Re-Equilibrating Sex Ratios: Adjustment of Reaction Norms in Species With Temperature-Dependent Sex Determination.

Fisher's general principle for sex allocation holds that population sex ratios are typically balanced because parents producing the rare sex are benefited and the rare sex alternates over time. In species that have temperature-dependent sex determination (TSD), thermal reaction norms need to be adjusted at the population level to avoid extremely biased sex ratios and extinction. Extant species with TSD experienced drastic climatic changes in the geological past and must necessarily have mechanisms of adaptation. I propose here a conceptual framework to explain how TSD curves could be adjusted by means of natural selection, based on Fisher's equilibrium sex-ratio principle. Through a process that alternatively favors mothers that tend to produce the rare sex under new temperatures, sex ratios eventually return toward a theoretical equilibrium. Prerequisites for this model are variability among mothers in the tendency to produce a particular sex at a given temperature (i.e., variability in the thermal reaction norm), inheritance of this trend, and higher fitness of the rare sex. This straightforward mechanism could facilitate thermal adaptation in species with TSD over multiple generations.

Quality of life outcomes in patients undergoing facial gender affirming surgery: A systematic review and meta-analysis.

Background: Facial gender-affirming surgery (FGAS), one of many transition-related surgeries (TRSs), "feminizes" the faces of transgender and gender diverse (TGD) patients undergoing transition. However, it is difficult to demonstrate the medical necessity of FGAS in terms of postoperative quality of life (QoL) outcomes due to a lack of standardized assessment tools. Thus, FGAS remains largely unsubsidized in North America. Methods: A systematic review of online databases was conducted according to PRISMA guidelines. Screening and quality assessment was conducted by two independent blinded reviewers (KJ and GR). For statistical analysis, data from different Likert-scale-like questionnaires were extracted and coalesced into three-point scales on a data table of seven QoL domains; "Pre-" and "Postoperative femininity," "Psychological satisfaction," "Social Integration and Functioning," "Aesthetic Satisfaction," "Physical Health," and "Satisfaction with Surgical Results." Results: From 2000 to 2022, 1837 patients and 3886 procedures from 19 studies were included. Weighted averages across all QoL domains reflected statistically significant improvement compared to neutral following FGAS (p < 0.001). Three studies used the same questionnaire, which showed that out of all eight questions regarding facial appearance, FGAS patients most strongly agreed the surgery was important to their ability to live as a woman (mean = 4.56/5, n = 137). Secondary outcomes showed the most common complications were hardware palpability (3.45%, n = 145) and aberrant scarring (2.17%, n = 423) with an overall revision rate of 2.17% (n = 423). The most common procedure was fronto-orbital remodeling. Conclusion: FGAS significantly improves QoL with minimal risk to life and supports the literature in defining FGAS as a medically necessary procedure comparable to other TRSs.

The evolution of a large-scale facial gender affirmation program: A comparative outcomes analysis.

BACKGROUND: The volume of facial feminization surgery (FFS) performed has increased tremendously over the last decade as new gender affirmation programs have formed. Advancements in surgical planning and treatment protocols have resulted in complex, multiprocedural FFS operations. This study examines the characteristics and outcomes of a large-scale FFS program over a 5-year lifespan. METHODS: A retrospective analysis was performed of all patients who underwent FFS in a high-volume integrated healthcare system from program initiation in 2018-2019 (early cohort) to maturation in 2021-2022 (late cohort). Patient charts were reviewed for demographic factors, operative details, complications, postoperative Emergency Department or Urgent Care (ED/UC) visits, revisions, and readmissions. Patient characteristics and outcomes were compared between early and late cohorts. RESULTS: A total of 191 patients were included, with 109 in the early cohort and 82 in the late cohort. Patient demographics were similar except mean age (40.3 years early cohort versus 36.3 years late cohort, p = 0.03). Patients in the late cohort had longer operations (5.40 h versus 6.16 h, p = 0.008), with a greater percentage of patients receiving genioplasty, rhinoplasty, fat grafting, or lip lift. Despite this, fewer patients in the late cohort were admitted postoperatively (62.4% versus 13.4%, p < 0.001). There were no differences in total complications, minor complications, revisions, ED/UC visits, or readmissions. However, major complications were significantly more common in the early cohort (4.6% versus 0.0%, p = 0.05). CONCLUSION: As a nascent FFS program matures, the number of procedures in a single operation increased along with operative length. Major complications and postoperative admission rates decreased while total complications remained low.

