1 INTRODUCTION

Individuals who experience gender incongruence (GIC) have a gender that does not align with their secondary sexual characteristics or assigned sex (male or female) at birth. Despite a singular diagnosis, there remains great diversity among these patients—transgender men and women, male, female, and non-binary.1 This article focuses on transgender women, transfeminine, and gender diverse patients, and these patients and communities will be referred to as “transgender and gender diverse” (TGD). “Cisgender” (cis) is a term used to describe an individual who identifies with their gender and sex assigned at birth, and cis women are sometimes used as comparator groups to TGD patients after vaginoplasty.

Prior to GIC as a diagnosis, the diagnosis of gender dysphoria (GD) emerged in 2013 within the newly published Diagnostic and Statistical Manual of Mental Disorders: DSM-5 (DSM-5), after historically diagnosing individuals with gender identity disorder (GID).2, 3 The de-pathologizing of gender identity and gender nonconforming patients continues with the acceptance of GIC in the International Classification of Disease-11 (ICD-11), as a new diagnosis that exists outside of the mental health section.1, 4 Activists, medical providers, and advocates within TGD communities have worked to destigmatize the diagnosis yet maintain its validity as a medical condition to provide insurance coverage for medical and surgical interventions.1, 5

The World Professional Association of Transgender Health (WPATH) guides healthcare professionals (HCPs) regarding medical and surgical care for TGD patients through their Standards of Care (SoC) v.7 (2013).6 These guidelines give insight to HCPs in behavioral health (psychiatry and psychology), medical treatment (primary care, endocrinology, gynecology, and urology), and surgical interventions (plastic and reconstructive surgery, urology, gynecology, otolaryngology). Patients seeking surgical interventions require a medical documentation of GIC/GD, and for genital gender-affirming surgery (GAS), patients must provide two medical referrals, live in their congruent gender identity and receive hormone therapy (ie, estrogen, androgen inhibitors, and progesterone) for 12 months prior to surgery unless hormone therapy is contraindicated.6 While the WPATH SoC are guiding principles for an international audience, each healthcare system has individual interpretation and implementation of these guidelines. Some countries require TGD patients to undergo genital GAS or otherwise be sterilized to change their legal gender. Other countries do not require a diagnosis conferred by external assessment prior to surgery.7

Genital GAS can be a critical step for some TGD patients as genitals can be a specific source of GIC. Not all TGD patients experience their genitals as a source of GIC, and many patients do not seek GAS for varying reasons. In this article, “vaginoplasty” will serve as the overarching term when referring to genital reconstructive surgery for TGD patients, including orchiectomy, penectomy, clitoroplasty, labiaplasty and the creation of a vaginal canal—vaginoplasty—and urethral neo-meatus. Surgical techniques for vaginoplasty vary depending on the donor tissue used when constructing the vaginal canal, including autologous skin grafts or flaps (i.e. intestine or peritoneum) allografts, or xenografts.8-14 Penile inversion vaginoplasty (PIV), using penile and scrotal skin to line the canal, is the most common technique reported in the literature.15 Experienced surgeons have demonstrated that this reconstructive procedure is safe and improves quality of life (QoL).8, 9, 16 Sexual health following genital surgery is a priority for many individuals and is an important aspect of overall QoL. For TGD patients, sexual activity can help to affirm an individual's gender identity.17, 18 As genitals may be a source of dysphoria, TGD patients with genital GIC frequently refrain from engaging with their genitals sexually.18, 19

While previous literature on sexual function and satisfaction has focused on cis women with vaginal agenesis and patients born with Differences of Sexual Development (DSD), there has not been an in-depth review of sexual function in TGD patients after vaginoplasty.20, 21 Published reviews of vaginoplasty in TGD patients have focused on surgical techniques or quality of life, which can encompass sexual health but a systematic review investigating specifically the sexual health outcomes of vaginoplasty has not been performed.15, 22 The literature review by Holmberg et al. (2019) discussed the multifaceted aspects of sexual health within the TGD communities including both transgender men and women, with and without hormone treatment, and undergoing or not undergoing surgical interventions.23 Focusing on a narrower patient cohort of TGD patients postoperative vaginoplasty, this systematic review will serve as a condensed reference of all primary published literature or peer-reviewed research in English or with English translation that features vaginoplasty outcome data on sexual health among TGD patients. We aim to highlight opportunities for future research investigating sexual health outcomes in this population.

