Increasing numbers of transgender and nonbinary youth are now accessing gender-affirming medical interventions, which have been demonstrated to improve health and well-being. This Perspective addresses how the needs of transgender and nonbinary youth, up to age 18, can be addressed through individualized gender-embodiment care. We first review standard medical therapies, including gonadotropin-releasing hormone analogues, 17β-oestradiol, testosterone, steroidal antiandrogens and progestins, followed by presenting novel approaches to individualizing gender healthcare for transgender and nonbinary youth, consisting of selective oestrogen receptor modulators, 5α-reductase inhibitors, aromatase inhibitors and non-steroidal antiandrogens. Ethical guidance for off-label prescribing is provided, grounded in the principles of evidence, benefit, safety, respect, care, communication, transparency, equity and innovation. These ethical principles are applied in three clinical scenarios in which off-label therapies are considered. We conclude that standard medical therapies are ethically justified and that novel therapies can be ethically acceptable when carefully considered in the context of an individual youth's care plan and taking into account the available theoretical, clinical and research evidence as well as the potential benefits and potential risks. In keeping with the principle of innovation, we encourage clinicians and researchers to share evidence of medical innovations that support the gender health of transgender and nonbinary youth.

Primary care providers have reported feeling ill-equipped to care for transgender and gender diverse (TGD) patients because of lack of training, and their treatment of acne has been shown to be variable and not standardized. This is an important practice gap, as TGD youth represent a historically underserved population in medicine, despite data suggesting that up to 9.2% of high school-age adolescents identify as TGD. Although needs and expectations for quality health-care in TGD youth do not necessarily differ from their cisgender peers, TGD adolescents have unique considerations in their care and are at risk for negative social and emotional outcomes secondary to minority stress, discrimination, and rejection by peers and family. Acne is estimated to affect approximately 85% of adolescents and is associated with negative mental health outcomes, including suicidal ideation, low self-esteem, and depression. As such, knowledgeable and culturally informed care of acne in TGD adolescents has important implications for quality of life for patients who desire effective treatment. This review article addresses these practice gaps by summarizing an approach to acne evaluation and management with an emphasis on appropriate regimens for TGD youth, and the unique psychosocial and medical considerations for this population.

There are many FDA-approved drugs for advanced prostate cancer (PC), yet public interest in these drugs is not well understood. We compared public interest and state-level predictors of interest in five common oral adjunctive hormonal therapies.

Google Trends™ was queried for: "Enzalutamide", "Abiraterone Acetate", "Bicalutamide", "Apalutamide", and "Darolutamide" in the United States from January 2004 to November 2022. Data are presented as relative search index (RSI) by month. RSI ranges from 0 to 100 with 100 being peak popularity, 50 being half of the peak popularity, and 0 representing insufficient data to be determined.

Several drugs abruptly increased in popularity following FDA approval including abiraterone, enzalutamide, and apalutamide. All drugs decreased in popularity from January 2020 to July 2020, corresponding with the COVID-19 pandemic. In the most recent 5 years, enzalutamide and abiraterone were the most common searched drugs, with bicalutamide a close 3rd place. States that did not expand Medicaid were significantly more likely to have bicalutamide as the top search drug vs. states that expanded Medicaid (p = 0.012). Across all states with data (n = 39), higher bicalutamide RSIs were significantly associated with lower household income (r = 0.385, p = 0.02) and greater percent of uninsured adults (r = 0.426, p = 0.007). This is the first study using Google Trends to compare advanced PC drugs by search popularity.

Despite the emergence of more effective medications, bicalutamide remains relatively popular, particularly in states with lower household income, more uninsured adults, or those that did not expand Medicaid, possibly due to its lower cost.

Gender-affirming bilateral orchiectomy (GABO) may be completed as either a standalone procedure (sGABO) or at the same time as gender-affirming vaginoplasty (vGABO). GABO is postulated to decrease gender-affirming hormone therapy (GAHT) dosages and reduce gender dysphoria, but these phenomena are not empirically described in the medical literature.

The primary aim of this study was to describe changes in GAHT dosages after sGABO and vGABO. A secondary aim was to assess sGABO patients' preoperative decision-making priorities and postoperative satisfaction.

A retrospective chart review identified 204 patients who completed GABO as either a standalone procedure (64% of patients) or at the same time as vaginoplasty (36%). Patient demographic data, surgical outcomes, and pre- and postoperative GAHT dosage data were recorded. Patients completed an opinion questionnaire to assessed decision-making priorities, as well as postoperative satisfaction and changes in quality-of-life measures.

Primary outcomes included pre- and postoperative dosages of estradiol, progesterone, and spironolactone. Secondary outcomes included sGABO patient priorities, satisfaction with sGABO, changes in quality-of-life measures between sGABO and vGABO patients, and sGABO recommendations to future patients.