Penile Inversion Vaginoplasty: An Evolving Technique.

Penile inversion vaginoplasty (PIV) is the most common surgical technique used in "gender-affirming bottom surgery." During this process, penile tissue is used to create a functional neo-vagina, allowing the individual to experience a more aligned physical manifestation of their "gender" identity. In this technical note, we describe the steps and nuances used by the senior author to ensure reliable aesthetic and functional outcomes, contributing to the overall well-being and satisfaction of transgender patients.

Functional and Cosmetic Considerations in Gender-Affirming Feminization Rhinoplasty.

Gender-affirming facial surgery is increasing in prevalence, and rhinoplasty plays an integral role in its success. The nose displays considerable gender dimorphism, and maneuvers performed during gender-affirming rhinoplasty may differ considerably from those performed during cis-gender surgery. During feminization rhinoplasty in particular, cosmetic goals often rely on reductive techniques such as osteotomies, dorsal reduction, sidewall narrowing, tip narrowing, and alar base narrowing. These maneuvers collectively have important ramifications when considering the functional aspects of the nose. Herein, we outline the status of feminization rhinoplasty, and the interplay of cosmetic and functional considerations of the field.

Three feminizing Wolbachia strains in a single host species: comparative genomics paves the way for identifying sex reversal factors.

Introduction: Endosymbiotic bacteria in the genus Wolbachia have evolved numerous strategies for manipulating host reproduction in order to promote their own transmission. This includes the feminization of males into functional females, a well-studied phenotype in the isopod Armadillidium vulgare. Despite an early description of this phenotype in isopods and the development of an evolutionary model of host sex determination in the presence of Wolbachia, the underlying genetic mechanisms remain elusive. Methods: Here we present the first complete genomes of the three feminizing Wolbachia (wVulC, wVulP, and wVulM) known to date in A. vulgare. These genomes, belonging to Wolbachia B supergroup, contain a large number of mobile elements such as WO prophages with eukaryotic association modules. Taking advantage of these data and those of another Wolbachia-derived feminizing factor integrated into the host genome (f element), we used a comparative genomics approach to identify putative feminizing factors. Results: This strategy has enabled us to identify three prophage-associated genes secreted by the Type IV Secretion System: one ankyrin repeat domain-containing protein, one helix-turn-helix transcriptional regulator and one hypothetical protein. In addition, a latrotoxin-related protein, associated with phage relic genes, was shared by all three genomes and the f element. Conclusion: These putative feminization-inducing proteins shared canonical interaction features with eukaryotic proteins. These results pave the way for further research into the underlying functional interactions.

The Type I+ Forehead in Facial Feminization Surgery.