2 METHODS

We reported our systematic review search strategy following the PRISMA guidelines (2009), and registered our review with PROSPERO (CRD42021224014) outlining our eligibility criteria (Table 1) prior to conducting our search (Appendix 1).24 Our inclusion criteria required the article to feature TGD patients after vaginoplasty procedure and report at least one measurable sexual health outcome within our set parameters.

TABLE 1. Inclusion and exclusion criteria Inclusion criteria Exclusion criteria Study design Primary literature (case report, case series, retrospective, or prospective-cohort studies, RCT) Literature reviews Population Trans women/Transfeminine patients Cis women patients only or did not isolate trans women separate from cis women All ages Patients with DSD, despite socially being raised as male, unless anatomy is explicitly specified Intervention All surgical techniques for vaginoplasty Vulvoplasty only Orchiectomy only Outcomes Outcome measurements featuring sexual function/health Studies reporting outcome measures of QoL without sexual health Studies reporting vaginal caliber and/or depth studies without sexual health Studies reporting sexual orientation without reference to actual practiced sexual activity Language No English translation available Abbreviations: DSD, Disorders/Differences of Sexual Development; QoL, quality of life; RCT, randomized controlled trial.

The sexual health outcome measurement parameters (10) that were considered during extraction were as follows:

Desire/interest. Arousal. Erogenous sensation of genitals. Sexual activity. Lubrication/secretions. Satisfaction. Pleasure. Orgasm. Interferences/disruptions to sexual activity. Therapeutic aids.

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These measurement parameters were compiled from the domains measured by the Female Sexual Function Index (FSFI) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction measure (SexFS) v.2.0.25, 26 Articles were included if TGD patients could be isolated as a patient population but were excluded if postoperative TGD patients were combined with cis women or preoperative TGD patients. Exclusion criteria included reviews and meta-analyses or articles that only published quality of life outcomes without specifics metrics relating to sexual health. Further, articles that featured patients with DSD were predominantly excluded due to the unpredictable variation in anatomy.

2.1 Search strategy

A medical librarian (S.K.) with expertise in systematic searching composed a search utilizing a mix of subject headings and keywords that represented the concepts of TGD patients, vaginoplasty, and sexual health. The databases MEDLINE via PubMed, Embase via Elsevier, Scopus via Elsevier, and APA PsycINFO via Ebsco were searched from inception until December 7, 2020. All results were compiled in EndNote and then imported into Covidence software (covidence.org). Full search strategies are available in Appendix 1.

2.2 Study selection and screening process

Covidence software removed most duplicates imported. As a preliminary screening phase of title and abstract, studies were reviewed using the eligibility criteria outlined in Table 1 by two independent authors (C.K., A.P., or G.B.), and conflicts were resolved by a third author. Full texts were screened in the same manner requiring two authors to agree, and a reason required for exclusion. If not originally written in English, an English translation was necessary to be included in the study.

2.3 Data collection process and data items

All studies that include sexual health and function after vaginoplasty were thoroughly reviewed. The data extracted included author that published the study, year of publication, location of correspondence, study design, research presentation format, level of evidence, number of TGD patients after vaginoplasty included in study, mean/median age, mean/median follow-up, percentage of patients with revisions after primary vaginoplasty, technique of surgery (vaginal graft/flap material), evaluation method of outcomes (interview, questionnaire, etc.), parameters measured of sexual health (desire, orgasm, pleasure, activity, etc.), and a summary of findings specific to sexual health. All data extraction was completed by the first author (C.K.) and confirmed by second author (A.P.). Level of evidence was evaluated using the Oxford Center for Evidence-based Medicine: Levels of Evidence (2009), and reasoning for a study's limitations were assessed based on sample size, study design, and potential bias.27

2.4 Risk of bias in individual studies

The risk of bias will be completed after interpretation of the findings and completed using the Risk of Bias in Systematic Reviews (2016).28

3 RESULTS

From a total of 4,244 texts, the screening process yielded 140 studies that met our eligibility criteria (Figure 1). There were 123 peer-reviewed publications and 17 conference abstracts without full articles published. The oldest literature included is from 1974 (Markland & Hastings).29 Eligible texts were reviewed from a total of 28 countries and 69 cities (Figure 2). During the full-text screening phase, the majority of excluded texts were due to the outcomes not including any parameters directly referring to sexual health (109 studies). Many of these excluded studies may have reported sexual health outcomes under the guise of “functional outcomes” in postoperative outcomes without direct reference to sexual health. 25 studies were unable to be retrieved through New York University Grossman School of Medicine, Duke University School of Medicine and Research Gate (researchgate.net). 23 studies were excluded due to lack of English translations. 19 studies featured sexual health data for TGD patients after vaginoplasty but were unable to be included because the results were combined with another population.