The sGABO and vGABO patients experienced a statistically significant dosage reduction in all three GAHT assessed: estradiol, progesterone, and spironolactone (P < .05). All patients discontinued spironolactone postoperatively. Zero complications related to GABO were recorded for patients in either group. The patient questionnaire revealed that sGABO patients prioritize decreasing endogenous testosterone and reducing their GAHT as most important in their decision to undergo sGABO prior to vaginoplasty. A majority of sGABO patients reported improvement in all nine quality-of-life indices. None of the sGABO patients would recommend against sGABO to a friend who is waiting for vaginoplasty.

For patients who are interested in vaginoplasty, sGABO may serve as a more immediate, low-risk, intermediary step that comes with the benefits of GABO, including significant GAHT medication reduction and gender dysphoria relief.

This study offers a comprehensive evaluation of the impact of GABO on patients, combining empirical data with subjective patient feedback. Limitations include the retrospective design and the use of unvalidated survey questions.

Prevaginoplasty GABO is a viable option to more immediately alleviate gender dysphoria and reduce GAHT medications for patients who are interested in gender-affirming vaginoplasty.

Three-dimensional (3D) imaging techniques are promising new tools for measuring breast volume, for example in gender-affirming therapy. Transgender individuals can be treated with gender-affirming hormone therapy (GAHT). A robust method for monitoring breast volume changes is critical to be able to study the effects of feminizing GAHT. The primary aim of this study was to compare the accuracy of three 3D devices (Vectra XT, Artec LEO and iPhone XR) for measuring modest breast volume differences using a mannequin. The secondary aim of this study was to evaluate these methods in several performance domains. We used reference prostheses of increasing volumes and compared the volumes using GOM-inspect software. For Vectra XT 3D images, manufacturer-provided software was used to calculate volumes as well. The scanning methods were ranked based on their performance in a total of five categories: volume estimations, costs, user-friendliness, test subject-friendliness and technical aspects. The 3D models analyzed with GOM-inspect showed relative mean estimate differences from the actual volumes of 9.1% for the Vectra XT, 7.3% for the Artec LEO and 14% for the iPhone XR. For the Vectra XT models analyzed with the built-in software this was 6.2%. Root mean squared errors (RMSE) calculated based on the GOM-inspect volume analyses showed mean RMSEs of 2.27, 2.54 and 8.93 for the Vectra XT, Artec LEO and iPhone XR, respectively. The Vectra software had a mean RMSE of 3.00. In the combined performance ranking, the Vectra XT had the most favorable ranking, followed by the Artec LEO and the iPhone XR. The Vectra XT and Artec LEO are the preferred scanners to monitor breast development due to the combination of higher accuracy and overall performance. The current study shows that 3D techniques can be used to adequately measure modest breast volume differences and therefore will be useful to study for example breast changes in transgender individuals using feminizing GAHT. These observations may also be relevant in other fields of 3D imaging research.

Gender-affirming hormone therapy (GAHT) is a common medical intervention sought by transgender and gender diverse (TGD) individuals. Initiating GAHT in accordance with clinical guideline recommendations ensures delivery of high-quality care. However, no prior studies have examined how current GAHT initiation compares to recommended GAHT initiation.

This study assessed guideline concordance around feminizing and masculinizing GAHT initiation in the Veterans Health Administration (VHA).

The sample included 4,676 veterans with a gender identity disorder diagnosis who initiated feminizing (n=3,547) and masculinizing (n=1,129) GAHT between 2007 and 2018 in VHA. Demographics and health conditions on veterans receiving feminizing and masculinizing GAHT were assessed. Proportion of guideline concordant veterans on six VHA guidelines on feminizing and masculinizing GAHT initiation were determined.

Compared to veterans receiving masculinizing GAHT, a higher proportion of veterans receiving feminizing GAHT were older (≥60 years: 23.7% vs. 6.3%), White non-Hispanic (83.5% vs. 57.6%), and had a higher number of comorbidities (≥7: 14.0% vs. 10.6%). A higher proportion of veterans receiving masculinizing GAHT were Black non-Hispanic (21.5% vs. 3.5%), had posttraumatic stress disorder (43.0% vs. 33.9%) and positive military sexual trauma (33.5% vs.16.8%; all p-values<0.001) than veterans receiving feminizing GAHT. Among veterans who started feminizing GAHT with estrogen, 97.0% were guideline concordant due to no documentation of contraindication, including venous thromboembolism, breast cancer, stroke, or myocardial infarction. Among veterans who started spironolactone as part of feminizing GAHT, 98.1% were guideline concordant as they had no documentation of contraindication, including hyperkalemia or acute renal failure. Among veterans starting masculinizing GAHT, 90.1% were guideline concordant due to no documentation of contraindications, such as breast or prostate cancer. Hematocrit had been measured in 91.8% of veterans before initiating masculinizing GAHT, with 96.5% not having an elevated hematocrit (>50%) prior to starting masculinizing GAHT. Among veterans initiating feminizing and masculinizing GAHT, 91.2% had documentation of a gender identity disorder diagnosis prior to GAHT initiation.