BACKGROUND: Feminizing fronto-orbital reconstruction involves one of four possibilities with the Ousterhout Type III anterior table frontal sinus osteotomy and setback performed in most patients while the Type I reduction recontouring is reserved for patients without frontal sinuses or thick anterior tables. However, patients with frontal sinuses and either a moderately thick anterior table or a shallow frontal sinus in the sagittal plane represent an intermediate morphology. For such morphologies, we introduce the novel Type I+ fronto-orbital reconstruction technique, consisting of frontal bone recontouring supplemented with anterior table reconstruction and split cranial bone graft. METHODS: Transgender and gender non-conforming patients who underwent Type I+ or Type III feminizing fronto-orbital reconstruction (2019-2023) were included for retrospective review and comparison of techniques. RESULTS: In the 123 patients (mean age 32.2 ± 9.5 years) included, 6.5% underwent Type I+ and 94.5% underwent Type III feminizing fronto-orbital reconstruction. Morphologically, Type I+ patients displayed a shallower frontal sinus compared to Type III patients (median anterior to posterior table depth 4.1[interquartile range, IQR, 1.1-5.0] versus 9.8[IQR 7.5-12.0]mm, p<0.001). At the maximum prominence, Type I+ patients also demonstrated thicker anterior tables compared to Type III patients (median 6.6[IQR 5.0-8.8] versus 2.2[IQR 0.4-4.7]mm, p=0.001). Patients receiving Type I+ procedures underwent an anterior table reduction of 2.7±1.2mm versus 4.2 ± 1.2mm for Type III procedures in the sagittal plane (p=0.002). CONCLUSIONS: The current work introduces a novel solution to an intermediate frontal sinus phenotype for gender-affirming facial feminization surgery. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of spironolactone and cyproterone acetate on breast growth in transgender people: a randomized clinical trial.

CONTEXT: Transgender people with sex recorded male at birth desiring feminization commonly use cyproterone acetate or spironolactone as anti-androgens with estradiol, but the optimal anti-androgen is unclear. OBJECTIVE: To assess the effect of anti-androgens on breast development. We hypothesized this would be greater in those treated with cyproterone acetate than spironolactone due to more potent androgen receptor antagonism and suppression of serum total testosterone concentrations. DESIGN: Randomised clinical trial 2020-2022. SETTING: Outpatient endocrinology clinic. PARTICIPANTS: Transgender people aged 18+ years old commencing feminizing gender affirming hormone therapy. INTERVENTIONS: Standardized estradiol therapy plus either spironolactone 100mg daily or cyproterone acetate 12.5mg daily for six months. MAIN OUTCOME MEASURES: Primary outcome was breast development as measured by the breast chest distance. Secondary outcomes included estimated breast volume, suppression of serum total testosterone concentration <2nmol/L and Gender Preoccupation and Stability Questionnaire (GPSQ). RESULTS: Sixty-three people (median age 25 years) were enrolled, randomized and included in intention-to-treat analysis (cyproterone acetate n=32, spironolactone n=31). At six months, there was no between-group difference in breast chest distance (mean difference 0.27 cm, 95% CI -0.82 to 1.35, p=0.6) or estimated breast volume (mean difference 17.26 mL, 95% CI -16.94 to 51.47, p=0.3). Cyproterone acetate was more likely to suppress serum testosterone concentration to <2 nmol/L (odds ratio 9.01, 95% CI 1.83 to 4.44, p=0.008). Changes in GPSQ were similar between groups. CONCLUSION: Anti-androgen choice should be based on clinician and patient preference with consideration of side effects. Further research is needed to optimize breast development in transgender people.

Soft-tissue complications after facial feminization bone surgery.

The soft tissues have a considerable impact on whether the results of facial feminization surgery are favorable. Complications or suboptimal results related to the soft tissue may be due to poor choice of surgical approach, improper execution of the surgical technique, a lack of assistance when resuspending the soft tissues during closure, or deficient readaptation of the overlying soft tissue to the new bone contour. This article identifies the possible poor soft-tissue outcomes that may occur after facial feminization bone surgery, describing strategies to prevent them and treatment alternatives.

Computerized Surgical Planning in Gender Affirming Facial Surgery.

Computerized Surgical Planning (CSP) is a surgical tool that enables precise bony changes through the creation of custom cutting guides and/or custom plates. CSP has been shown to be a safe and effective tool in gender affirming facial surgery as well, specifically with regard to frontal sinus setback, zygomatic remodeling, genioplasty, and mandibular angle and body reshaping. CSP aids in trainee education, improves symmetry, reduces operative time, and can produce idealized results during complex revisions. Overall, CSP is a valuable tool in the field of gender affirming facial surgery that helps surgeons achieve optimal aesthetic and safety outcomes for patients.

Update of Vocal Fold Shortening With Retrodisplacement of Anterior Commissure for Voice Feminization.