PRISMA flow diagram showing the article screening process for this systematic review using the Covidence software.

Geographic locations of corresponding authors in 140 studies from 69 cities internationally.

3.1 Study characteristics

A breakdown of the different studies’ designs is represented in Figure 3, including case reports, case series, cross-sectional studies, retrospective-, and prospective-cohort studies. There were no randomized controlled trials. Retrospective cohort studies (33%) and cross-sectional questionnaire/physical examination studies (33%) were the most common study design. The most common vaginoplasty surgical technique reported was PIV (81 studies). Table 2 shows a breakdown of the various vaginoplasty techniques included. The studies varied in their specificity of describing each technique, and many articles featured hybrid surgical techniques for constructing the vaginal lining (eg, penoscrotal vaginoplasty flap or PIV with scrotal skin graft). PIV is the most broadly encompassing grouping. 17 studies presented outcomes of only revision surgeries following primary vaginoplasty. The range of follow-up varied from 82 days (Acar et al., 2020) to 7997 days (van der Sluis et al., 2016).30, 31 This review accounts for the experience of 6,953 patients.

Percentage of different study designs in 140 studies.

TABLE 2. Vaginoplasty techniques and patients reported for 140 studies Vaginoplasty Technique Studies reporting technique, N Penile inversion skin flap 79 Intestinal flap 29 Revision procedure without changing vaginal tissue lining 4 Peritoneal flap 3 Buccal mucosa grafting 2 Skin graft 2 Scrotal skin flap 1 Perineal-scrotal flap 1 Acellular dermal allograft 1 Pudendal groin flap 1 Double-skin flap 1 Amnion graft 1 Unspecified 30 Total 155a a 15 studies featured cohorts with multiple techniques.
Revision specific studies 17b b Studies only featured outcomes following revision of a primary vaginoplasty at their own or another institution.
Abbreviation: N, number of studies. a 15 studies featured cohorts with multiple techniques. b Studies only featured outcomes following revision of a primary vaginoplasty at their own or another institution. 3.2 Sexual health parameters

Within the reviewed data, the most common sexual health parameter reported is sexual activity while therapeutic aids and pleasure were the least reported parameters (Figure 4). Europe for all parameters except pleasure and therapeutic aids reported the most on sexual health.

Sexual health outcomes represented in the literature (N = 140) divided by continental representation.

3.3 Desire/Interest

28 studies presented outcomes of desire/interest in sexual activity.31-58 This parameter also encompassed sexual fantasies and libido. It was reported by a Likert scale or by interview testimonies. 20 articles measured desire within an aggregated final score with validated questionnaires, including the FSFI, Brief Index of Sexual Function for Women (BISF-W), World Health Organization Quality of Life (WHOQOL-100) or Quality of Sexual Function (Q-SF).25, 31-41, 46-49, 53-56, 59-61 Kerckhof et al. (2019) presented that 18.3% of women postoperatively reported low sexual desire, and Rehman et al. (1999) observed that 7.1% of women postoperatively loss their desire for sex completely.42, 50 4.5% reported too strong of sexual desire.42 Lawrence (2005) presented a shift in desire for sexual experience postoperatively with increased interest in sexual activity with men.43 LeBreton et al. (2017) used an adapted version of the Derogatis Fantasy Scale reporting that patients less frequently have fantasies postoperatively than preoperatively.44, 62 This finding is in direct contrast with the findings of Schroder & Carroll (1999) who reported that there was a twofold to threefold increase in sexual fantasies postoperatively when controlled for sexual orientation.51 Wierckx et al. (2014) showed a statistically significant connection between patients experiencing more spontaneous sexual desire postoperatively than patients awaiting surgery (p = 0.002).57 Lothstein (1980) also reported increase in patient's sexual behavior being more “flexible and spontaneous.”45 All nine of the patients from Lindemalm et al. (1986) reported an unchanged libido postoperatively.58

