Current Opinion in Gynecology and Obstetrics Transgender Health Simplified: A Concise Guide to the Gynecologist

Most healthcare providers, gynecologists included, will encounter, care for and treat transgender patients. As such, gynecologists should be familiar with the basics of transgender care. This includes knowing how to create a trans-friendly clinic environment, knowing and adhering to screening guidelines, understanding the basics of cross hormone therapy and sex reassignment surgery. This article will review these topics, and other, that can allow the gynecologist to offer the best care to her/his transgender patients.


Introduction Epidemiology
The prevalence of transgender individuals has been difficult to estimate for numerous reasons.The few studies that have attempted, have focused on the transsexual population and have been mainly results of surveys or those individuals who have chosen to seek medical and/or surgical treatment.The reported prevalence of transgender individuals has ranged from 1:11,900 to 1:45,000 for male-to-female and 1:30,400 to 1:200,000 for female-to-male [1].It is thought that these are underestimations and the prevalence of transgendered people is much higher [1], [2], [3].

The role of the gynecologist
Most healthcare providers are going to care for transgender patients, however many report they do not feel comfortable or do not know enough about it.
Gynecologists occupy a key position in transgender care as they can be providers of primary care, cross hormone therapy, and gender affirmation therapy for both transmen or transwomen.The American College of Obstetricians and Gynecologists (ACOG) recognizes the need to improve transgender healthcare by improving training, knowledge, and comfort in caring for these patients.[4,5].Training for future obstetricians/gynecologists (OB/ GYNs) needs to improve as many OB/GYN residency directors feel that educational activities are needed in their program in improve transgender health knowledge.[6]One study demonstrated that merely 60 minutes of didactics offered to resident physicians increased physician willingness to utilize hormone therapy for their transgendered patient population [7].The purpose of this review is to provide today's gynecologists with a concise yet thorough review of important aspects of transgender health including defining common terminology, primary care considerations, how to make a gynecology clinic more trans-friendly, cross hormone therapy, and sex ISSN: 2637-4617 reassignment surgery basics.

Back to Basics: Defining the Terms
The term transgender is, in fact, a general term describing an individual whose gender identity and expression are not in accordance with their natal sex.
While there is a continued discussion about the nuanced differencesin various terms, we review the terms that are most common and most pertinent to the clinical practice of a gynecologist in table 1.This table has been made as a reference because of the many previously used words, such as 'hermaphrodite' having been used to describe intersex, that should be avoided and are now considered pejorative and outdated [8] (Table 1).

Trans-friendly Clinic
The 2015 US Transgender Survey notes, approximately one third of transgender patients stated they had at least one negative experience related to being transgender when seeking healthcare in the past year alone.The experiences patients reported included; being refused treatment, verbal harassment, physical or sexual assault, or having to educate their provider regarding transgender people in order to get proper care [9].A provider's attitude towards transgender patients can

Cross dresser
People who wear clothing, jewelry, and/or make-up not traditionally or stereotypically associated with their anatomical sex, and who generally have no intention or desire to change their anatomical sex.

Transsexual
People whose gender identity differs from their assigned sex at birth and who often live full-time as a member of the sex opposite of their birth designated sex and who may or may not (1) take hormones or have surgery or (2) be gender dysphoric Cross hormone therapy Administration of exogenous endocrine agents to induce feminizing or masculinizing changes LGBTIQQAA Lesbian-gay-bisexual-transexual-intersex-queer-questioning-Asexual-Ally has also published resources to help physicians provide better care for transgender patients [11].
A more extensive model of care for the transgender community has been one of establishing transgender clinics which are composed of providers from various medical specialties with expertise in transgender health.Bringing together psychiatrists, gynecologists, plastic surgeons, family practitioners, internists, and endocrinologists under one umbrella may streamline care of transgender individuals and encourage them to seek medical assistance when necessary.We recognize that not all facilities have the resources or motivations to establish a transgender clinic, but all gynecologists can attempt to make their clinic more trans-friendly.

Primary Care Considerations
Gynecologists can play an invaluable role in providing primary care services to their patients.Specifically, for transgender patients this may include: assessing access to mental healthcare providers, STD screening, depression screening, offering contraception, and cancer screening.
Frequently, opportunities for primary or preventive care (which would be standard of care in a 'cis' patient) are missed in the transgender population, partly due to the provider preoccupation with a patient's transgender status or use of hormone therapy; this has been termed the "Transgender Broken Arm Syndrome" [12].Gynecologists must be aware of this shortcoming, and attempt to address common primary care issues at each of their transgender patient's visit.Depression screening should be consistently performed as transgender individuals are at increased risk of depression and suicidality [13].Facilitating and arranging follow-ups with mental health professionals is also very important.Additionally, inquiring about a patient's housing situation is crucial, as transgender individuals are at increased risk of homelessness, which also increases their exposure to STDs (including HIV).This is often a result of a reliance on 'survival sex' (the trading of sexual acts for basic needs) [4].The treatment of STDs is unchanged between the cis and transgender patient.
As with all patients, cancer screening opportunities should not be missed when the transgender patient is seen in the gynecology clinic.The US Preventive Services Taskforce (USPSTF) cancer screening guidelines are not significantly different in the transgender and cisgender patient, however there is considerable confusion when it comes to screening guidelines for the breast and genitourinary tract organs.
Tables 2 and 3 clarify the cancer screening guidelines for breast and genito-urinary organs in transmen and transwomen.