We observed high concordance between current GAHT initiation practices in VHA and guidelines, particularly for feminizing GAHT. Findings suggest that VHA clinicians are initiating feminizing GAHT in concordance with clinical guidelines. Future work should assess guideline concordance on monitoring and management of GAHT in VHA.

•The risk of venous thromboembolism (VTE) is not increased in women using long-acting reversible contraceptive methods (LARCs) with progestogens. •Oral contraceptives with levonorgestrel or norgestimate confer half the risk of VTE compared to oral contraceptives containing desogestrel, gestodene or drospirenone. •Progestogen-only pills do not confer an increased risk of VTE. •Women using transdermal contraceptive patches and combined oral contraceptives (COCs) are at an approximately eight times greater risk of VTE than non-users of hormonal contraceptives (HCs), corresponding to 9.7 events per 10,000 women/years. •Vaginal rings increase the risk of VTE by 6.5 times compared to not using HC, corresponding to 7.8 events per 10,000 women/years. •Several studies have demonstrated an increased risk of VTE in transgender individuals receiving hormone therapy (HT). •Hormone therapy during menopause increases the risk of VTE by approximately two times, and this risk is increased by obesity, thrombophilia, age over 60 years, surgery and immobilization. •The route of estrogen administration, the dosage and type of progestogen associated with estrogen may affect the risk of VTE in the climacteric. •Combined estrogen-progesterone therapy increases the risk of VTE compared to estrogen monotherapy. •Postmenopausal HT increases the risk of thrombosis at atypical sites.

Androgen receptor (AR) plays a crucial role in various physiological processes. Dysregulation of AR signaling has been implicated in several diseases, such as prostate cancer and androgenetic alopecia. Therefore, the development of drugs that specifically target AR has gained significant attention in the field of drug discovery. This review provides an overview of the synthetic routes of clinically approved small molecule drugs targeting AR and discusses the clinical applications of these drugs in the treatment of AR-related diseases. The review also highlights the challenges and future perspectives in this field, including the need for improved drug design and the exploration of novel therapeutic targets. Through an integrated analysis of the therapeutic applications, synthetic methodologies, and mechanisms of action associated with these approved drugs, this review facilitates a holistic understanding of the versatile roles and therapeutic potential of AR-targeted interventions. Overall, this comprehensive review serves as a valuable resource for medicinal chemists interested in the development of small-molecule drugs targeting AR.

In 2011, the Veterans Health Administration (VHA) established a policy for the delivery of transition-related services, including gender-affirming hormone therapy (GAHT), for transgender and gender diverse (TGD) patients. In the decade since this policy's implementation, limited research has investigated barriers and facilitators of VHA's provision of this evidence-based therapy that can improve life satisfaction among TGD patients.

This study provides a qualitative summary of barriers and facilitators to GAHT at the individual (e.g., knowledge, coping mechanisms), interpersonal (e.g., interactions with other individuals or groups), and structural (e.g., gender norms, policies) levels.

Transgender and gender diverse patients (n = 30) and VHA healthcare providers (n = 22) completed semi-structured, in-depth interviews in 2019 regarding barriers and facilitators to GAHT access and recommendations for overcoming perceived barriers. Two analysts used content analysis to code and analyze transcribed interview data and employed the Sexual and Gender Minority Health Disparities Research Framework to organize themes into multiple levels.

Facilitators included having GAHT offered through primary care or TGD specialty clinics and knowledgeable providers, with patients adding supportive social networks and self-advocacy. Several barriers were identified, including a lack of providers trained or willing to prescribe GAHT, patient dissatisfaction with prescribing practices, and anticipated or enacted stigma. To overcome barriers, participants recommended increasing provider capacity, providing opportunities for continual education, and enhancing communication around VHA policy and training.

Multi-level system improvements within and outside the VHA are needed to ensure equitable and efficient access to GAHT.

Hormonal replacement therapy (HRT) is used for symptomatic treatment of menopause. Some evidence suggests a proconvulsant effect of estrogen and an anticonvulsant role of progesterone. Thus, the use of exogenous sex steroid hormones might influence the course of epilepsy in peri- and postmenopausal women with epilepsy (WWE). We conducted a systematic review on the impact of HRT on the frequency of seizures of WWE.

PubMed and Scopus were searched for articles published from inception until August 2022. Abstracts from the past 5 years from the European Academy of Neurology and European Epilepsy Congresses were also reviewed. Article reference lists were screened, and relevant articles were retrieved for consultation. Interventional and observational studies on WWE and animal models of estrogen deficiency were included. Critical appraisal was performed using the revised Cochrane risk-of-bias tool for randomized trials and ROBINS-E tool.

