The pathophysiological case for collagen-targeted therapy begins with what goes wrong in the vaginal wall. According to the review, vaginal laxity is characterized by reduced total collagen content, an imbalanced ratio of type I to type III collagen, disorganized collagen fiber alignment, and degradation of elastic fibers, collectively compromising tissue resilience and elasticity. Pregnancy and childbirth exert the most profound impact on vaginal and pelvic floor anatomy, while aging, menopause, obesity, and chronic elevation of intra-abdominal pressure contribute as well. Estrogen decline accelerates the process: the postmenopausal drop in estrogen promotes mucosal atrophy and collagen loss, and because estrogen receptors are densely expressed in vaginal, urethral, and bladder tissues, hormonal withdrawal triggers concurrent deterioration across multiple pelvic floor compartments.

Crucially, the review frames vaginal laxity not as an isolated complaint but as one manifestation within the broader spectrum of pelvic floor dysfunction. Women with vaginal laxity show a significantly elevated risk of concurrent stress urinary incontinence, and the same collagen-mediated pathologies, including decreased total collagen, an elevated type I/III ratio, and disruption of elastic fibers, have been documented in the urethral and periurethral connective tissues of women with stress urinary incontinence and in pelvic organ prolapse. At the molecular level, matrix metalloproteinase-1 degrades both type I and type III collagen, its activity regulated by tissue inhibitor of metalloproteinase-1, and this MMP/TIMP imbalance has been identified in the urethral sphincter complex of patients with stress urinary incontinence. Xue and colleagues further showed that transforming growth factor-beta 1 cooperatively suppresses the beta-catenin signaling pathway, reducing collagen synthesis and enhancing degradation in vaginal wall tissue from prolapse patients.

Why type III collagen specifically? The review explains that type III collagen is the principal collagen of reticular fibers and embryonic tissues, contributing to tissue elasticity and wound healing, and in the vaginal wall it plays a particularly important role in maintaining distensibility and elasticity. Its relative deficiency and disorganization are well documented in affected tissues, so replenishing this subtype directly addresses the observed imbalance. Traditional collagen biomaterials derived from bovine, porcine, or marine sources carry notable limitations: batch-to-batch variability, potential immunogenicity from xenogeneic epitopes such as the galactose-alpha-1,3-galactose epitope absent in humans, and the risk of pathogen transmission including prions and zoonotic viruses. Recombinant humanized collagen, produced via recombinant DNA technology in expression systems such as yeast or bacteria, contains no xenogeneic contaminants, exhibits consistently low immunogenicity, eliminates animal-derived pathogen risk, and offers high batch-to-batch reproducibility, though it is more expensive and may require additional processing to achieve proper triple-helix folding.

The engineered protein forms reticular fibers adopting a triple-helical conformation with a helical angle of 164.88 degrees, and the freeze-dried fiber format gives it distinctive material properties. The lyophilized fibers exhibit a loose, porous microfibrous morphology; upon implantation they rapidly absorb water and swell, while their mechanical strength can be tuned to match native soft tissues, supporting conformity to the vaginal wall. The porous scaffold facilitates cellular infiltration and host tissue ingrowth, and its degradation kinetics are synchronized with the host’s tissue remodeling process, delivering transient mechanical support while promoting de novo collagen deposition and reducing the risk of permanent foreign-body retention. The review contrasts this format with alternatives: hydrogels conform well but lack mechanical strength, sponges are less amenable to minimally invasive delivery, films serve barrier functions rather than volumetric augmentation, and injectable solutions are rapidly resorbed. Freeze-dried fibers preserve the native triple-helix conformation, maintain bioactivity, and confer long shelf stability without refrigeration, though the lyophilized structure may be fragile and prone to fragmentation during handling.