3.4 Arousal

28 studies showed outcomes of arousal.31-36, 39-43, 46-56, 63-69 Arousal encompassed “urge” and any measurable physiological changes reported during arousal. 18 studies encompassed arousal within a standardized questionnaire (FSFI, BISF-W, Q-SF).31-36, 39-41, 46-49, 52-56 Studies reported between 46.9% and 100% of patients able to be aroused postoperatively (median 85.7%).31-33, 35, 51, 64, 65, 67, 68 Kerckhof et al. (2019) found that a significantly lower percentage of patients (15.9%) had difficulties with sexual arousal postoperatively when compared with preoperative patients while controlling for hormone treatment.42 Only one study (Bizic et al., 2014) qualified sexual arousal and reported that 75% of patients were satisfied with their arousal postoperatively.63 For some patients, sexual arousal produced a painful experience due to corpora tissue remnant.63, 69, 70 Rossi Neto et al. (2012) reported that 15% underwent revision procedures to remove excessive tissue and prevent the painful sensation in a cohort of 332 TGD patients after PIV.69 In a small sample size of 9 patients, 6 (66.7%) reported engorgement of the clitoris during arousal, while 4.6% in a sample of 202 patients reported urethral engorgement with sexual arousal.66, 71

3.5 Erogenous sensation of genitals

46 studies measured or reported on erogenous sensation of post-surgical genitalia including the vulva, clitoris, anus, or mons pubis.11, 13, 18, 19, 30, 33, 35, 44, 45, 48, 51, 66, 67, 70-103 General erogenous sensation ranged from 51.4% to 100% (median 97.7%) in 529 patients.11, 13, 30, 74, 80, 88, 89, 91, 100, 101 Only De Andrade (2013) reported a qualified scale for genital sensibility, receiving a 9.4/10 among 7 patients.75 The clitoris is the most reported area of erogenous sensation. 16 studies reported clitoral sensation ranging between 73.9 and 100% (median of 97%) in 1053 patients postoperative of PIV skin flaps (13 studies), PIV and oral epithelialization (1 study), PIV or intestinal flap (1 study) and double flap (1 study).48, 66, 67, 71, 72, 76, 77, 81-84, 86, 87, 92, 93, 98 Four studies qualified the clitoral sensation on various scales, and a rating from 103 patients post-operative PIV reported 8.4–8.5/10 for clitoral sensation.42, 67, 69, 72 Objective measurements pressure and vibratory thresholds of clitoral sensation demonstrated ranges from 0.4–12.1 g/mm2 to 0.2–0.5 μm, respectively, for 77 TGD patients.44, 96, 97 Clitoral sensation corresponded with arousal, pleasure of sexual activity, overall happiness with sexual function and sexual satisfaction.44, 51, 67, 85, 99 Patient-reported vaginal sensation was reported in 3 studies ranging from 92 to 100% (median of 100%) of 342 patients post-operative PIV (2 studies) and intestinal flap (1 study) techniques.18, 86, 95 Two studies discuss the erogenous sensation of the mons pubis where the dorsal penile neurovascular bundle is fixated.18, 98 Patients reported that the sensation of pressure to the area as pleasurable, and one patient reported the erogenous sensation being equivalent to her clitoris, achieving orgasm with stimulation.18, 98

Kanhai (2016) presented differences between two erogenous pedicled areas derived from the penis glans—the clitoris and a “sensate pedicled spot” at the anterior of the vaginal canal.84 46/50 patients (92%) reported erogenous sensibility in the clitoris around 7.6 weeks postoperatively, 44/50 patients (88%) reported erogenous sensibility in the sensate pedicled spot at 12.6 weeks.84

3.5.1 Complications related to sensation

Complications to erogenous sensation include hypersensitivity, lack or diminished sensation, necrosis of the clitoris and scarring.18, 70, 76, 79, 81, 84, 103 Among the first 200 patients of a single surgeon study, 44% experienced hypersensitivity 3 months post-operatively with the PIV technique.18 This complication diminished among the next 100 cases and was reported as 6.7% for 15 patients of a single surgeon study after pudendal groin flap vaginoplasty.18, 103 Despite clitoral scarring, clitoral necrosis, or diminished erogenous sensation, 16.7% - 100% maintained sensitive clitoris, and erogenous sensation improved over the course of continued follow-up or post-operative revision procedures.70, 76, 79, 81, 84

3.6 Sexual activity

98 studies reported outcomes on sexual activity and behaviour.11, 18, 19, 29-31, 33-38, 41-45, 47, 48, 50-53, 58, 63-65, 67-