Impact of gender-affirming hormone therapy on the development of COVID-19 infections and associated complications:A systematic review

BACKGROUND 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.AIM To investigate the potential role of GAHT in the development of COVID-19 infections and complications.METHODS 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.RESULTS 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.CONCLUSION 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.

Weight stigma mitigating approaches to gender-affirming genital surgery

The use of body mass index(BMI)to determine eligibility for gender-affirming surgery in transgender and nonbinary individuals has been contested.While BMI thresholds are often meant to be protective,restricting patients from access to surgery can also cause harm.There is a rationale for the continued use of BMI,but the inherent problems with it must also be recognized,including how weight stigma impacts patients’access to gender-affirming surgery and influences clinical care.This article uses a narrative review of current literature to discuss how high BMI affects surgical outcomes in gender-affirming genital surgeries,as well as analogous procedures,existing de facto BMI thresholds,and how to both minimize the harms of proceeding with surgery in patients with a high BMI or the harms of delaying for weight loss.BMI factors into surgical decision-making based on the existing literature,which demonstrates that high BMI is associated with increased surgical risk,including higher incidences of surgical site infections and poor wound healing,as well as the possibility of free flap complications,which are a component of certain genital procedures.This patient population is at higher risk for eating disorders,and it is prudent to find alternatives to requiring patient self-monitored weight management.The impacts of weight stigma should be considered when treating gender-affirming surgery patients,and further data and research are needed to augment shared decision-making and lead to practice change.

Serum estradiol levels decrease after oophorectomy in transmasculine individuals on testosterone therapy

Transmasculine individuals,considering whether to undergo total hysterectomy with bilateral salpingectomy,have the option to have a concomitant oophorectomy.While studies have evaluated hormone changes following testosterone therapy initiation,most of those patients have not undergone oophorectomy.Data are currently limited to support health outcomes regarding the decision to retain or remove the ovaries.We performed a retrospective chart review of transmasculine patients maintained on high-dose testosterone therapy at a single endocrine clinic in Vancouver,British Columbia,Canada.Twelve transmasculine individuals who underwent bilateral oophorectomy and had presurgical and postsurgical serum data were included.We identified 12 transmasculine subjects as controls,who were on testosterone therapy and did not undergo oophorectomy,but additionally matched to the first group by age,testosterone dosing regimen,and body mass index.There was a statistically significant decrease in the estradiol levels of case subjects postoophorectomy,when compared to presurgical estradiol levels(P=0.02).There was no significant difference between baseline estradiol levels between control and case subjects;however,the difference in estradiol levels at follow-up measurements was significant(P=0.03).Total testosterone levels did not differ between control and case subjects at baseline and follow-up(both P>0.05).Our results demonstrate that oophorectomy further attenuates estradiol levels below what is achieved by high-dose exogenous testosterone alone.Correlated clinical outcomes,such as impacts on bone health,were not available.The clinical implications of oophorectomy versus ovarian retention on endocrinological and overall health outcomes are currently limited.

Management of urethral strictures after masculinizing genital surgery in transgender men

Transgender men undergoing phalloplasty and metoidioplasty have a high rate of urethral stricture.Evaluation of stricture includes evaluation of symptoms and uroflow,cystoscopy,and retrograde urethrogram.Important anatomic differences between the phallus of cis-gender and transgender men increase the likelihood and complexity of treating urethral strictures in transgender men after surgery.Urethral strictures after masculinizing procedures are more likely to require open surgical treatment and recur after treatment.There is a paucity of data,but less invasive options such as dilation and urethrotomy have had minimal success.Open surgical options with a variety of techniques,including one-stage and two-stage techniques,have higher success rates in treating strictures,but there is minimal comparative data on outcomes.We present a review on management options for urethral reconstruction in transgender men and our data on urethroplasty for these patients.

Strategies to prevent and mitigate common complications in gender affirming penile inversion vaginoplasty

While the number of gender-affirming procedures continues to boom all over the world,resulting complications from genital surgeries are on the rise as well.This paper aims to review some of the most commonly described complications of gender-affirming vaginoplasties and provide our expert opinion on how to mitigate them based on the senior author’s experience.Specifically,poor cosmesis,soft tissues related complications,rectal and urethral injuries,neovaginal stenosis,as well as intraoperative and postoperative bleeding will be addressed.

A narrative review of outcomes following metoidioplasty:complications and satisfaction

Metoidioplasty consists of lengthening and straightening the hormonally hypertrophied clitoris.The goals of the procedure include masculinizing the external genitalia and enabling standing micturition.Metoidioplasty may be performed as a stand-alone procedure or an interval procedure prior to phalloplasty.While most often performed with urethral lengthening,metoidioplasty may also be performed as a“simple release”(i.e.,without urethral lengthening).Secondary procedures typically include scrotoplasty and placement of testicular implants.While satisfaction with this procedure is high,complications can occur.Complications are commonly categorized as either urologic(i.e.,strictures and fistula)or wound healing(i.e.,wound disruption,infection,bleeding,etc.).This narrative review discusses postoperative outcomes,including both satisfaction and complications.Published data on complications include fistula and stricture rates from 0%-50% and 0%-63%,respectively.Overall satisfaction with appearance ranges from 48%-100%,and patient ability to void while standing ranges from 67%-100%.Metoidioplasty is a safe and effective procedure for transgender men.Further research regarding surgical techniques and outcomes will help reduce complications and improve overall patient satisfaction.