The proposed mechanism of action operates through three complementary pathways. First, physical support and structural filling: the fibers rapidly fill the submucosal layer and fascial spaces, immediately increasing vaginal wall thickness and tissue tautness, while physical crosslinking between fibers enhances tensile strength and elastic modulus. Second, biochemical regeneration: recombinant humanized type III collagen can be internalized by fibroblasts and significantly upregulates the expression of endogenous collagen-encoding genes COL1A1 and COL3A1, driving de novo synthesis of types I and III collagen, upregulating TIMP-1 while suppressing MMP-1 and MMP-2, and inducing elastin secretion to restore recoil capacity. Third, microenvironment modulation: the material upregulates VEGF, CD31, and CD34 expression, increasing microvessel density and local blood supply, while inhibiting the NF-kappaB/YAP signaling pathway to attenuate inflammatory responses. The review cautions, however, that several of these specific molecular pathways have been characterized primarily in non-vaginal tissue models, such as hypertrophic scar and endometrial immune microenvironment studies, and require direct validation in vaginal tissue.

The clinical evidence comes from a single small trial. In 2024, Chen and colleagues reported the world’s first prospective, randomized, two-center clinical trial evaluating the fibers for vaginal laxity, enrolling 84 women across two centers in China. The study group of 42 patients received the fibers in combination with a medical type III collagen vaginal gel as delivery vehicle, while the control group of 42 received the gel alone. At the 4-week assessment, the quantitative improvement rate in vaginal laxity grading scores was 88.10 percent in the study group versus 30.95 percent in the control group, a highly significant difference. After accounting for the gel vehicle effect, the independent efficacy rate of the fibers was estimated at 57.14 percent. The study group also showed significantly greater improvements in total Female Sexual Function Index and Vaginal Laxity Questionnaire scores, with the most pronounced gains in vaginal lubrication, alleviation of dyspareunia, sexual satisfaction, and subjective arousal. No serious adverse events were reported in either group.

The review insists on heavy caveats when interpreting these results. The comparator was a collagen gel rather than an established active treatment such as radiofrequency or laser therapy, so relative efficacy against energy-based modalities remains unknown. Follow-up lasted only four weeks, the study was conducted exclusively in a Chinese population, and the published report provides limited details on allocation concealment, blinding, and intention-to-treat analysis, limiting formal risk-of-bias assessment. Notably, the design isolates the incremental effect of the freeze-dried fiber format rather than the effect of collagen per se. The safety database is similarly limited: while recombinant humanized collagen lacks the alpha-Gal epitope and clinical studies in dermal fillers and wound care have reported generally mild, transient local reactions, long-term immunological data with repeated vaginal administrations are lacking, and the vaginal microbiome’s response to an exogenous biomaterial is unknown. Degradation products from the non-cross-linked native form are considered biologically benign, but the review warns that the physical presence of a fibrous scaffold could theoretically sustain chronic low-grade inflammation if degradation is too slow.

Positioned within the current therapeutic landscape, surgical vaginoplasty remains the gold standard for moderate-to-severe cases with long-term efficacy but higher risk and four-to-eight-week recovery, while radiofrequency and laser therapies offer moderate short-term efficacy with limited durability beyond six to twelve months, and pelvic floor muscle training is safe but has limited efficacy for structural laxity. The fibers occupy a distinctive niche as a minimally invasive, biologically active intervention combining immediate structural filling with endogenous regenerative stimulation, but the review emphasizes that promotional bias pervades much of the collagen biomaterial literature, with studies overemphasizing advantages while insufficiently addressing limitations. The field also lacks standardized diagnostic criteria, severity grading systems, and outcome measures for vaginal laxity, making inter-study comparisons unreliable.

The authors conclude that recombinant humanized type III collagen freeze-dried fibers represent an emerging, biologically plausible intervention that warrants further investigation, but the evidence base remains insufficient to support them as an established treatment. Key knowledge gaps include the absence of large-scale multicenter trials with long-term follow-up, no consensus on optimal dosage, frequency, and treatment duration, the need for head-to-head comparisons with established therapies, and uncertain generalizability to other populations. The potential applicability to broader pelvic floor disorders such as stress urinary incontinence and pelvic organ prolapse, while supported by preclinical evidence that recombinant humanized collagen promotes extracellular matrix remodeling in a rat model of simulated birth injury by restoring fibroblast function and stimulating angiogenesis, remains entirely speculative pending dedicated trials. For now, the fibers stand as a promising but unproven regenerative approach whose true clinical value will be determined only by rigorous, well-designed comparative research.