Of 497 articles screened, 13 studies were included, including three human studies. One cross-sectional study showed a decrease in seizure frequency in WWE using combined HRT, a case-control study showed an increase in comparison with controls, and a randomized clinical trial found a dose-dependent increase in seizure frequency in women with focal epilepsy taking combined HRT. Ten studies addressing the impact of HRT in rat models were also included, which showed conflicting results.

There is scarce evidence of the impact of HRT in WWE. Further studies should evaluate the harmful potential, and prospective registries are needed for monitoring this population.

Estrogen therapy is associated with an increased risk of venous thromboembolism (VTE). A large proportion of transfeminine patients use estrogen therapy before undergoing gender-affirming surgery. Many surgeons implement the discontinuation of hormone therapy before surgery. This study sought to evaluate the perioperative risk of VTE in transfeminine patients undergoing the procedure of facial feminization.

Retrospective chart reviews were performed of all patients who underwent facial feminization by a single surgeon at an urban academic institution from 2014 to 2020. Patient characteristics including comorbidities, Caprini score, VTE chemoprophylaxis, and perioperative hormone therapy management were reviewed. The incidences of VTE during perioperative hospital stay and within 1 week and 6 months after the surgical procedure were examined.

There were 296 facial feminization procedures performed on 282 distinct patients who met criteria for inclusion in the study. Hormone therapy was prescribed to 83.6% of patients, 69.5% of whom reported that they held these medications before the procedure. Of those holding, 84.1% of patients reported they discontinued these medications between 2 and 4 weeks. No patients received VTE chemoprophylaxis. There were 0 VTE incidents during the patients' perioperative period up to 6 months postprocedure.

Our findings support that transfeminine patients who use estrogen hormone therapy are at a minimal risk to experience VTE when undergoing facial feminization procedures. Future directions include evaluating the psychologic effect of discontinuing hormone therapy to help guide perioperative decision making.

Literature focused on cancer screening and management is lacking in the transgender population.

To action to increase contributions to the scientific literature that drives the creation of cancer screening and management protocols for transgender and gender nonconforming (TGNC) patients.

We performed a systematic search of PubMed on January 5th, 2022, with the following terms: "TGNC", OR "transgender", OR "gender non-conforming", OR "gender nonbinary" AND "cancer screening", AND "breast cancer", AND "cervical cancer", AND "uterine cancer", AND "ovarian cancer", AND "prostate cancer", AND "testicular cancer", AND "surveillance", AND "follow-up", AND "management". 70 unique publications were used. The findings are discussed under "Screening" and "Management" categories.

Screening: Current cancer screening recommendations default to cis-gender protocols. However, long-term gender-affirming hormone therapy and loss to follow-up from the gender-specific specialties contribute to a higher risk for cancer development and possible delayed detection. The only known screening guidelines made specifically for this population are from the American College of Radiology for breast cancer. Management: Prior to undergoing Gender Affirmation Surgery (GAS), discussion should address cancer screening and management in the organs remaining in situ. Cancer treatment in this population requires consideration for chemotherapy, radiation, surgery and/or reconstruction. Modification of hormone therapy is decided on a case-by-case basis. The use of prophylactic vs aesthetic techniques in surgery is still debated.

When assessing transgender individuals for GAS, a discussion on the future oncologic risk of the sex-specific organs remaining in situ is essential. Cancer management in this population requires a multidisciplinary approach while the care should be highly individualized with considerations to social, medical, surgical and gender affirming surgery related specifications. Special considerations have to be made during planning for GAS as surgery will alter the anatomy and may render the organ difficult to sample for screening purposes. A discussion with the patient regarding the oncologic risk of remaining organs is imperative prior to GAS. Other special considerations to screening such as the conscious or unconscious will to unassociated with their remaining organs is also a key point to address. We currently lack high quality studies pertinent to the cancer topic in the gender affirmation literature. Further research is required to ensure more comprehensive and individualized care for this population.

Gender-affirming hormone therapy guidelines describe the estradiol (E2) doses for intramuscular (IM), but not subcutaneous (SC), routes. The objective was to compare the SC and IM E2 doses and hormone levels in transgender and gender diverse individuals.

This is a retrospective cohort study at a single-site tertiary care referral center. Patients were transgender and gender diverse individuals who received injectable E2 with at least 2 E2 measurements. The main outcomes were the dose and serum hormone levels between the SC and IM routes.

There were no statistically significant differences in age, body mass index, or antiandrogen use between patients on SC (n = 74) and those on IM (n = 56). The weekly doses of SC E2, 3.75 mg (IQR, 3-4 mg), were statistically significantly lower than those of IM E2, 4 mg (IQR, 3-5.15 mg) (P =.005); however, the E2 levels achieved were not significantly different (P =.69), and the testosterone levels were in the cisgender female range and not significantly different between routes (P =.92). Subgroup analysis demonstrated significantly higher doses in the IM group when the E2 and testosterone levels were >100 pg/mL and <50 ng/dL, respectively, with the presence of the gonads or use of antiandrogens. Multiple regression analysis demonstrated that the dose was significantly associated with the E2 levels after adjusting for injection route, body mass index, antiandrogen use, and gonadectomy status.