OBJECTIVES: To assess the efficacy and long-term durability of the enhanced technique of Type II Vocal Fold Shortening and Retrodisplacement of the Anterior Commissure (VFSRAC) for voice feminization compared with the preceding Type I method. METHODS: A retrospective analysis encompassed 506 patients drawn from a cohort of 1025 MtF transgender women who underwent VFSRAC between 2003 and 2021. The study period included cases from 2015 to 2021, during which the Type II update technique was implemented, involving a modification to the suture technique. Subjective and perceptual evaluations, aerodynamic and acoustic assessments, real-time pitch analysis, and videostroboscopic reviews were conducted pre- and postoperatively in the MtF transgender women cohort. Comparative statistical analyses were performed to discern differences between the earlier Type I method (2003-2014) and the more recent Type II method (2015-2021). RESULTS: The preoperative mean speech fundamental frequency (sF0) for Type II VFSRAC was 134.5 Hz. Postoperatively, the mean sF0 increased to 196.7 Hz, 212.3 Hz, and 207.5 Hz at 3 months, 6 months, and beyond 1 year, respectively, exceeding outcomes observed with the Type I method. Postoperative subjective and objective assessments indicated an augmentation in voice femininity. Acoustic and aerodynamic indices were within the normal range, and the regularity of the vocal fold mucosal wave was preserved within normal parameters. These results suggest that patients achieved a natural phonation pattern after surgery. CONCLUSIONS: The application of our updated type II VFSRAC has demonstrated feasibility and consistently yielded favorable results for individuals desiring a naturally feminine voice. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Case report: A pregnant woman accidental treated with spironolactone in mid-gestation.

Spironolactone, a potassium-sparing diuretic, is used to treat hypertension, heart failure, and certain hyperandrogenic disorders. Its use during pregnancy is not recommended due to the risk of feminizing male fetuses, primarily because of its antiandrogenic activity. However, human data remain scarce and largely inconclusive. Here, we present the first case of a 25-year-old pregnant woman, at 16 weeks of gestation, who was inadvertently exposed to spironolactone (240 mg/day) for 1 week due to a pharmacy dispensing error. The patient subsequently delivered a healthy male infant with normal genitalia at 38 weeks of gestation following vaginal delivery. Current follow-up shows that the infant is healthy and developing normally. This article summarizes the potential causes of spironolactone-induced anomalous genital development and explores the safety of new-generation mineralocorticoid receptor antagonists (MRAs) during pregnancy. The mechanisms behind spironolactone-induced anomalous genital development in male fetuses have not been fully elucidated. Spironolactone competes with dihydrotestosterone for binding to androgen receptors and inhibits enzymes involved in androgen biosynthesis, which may partly explain its antiandrogenic effects. Recent advancements in MRAs have led to the development of compounds with higher selectivity for the mineralocorticoid receptor, thereby reducing the incidence of antiandrogen side effects. These new-generation MRAs may be effective alternatives during pregnancy, but more data are needed to establish their safety in pregnant women. This case contributes to the limited but growing body of literature on the safety profile of spironolactone in pregnancy, providing insights into its effects during a critical period of fetal development.

Evidence for feminized genetic males in a flea beetle using newly identified X-linked markers.

The equilibrium of sex ratios in sexually reproducing species is often disrupted by various environmental and genetic factors, including endosymbionts like Wolbachia. In this study, we explore the highly female-biased sex ratio observed in the flea beetle, Altica lythri, and its underlying mechanisms. Ancient hybridization events between Altica species have led to mitochondrial DNA introgression, resulting in distinct mitochondrial haplotypes that go along with different Wolbachia infections (HT1-wLytA1, HT1*- uninfected, HT2-wLytA2, and HT3-wLytB). Notably, beetles with some haplotypes exclusively produce female offspring, suggesting potential Wolbachia-induced phenomena such as feminization of genetic males. However, the observed female bias could also be a consequence of the ancient hybridization resulting in nuclear-cytoplasmic conflicts between introgressed mtDNA and nuclear genes. Through transcriptomic analysis and the program SEX-DETector, we established markers for genotypic sex differentiation for A. lythri, enabling genetic sexing via qPCR. Our findings suggest that feminization of genetic males is contributing to the skewed sex ratios, highlighting the intricate dynamics of sex determination and reproductive strategies in this flea beetle. This study provides valuable insights into the dynamics of genetic conflicts, endosymbionts, and sex ratios, revealing the novel phenomenon of genetic male feminization in the flea beetle A. lythri.