Subject of Research: Recombinant humanized type III collagen freeze-dried fibers for vaginal laxity

Article Title: Recombinant humanized type III collagen freeze-dried fibers for vaginal laxity: a narrative review of mechanisms, clinical evidence, and potential relevance to pelvic floor dysfunction

Article References: Shi, R., & Wang, L. (2026). Recombinant humanized type III collagen freeze-dried fibers for vaginal laxity: a narrative review of mechanisms, clinical evidence, and potential relevance to pelvic floor dysfunction. Frontiers in Medicine, 13, Article 1941555. https://doi.org/10.3389/fmed.2026.1941555

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1941555

Keywords: vaginal laxity, collagen type III, recombinant humanized collagen, pelvic floor dysfunction, regenerative medicine, tissue engineering, biomaterials, gynecology, narrative review, Frontiers in Medicine, Recombinant, humanized

The review, led by Ragav Chona and Gianni R. Lorello and conducted according to Joanna Briggs Institute methodology with pre-registration on the Open Science Framework, searched ten bibliographic databases from inception through 30 July 2025, combining controlled vocabulary for pelvic pain and transgender health with free-text keywords covering gender-affirming hormone therapy, vaginoplasty and dilation-related pain. From 6,534 records, the team screened 3,823 unique titles and abstracts and ultimately included 24 reports representing 23 unique cohorts and 5,527 transgender and gender-diverse participants. Inter-reviewer agreement at screening was nearly perfect, with a Cohen’s kappa of 0.99, and the reviewers also performed an exploratory risk-of-bias appraisal using design-specific checklists, the Cochrane RoB 2 tool and ROBINS-I.

What the synthesis found is a field dominated by observational and descriptive work. Of the 24 reports, ten were cross-sectional or psychometric studies, four were retrospective cohorts or audits, two were prospective cohorts, four were qualitative, three were case reports, and just one was a randomised trial. Thirteen reports came from North America, five from Europe, two each from Brazil and Australia, and two used international samples; no report was based in Africa or Asia. Fourteen reports focused on transmasculine people or other participants assigned female at birth, seven on transfeminine people, and three on mixed groups. Critically, only one report applied a formal duration-defined chronic pelvic pain criterion of at least three months, meaning most prevalence figures in the literature describe broader pelvic and genital symptom burden rather than chronic pelvic pain itself.

That single duration-defined study, drawing on more than 2,500 trans men and gender-diverse adults assigned female at birth in the PRIDE Study, estimated a chronic pelvic pain prevalence of 17.7 percent. Around it, heterogeneous symptom estimates ranged from 9.6 percent vulvar pain to 72.2 percent pelvic pain after starting testosterone, with dyspareunia reported in 61.5 percent of one transmasculine sample, pelvic pain in 36.0 percent of transmasculine participants on testosterone for at least a year, and 50.7 percent preoperative pelvic pain among transgender men undergoing hysterectomy. The reviewers are emphatic that these figures cannot be pooled or read as a prevalence range, because the samples, definitions and measures differ so wildly, but together they signal a real and recurrent clinical problem in selected populations.

The most scientifically intriguing thread concerns testosterone. Several studies described new-onset cramping or suprapubic pain after testosterone initiation, sometimes with dysorgasmia or breakthrough bleeding despite amenorrhoea, while the one duration-defined study found current testosterone use associated with lower chronic pelvic pain prevalence than non-use. The review argues these findings should not be read as either a protective or a causative effect. Supporting biological context comes from histological work outside the included studies: high-dose testosterone exposure has been linked to loss of vaginal epithelial layers, glycogen depletion and reduced oestrogen-receptor expression, while uterine and endometrial case series show heterogeneous responses, with some specimens showing active or proliferative endometrium despite amenorrhoea. The plausible interpretation is mechanistic heterogeneity: testosterone may suppress cyclic uterine, ovarian or peritoneal activity and ease pain in some people, while in others incomplete ovarian suppression, residual endometrial activity or hypoestrogenic tissue effects may drive dryness, irritation, dyspareunia and pelvic floor guarding.

