DOES SURGERY AND BIO-CHEMICALS IMPROVE HEALTH OF TRANSGENDERED INDIV
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SPECIAL ARTICLE
Open Access
Do hormones and surgery improve the health of adults with gender incongruence? A systematic review of patient reported outcomes
Kelsey Ireland BSci (BiomedSc), MD, Madeleine Hughes BMedSc (Hons), Nicola R. Dean MBChB, FRACS (Plas)
First published: 20 February 2025
Citations: 2
K. Ireland BSci (BiomedSc), MD; M. Hughes BMedSc (Hons); N. R. Dean MBChB, FRACS (Plas).
Abstract
Background
Gender diverse people in Australia have higher levels of psychological stress, suicidal ideation and suicide attempts and have poorer self-reported health than cisgender people.
Objectives
To determine if adults who experience gender incongruence have improved health-related quality of life and mental health with gender affirming treatment (hormone therapy and surgery), compared with no treatment.
Data sources
PubMed, Web of Science, Embase and Psych Info.
Review methods
A systematic review of peer-reviewed publications in English from January 2010 to October 2022. Studies were included where: participants were treated with gender affirming surgery or hormone therapy for minimum 3 months and; validated patient reported outcome measures of health-related quality of life or mental health were reported. Quality of evidence assessment was undertaken using the Let Evidence Guide Every New Decision evaluation tool.
Results
Eighty-one publications were included for analysis. The systematic review indicated that there were significant improvements in the domains of mental illness, gender dysphoria, body image and health-related quality of life following gender affirming medical treatment as measured by a variety of patient reported outcomes. Meta-analysis showed significant improvement in body image (z = 4.47, P < 0.001) and health-related quality of life for psychological (z = 1.99, P = 0.047) and social relationships (z = 3.09, P = 0.002) following gender affirming surgery.
Conclusions
There is evidence that hormones and surgery as a collective for adults with gender incongruence has therapeutic value and should be considered for funding within Australia’s healthcare systems. The development and implementation of patient-reported outcome tools tailored for purpose (GENDER Q) will facilitate future research.
Introduction
Gender incongruence describes a difference between a person’s assigned gender at birth, decided by their primary sex characteristics, and the gender that they identify with.1 Gender dysphoria is used to describe the psychological distress that is often experienced with gender incongruence.2 Gender affirming treatments are aimed at alleviating both gender incongruence and dysphoria by allowing people to express their gender identity and supporting changes in primary and secondary sex characteristics. These treatments could include some or all of psychotherapy, hormone therapy, change in gender expression, and surgery.2
Gender diverse people in Australia have overall poorer health compared to cisgender Australians.3–5 They report significantly higher levels of psychological stress, suicidal ideation and suicide attempts and have poorer self-reported health than cisgender people.3, 5, 6 In gender diverse people, lifetime diagnosis of depression ranges from 45% to 73% and anxiety from 40% to 67%, compared to 14% and 26%, respectively in the general Australian population.3–5, 7, 8 Zwickl and colleagues found that suicidality correlated with a desire for surgical procedures, implying that barriers to accessing surgery may be linked to suicidal ideation.9
Australia currently has no specific government funding for gender affirming treatments in adults. Decision-making principles guiding government funding for health services vary globally, but commonly include whether the treatment has therapeutic value, its clinical effectiveness and cost effectiveness.10 Conversely, where there is an absence of health impairment (e.g., cosmetic concerns), then individuals are generally expected to pay for services unsubsidised.11
Using studies that employed validated patient-reported outcome measures (PROMs), this systematic review examines the impact of gender affirming medical interventions on health-related quality of life (HRQoL) and mental health. PROMs are particularly valuable as they come directly from patients, without any interpretation or adjustment by researchers and are the most direct way of measuring health impairment for individuals.
Most systematic reviews look at a particular drug or surgical procedure. This study addresses whether gender affirming treatments in general should attract government funding. Therefore, this review looks at gender affirming treatment as a collective. This approach is consistent with the emergent best practice model and gives a high-level overview of this largely unfunded area at a time when Australian healthcare providers are considering the merit of providing these services.12 The downside is the inherent heterogeneity of publications and resulting limits on analysis.