Outcome of isolated and combined direct feminization laryngochondroplasty: Our first 20 cases.

This retrospective study describes the surgical outcomes of our first 20 transgender women to undergo feminization thyroid laryngochondroplasty (FLC) by a direct transvestibular FLC (DTV-FLC) approach from December 2019 to October 2023. The medical records of all patients were retrieved and reviewed. Data on the operative, postoperative, and follow-up courses, complications, and functional and cosmetic outcomes were retrieved. The cosmetic results were evaluated by four independent facial plastic surgeons. Thirteen patients underwent DTV-FLC combined with genioplasty or genioplasty with mandibular angle reduction and seven underwent isolated DTV-FLC. DTV-FLC was feasible in all planned cases. Complications (skin flap perforation, thyroid cartilage fracture, mental hypoesthesia, hematoma, dehiscence of the vestibular incision, vestibular scar adhesions, and anemia) were minor and resolved spontaneously. The preoperative grade of thyroid cartilage protrusion was 1.9 ± 0.9 on a scale from 1 to 3. The postoperative cosmetic results of 18 patients were judged as having improved (a score of 2.1 ± 0.8 on a scale from -1 to 3). Eighteen patients were satisfied with the cosmetic result, one was dissatisfied (the revision surgery patient), and one was lost to follow-up. In conclusion, DTV-FTLC is a valid surgical approach for FLC, yielding high patient satisfaction and good cosmetic results.

Lip feminization: A review.

Background: Facial feminization involves a broad array of procedures tailored to transgender women, with lip feminization emerging as a crucial element because of its significant impact on gender expression. Despite its importance, there is a dearth of studies singularly dedicated to lip feminization within this demographic. Objectives: This review aimed to consolidate knowledge on various techniques (surgical and nonsurgical), outcomes, and patient satisfaction related to lip feminization, thereby highlighting its integral role in facial feminization and its significance in affirming transgender women's identity. Methods: A systematic search of PubMed, MedLine, and Embase databases was conducted, focusing on studies published up to April 18, 2024. Inclusion criteria were centered on articles addressing the techniques and outcomes of lip feminization. A rigorous screening process was applied to identify relevant literature, which was then reviewed for data extraction on techniques, outcomes, complications, and patient satisfaction. Results: Among the initial 28 publications, 21 articles remained. These studies provided insights into surgical and nonsurgical techniques for lip feminization and reported high-satisfaction rates within a broader scope of facial feminization surgeries. Notably, specific data on lip feminization were sparse and often extrapolated either from broader facial feminization research or studies on cisgender populations. Conclusion: This review established that lip feminization is a crucial but under researched aspect of gender-affirming care. Recognizing the high-satisfaction rates reported for facial feminization, this study advocated for detailed, procedure-specific research to optimize outcomes for transgender women seeking lip feminization.

Methodology for developing data-rich Key Event Relationships for Adverse Outcome Pathways exemplified by linking decreased androgen receptor activity with decreased anogenital distance.

The Adverse Outcome Pathway (AOP) framework has gained widespread acceptance in toxicological disciplines as a tool for aiding chemical hazard assessment. Despite increased activity in AOP development, progress towards a high volume of fully endorsed AOPs has been slow, partly due to the challenging task of constructing complete AOPs according to the AOP Developer's Handbook. To facilitate greater uptake of new knowledge units onto the open-source AOP-wiki platform, a pragmatic approach was recently proposed. This approach involves considering Key Event Relationships (KERs) for individual development through systematic approaches, as they represent essential units of knowledge from which causality can be inferred; from low complexity test data to adverse outcomes in intact organisms. However, more broadly adopted harmonized methodologies for KER development would be desirable. Using the AOP Developer's Handbook as a guide, a KER linking 'decreased androgen receptor (AR) activity' with 'reduced anogenital distance (AGD)' was developed to demonstrate a methodology applicable for future developments of KERs requiring systematic literature retrieval approaches.