A second major context is gender-affirming surgery. Postoperative pelvic and genital pain, dyspareunia and dilation-related difficulties are common early after urogenital surgery and, in the available follow-up, often improve during the first postoperative year, but longer-term cohorts have documented dyspareunia, lower abdominal pain and pelvic floor distress more than a decade after surgery. Reported pain generators include introital and neovaginal stenosis, scarring and granulation tissue, neuroma and nerve irritation, urethral complications, and rare structural pathology such as a pubic aneurysmal bone cyst that caused chronic groin pain and resolved after resection. The reviewers frame these trajectories within the established persistent postsurgical pain literature, involving peripheral injury, central sensitisation and psychosocial context, and argue that doing so supports routine outcome measurement and early identification of complications without pathologising gender-affirming surgery itself.

Across both transmasculine and transfeminine participants, pelvic floor neuromuscular impairments emerged as a recurring and potentially modifiable contributor, with hypertonicity, myofascial trigger points and coordination deficits described alongside dilation pain, orgasm-associated cramping and mixed urinary or bowel symptoms. One cross-sectional study of transgender men on testosterone found pelvic floor dysfunction in 94.1 percent of participants. Yet the treatment evidence is sobering: the only randomised trial, comparing routine postoperative pelvic floor physiotherapy with standard care after vaginoplasty, found no differences at 12 weeks in ease or pain with dilation, pelvic floor symptoms, vaginal length or subjective improvement. That argues against routine physiotherapy for every surgical patient, the reviewers note, but does not establish that targeted rehabilitation is ineffective for people with examination-confirmed hypertonicity, myofascial pain or function-limiting dilation pain, which case reports suggest can respond to manual release, down-training, biofeedback and graded dilator retraining.

The review also identifies psychosocial and trauma-related factors as a fourth interacting domain. Adverse childhood experiences, sexual trauma and minority stress, the chronic stigma-related stressors associated with marginalised group status, were associated with higher pain burden and multisite pain, and qualitative studies describe dysphoria, layered isolation, non-affirming healthcare experiences and delayed help-seeking among transgender and non-binary people with endometriosis, including diagnostic delays approaching ten years. The authors are careful to stress that these factors must not be used to psychologise symptoms or dismiss peripheral pain generators; rather, trauma-informed, gender-affirming communication can support trust, consent for examination and engagement with rehabilitation, while clinicians maintain diagnostic breadth across gynaecological, urological, gastrointestinal, musculoskeletal, neuropathic and psychosocial domains.

To translate the evidence into practice, the team proposes a six-step, evidence-informed diagnostic framework: confirm the pain phenotype and chronicity with a body map and validated scales; establish anatomy and exposure context, including hormone formulation, surgical history and bleeding patterns, without inferring anatomy from gender identity; screen for overlapping contributors; perform a consent-based, tailored examination; select targeted tests guided by symptoms rather than a routine panel; and triage and coordinate multidisciplinary care. The framework is explicitly pragmatic rather than validated, but it embodies the review’s central clinical message: pelvic pain during masculinising hormone therapy or after gender-affirming surgery should prompt structured evaluation, not be assumed to be a routine effect of testosterone or surgery, and no single contributor, hormonal, surgical, anatomical or psychosocial, should be blamed alone.

