Recent insights into the role of hormones during development and their functional regulation.

Introduction: Hormones play a vital role in development from conception to birth and throughout the human lifespan. These periods are logically divided into fetal development, pre-pubertal growth, puberty, and adulthood. Deviations from standard physiological levels and release patterns of constituent hormones can lead to pathology affecting the normal developmental trajectory. Research is ongoing to better understand the mechanisms of these hormones and how their modulation affects development. Methods: This article focuses on recent developments in understanding the role hormones play in development. We also cover recent discoveries in signaling pathways and hormonal regulation. Results: New and continuing research into functional hormone regulation focuses on sex hormones, gonadotropic hormones, growth hormones, insulin-like growth factor, thyroid hormone, and the interconnectedness of each of these functional axes. Currently, the abundance of work focuses on fertility and correction of sex hormone levels based on an individual's condition and stage in life. Discussion: Continuing research is needed to fully understand the long-term effects of hormone modulation in growth and sexual development. The role of each hormone in parallel endocrine axes should also be more thoroughly investigated to help improve the safety and efficacy in endocrine pharmacotherapeutics.

Masculinizing hormone therapy effect on breast tissue: Changes in estrogen and androgen receptors in transgender female-to-male mastectomies.

PURPOSE: Almost two percent of individuals in the United States identify as gender non-conforming. In the female-to-male (FTM) transgender population, masculinizing hormone therapy with testosterone is commonly prescribed in gender transition. To date, the effects of exogenous androgens on breast tissue and its roles in altering breast cancer risk are poorly understood. This study examines the histopathologic findings in gender affirming mastectomy (GAM) in transgender FTM patients and the effects of exogenous androgens on estrogen receptors (ER) and androgen receptors (AR). METHODS: A retrospective review of pathology specimens obtained between 2017 and 2020 was performed comparing androgen exposed breast tissue with breast tissue without androgen exposure. Breast specimens were obtained from patients who underwent FTM GAM with recorded exogenous androgen exposure. Control breast specimens were obtained from reduction mammoplasty (RM) procedures in cisgender women which were aged matched to the GAM cohort, as well as postmenopausal women with benign/prophylactic mastectomy procedures; all controls were without androgen exposure. The histopathologic findings were assessed. Immunohistochemistry for AR and ER was performed and the score interpreted by digital image analysis. RESULTS: Androgen-exposed breast tissue revealed dense fibrotic stroma, lobular atrophy, thickened lobular basement membranes, and gynecomastoid changes. Longer duration of androgen exposure resulted in a more pronounced effect. The incidence of atypia or cancer was lower in GAM than RM cohort. ER and AR expression was highest in transgender male breast tissue with intermediate duration of exogenous androgen exposure. CONCLUSION: Increased androgen exposure is associated with lobular atrophy and gynecomastoid changes in breast parenchyma. Overall, ER and AR are expressed strongly in lobular epithelium in patients with prolonged androgen exposure. Exogenous testosterone does not appear to increase risk for breast cancer. Additional studies are needed to investigate the mechanism responsible for these changes at a cellular level and its role in cancer development.

Delayed, dramatic breast swelling in a transgender woman: a case report.

