient might be regretful (eg, feeling loneliness, suicide attempts).

Authors and
Year of Publication

Study Selection
A total of 74 articles were identified in the search, and 2 additional records were identified through other sources. After the first-step screening process, 39 articles were relevant based on the information provided in their titles and abstracts. After the second-step process, a total of 27 articles were included in the systematic review and metanalysis (Fig. 1).

Quality Assessment
Based on the NIH quality assessment tool, the majority of article ranged between "poor" and "fair" categories. 24 (See Supplemental Digital Content 2, which displays the score of each reviewed study. http://links.lww.com/PRSGO/B599.)

Reasons for Regret
The most prevalent reason for regret was the difficulty/dissatisfaction/acceptance in life with the new gender role. 23,29,32,36,44 Other less prevalent reasons were "failure" of surgery to achieve their surgical goals in an aesthetic level and psychological level. 29,32,36,47 Based on the reasons presented, we classified the types of regrets according to Pfäfflin's types of regret and Kuiper and    Cohen-Kettenis classification. According to Pfäfflin's types, 28 patients had minor regret, and 34 patients had major regret. 14,20,23,29,32,36,41,44,45 Based on the Kuiper and Cohen-Kettenis regret classification, 35 patients had clear regret, 26 uncertain regret, 1 regret, and none presented with regret assumed by others. 23 In Table 5 and 6, the reasons and classifications are shown.

Meta-regression and Publication Bias
No covariates analyzed affected the pooled endpoint in this metanalysis. The Funnel Plot shows asymmetry between studies (Fig. 5). The Egger test resulted in a P value of 0.0271, which suggests statistical significance for publication bias. The Trim & Fill method imputed 14 approximated studies, with limited impact of the adjusted results. The change in effect size was from 0.010 to 0.005 with no statistical significance (Fig. 6).

Sensitivity Analysis
When excluding studies with sample sizes less than 10 and high-risk biased studies, the pooled prevalence was similar 1% (CI <1%-3%) compared with the pooled prevalence when those studies were included 1% (CI <1%-2%).