Both the SC and IM E2 achieve therapeutic E2 levels without a significant difference in the dose (3.75 vs 4 mg). SC may achieve therapeutic levels at lower doses than IM .

Gender Medicine is rapidly emerging as a branch of medicine that studies how many diseases common to men and women differ in terms of prevention, clinical manifestations, diagnostic-therapeutic approach, prognosis, and psychological and social impact. Nowadays, the presentation and identification of many pathological conditions pose unique diagnostic challenges. However, women have always been paradoxically underestimated in epidemiological studies, drug trials, as well as clinical trials, so many clinical conditions affecting the female population are often underestimated and/or delayed and may result in inadequate clinical management. Knowing and valuing these differences in healthcare, thus taking into account individual variability, will make it possible to ensure that each individual receives the best care through the personalization of therapies, the guarantee of diagnostic-therapeutic pathways declined according to gender, as well as through the promotion of gender-specific prevention initiatives. This article aims to assess potential gender differences in clinical-radiological practice extracted from the literature and their impact on health and healthcare. Indeed, in this context, radiomics and radiogenomics are rapidly emerging as new frontiers of imaging in precision medicine. The development of clinical practice support tools supported by artificial intelligence allows through quantitative analysis to characterize tissues noninvasively with the ultimate goal of extracting directly from images indications of disease aggressiveness, prognosis, and therapeutic response. The integration of quantitative data with gene expression and patient clinical data, with the help of structured reporting as well, will in the near future give rise to decision support models for clinical practice that will hopefully improve diagnostic accuracy and prognostic power as well as ensure a more advanced level of precision medicine.

There is a recognized need for evidence to inform breast cancer screening guidelines and services for transgender people, who face barriers to accessing appropriate and inclusive health care.

This review summarized evidence for breast cancer risk and screening guidelines in transgender individuals, including the potential impact of gender-affirming hormone therapy (GAHT); factors that may influence screening decision-making and behaviors; and considerations for providing culturally safe, high-quality screening services.

A protocol was developed based on the Joanna Briggs Institute scoping review methodology. Searches were performed in Medline, Emcare, Embase, Scopus, and the Cochrane Library for articles reporting information on the provision of culturally safe, high-quality breast cancer screening services for transgender people.

We identified 57 sources for inclusion: 13 cross-sectional studies, 6 case reports, 2 case series, 28 review or opinion articles, 6 systematic reviews, 1 qualitative study, and 1 book chapter. Evidence on rates of breast cancer screening among transgender people and the association between GAHT and breast cancer risk was inconclusive. Factors negatively associated with cancer screening behaviors included socioeconomic barriers, stigma, and lack of health provider awareness of transgender health issues. Breast cancer screening recommendations varied and were generally based on expert opinion due to the lack of clear evidence. Considerations for providing culturally safe care to transgender people were identified and mapped to the areas of workplace policies and procedures, patient information, clinic environment, professional conduct, communication, and knowledge and competency.

Screening recommendations for transgender individuals are complicated by the lack of robust epidemiological data and clear understanding of the role GAHT may play in breast cancer pathogenesis. Guidelines have been developed based on expert opinion and are subsequently not uniform or evidence based. Further work is required to clarify and consolidate recommendations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can produce a wide range of clinical manifestations from asymptomatic to life-threatening. Various researchers have worked to elucidate the pathogenic mechanisms underlying these variable presentations. Differences in individual responses to systemic inflammation and coagulopathy appear to be modulated by several factors, including sex steroid hormones. Transgender men or non-binary individuals who undergo gender-affirming hormone therapy (GAHT) are a unique population of interest for exploring the androgen-mediated coronavirus disease 2019 (COVID-19) hypothesis. As the search for reliable and effective COVID-19 treatments continues, understanding the risks and benefits of GAHT may mitigate COVID-19 related morbidity and mortality in this patient population.

To investigate the potential role of GAHT in the development of COVID-19 infections and complications.

This systematic review implemented an algorithmic approach using PRISMA guidelines. PubMed, Scopus, Google Scholar top 100 results, and archives of Plastic and Reconstructive Surgery was on January 12, 2022 using the key words "gender" AND "hormone" AND "therapy" AND "COVID-19" as well as associated terms. Non-English articles, articles published prior to 2019 (prior to COVID-19), and manuscripts in the form of reviews, commentaries, or letters were excluded. References of the selected publications were screened as well.