Methods
A search of PubMed, Web of Science, Embase and Psych Info was performed in October 2022 using terms ‘transgender’ and ‘gender affirming hormones’ or ‘gender affirming surgery’ and ‘quality of life’ or variants thereof (Table S1). Two independent researchers conducted study selection and critical appraisal using PRISMA guidelines.13
Inclusion and exclusion criteria
Peer-reviewed original research that was published in English from January 2010 to October 2022 was included. Studies were included where participants were treated with either gender affirming surgery or hormones for 3 months or more and which reported on validated PROMs of HRQoL or mental health. Treatment with puberty blockers or dedicated paediatric studies were excluded, as were studies with fewer than 10 participants.
Eligibility screening and data extraction
Articles were imported into Covidence®14 and duplicates were removed. Titles, abstract, article screening and data extraction was completed by two independent authors (KI and ND) according to inclusion/exclusion criteria. Disagreements were resolved by discussion between the two authors. Data collected included study design, participants, treatment details, validated PROMs and individual outcome results.
Quality of evidence assessment
A quality of evidence assessment of included studies was undertaken by two other reviewers (MH and TC) using the Let Evidence Guide Every New Decision (LEGEND) evidence evaluation tool.15 Disagreements were resolved by consensus discussions between the two reviewers.
Study assessment and statistical analysis
All studies were assessed for their use of PROMs and whether study results were supportive, neutral, or unsupportive of the treatment intervention. Health and well-being parameters were divided by the authors into the categories: HRQoL, gender dysphoria, self-esteem and body image, mental illness and sexual health. Where studies were prospective, standardized mean changes (SMC) were calculated, along with corresponding 95% confidence intervals (CI), and graphed on a forest plot. Study heterogeneity was assessed by inspection of forest plots and I2 statistics.
For instances where the same PROM was used in at least four prospective studies and results data were comparable and adequately complete, a meta-analysis of results was performed.
Meta-analysis was performed using a mixed-effects model accounting for cluster effect by study, assuming a compound symmetry covariance structure. Analyses were performed using R version 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria) with the metafor package (version 4.4.0).
Results
The PRISMA flowchart is shown in Figure 1.13 Following the removal of duplicates, 2840 abstracts were screened, yielding 193 studies for full review. After a full text review, 81 studies were included in the final analysis. Studies were organized and analyzed according to the health domains measured. Geographical dispersion of studies is displayed in Figure 2.
Detailed assessments of publications are summarized in Tables S2–S6.16–96 Of the 81 publications that met inclusion criteria, the majority had results that were supportive of gender affirming treatment interventions (hormones or surgery or combined hormones and surgery).
Thirty publications consisted entirely of, or contained within them, prospective studies with sufficient pre and post-intervention data to derive SMCs and 95% CI. The results of these are presented in the forest plots of Figures 3–7.
The 81 publications meeting inclusion criteria allowed for meta-analysis for three PROMs; the body image scale (BIS), for measuring improvement in body image, the World Health Organisation Quality of Life Scale (WHOQOL) for HRQoL and the Rosenburg Self-esteem scale (RSES) for self-esteem (Fig. 8). Further details on each health dimension are below:
Mental illness
There were 35 publications that measured mental illness after gender affirming treatments (Supplementary Table 2). There were 16 prospective studies, 14 with sufficient data for SMC and 95% CI calculation (Fig. 3).16–18, 22–24, 26, 28, 31, 32, 34, 35, 39, 43, 44, 47 There was heterogeneity in the studies, with 21 different PROMs used, the most frequent being the Patient Health Questionnaire-4 or -9,16, 22, 34, 36, 39–41, 44, 45 the Beck Depression Inventory,25, 26, 28, 30, 48, 49 the Hospital Anxiety and Depression Scale17, 29, 32, 47, 50 and the Symptom Checklist 9027, 28, 31, 43, 45 (or revised version). Meta-analysis was not performed as the threshold number of comparable studies using the same PROM was not reached.