The limitations the authors acknowledge are as instructive as the findings. Chronicity definitions varied or were absent in 19 of 24 reports, no validated transgender-specific chronic pelvic pain measure exists, key variables such as hormone dosing, serum levels and surgical technique were inconsistently captured, and convenience sampling may over-represent those with higher symptom burden. Race and ethnicity were rarely analysed, though descriptive data hinted at higher pain prevalence among several non-White identity groups. The research agenda that follows is clear: prospective longitudinal cohorts beginning at or before hormone initiation, validated and inclusive patient-reported outcome measures, adequately powered trials of hormonal, rehabilitative, surgical and multidisciplinary strategies, and community-engaged, intersectional data collection. For now, the review’s verdict stands: chronic pelvic pain in transgender and gender-diverse people is real, common in the settings studied, and demanding of the same rigorous, biopsychosocial, equity-focused attention that has transformed care for everyone else.

Subject of Research: Chronic pelvic and genital pain in transgender and gender-diverse people

Article Title: Chronic pelvic and related genital pain in transgender and gender-diverse people: a scoping review

Article References: Chona, R., Sabbah, S. G., Englesakis, M., Di Renna, T., Drodge, O., Rosenbloom, B. N., Leonardi, M., & Lorello, G. R. (2026). Chronic pelvic and related genital pain in transgender and gender-diverse people: a scoping review. eClinicalMedicine, 101, Article 104252. https://doi.org/10.1016/j.eclinm.2026.104252

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104252

Keywords: chronic pelvic pain, transgender health, gender-affirming hormone therapy, testosterone, vaginoplasty, pelvic floor dysfunction, scoping review, minority stress, central sensitisation, dyspareunia, gender-affirming surgery, pain medicine

The study, led by Ling Li and Daoming Tian of the Center for Pelvic Floor Disorders at the First Affiliated Hospital of Kunming Medical University, recruited sixteen healthy Asian women between the ages of eighteen and thirty who had never been pregnant. This nulligravid population is a crucial reference point. Pelvic floor dysfunction, including prolapse and incontinence, affects a large share of women worldwide, but clinicians still lack a firm baseline for what the uninjured, youthful pelvic floor does when asked to perform. Without that baseline, it is difficult to say whether a given measurement in a patient is abnormal or simply part of natural variation.

To capture the pelvic floor in action, the team used a 3.0 Tesla MRI scanner, a field strength high enough to resolve fine soft-tissue detail in the midsagittal plane, the side-on view that slices the pelvis down the middle. Each participant was imaged three times in quick succession: once at rest, once while performing a maximal Valsalva maneuver, meaning a forced exhalation against a closed airway that raises intra-abdominal pressure, and once while performing a maximal voluntary pelvic floor contraction, the deliberate squeeze familiar to anyone who has practiced Kegel exercises. The researchers then measured a battery of anatomical landmarks in each state, from the position of the bladder neck and anorectal junction to the angle of the levator plate, the length of the urethra and vaginal walls, and the area of the levator hiatus, the opening through which the urethra, vagina, and rectum pass.

One of the study’s technical strengths lies in how those measurements were made. Rather than relying on raw scanner coordinates, which shift depending on how a patient is positioned on the table, the team applied a Pelvic Inclination Correction System, or PICS, coordinate framework. This approach corrects for pelvic tilt and establishes a reproducible reference line running from the pubis to the sacrococcygeal joint, allowing landmarks measured in different women and different states to be compared on equal footing. All measurements were performed independently by two radiologists using specialized segmentation software, and the average of their readings was used in the final analysis.

The reliability of those readings was generally strong. Intraclass correlation coefficients, which quantify how closely two observers agree, ranged from 0.858 to 0.999 across the three states, values that in most imaging studies would be considered excellent. The authors were careful, however, to note that some of the confidence intervals around those estimates were wide and dipped below 0.75, particularly during the Valsalva and contraction maneuvers. In a cohort of only sixteen participants, a single outlier can stretch those intervals considerably, a limitation the researchers acknowledge openly.