The database search resulted in the final inclusion of 14 studies related to GAHT COVID-19. Of the included studies, only two studies directly involved and reported on COVID-19 in transgender patients. Several clinical trials looked at the relationship between testosterone, estrogen, and progesterone in COVID-19 infected cis-gender men and women. It has been proposed that androgens may facilitate initial COVID-19 infection, however, once this occurs, testosterone may have a protective effect. Multiple clinical studies have shown that low baseline testosterone levels in men with COVID-19 are associated with worsening outcomes. The role of female sex hormones, including estrogen and progesterone have also been proposed as potential protective factors in COVID-19 infection. This was exemplified in multiple studies investigating different outcomes in pre- and post-menopausal women as well as those taking hormone replacement therapy. Two studies related specifically to transgender patients and GAHT found that estrogen and progesterone could help protect men against COVID-19, and that testosterone hormone therapy may increase the risk of contracting COVID-19.

Few studies were found related to the role of GAHT in COVID-19 infections. Additional research is necessary to enhance our understanding of this relationship and provide better care for transgender patients.

To assess the incidence of hyperkalemia in transgender women using spironolactone.

This was a retrospective chart review of transgender women who received gender-affirming hormone therapy that included spironolactone between January 2000 and September 2018. Forty-four participants who had paired potassium concentrations documented and were on spironolactone were included and analyzed. Study outcomes included the incidence of hyperkalemia (serum potassium concentrations > 5.0 mmol/L), the relationship between the duration of treatment and degree of hyperkalemia, and difference between serum potassium concentrations at the beginning of spironolactone treatment versus last serum potassium concentrations.

The median age of the participants was 36.5 years. The cohort was predominantly non-Hispanic White (32/44). No serum potassium concentration was >5.5 mmol/L, and all participants had serum creatinine level of <2 mg/dL. Median duration of treatment was 25 months (range 2-92 months) and 140 potassium measurements were available. The mean potassium concentration (3.87 mmol/L) before the initiation of spironolactone was lower than the mean potassium concentration (4.03 mmol/L) while on spironolactone (mean difference, 0.16 mmol/L, P = .013). The regression β, that is, the average change in potassium concentration per 1 additional month of treatment duration, was -.001 (95% CI [-.004, .001]; P = .255) signifying no relation between treatment duration and spironolactone use.

No participant had laboratory evidence of significant hyperkalemia (K > 5.5 mmol/L) after initiation of spironolactone. Frequent measurement of potassium concentrations might be unnecessary in transgender women taking spironolactone in patients with serum creatinine levels of <2 mg/dL.

Obstetrician-gynecologists (OBGYNs) are often involved in caring for transgender patients but may not be equipped with knowledge about transgender-specific care. The aim of this study was to assess the knowledge base and comfort level of OBGYNs in Hawai'i with regard to health care for transgender people. This was a cross-sectional survey of OBGYNs in the American College of Obstetricians and Gynecologists (ACOG) Hawai'i section. The survey was distributed in-person and electronically to a listserv of OBGYNs between October 2017 and August 2018. This survey assessed practice environment, experience with transgender care, and knowledge of health care needs and recommendations for transgender patients. The response rate to this survey was 28%. Approximately half of respondents worked within the University of Hawai'i system and 47% were private practitioners. A majority (79%) of the respondents had unisex restroom facilities in their offices; however, only a fifth of respondents had gender-inclusive intake forms. Respondents were more comfortable providing care for trans men, people who were assigned female sex at birth but identify as male, compared to trans women, people who were assigned male sex at birth but identify as female (53% vs 38%). Knowledge of preventive care was variable. Most respondents had limited knowledge regarding gender-affirming hormone therapy and requirements for gender affirming surgery (67% and 52% respectively). Despite their limited experience, OBGYNs in Hawai'i demonstrated a willingness to provide care for transgender patients. Efforts should be made to educate OBGYNs on quality care for transgender people, particularly gender affirming hormone therapy.

Cardiovascular risk could be increased in transgender persons, but the mechanism is undetermined.

The aim of this study was to assess the risk of cardiovascular outcomes in Danish transgender persons compared to controls.

The study design was a historical register-based cohort study in Danish transgenders and age-matched controls. The main outcome measure was cardiovascular diagnosis (any CVD) including medicine prescriptions for CVD during 2000-2018. The transgender cohort (n = 2671) included persons with International Classification of Diseases-10 diagnosis code of 'gender identity disorder' (n = 1583) and persons with legal sex change (n = 1088), 1270 were assigned female at birth (AFAB) and 1401 were assigned male at birth (AMAB). Controls (n = 26 710) were matched by age (n = 5 controls of same and n = 5 controls of other birth sex) of the respective transgender.

The median (interquartile range) age at study inclusion was 22 (18; 29) years for AFAB and 26 (21; 39) years for AMAB. The mean (s.d.) follow-up time was 4.5 (4.2) years for AFAB and 5.7 (4.8) years for AMAB. The hazard ratio (HR) for any CVD was significantly higher in transgenders vs controls of same and other birth sex, with highest adjusted HR in transgenders AFAB vs control men: 2.20 (95% CI: 1.64;2.95), P < 0.001. Gender-affirming hormone treatment (GAHT) explained part of elevated risk of CVD in transgenders AFAB, whereas GAHT did not contribute to the elevated risk of CVD in transgenders AMAB.