In regard to the effect of hormone therapy, significant improvements in depression were seen post initiation of therapy in most studies.16, 17, 23, 28, 31, 44 Patients treated with gender affirming hormones had lower suicide screening scores18 and improvements in general mental illness scores.23, 24, 28, 31 Anxiety scores were mixed, with some showing significant improvement post hormone therapy initiation23, 31, 44 and others showing no improvement.17, 24 Cross-sectional studies involving hormone therapy also supported an association between hormone therapy and a meaningful improvement in mental illness,20, 25, 29, 30, 46, 50 specifically depression20, 25, 29, 30, 46, 50 and anxiety.20, 25, 29 Although scores were found to improve following hormone treatment, they may remain lower than the general population.41
Surgery was also found to improve mental illness in prospective studies, with lower levels of depression in patients after gender affirming surgery, specifically post vaginoplasty22, 39 and gender affirming mastectomy.34 Cross-sectional data strongly supported an association between undergoing gender affirming surgery and decreased psychological distress.19, 21 In retrospective studies, levels of depression were found to normalize to the level of the general population following vaginoplasty and phalloplasty.40, 48
Combined gender affirming hormone and surgical treatment resulted in an improvement in mental health scores in short and long term follow up.38, 43, 45 Prospective studies that analyzed longitudinal treatment with hormone therapy followed by surgery suggested that the largest improvement in mental health followed hormone treatment.31 Some cross-sectional studies supported this effect of hormones, with significantly higher mental health scores in hormone-treated patients and both hormone and surgery-treated patients but no difference between the two groups.25, 29
Gender dysphoria
Gender dysphoria after gender affirming treatments was examined in 10 studies (Table S3). Of these studies, eight were prospective cohort studies24, 26, 28, 32, 51–54 with adequate results data to allow SMC and 95% CI calculation (Fig. 4). The threshold for performing meta-analysis was not met.
Seven different PROMs were used to evaluate levels of gender dysphoria across the studies. The Utrecht Gender Dysphoria Scale26, 53, 55 and the Transgender Congruence Scale32, 38, 51 were the most used.
For hormone treatment, gender dysphoria was found to improve significantly in the three prospective studies that met criteria.24, 28, 52 Surgery also resulted in improvement in gender dysphoria, specifically mastectomy51, 54 and facial feminization surgery.32 Gender dysphoria improved post-combined hormone and surgical treatment with genital surgery accounting for the majority of improvement in one study.53
Self-esteem and body image
Self-esteem and body image after gender affirming care were assessed in 28 studies (Table S4). Of these, 13 were prospective cohort studies22, 24, 26, 28, 32, 34, 39, 47, 51, 54, 56, 61, 65 with sufficient data for calculation of SMC and 95% CI (Fig. 5).
The RSES22, 24, 27, 39, 40, 47, 49, 50, 54, 62, 65 followed by the BIS26, 32, 38, 47, 51, 54, 61 and Female/Male Genital Self-Imaging Scale58–60, 63, 67 were the most used PROMs in the sphere of self-esteem and body image.
For combined hormone and surgery, meta-analysis of prospective studies showed a significant improvement in self-esteem (using RSES, Fig. 8b).