DISCUSSION
The prevalence of regret in the TGNB population after GAS was of 1% (CI <1%-2%). The prevalence of regret for transfemenine surgeries was 1% (CI <1%-2%), and the prevalence for transmasculine surgeries was <1% (CI <1%-<1%). Traditionally, the landmark reference of regret prevalence after GAS has been based on the study by Pfäfflin in 1993, who reported a regret rate of 1%-1.5%. In this study, the author estimated the regret prevalence by analyzing two sources: studies from the previous 30 years in the medical literature and the author's own clinical practice. 20 In the former, the author compiled a total of approximately 1000-1600 transfemenine, and 400-550 transmasculine. In the latter, the author included a total of 196 transfemenine, and 99 transmasculine patients. 20 In 1998, Kuiper et al followed 1100 transgender subjects that underwent GAS using social media and snowball sampling. 23 Ten experienced regret (9 transmasculine and 1 transfemenine). The overall prevalence of regret after GAS in this study was of 0.9%, and 3% for transmasculine and <0.12% for transfemenine. 23 Because these studies were conducted several years ago and were limited to specific countries, these estimations may not be generalizable to the entire TGNB population. However, a clear trend towards low prevalences of regret can be appreciated.
The causes and types of regrets reported in the studies are specified and shown in Table 5 and 6. Overall, the most common reason for regret was psychosocial circumstances, particularly due to difficulties generated by return to society with the new gender in both social and family enviroments. 23,29,32,33,36,44 In fact, some patients opted to reverse their gender role to achieve social acceptance, receive better salaries, and preserve relatives and friends relationships. These findings are in line with other studies. Laden et al performed a logistic regression analysis to assess potential risk factors for regret in this population. 46 They found that the two most important risk factors predicting regret were "poor support from the family" and "belonging to the non-core group of transsexuals." 46 In addition, a study in Italy hypothesized that the high percentage of regret was attributed to social experience when they return after the surgery. 33 Another factor associated with regret (although less prevalent) was poor surgical outcomes. 20,23 , 36 Loss of clitoral sensation and postoperative chronic abdominal pain were the most common reported factors associated with surgical outcomes. 14,36 In addition, aesthetic outcomes played an important role in regret. Two studies mentioned concerns with aesthetic outcomes. 14,47 Only one of them quoted a patient inconformity: "body doesn't meet the feminine ideal." 14 Interestingly, Lawrence et al demonstrated in their study that physical results of surgery are by far the most influential in determining satisfaction or regret after GAS than any preoperative factor. 36 Concordantly, previous studies have shown absence of regret if sensation in clitoris and vaginal is achieved and if satisfaction with vaginal width is present. 36 Other factors associated to regret were identified. Blanchard et al in 1989 noted a strong positive correlation between heterosexual preference and postoperative regret. 32 All patients in this study who experienced regret were heterosexual transmen. 32 On the contrary, Lawrence et al in 2003 did not find such correlation and attributed their findings to the increase in social tolerance in North American and Western European societies. 36 Bodlund et al found that clinically evident personality disorder was a negative prognostic factor for regret in patients undergoing GAS. 48 On the other hand, Blanchard et al did not find a correlation among patient's education, age at surgery, and gender assigned at birth. 32 In the present review, nearly half of the patients experienced major regret (based on Pfäfflin classification), meaning that they underwent or desire de-transition surgery, that will never pass through the same process again, and/or experience increase of gender dysphoria from the new gender. One study found that 10 of 14 patients with regret underwent de-transition surgeries (8 mastectomies, 2 vaginectomies, 2 phalloplasties, 2 testicular implants removal, and 1 breast augmentation) for reasons of social regret, true regret or feeling non-binary. 23 On the other hand, based on the Kuiper and Cohen Kettenis' classification, half of the patients in this review had clear regret and uncertain regret. This means that they freely expressed their regret toward the procedure, but some had role reversal to the former gender and others did not. Interestingly, Pfäfflin concluded that from a clinical standpoint, trangender patients suffered from many forms of minor regrets after GAS, all of which have a temporary course. 20 This is an important consideration meaning that the actual true regret rate will always remain uncertain, as temporarity and types of regret can bring a huge challenge for assessment.
Regret after GAS may result from the ongoing discrimination that afflicts the TGNB population, affecting their freely expression of gender identity and, consequently feeling regretful from having had surgery. 15 Poor social and group support, late-onset gender transition, poor sexual functioning, and mental health problems are factors associated with regret. 15 Hence, assessing all these  potential factors preoperatively and controlling them if possible could reduce regret rates even more and increase postoperative patient satisfaction. Regarding transfemenine surgery, vaginoplasty was the most prevalent. 14, 19, 23, 30-33, 35, 36, 44, 45 Interesintgly, regret rates were higher in vaginoplasties. 14,36,44 In this study, we estimated that the overall prevalence of regret after vaginoplasty was 2% (from 11 studies reviewed). This result is slightly higher than a metanalysis of 9 studies from 2017 that reported a prevalence of 1%. 13 Moreover, vaginoplasty has shown to increase the quality of life in these patients. 13 Mastectomy was the most prevalent transmasculine surgery. Also, it showed a very low prevalence of regret after mastectomy (<1%). Olson-Kennedy et al demonstrated that chest surgery decreases chest dysphoria in both minors and young adults, which might be the major reason behind our findings. 38 In the current study, we identified a total of 7928 cases from 14 different countries. To the best of our knowledge, this is the largest attempt to compile the information on regret rates in this population. However, limitations such as significant heterogeneity among studies and among instruments used to assess regret rates, and moderate-tohigh risk of bias in some studies represent a big barrier for generalization of the results of this study. The lack of validated questionnaires to evaluate regret in this population is a significant limiting factor. In addition, bias can occur because patients might restrain from expressing regrets due to fear of being judged by the interviewer. Moreover, the temporarity of the feeling of regret in some patients and the variable definition of regret may underestimate the real prevalence of "true" regret.
Based on this meta-analysis, the prevalence of regret is 1%. We believe this reflects and corroborates the increased in accuracy of patient selection criteria for GAS. Efforts should be directed toward the individualization of the patient based on their goals and identification of risk factors for regrets. Surgeons should continue to rigorously follow the current Standard of Care guidelines of the World Professional Association for Transgender Health (WATH). 49

CONCLUSIONS
Our study has shown a very low percentage of regret in TGNB population after GAS. We consider that this is a reflection on the improvements in the selection criteria for surgery. However, further studies should be conducted to assess types of regret as well as association with different types of surgical procedure.