The risk of cardiovascular diagnosis was increased in transgenders. The mechanism should be further investigated.

Despite receiving Gender-Affirming Hormone Therapy or Gender-Affirming Surgery, which may adversely impact their fertility, people with Gender Dysphoria (GD) may desire to form families. In this study, we aimed to quantitatively display fertility desire from the perspective of these individuals, despite all the legal challenges they face. The single center, cross-sectional comparative study included individuals with GD and cisgender volunteers. A Sociodemographic Data Form, the Fertility Desire Data Form, the Childbearing Motivations Scale and the Fertility Desire Scale were used. Of the 414 participants, 171 were individuals with GD (110 FtM; 61 MtF) and 243 were cisgender volunteers (142 cis-males; 101 cis-females). While 22% of the people with GD stated that they had regrets about not undergoing fertility preservation, 16% stated that they would like this process if it were legal. People with GD, particularly MtF, want to have children more than cisgenders. Moreover, people with MtF exhibited less negative motivations toward becoming parents, despite having reservations regarding the socioeconomic aspect of parenthood. Our findings indicate that fertility desire in people with GD is not less in comparison to cisgender people. Healthcare professionals should not forget to offer fertility preservation options as part of clinical practice before Gender-Affirming Therapy.

To characterize patient preferences regarding gender-affirming hormone therapy (HT) providers and telemedicine use.

Between May and October 2019, a survey was administered to adult patients attending a tertiary medical center's HT clinic. The survey included questions on demographics, barriers to care, and preferences for HT follow-up care. Interest in telemedicine was measured using a Likert scale. Multivariable logistic regression was used to identify patient factors associated with interest in telemedicine.

Among 111 patients, 63.1% (n=70) preferred an in-person visit with a specialist and 21.6% (n=24) preferred a video visit with their specialist. While only 15.3% (n=17) preferred follow-up with a primary care provider (PCP), 71.0% (n=80) felt comfortable transitioning future care to a PCP. Notably, 52.3% (n=58) of patients were interested in a telemedicine visit. Factors associated with interest in telemedicine included identifying as a transgender man (aOR 3.94, 95% CI [1.24-12.53], p=0.02), minority race/ethnicity (aOR 6.71, 95% CI [1.79-25.17], p=0.005), no need to travel (aOR 3.34, 95% CI [1.14-9.85], p=0.03), no concerns about video visits (aOR 14.66, 95% CI [4.34-49.56], p<0.0001), and concern about their PCP offering a broad range of gender services (aOR 8.63, 95% CI [2.41-29.67], p=0.0006).

Patients presenting for HT follow-up prefer continued care with a specialist. However, patients were willing to transition care to PCPs and were interested in telemedicine before the COVID-19 pandemic.

Infertility affects 15% of men and contributes to nearly half of all cases of infertility. Infertile men usually have impaired spermatogenesis, presenting as azoospermia or various degrees of asthenospermia and oligozoospermia. Spermatogenesis is a complex and coordinated process, which is under precise modulation by the hypothalamic-pituitary-gonadal (HPG) axis. An aberrant hormone profile, especially an imbalance between testosterone (T) and estradiol (E2), plays an essential role in male infertility. In the male, E2 is produced mainly from the conversion of T by the aromatase enzyme. Theoretically, reducing an abnormally elevated T:E2 ratio using aromatase inhibitors (AIs) could restore the balance between T and E2 and optimize the HPG axis to support spermatogenesis. For decades, AIs have been used to treat male infertility empirically. However, owing to the lack of large-scale randomized controlled studies and basic research, the treatment efficacy and safety of AIs in male infertility remain controversial. Therefore, there is a need to summarize the clinical trials and relevant basic research on the application of AIs in the treatment of male infertility.

In this narrative review, we summarized the application of AIs in the treatment of male infertility, including the pharmacological mechanisms involved, clinical trials focused on patients with different types of infertility, factors affecting treatment efficacy and the side-effects.

A literature search was performed using MEDLINE/PubMed and EMBASE, focusing on publications in the past four decades concerning the use of AIs for treating male infertility. The search terms included AI, male infertility, letrozole, anastrozole, testolactone, azoospermia, oligozoospermia, aromatase polymorphisms, obesity and antiestrogens, in various combinations.

Clinical studies demonstrate that AIs, especially nonsteroidal letrozole and anastrozole, could significantly inhibit the production of E2 and its negative feedback on the HPG axis, resulting in increased T and FSH production as well as improved semen parameters in infertile men. Large-scale surveys suggest that obesity may result in symptoms of hypogonadism in both fertile and infertile males, such as decreased semen quality and attenuated sexual function, which can be improved by AIs treatment. Polymorphisms of the aromatase gene CYP19A1, including single nucleotide polymorphisms and tetranucleotide TTTA repeats polymorphism (TTTAn), also influence hormone profiles, semen quality and treatment efficacy of AIs in male hypogonadotropic hypogonadism and infertility. The side-effects of AIs in treating male infertility are various, but most are mild and well tolerated.