Both the prospective cohort studies looking at hormone treatment alone found RSES scores to be similar pre and post-hormone treatment.24, 65 Similarly, scores in those treated with hormones were not significantly different from those with no hormone treatment in a cross-sectional study using RSES27; however, studies using other self-esteem scales indicated an association between improved self-esteem and hormone treatment.30
For surgery, the effect specifically on self-esteem was varied. In prospective studies, self-esteem improved significantly post vaginoplasty22, 39 but no significant change was seen following gender affirming mastectomy54 or phalloplasty.47 However, retrospective studies indicated post-vaginoplasty and post-phalloplasty patients reached self-esteem scores in line with the general population.40, 62
Prospective, cross-sectional and retrospective data found that body image (as distinct from self-esteem) improved with hormone therapy27, 28, 38, 57 with only one study showing no improvement.64
Surgery including gender affirming mastectomy,34, 51, 54, 56 facial feminisation surgery32 and gender affirming genital surgery26, 61 was shown to improve body image. This improvement reached significance in meta-analysis of prospective studies that reported the BIS (Fig. 8a). Cross-sectional and retrospective data also suggested an association between improved body image and gender affirming surgery.38, 57, 63, 64, 66 In some studies, post-operative gender affirming genital surgery patients scored similarly on genital self-imaging scales to the general population.58–60, 67
Health-related quality of life
HRQoL following gender affirming medical treatment was assessed via PROMs in 44 studies (Table S5). There were 19 prospective cohort studies, 17 with appropriate data for inclusion in the forest plots of generic and condition specific HRQoL (Figs 6, 7).16, 22, 24, 26, 34, 52, 53, 56, 65, 69, 73, 74, 77–81, 83, 92
PROMs used to assess HRQoL were heterogenous, with 12 different PROMs used. The most commonly used PROMs were the WHOQOL22, 26, 27, 41, 64, 69, 74, 75, 77, 79, 84, 88, 90 and the Short Form 36-question Health Questionnaire (SF36) (or brief version).20, 24, 33, 48, 52, 53, 56, 70, 71, 76, 78, 82, 83, 86, 91, 93, 94 Although the SF36 was frequently used, there were too few studies reporting physical component or mental component summary scores, or the raw dataset to calculate them to facilitate meta-analysis, despite publication authors being contacted for raw data. For the WHOQOL, meta-analysis of four surgery studies was performed, with the psychological and social relationship domains reaching significance (Fig. 8c–f).
For hormone treatment, the results of prospective studies assessing HRQoL pre and post-gender affirming hormones were extremely varied depending on PROM used. One study showed significant improvement in the general health domain of the SF-36.24 Others showed no improvement in any domains of the SF-36.52, 53 Similarly, no improvements in HRQoL were found post-hormone therapy using the Quality-of-Life Enjoyment and Satisfaction Questionnaire.16 There was significant improvement in the sexual health domain but not in any other domain post-hormone treatment using the WHOQOL.79 More targeted PROMs showed significant improvement in voice-related QoL73 and improvements in HRQoL related to facial aesthetics (FACE-Q).65
Cross-sectional studies that compared HRQoL in people who had undergone hormone treatment demonstrated improved HRQoL (measured using the SF-36) in some,20, 76, 82 but not all studies.33, 94 There was no association between hormone treatment and improvement in WHOQOL scores.27, 64 One study showed that hormone treatment was associated with improved psychological aspects of HRQoL, but not overall functioning.30
For surgery, prospective studies showed a clear improvement in HRQoL following gender affirming mastectomy (using both BREAST-Q and WHOQOL) and gender affirming breast augmentation (using BREAST-Q).34, 56, 69, 77, 92 Outcomes of HRQoL after genital surgery were more variable. Post-operative vaginoplasty patients had significantly improved WHOQOL scores in one study.22 However, another study showed improvements in psychological and social relationships domains but a decrease in physical health and level of independence.74 Vaginoplasty did not result in significant improvement in SF-36 scores,78 whilst masculinizing genital surgery showed significant improvements in SF-36 in all domains.83 A single prospective study demonstrated lower SF-36 scores post-gender affirming genital surgery.53 Other gender affirming surgery including hysterectomy, oophorectomy and facial feminisation surgery, showed a clear improvement in HRQoL.77, 80, 81 Cross-sectional studies showed an association between improved HRQoL and gender affirming surgery.64, 68, 70, 84
Sexual health
Eight studies reported PROM data measuring sexual health (Table S6). None of these reached the threshold for either forest plot construction or meta-analysis.
Quality of evidence assessment
Overall, quality of evidence ranged from level 3 to level 4 according to the Oxford Centre for Evidence-based Medicine Levels of Evidence97 (Tables 1 and S7).Table 1. Summary of LEGEND evidence appraisal
| LEGEND evidence level | Prospective cohort study | Retrospective cohort study | Cross-sectional study | Case series | Case–control study |
|---|---|---|---|---|---|
| [3a] Good quality prospective cohort study | 13 | ||||
| [3b] Lesser quality prospective cohort study | 21 | ||||
| [4a] Good quality retrospective cohort study | 1 | ||||
| [4b] Lesser quality retrospective cohort study | 13 | ||||
| [4a] Good quality cross-sectional study | 19 | ||||
| [4b] Lesser quality cross-sectional study | 7 | ||||
| [4a] Good quality descriptive/epidemiological study | 0 | ||||
| [4b] Lesser quality descriptive/epidemiological study | 4 | ||||
| [4a] Good quality Case–control study | 3 | ||||
| [4b] Lesser quality Case–control study | 0 |
Discussion
This systematic review provides evidence that for adults with gender incongruence, gender affirming care provides health benefits. This evidence reaches significance in meta-analysis for body image (BIS), self-esteem (RSES) and psychological and social relationship domains of HRQoL (WHOQOL). Individual analysis of studies assessing gender dysphoria and mental health also suggest improvement. No other systematic review of the last 10 years has looked at adult gender affirming medical interventions as a collective.