When the three states were compared statistically using repeated-measures analysis of variance, with a false discovery rate correction applied across thirty-three endpoint tests to guard against spurious findings, thirty-two of the thirty-three endpoints showed evidence of state-related differences. In other words, nearly every measurable feature of pelvic floor morphology changed significantly depending on whether the woman was resting, straining, or squeezing. The largest differences emerged between the two active maneuvers, Valsalva and voluntary contraction, which turned out to be far from mirror images of each other.

The numbers tell a striking story. During voluntary contraction compared with Valsalva, the anorectal junction moved upward by an average of 18.50 millimeters, the upper levator plate angle decreased by about 30.44 degrees, the M-line displacement, a measure of pelvic floor descent, was smaller by 12.69 millimeters, and the levator hiatus area shrank by 2.41 square centimeters. In plain terms, when these women actively squeezed their pelvic muscles, the entire pelvic floor lifted, the muscular plate behind the anus tilted into a more horizontal, supportive orientation, and the opening in the levator muscle narrowed. During straining, the opposite occurred: the hiatus widened, the organs descended, and the pelvic floor flattened under pressure.

Perhaps the most intriguing observation concerns the uterovaginal axis, the line running from the uterine fundus down through the cervix and vagina. The researchers sampled points along this axis and tracked their displacement across states, finding hints that different segments of the axis move by different amounts during contraction. This suggests that the pelvic floor does not behave as a single rigid sheet but as a segmented, coordinated system in which the upper and lower portions may respond differently to muscular effort. The authors describe this as a hypothesis-generating finding, one that will require three-dimensional imaging and concurrent functional measurements to confirm.

The clinical implications could be substantial. Dynamic MRI of the pelvic floor is already used to diagnose prolapse and obstructed defecation, but interpretation depends on reference values, and most existing norms come from older or parous women. By documenting how a healthy young pelvic floor responds to maximal effort, this study provides a physiological anchor for distinguishing normal function from early dysfunction. It also highlights a subtlety that matters in the clinic: straining and squeezing are not simply opposite ends of one spectrum but distinct neuromuscular configurations, and a patient’s ability to perform each correctly can reveal different problems. A woman who bears down when she intends to squeeze, a common error in pelvic floor rehabilitation, would show a pattern on dynamic MRI that is unmistakably different from a correct contraction.

The authors are appropriately cautious about how far these findings can be pushed. Sixteen women, all from a single ethnic group and a single hospital, cannot define the full range of human pelvic floor anatomy, and the nonparametric sensitivity analyses were not fully concordant with the primary results, a reminder that some findings may not survive in larger samples. Still, as an exploratory map of the living pelvic floor in motion, the study is a valuable first step. It shows that with careful coordinate correction, rigorous observer agreement, and modern 3.0 Tesla imaging, the invisible mechanics of pelvic support can be measured with precision, opening the door to better baselines, better diagnostics, and perhaps one day, imaging-guided pelvic floor training tailored to each woman’s own anatomy.

Subject of Research: Dynamic MRI assessment of pelvic floor morphology in young healthy nulligravid women during rest, Valsalva, and voluntary contraction

Article Title: Dynamic MRI of pelvic floor morphology in young, healthy Asian nulligravid women: an exploratory study across rest, Valsalva, and voluntary contraction

Article References: Li, L., Tian, D., Zeng, Y., Wang, X., Luo, Q., & Shen, J. (2026). Dynamic MRI of pelvic floor morphology in young, healthy Asian nulligravid women: an exploratory study across rest, Valsalva, and voluntary contraction. BMC Medical Imaging. https://doi.org/10.1186/s12880-026-02853-8

Image Credits: AI Generated

DOI: 10.1186/s12880-026-02853-8

Keywords: pelvic floor, dynamic MRI, nulligravid women, Valsalva maneuver, pelvic floor contraction, levator hiatus, pelvic organ prolapse, PICS coordinates, 3.0 Tesla MRI, pelvic floor dysfunction, levator ani, urogynecology

The research team, led by Susanna Weidlinger and colleagues, searched MEDLINE, Embase, Scopus and the Cochrane Central Register of Controlled Trials for studies published from 2013 to June 2026, a cut-off chosen to coincide with the replacement of gender identity disorder with gender dysphoria in the DSM-5. From 3,548 records identified, 2,252 unique publications were screened and 212 went to full-text assessment. Eleven studies ultimately met the inclusion criteria, drawn from five countries, six of them from the United States. Together they enrolled 4,176 transmasculine individuals, of whom 2,891 were receiving testosterone therapy. Study designs ranged from a single prospective cohort to five retrospective cohorts, three cross-sectional surveys, one retrospective case series and one qualitative interview study, with sample sizes spanning just 14 participants to more than 2,500.