The application of AIs in treating male infertility has been off-label and empirical for decades. This narrative review has summarized the target patients, dose, treatment duration and side-effects of AIs. Polymorphisms of CYP19A1 that may affect AIs treatment efficacy were also summarized, but a full understanding of the mechanisms involved in AIs action requires further study.

Based on the possible effects of androgens on the course of COVID-19, it can be posited that Gender-Affirming Hormone Therapy (GAHT) may affect the course of the disease in people with GD. We aimed to investigate the relationship between GAHT and contracting COVID-19, as well as the severity of the disease in individuals with Gender Dysphoria (GD). The single center, cross-sectional, web-based survey was completed by people with GD who received GAHT. The questionnaire contained three parts: a sociodemographic data form; a GAHT data form; a COVID-19-related data form. Of the 238 participants, 179 were individuals with female-to-male (FtM) and 59 male-to-female (MtF) GD. We detected that the risk of contracting COVID-19 increased 3.46 times in people with FtM GD, who had received testosterone therapy, in comparison to people with MtF GD, who received estrogen and anti-androgen therapy. Additionally, people with FtM GD who contracted COVID-19 had received longer testosterone therapy when compared to those who did not contract COVID-19. Our findings indicate that individuals with FtM GD who receive testosterone treatment within the scope of GAHT are at higher risk of contracting COVID-19 and that the clinicians who follow-up on GAHT should be more careful about this issue.

In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

The case of a transgender female who developed gallstone pancreatitis in the context of estrogen use for gender-affirming hormone therapy is reported.

A 24-year-old Caucasian transgender female presented to the emergency department for abdominal pain and vomiting after referral from urgent care for suspected pancreatitis. Her home medications included estradiol, medroxyprogesterone, and spironolactone for gender-affirming hormone therapy and omeprazole for reflux. The patient reported minimal alcohol intake, presented with mildly elevated triglyceride levels, and did not have a family history of pancreatitis or gallstone disease. She underwent a laparoscopic cholecystectomy on hospital day 4 and was given a postoperative diagnosis of chronic cholecystitis, cholelithiasis, and pancreatitis. Given her history and the present illness, the use of estrogen therapy is a likely risk factor for the development of gallstone pancreatitis.

Estrogen is a cornerstone of gender-affirming hormone therapy used by transgender women; however, in addition to its role in gender identity confirmation, estrogen can result in drug-induced pancreatitis.

The purpose of this review is to provide an up-to-date overview of gender-affirming hormone therapy, including the various hormone regimens available, the efficacy and potential risks of these treatments, and considerations for surveillance and long-term care.

Recent studies reaffirm that hormone therapy has positive physical and psychological effects for many transgender individuals. The overall risks of treatment are low. Transgender women may have an increased risk of venous thromboembolism and breast cancer based on recent cohort studies, but these findings have yet to be confirmed with randomized controlled trials. Important long-term considerations include metabolic, cardiovascular, and skeletal health.

High-quality, long-term studies on the effectiveness and safety of various gender-affirming hormone treatment regimens are lacking, but the currently available evidence suggests that it is overall safe and effective with appropriate oversight.

To provide an overview of the current state of knowledge of fertility risks of gender-affirming therapy, review fertility preservation options for transgender individuals and ways to minimize gender dysphoria during fertility treatment, and identify gaps in knowledge.

Recent studies have corroborated older data that gender-affirming hormone therapy creates histopathological changes in the gonads; however, the newer data suggests that some function of the gametes may be preserved. One study in transgender men reported successful in-vitro maturation of testosterone-exposed oocytes with normal spindle structures, and recent studies in transgender women reveal early spermatogenesis in estradiol-exposed testes and some recovery of semen parameters following cessation of hormones. Particular attention has recently been given to fertility preservation in transgender adolescents, revealing unmet informational needs in this population and very few are actually pursuing fertility preservation, even with counseling.

There is currently a paucity of data on the fertility effects of gender-affirming hormones, necessitating fertility preservation counseling prior to initiation of therapy. Several modifications can be made to fertility preservation protocols and procedures to decrease gender dysphoria or distress in transgender individuals, but outcome data is still lacking. Achieving high-quality data collection will likely require cooperation across multiple institutions.

This review discusses established transgender individuals on hormones who have reached their desired post-pubertal phenotype. Current guidelines have not clearly integrated specific considerations for the older population. This review focuses on changes in physiology with age, recommended maintenance therapy and safety evaluation to mitigate the risks of hormone therapy with a focus on the older population.