When reviewing hormone therapy, White Hughto’s, Rowniak’s and Baker’s systematic reviews of the effects of hormone therapy found low level evidence to support improved psychological functioning and HRQoL.98–100 A more recent review by Australian colleagues van Leerdam, Zajac and Cheung agreed that the majority of studies show hormone therapy improves gender dysphoria, body image, mental illness and HRQoL.101 Since the time of accessing the data for the current systematic review, Nolan and colleagues have published strong evidence of testosterone therapy improving gender dysphoria and depression in a Randomized Clinical Trial using established PROMs.102
Regarding gender affirming surgery, Oles and colleagues’ most recent and overarching two-part systematic review concluded that gender affirming surgery is safe, effective, and medically necessary.103, 104 Previous systematic reviews including those of Swan and colleagues, Eftekhar Passos and Ebrahimzadeh all had the common findings that HRQoL was improved, as was mental health, but the quality of studies and volume of comparable data was limited.105–108 A further factor impeding interstudy comparison is the conceptual variation between countries. Iran’s academic literature on gender affirming surgery retains the notion of gender as binary, whereas most others now provide for non-binary trans individuals. Passos and colleagues also concluded that an informed consent model, rather than ‘gatekeeping’, was appropriate to facilitate patient choice.108 Importantly, a recent systematic review including 7028 transgender patients showed that the prevalence of regret after gender affirming surgery was extremely low (1%, 95% CI < 1–2%).109
Validated PROMs are a way of measuring outcomes that come directly from the patient themselves, which reduces the risk of bias introduced by the opinions of the researcher when compared to methods reliant on researcher observations. The current study agreed with the findings of Oles and others that the wide variation of PROMs and the fact that few have been validated in the transgender population is problematic and hampers comparability of results and meta-analysis.103, 104 The BIS, which was developed for use in this population, is the exception and subsequently had significant results.110 This field would clearly benefit from a widely accepted, high-quality PROM validated with gender diverse people and treatment in mind. It seems likely that the upcoming GENDER Q will fill that need.111
Limitations
This review only examined studies published in English. Undoubtedly, inclusion of articles published in other languages would have been preferable. The studies included in this systematic review were heterogeneous. The fact that studies in this review used such a variety of PROMs precluded meta-analysis for most PROMs and this is a technical limitation on the strength of the review. More homogenous use of a high-quality-population-specific PROMs would be valuable for future research.
Conclusion
There is evidence that hormones and surgery as a collective for adults with gender incongruence have therapeutic value and should be considered for funding within the Australian healthcare system. The development of sound data collection systems for both encoded clinical activity and patient reported outcomes (using the GENDER Q) should be built hand in hand with the development of funded services. Installation of such systems from early on will establish Australia well for the delivery of truly patient-centred care and will facilitate both clinical audit and future research.
Acknowledgements
The authors thank Tamara Crittenden BAppSc (Hons), PhD and Salem Leemaqz MAppStat, PhD. Open access publishing facilitated by Flinders University, as part of the Wiley – Flinders University agreement via the Council of Australian University Librarians.
Author contributions
Kelsey Ireland: Conceptualization; data curation; formal analysis; investigation; methodology; writing – original draft; writing – review and editing. Madeleine Hughes: Formal analysis; writing – review and editing. Nicola R. Dean: Conceptualization; data curation; formal analysis; methodology; supervision; writing – original draft; writing – review and editing.
Conflicts of interest
None declared.
Supporting Information
References
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May 2025
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