Background: As the number of gender-affirming procedures performed in the United States increases, physicians caring for gender-nonconforming patients, regardless of practice location and focus, will likely encounter transgender women with breast implants. Increasingly, transgender women are seeking breast feminization. However, this population is less consistently receiving surveillance and routine breast care than cisgender women. Aim: This report aims to add to the growing body of knowledge addressing breast augmentation complications in transgender women and to highlight disparities in healthcare. Methods: A case of breast implant-associated seroma at our institution was analyzed through chart review. A literature review was conducted using PubMed to gather all articles discussing breast implant-associated fluid collections in transgender patients. Prior to publication of this report, a Waiver of Consent was granted by the E.R.'s Institutional Review Board for the study under which this article was prepared. Results: Our patient was an African American transgender woman presenting initially at age 60 with significant asymmetry due to dramatic swelling of her left breast. The patient underwent bilateral breast augmentation outside of the United States 2 decades prior. The patient noted a gradual painless increase in her left breast size starting 3 years prior. She admitted that she was hesitant to seek a second opinion after being treated dismissively by another surgeon. Subsequent management included mammography and mirrored recommendations for late breast implant-associated seromas in cisgender patients: ultrasound, aspiration for cytology and culture, and removal of the implant and capsule. Outcomes: The fluid collection in our patient was determined to be a chronic hematoma and was managed surgically. Though this patient eventually achieved a good outcome, treatment was delayed due to barriers she faced as a transgender woman. Clinical Implications: Literature demonstrates that recommended management of late-onset breast-implant-associated seroma does not differ based on gender identity; however, transgender and GNC adults are more likely to receive less thorough care than cisgender women. Any patients undergoing breast augmentation with implants should be routinely evaluated for late complications, including seromas, which require prompt attention and methodical evaluation due to their potentially malignant nature. Strengths and Limitations: This article is limited in that it is a single report of breast seroma. It is strengthened by a PubMed review gathering all articles discussing breast-implant-associated fluid collections in transgender patients. Conclusion: We propose better education of physicians on how to care for transgender and gender-diverse patients should help mitigate the neglect and late presentation of such medical conditions in this vulnerable and marginalized population.

Human Breast Organoid Models for Lactation Research.

The human mammary gland is the major organ involved in lactation. In the mammary gland, alveoli secrete milk and myoepithelial cells contract to propel the milk through branched structures called ducts and eventually to the nipple. It is through this process of lactation that infants receive milk, which is essential for proper infant growth and development. The lactation process is comprised of sophisticated interactive networks at the cellular level that are not well understood. Whereas the majority of published mammary gland lactation studies have relied on mouse mammary glands, recent advancements in techniques to study mammary glands enable in vitro reproduction of lactation using human-representative frameworks. Currently, the 3D breast organoid is the state-of-the-art model in human mammary gland research, utilizing induced pluripotent stem cells (iPSCs) or processed patient-derived breast tissues embedded in a special matrix that are then able to grow into complex structures that recapitulate aspects of native human breast tissue. Gaining comprehensive biological insight into the process of lactation through these breast tissue-mimetic 3D models is essential for further studies on lactation-associated human mammary gland diseases, human milk composition, and potential solutions to challenges in maternal milk accessibility. In this short review, the benefits and potential utility of 3D breast organoids in understanding the underlying science of lactation and advancing further human mammary gland studies are discussed.

Gender-affirming microvascular breast reconstruction.

Gender-affirming surgery (GAS), including breast feminization, is requested and performed with increasing frequency. Transgender women may seek chest feminization surgery to address gender dysphoria, and such procedures have been shown to increase psychosocial and sexual well-being. Despite the potential effects of hormone therapy and androgen blockade on breast development, the results of glandular growth in adult transgender women are typically disappointing and are often inadequate to achieve the patient's goals. When evaluating options for breast construction, an implant-based approach meets the needs of most patients. However, patient choice, implant complications, acquired and congenital alterations of chest anatomy and the unique challenges of feminizing a natal male chest occasionally require consideration of other options. We review the few cases of gender-affirming breast reconstruction using autologous tissue published in the literature and summarize the senior author's approach and technique. We also review two cases of autologous chest feminization by the senior author. Ultimately, while implant-based reconstruction should continue to be the default procedure and offered to the majority of patients, several factors need to be considered when determining the optimal approach to breast feminization for a given patient. In patients with congenital or acquired deformities or a variety of factors where a reasonable outcome cannot be achieved with implants, autologous reconstruction should remain an option.

Defining sexual dimorphism in masculinizing chest surgery using 3-dimensional imaging.