[Frontotemporal volumetry to rejuvenate and re-feminize the face]. / Volumétrie frontotemporale pour rajeunir et re-féminiser le visage.

The author became interested in facial volume in the 1990s, during the period when he oversaw the feminization of the facial skeleton to improve the social integration of male transsexual patients. At that time, it was skeletal surgery. Very quickly, these techniques were extended to genetic women who wanted a more feminine face. The study of facial aging allowed the author to define criteria for frontotemporal aging, particularly an evolution with age towards a frontotemporal masculinization. The volumetric frontotemporal correction has thus become an essential element of facial rejuvenation. The evolution then, naturally took place towards the concept of frontotemporal beauty.

Feminization of the Forehead: A Scoping Literature Review and Cohort Study of Transfeminine Patients.

BACKGROUND: Facial feminization may be performed to alleviate gender dysphoria among transfeminine patients. The upper third of the face has several characteristics, including hairline shape and position, brow position, and forehead protrusion, that may confer feminine identity. The purpose of this study is to conduct a scoping literature review of techniques performed for forehead feminization and to additionally study clinical outcomes within an institutional cohort. METHODS: A systematic literature review was conducted to review articles that discussed techniques and clinical outcomes associated with procedures performed for feminization of the upper third of the face. A retrospective review of patients undergoing such procedures by the senior author was then conducted. Variables collected included demographic factors, operative details, and postoperative outcomes such as complications, revisions, and re-operations. RESULTS: Initial review yielded sixty-seven articles. Title and abstract review followed by standardized application of inclusion and exclusion criteria resulted in a total of twenty-two studies for analysis. Priorities of forehead feminization entail frontal bossing reduction, frontonasal angle widening, orbital contouring, brow lifting, and hairline advancement. Eighty-five patients were included for analysis. The majority were of Caucasian race (56%) and had type 3 forehead classification (92%). The average planned setback of the anterior table was 4.12 mm. CONCLUSIONS: The core tenets of the feminization of the forehead lie in the overall creation of a harmonic curvature of the forehead with other facial features. Our multi-pronged analysis presents an updated review of these principles, which may help plastic surgeons in performing procedures to feminize the upper third of the face. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.

Exploring the evolution of facial feminization and masculinization surgery: a bibliometric analysis and visualization study.

BACKGROUND: This study aims to conduct a bibliometric analysis of the current literature related to facial feminization surgery (FFS) and facial masculinization surgery (FMS) to understand the patterns, trends, and evolution of research topics. In addition, it aims to objectively identify the important articles that constitute the primary backbone of the FFS/FMS literature and provide a resource for education and new studies in this emerging field. RESULTS: Using the principles of the Leiden Manifesto, 384 publications from the Web of Science from 1987 to 2023 were analyzed. The analysis included cross-country collaboration, keyword trends, affiliations, co-citation networks, and clustering. The results showed an increasing trend in FFS/FMS publications, with the USA leading in both publications (n = 238) and citations (n = 2420). The most cited journal was the Journal of Plastic and Reconstructive Surgery. The results indicate a high growth rate, with an H-index of 34 and an average citation of 11.41 per article. Co-occurrence analysis revealed evolving keywords such as "forehead" (n = 52) and "quality of life" (n = 44). The timeline view illustrated the terms reflecting current areas of interest such as #patient satisfaction and #gender-affirming care. CONCLUSION: The study reveals the influence of countries, institutions, authors, and emerging trends, supporting the anticipation that FFS/FMS will be a critical field of study in the future. The findings contribute to understanding the global landscape of FFS/FMS research, facilitating informed decision-making for researchers, and clinicians in the field of maxillofacial surgery.