The pooled prevalence of pelvic pain among transmasculine people on testosterone was 39 percent, with a 95 percent confidence interval of 23 to 55 percent. That figure exceeds the estimated 5 to 25 percent prevalence of chronic pelvic pain in cisgender women worldwide, although the authors caution that direct comparison is limited by differences in populations, pain definitions and how symptoms were ascertained. Among those on testosterone who were not scheduled for gender-affirming surgery, the pooled prevalence was lower at 28 percent, while in surgical cohorts, where pelvic pain was often documented as an indication for hysterectomy, it climbed to 50 percent. Strikingly, prevalence among those not taking testosterone was 41 percent, statistically indistinguishable from the figure in testosterone users, offering no evidence of a clear protective or harmful association.

Perhaps the most clinically consequential results concern what happens to pain over time. Among individuals with preexisting pelvic pain, symptoms persisted after testosterone initiation in a pooled 72 percent of cases, while only 26 percent experienced improvement or remission. One study reported worsening in 24 percent of participants. Meanwhile, roughly 31 percent of previously asymptomatic individuals reported new-onset pelvic pain after starting testosterone, though this estimate carries an extremely wide confidence interval of 5 to 65 percent and rests on just three studies with very different designs. A retrospective clinical cohort reported new-onset pain in 71 percent of affected patients, a cross-sectional study of adolescents found 17 percent, and a prospective online cohort found 11 percent, a spread that reflects differences in recruitment, symptom documentation and ascertainment methods.

The statistical picture is dominated by heterogeneity. The I-squared statistic exceeded 99 percent for most prevalence estimates, meaning that nearly all of the observed variation between studies reflects real differences rather than chance. Study populations ranged from highly selected surgical cohorts to large community samples recruited through online transgender health networks, and pain was variously defined as chronic pelvic pain lasting three months or longer, cyclic and acyclic lower abdominal pain, or simply any pain documented in medical records as a reason for surgery. No study used a validated pain assessment tool, and only a minority applied established time-based criteria for chronicity. The authors therefore present their pooled estimates as descriptive summaries of the literature rather than precise population-level parameters.

Methodological quality, assessed with Joanna Briggs Institute checklists, ranged from moderate to high, with three studies rated high quality and eight moderate. A consistent weakness was the failure to address confounding, even where potential confounders were identified. The authors also flag a subtler problem: confounding by indication and possible reporting bias in surgical cohorts. Because insurance coverage for gender-affirming hysterectomy varies widely and often requires documented medical indications beyond gender dysphoria itself, clinicians and patients may have incentives to record pelvic pain to facilitate approval, potentially inflating prevalence in surgical subgroups. The contrast between 90 percent prevalence documented as a surgical indication in one cohort and 7 to 16 percent in community-based samples illustrates how much ascertainment context matters.

Why might pelvic pain be so common in this population despite testosterone’s suspected pain-protective properties? The authors sketch a multifactorial and still incompletely understood pathophysiology. First, testosterone induces vaginal epithelial atrophy, analogous to the genitourinary syndrome of menopause, which may increase susceptibility to dyspareunia, bacterial vaginosis and cystitis; one large study found that nearly two-thirds of transmasculine individuals experienced vulvovaginal pain during sexual activity, with current testosterone use independently associated with increased vaginal pain. Second, testosterone does not reliably suppress the ovaries: histological signs of recent ovulatory activity have been documented in roughly 30 to 40 percent of transmasculine individuals at oophorectomy, independent of serum testosterone levels, duration or preparation type, and endometrial activity persists in a substantial proportion. One cohort found that endometrial proliferation was significantly more frequent with transdermal gel and short-acting testosterone esters than with long-acting testosterone undecanoate, plausibly because fluctuating hormone levels allow intermittent recovery of follicular activity and local aromatisation of testosterone to estradiol.