There is no consensus on the ideal scar location and inframammary fold (IMF) placement in the gender-affirming double-incision mastectomy technique. Recent advances in imaging technology have facilitated noninvasive investigations into anatomic variability, in many cases, obviating the traditional approach of cadaveric dissection to answer anatomic questions. A better understanding of chest wall sexual dimorphism may allow surgeons who perform gender-affirming procedures to achieve more natural-appearing results. A total of 60 chests were analyzed using either cadaveric dissection (n = 30) or virtual dissection with 3-dimensional (3-D) reconstructions of computed tomography (CT) images (n = 30) using the Vitrea® software. Chest proportions were recorded using each technique, correlating surface anatomy with muscular and bony landmarks. Cadaveric and 3-D radiography chest analysis revealed that natal male chest walls are, on average, wider and longer than natal female chest walls. The pectoralis major muscle dimensions and the location of its insertion were not found to significantly differ between male and female chests. The male nipple-areolar complex (NAC) tended to be narrower in length and width, with a less projecting nipple than the female NAC. Finally, the IMF was found to lie over the interspace between the fifth and sixth rib in both male and female chests. Our findings confirm natal male and female IMF are positioned between the 5th and 6th ribs. This fact affirms the senior author's technique of masculinizing the chest, keeping the masculinized IMF at approximately the same level as the natal female IMF and following the pectoralis major muscle edges to define the resulting scar in a way that differs from previously reported techniques.

Incidence of Cancer and Role of Sentinel Lymph Node Biopsy in BRCA Mutation Carriers Undergoing Prophylactic Mastectomies.

INTRODUCTION: Breast surveillance in patients with BRCA mutations include mammography (MMG) and MRI. Patients may elect to undergo risk-reducing bilateral prophylactic mastectomies (BPM). Sentinel lymph node biopsies (SLNB) are frequently performed and associated with increased morbidity. This study sought to determine the correlation between preoperative imaging and the final pathology and evaluate the role of SLNB in these high-risk patients. METHODS: A prospective database identified BRCA patients who underwent BPM between 2006 and 2022. Imaging, pathology, and operative reports were reviewed. RESULTS: 170 patients with BRCA 1/2 mutations were identified. 162 (95.3%) had imaging within one year of BPM. Of these, 28 (17.3%) patients had a MMG/ultrasound, 53 (32.7%) had an MRI, and 81 (50%) had both; 21/162 (13.0%) patients had abnormal imaging. Bilateral SLNB were performed in 31 (18.2%) patients, of which 7 had abnormal imaging; unilateral SLNB were performed in 4 (2.4%) patients, of which 3 had abnormal imaging. 11/170 (6.4%) patients had a malignancy and only one (9%) of these patients had imaging abnormalities. 1/170 (0.6%) patient had an invasive carcinoma requiring an axillary lymph node dissection (ALND), and 10/170 (5.9%) patients had ductal carcinoma in situ (DCIS). 25/170 (14.7%) had ADH/ALH. Only 7/170 (4.1%) patients had imaging abnormalities and abnormal pathology. All SLNB and ALND performed demonstrated no metastatic disease. DISCUSSION: There is a high rate of discordance between preoperative imaging prior to surgery in BRCA patients undergoing prophylactic mastectomies and final pathology. This study does not support routine SLNB at the time of BPM.

ADMs and synthetic meshes improve implant-based breast reconstruction aesthetics, but at what cost?

Acellular dermal matrices (ADMs) have shown promise for use in reconstructive breast surgery as they improve aesthetic outcomes and decrease capsular contracture rates. However, concerns about their use remain because of the higher cost and complication profile. We report a single institution's implant-based-reconstruction (IBR) experience between 2007 and 2021, including cases performed by 51 plastic surgeons. For each stage of IBR, data on age, comorbidities, type of mesh used, and acute complications were collected. Of 1379 patients who underwent subpectoral IBR, 937 received an ADM or synthetic mesh as part of their reconstruction. 256 patients out of 264 treated with prepectoral IBR received an ADM or mesh. Infection and wound dehiscence rates were highest for patients who underwent prepectoral IBR with ADM. Both subpectoral and prepectoral IBR with ADM were associated with higher rates of infection and wound complications compared to without ADM or mesh, but only the difference among the subpectoral cohort reached statistical significance. Prepectoral IBR with ADM or mesh had the lowest rates of capsular contracture and aesthetic reoperations. Although the use of Vicryl® mesh in subpectoral IBR was associated with a higher risk of capsular contracture and skin flap necrosis compared to reconstruction with ADMs (10.53% versus 3.29%; p < 0.05), Vicryl® was associated with fewer aesthetic revisions. Our study demonstrated that prepectoral IBR with ADM or mesh resulted in the fewest aesthetic reoperations and the lowest rates of capsular contracture. Infection and wound dehiscence rates were notably higher for patients who had reconstruction with ADM.

The molecular consequences of androgen activity in the human breast.

Estrogen and progesterone have been extensively studied in the mammary gland, but the molecular effects of androgen remain largely unexplored. Transgender men are recorded as female at birth but identify as male and may undergo gender-affirming androgen therapy to align their physical characteristics and gender identity. Here we perform single-cell-resolution transcriptome, chromatin, and spatial profiling of breast tissues from transgender men following androgen therapy. We find canonical androgen receptor gene targets are upregulated in cells expressing the androgen receptor and that paracrine signaling likely drives sex-relevant androgenic effects in other cell types. We also observe involution of the epithelium and a spatial reconfiguration of immune, fibroblast, and vascular cells, and identify a gene regulatory network associated with androgen-induced fat loss. This work elucidates the molecular consequences of androgen activity in the human breast at single-cell resolution.

Assessment of Cranial Sexual Dimorphism Using 3D Reconstruction: Implications for Gender-Affirming Surgery.

BACKGROUND: As more centers offer gender-affirming procedures, dissemination of best practices is critical to ensuring quality care. This study is the first to use advanced 3-dimensional visualization software to characterize cranial differences between natal males and females, as they relate to planning for facial gender-affirming operations. MATERIALS AND METHODS: A retrospective analysis was conducted on randomly selected patients with facial computed tomography imaging performed at a single institution between February 2020 and July 2021. Patients with acquired bony deformity on computed tomography or documented history of hormone replacement therapy were excluded. The images were retrieved and analyzed using advanced 3-dimensional visualization software (Vitrea). Independent sample t tests were performed to analyze variation in typically sexually dimorphic facial features between natal males and females. RESULTS: We identified 50 patients (25 natal males and 25 natal females) who met the inclusion criteria. Ages ranged from 19 to 91. Natal males were found to have significantly greater frontosellar distances (difference between means, SEM: 2.7±1.2; P =0.03) and mandible volumes (difference between means, SEM: 14.0±4.2; P =0.002) than natal females. Statistical analysis revealed no significant differences in gonial angle, chin width, nasofrontal angle, or nasolabial angle between natal males and females. CONCLUSION: In this diverse sample of natal males and females, statistical analysis revealed that the sexually dimorphic facial characteristics most relevant to the planning of facial gender-affirming surgery are frontosellar distance and mandible volume. When planning facial gender-affirming surgery, we recommend that these characteristics be considered to achieve optimum results.

Three-Dimensional Video Microscopy: Potential for Improved Ergonomics without Increased Operative Time?

Three-dimensional (3D) video exoscopes are high-magnification stereo cameras that project onto monitors mounted in the operating room, viewable from different angles. Outside of plastic surgery, exoscopes have been shown to successfully improve the ergonomics of microsurgery, though sometimes with prolonged operating times. We compare a single surgeon's early experience performing free flap procedures from 2020 to 2021 using either a binocular microscope or a 3D video exoscope. Ten procedures were performed with the standard operating microscope and 8 procedures with the 3D exoscope. The microsurgeon, having minimal prior experience using an exoscope, reported less neck discomfort following the free flap procedures performed with the exoscope compared with the binocular surgical microscope. Total average operating time was comparable between the standard surgical microscope and the 3D exoscope (13.7 vs. 13.4 hours, p = 0.34). Our early experience using a 3D exoscope in place of a standard optical microscope demonstrated that the exoscope shows promise, offering an ergonomic alternative during microvascular reconstruction without increasing overall operating times. Future studies will compare free flap ischemia time between cases performed using the exoscope and the conventional binocular microscope. Medical Subject Headings authorized following words: free tissue flaps; operating rooms; ergonomics; microsurgery.

Toward Drainless Breast Reconstruction: A Pilot Study.