Third, pelvic floor dysfunction appears highly prevalent, reported in 94 percent of transmasculine individuals on testosterone in one study. The levator ani, the principal pelvic floor muscle, is highly androgen-responsive, and whether masculinising doses induce hypertonicity contributing to pain has not been directly studied. Fourth, psychosocial factors loom large: gender dysphoria, minority stress and barriers to care, including discrimination and discomfort with pelvic examinations, may amplify pain perception and reduce help-seeking. Notably, one study of gender minority individuals found that stress, rather than gender identity or hormone therapy type, was the factor most strongly associated with chronic pain, underscoring the relevance of a biopsychosocial framework. Endometriosis also remains relevant even under testosterone: one surgical series found intraoperatively confirmed endometriosis in nearly 27 percent of patients undergoing gender-affirming hysterectomy, with higher rates among those reporting pelvic pain.

The clinical implications are concrete. The authors recommend that clinicians counsel patients before treatment that pelvic pain is common both before and during testosterone therapy and that the hormone does not reliably resolve preexisting symptoms. Preexisting gynaecologic conditions should be evaluated where feasible before testosterone initiation, since prior pain, dysmenorrhea, endometriosis and ovarian cysts are associated with persistent symptoms. Gynaecologic follow-up should continue despite amenorrhea, given the evidence of residual ovarian and endometrial activity, and clinicians should maintain a low threshold for investigating new or worsening pain. Care environments should actively address barriers through inclusive language, trauma-informed approaches and alternatives such as self-collected specimens.

The review also maps the road ahead for research. Future studies should employ validated, multidimensional pain instruments that distinguish pain subtypes and mechanisms, and the recently validated Transmasculine and Gender Diverse Pelvic Symptom Index offers the first gender-affirming instrument designed specifically for this purpose. Prospective cohorts with standardised assessment before testosterone, during therapy and after hysterectomy or oophorectomy are needed to characterise pain trajectories and identify modifiable risk factors. The limitations are real: nearly all analyses showed extreme heterogeneity, most studies were cross-sectional, confounder control was sparse, prior hysterectomy status was incompletely reported, and the evidence base is concentrated in the United States and Australia, with no studies from low- and middle-income countries and none at all on transfeminine individuals. Publication bias also cannot be excluded. Even so, as the first quantitative synthesis of its kind, the analysis establishes that pelvic pain is a substantial and previously underappreciated burden in an underserved population, and it replaces a comforting assumption with a more honest, and more clinically useful, picture of what testosterone can and cannot do.

Subject of Research: Prevalence and clinical course of pelvic pain in transmasculine individuals receiving gender-affirming testosterone therapy

Article Title: Prevalence and clinical course of pelvic pain among transmasculine individuals on gender-affirming testosterone: a systematic review and meta-analysis

Article References: Weidlinger, S., Niggli, A., van Trotsenburg, M., Feil, K., Weidlinger, C., Vidal, A., Gulz, M., Pape, J., Laue, J., Leeners, B., von Wolff, M., Karrer, T., & Camastral-Urech, K. (2026). Prevalence and clinical course of pelvic pain among transmasculine individuals on gender-affirming testosterone: a systematic review and meta-analysis. eClinicalMedicine, 100, Article 104233. https://doi.org/10.1016/j.eclinm.2026.104233

Image Credits: AI Generated

DOI: Not provided

Keywords: pelvic pain, transmasculine, testosterone, gender-affirming hormone therapy, systematic review, meta-analysis, chronic pain, endometriosis, pelvic floor dysfunction, transgender health, gynaecology, minority stress