Implant-based breast reconstruction with immediate tissue expander placement is the predominant form of breast reconstruction in the United States. Closed-suction drains are frequently employed to minimize seroma accumulation, although they carry the risk of serving as a port of entry for bacteria, posing a concern in the presence of implanted materials such as breast implants or acellular dermal matrix. Introduction of a dual-port tissue expander designed to facilitate the collection and removal of seroma fluid provides a new way of performing breast reconstruction without external drains. Methods: We conducted a pilot study using the AlloX2 dual-port expander on five consecutive patients to demonstrate feasibility of this approach at Cedars-Sinai Medical Center by the two senior authors (E.R. and D.K.). Results: Patients averaged seven clinic visits before they were ready for expander exchange, totaling a mean of 137.5 days. Patients averaged 1.9 clinic visits before output was less than 40cm3 (1.6 for right breasts and 2.2 for left breasts), with two of the patients never reaching that output. There was one complication; a single patient had unilateral flap necrosis and implant exposure due to excessively large breasts and thin skin flaps, necessitating expander removal and latissimus flap reconstruction. The other four patients underwent successful implant reconstruction. Conclusions: This pilot study demonstrates the feasibility of breast reconstruction without external drains using a dual-port expander with built-in seroma reservoir. From these results, it is apparent that dual-port tissue expanders with built-in seroma reservoir offer a safe and effective way to perform breast reconstruction without drains in appropriately selected patients. A larger prospective cohort will be needed to definitively demonstrate lower infection and reconstructive failure rates.

Primary Use of the Deep Inferior Epigastric Pedicle for Free-flap Phalloplasty: Rationale, Technique, and Outcomes.

Most free-flap phalloplasty reports describe the femoral artery and great saphenous vein as recipient vessels, with the deep inferior epigastric artery and venae comitantes (DIEA/V) only rarely reported. We review our experience with preferentially using the DIEA/V as recipient vessels in gender-affirming free-flap phalloplasty, with DIEV as primary venous outflow. Methods: We retrospectively reviewed consecutive patients who underwent gender-affirming free-flap phalloplasty at our single institution from June 2017 through June 2021. The DIEA/V was used as recipient vessels, with the DIEA/V pedicle externalized via a passageway made through the external inguinal ring. Results: Thirty-eight consecutive free flaps (26 radial forearm free-flap phalloplasties, 10 anterolateral thigh phalloplasties, and two radial forearm free-flap urethroplasties) were performed. Mean age was 37.3 years; mean BMI was 25.7. Mean follow-up was 17.9 months. All flaps were anastomosed to the DIEA/V, without use of vein grafts. Most flaps (89.5%) had at least two veins anastomosed. To augment outflow, a saphenous vein branch was used in one of 38 (2.6%) cases and other superficial veins were used in two of 38 (5.3%) cases. One of 38 (2.6%) cases (early in our experience) resulted in total flap loss. Conclusions: Advantages of the DIEA/V as free-flap phalloplasty recipient vessels include a short, direct pathway for vessels, excellent donor-recipient vessel size match that allows end-to-end anastomoses, and elimination of risks associated with arterialized interposed veins. When venous outflow appears compromised, we recommend a low threshold to use additional local or saphenous veins, though this is rarely needed given the DIEV's reliability.

Surgical Treatment of Granulomatous Breast Deformities Caused by Injection of Foreign Substances in Transgender Women: A Case Series and Algorithm.

SUMMARY: Despite potentially devastating complications, free foreign substance injections for feminizing breast augmentation remain common among transgender women. To date, the literature regarding surgical treatment of these deformities among transgender women remains limited. The authors present a case series of transgender women presenting for surgical management of granulomatous breast deformities secondary to free foreign substance injections between January of 2016 and February of 2020. Seven transgender women presented for surgical management of complications secondary to free foreign substance injections of the breast. These patients ranged in age from 29 to 53 years, all identified as Hispanic/Latinx, and five were primarily Spanish speakers. All were recipients of public insurance. Six of the seven patients received free foreign substance injections outside of the United States, with an average time from initial injections to presentation of 19.3 ± 15.7 years. Three patients presented with a history of prior revisions by other surgeons. Four underwent staged reconstruction at the authors' institutions. Patients were followed for, on average, 10.7 ± 12.6 months after their initial surgery. There were no major complications. The most common minor complication was delayed wound healing. In the present series, the authors illustrate that, with careful consideration and patient selection, it is possible to perform safe and successful breast reconstruction for the management of foreign substance granulomas in transgender women. They also provide an algorithm based on patient-specific factors to guide treatment decisions in this patient population. Further research is needed to determine the generalizability and applicability of this algorithm. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

'Modified Phallourethroplasty' as a Surgical Alternative to Phalloplasty With Urethral Lengthening: Technique, How We Present This Option to Patients, and Clinical Outcomes.

BACKGROUND: Most complications after masculinizing genital gender-affirming surgery (gGAS) are associated with urethral lengthening (+UL). While many transmasculine patients desire +UL for standing urination, not all patients prioritize this benefit over the significantly increased risk of complications. Currently, phalloplasty without UL (-UL) appears to be seldom offered, and previous -UL techniques create genital anatomy that is visibly different from the anatomy created by phallourethroplasty+UL (P+UL). AIM: To describe a novel surgical technique to create a normal-appearing phallus tip, scrotum, and perineal urethral opening that avoids urethral complications associated with +UL. METHODS: We describe our surgical technique and approach to patient counseling. We report patient satisfaction outcomes from the first cohort of patients to undergo this 'modified phallourethroplasty' (-UL) approach to date. OUTCOMES: Among patients who elected phalloplasty over metoidioplasty, 13/40 (32.5%) patients elected P-UL. Prior to 1/2020, before we standardized how we presented this option to patients, 17.4% elected this option. Of the patients that elected P-UL, 8 have completed first-stage and 7 have completed second-stage surgeries. RESULTS: All patients that have undergone P-UL have expressed satisfaction with body image and urinary function. Among patients asked to rank which of 14 preoperative factors were most important (1 = most important, 14 = least important), having a normal-appearing phallus (mean rank 4.14) and minimizing complications (mean rank 8.14) were ranked more highly than ability to urinate in a standing position (mean rank 9.14). When asked what factors most influenced their choice to have -UL (ranked from 1 to 9), elimination of risks was rated the most important (mean rank 2.71) and expected decrease in risk of needing revision surgery was rated the second most important (mean rank 3.57). CLINICAL IMPLICATIONS: The significant reduction in +UL-related complications decrease morbidity, urgent revision surgeries, and cost to our healthcare system. STRENGTHS AND LIMITATIONS: Strengths include a novel technique that provides a surgical alternative to P+UL that eliminates the majority of phalloplasty related postoperative complications. Limitations include the small number of patients who have completed first and second stage surgery, and short follow up time. CONCLUSION: It is important to understand what factors drive individual patients' choices. Patients considering masculinizing gGAS should be offered both +UL and -UL options. The costs and benefits of each option should be presented objectively and in the context of each patient's unique priorities and needs. Smith SM, Yuan N, Lee G, et al. 'Modified Phallourethroplasty' as a Surgical Alternative to Phalloplasty With Urethral Lengthening: Technique, How We Present This Option to Patients, and Clinical Outcomes. Sex Med 2022;10:100495.

The Coronavirus (COVID-19) Effect on Public Sentiments Regarding Elective Plastic Surgery in the United States.

BACKGROUND: The SARS-CoV-2 coronavirus (COVID-19) has challenged the US's healthcare systems to adapt and innovate on multiple fronts. As the course of the COVID-19 pandemic changes, we explore the US public sentiments on resuming previously postponed elective plastic surgery procedures. METHODS: A prospective national survey of one thousand US adults was conducted to study public perception of elective plastic surgery procedures during the COVID-19 pandemic. Binomial logarithmic multivariable regression modeling was employed to study the response data. RESULTS: Nine hundred seventy-three participants were included in study. The majority (86.6%) believed elective plastic surgery should continue during the COVID-19 pandemic. Most (79.6%) would not delay obtaining plastic surgery more than 6 months. Participants expressed concerns of contracting COVID-19 at elective surgery centers (67.5%) or at hospitals (68.5%). Participants who reside in the Midwest (odds ratio [OR] 2.3, P < 0.05) and participants between the ages of 41 and 60 years old (OR 2.8, P < 0.03) were more likely to resume elective plastic surgery. Participants who had undergone a COVID-19 test (OR 0.13, P < 0.04), contracted the COVID-19 infection (OR 0.26, P < 0.03), or were older than 60 years (OR 0.41, P < 0.02) were less likely to resume elective plastic surgery. CONCLUSION: The majority of the US adult participants (1) agree with resuming elective plastic surgery services, (2) but harbor some concerns of contracting COVID-19 during their procedures, and (3) agree with the majority of safety protocols taken to prevent the spread of COVID-19.

Requirement of mental health referral letters for staged and revision genital gender-affirming surgeries: An unsanctioned barrier to care.

BACKGROUND: The World Professional Association for Transgender Health (WPATH) recommends referral letters from two mental health providers within one year of gender-affirming genital surgery (gGAS) to ensure patient readiness before primary surgeries. Many U.S. health insurance plans will not authorize second- and third-stage surgeries or revision surgeries without two referral letters. Such requirements are not supported by WPATH guidelines. OBJECTIVES: This study investigates insurance requirements for referral letters and their negative impact on care. MATERIALS AND METHODS: We retrospectively reviewed all gGAS cases over a 4-year period at our tertiary care medical center. Referral letter requirements for insurance authorization were documented. The nation's largest insurance companies, including commercial, state-, and federally funded plans, were contacted to confirm requirements. We prospectively recorded time needed to complete insurance authorization for a patient subset. WPATH publications were reviewed. RESULTS: Nearly all reviewed U.S. health insurance plans required annually updated referral letters for each gGAS procedure, including staged and revision surgeries. No updated letters changed clinical management. Referral letter requirements delayed care. WPATH states that letters should not be needed for staged surgeries. Some plans required letters even for initial surgical consultation, a practice not supported by WPATH. DISCUSSION AND CONCLUSION: Insurance companies' requirements for referral letters impede care and contradict WPATH guidelines. We advocate that, at minimum, referral letters should not be required for surgical consultations or for staged or revision surgeries after a patient has already had first-stage primary gGAS. Universal referral letter requirements provide minimal clinical value, delay care, increase costs, and exacerbate gender dysphoria by invalidating gender transition. As with all procedures, surgeons themselves should be responsible for assessing patients' surgical readiness. Significant changes in mental health status or social situation should prompt surgeons to seek reassessment. WPATH recommendations regarding referral letters should be clarified and consolidated into a single document.

Chest Feminization in Male-to-Female Transgender Patients: A Review of Options.

Management of a transgender (TG) woman's gender dysphoria is individualized to address the sources of her distress. This typically involves some combination of psychological therapy, hormone modulation, and surgical intervention. Breast enhancement is the most commonly pursued physical modification in this population. Because hormone manipulation provides disappointing results for most TG women, surgical treatment is frequently required to achieve the goal of a feminine chest. Creating a female breast from natal male chest anatomy poses significant challenges; the sexual dimorphism requires a different approach than that used in cisgender breast augmentation. The options and techniques used continue to evolve as experience in this field grows.

Effects of hormones and hormone therapy on breast tissue in transgender patients: a concise review.

PURPOSE: Hormone replacement therapy (HRT) has become a mainstay medical treatment option for management of gender dysphoria in transgender patients of both biologic sexes. Very little is known about the long-term effects of steroid hormone modulation on breast tissue in this population. Most of the data available on the effects of HRT on breast and reproductive tissues come from studies of postmenopausal cisgender women. Therapeutic regimens are often provider-dependent, and there, are no uniform guidelines in place for cancer surveillance in transgender patients. In this review, we present what forms of hormone therapy and hormone modulation are available to transgender patients, what is known about their effects on male and female breast tissue, and what other endogenous and exogenous factors contribute to the macroscopic and cellular changes observed. METHODS: A search for the existing literature focusing on therapeutic regimens and the effects of HRT on breast tissue provided the most current information available for this review. Recent evidence-based reports (since the year 2000) and reviews were given priority over anecdotal evidence and expert opinions when conflicting information was encountered. Older resources were considered when primary sources were needed. Given the paucity of available articles on this subject, all resources were given careful consideration. RESULTS: Information about the risks associated with HRT in the current literature and in this setting is limited and often conflicting, due to a scarcity of long-term studies tracking breast pathology among transgender men and women. CONCLUSIONS: We conclude that the long-term effects of off-label pharmaceutical use for modulation of hormone levels and sexual characteristics in transgender patients have not been well studied. The tendency of steroid hormones to promote the growth of certain cancers also raises questions about the safety of differing doses and drug combinations. Further clinical and laboratory study is needed to better establish safety and dosing guidelines in transgender patients.