Fertility Considerations
Before starting cross hormone therapy, a discussion with the patient regarding plans for future fertility is recommended due to the potential for impaired fertility from cross hormone therapy and sex reassignment  Testosterone administration can result in amenorrhea and is contraindicated in pregnancy, so it must be discontinued prior to conception.For transgender women, cryopreservation of sperm is considered the best option and should be initiated before cross hormone therapy.
A consultation with a Reproductive Endocrinology and Infertility specialist should be considered for further counseling and treatment.All transgender patients should be counseled on contraception until sex reassignment surgery is performed because hormone therapy is not an effective method of contraception [14].

Cross Hormone Therapy Simplified
For many transgender individuals, the initiation of gender affirming or cross hormone therapy is medically necessary for their wellbeing and quality of life [15,16].Transgender individuals may also choose to initiate hormone therapy to modify certain physical traits, halt undesired physical traits of their natal sex, and induce/ promote characteristics of their desired sex [17].
A diagnosis of gender dysphoria is necessary prior to the initiation of cross hormone therapy.As defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) gender dysphoria not only requires that the gender identity of a person not match their natal sex, but also involve a clinically significant distress or impairment created by this incongruence [14].This diagnosis can either be made by a mental healthcare provider, or a gynecologist with experience and comfort in diagnosing gender dysphoria [18].
The Endocrine Society Guidelines and the Guidelines for the Primary and Gender Affirming Care of Transgender and Gender Nonbinary People (referred to from here on out as the UCSF Guidelines) are commonly used by healthcare providers initiating, continuing and maintaining gender affirming hormone therapy [19,14].Various other hormone therapy regimens have been published.There are, however, no clinical trials that compare the various cross hormone therapy regimens in terms of safety and long term effects.The WPATH does not endorse one hormone regimen over another.

Feminizing Hormone Therapy
Feminizing hormone therapy protocols are based on two medications: estrogen and an anti-androgen, most commonly, spironolactone.Estrogen is used for its feminizing effect such as breast growth, female body fat pattern, and smother skin [20].Spironolactone is used to decrease the amount of estrogen needed to achieve these desired feminizing effects [21].Estrogen used in these regimens is usually 17-beta estradiol, which can be administered orally, sublingually, transdermally, and intramuscularly (IM).Conjugate equine estrogen and ethinyl estradiol are avoided given concerns of thrombotic events [22,23].Spironolactone is usually discontinued after a transwoman undergoes an orchiectomy as part of gender reassignment surgery [24].
The Endocrine Society lists the risks associated with estrogen use to include: thromboembolic disease (this risk is reduced if using transdermal estrogen [25]), cholelithiasis, breast cancer, coronary artery disease, cerebrovascular disease, and prolactinoma [16].The UCSF guidelines do not note an increased risk in prolactinoma, and recommend consultation with an oncologist in individuals with a history of an estrogen sensitive cancer, such as breast cancer [14].
The Endocrine Society Guidelines for feminizing hormone therapy and recommended monitoring schedule are seen in Figure 1.The UCSF Guidelines for feminizing hormone therapy and recommended monitoring schedule are seen in Figure 2.

Masculinizing Hormone Therapy
Masculinizing hormone therapy is based on testosterone, which can be given intramuscularly (IM), subcutaneously (SQ), and transdermally (by gel, cream or patch) or orally.The most commonly used formulations are IM or SQ testosterone enanthate and cypionate.The goal of masculinizing hormone therapy is suppression of secondary female characteristics, as well as the development of secondary male sexual characteristics such as deepening of the voice, increase in body muscle mass, redistribution of subcutaneous fat, and an increase in body and facial hair [10].Most of the masculinization hormone therapy protocols are similar to those used to treat genetic males with hypogonadism [26].While one study suggested that natal male-level estradiol levels were achieved in only 29% of transmen on cross hormone therapy for six months [27], newer research suggests that estradiol levels in transmen on cross hormone therapy were in the normal male levels after 6 years of follow up [28].This newer data suggests that anti-estrogens (aromatase inhibitors and selective estrogen receptor modulators) may not be necessary for maintaining male level testosterone and estrogen in transmen on testosterone [28].A gynecologist caring for a transgender male patient must remember than cross hormone therapy does not always cause ovulation suppression, as such, a discussion about contraception is necessary.A copper intrauterine device (IUD) may be a suitable form of contraception for many transmen as it does not interfere with their cross hormone therapy regimen [29].While fertility may be affected by long term testosterone use, transgender males have been able to temporarily stop testosterone to achieve a pregnancy [30].If transmen continue to menstruate on testosterone therapy, then consideration is given to adding a progestin or endometrial ablation [19].The reported adverse events noted with testosterone therapy include migraines, acne, androgenic alopecia, and elevated liver enzymes [31], [1].
The Endocrine Society Guideline for masculinizing hormone therapy and recommended monitoring schedule are seen in Figure 3.The UCSF Guidelines for feminizing hormone therapy and recommended monitoring schedule are seen in Figure 4.

Transgender Surgeries: Basics
The gynecologist should be familiar with the surgical procedures that transmen and transwomen undergo, as it is frequently the gynecologist who will be following up these patients long term.These transgender procedures are referred to as sex reassignment surgery (SRS).In its 2011 guidelines, WPATH established criteria for initiation of SRS for the treatment of gender dysphoria.The criteria for breast surgery (mastectomy or mammoplasty) are: 1-peristent, well documented gender dysphoria, 2-ability to understand informed consent, 3-adult age (parental consent needed for underage patients), 4-if present, medical or psychiatric illnesses well controlled.Referral from one mental health professional is needed.Cross hormone therapy is not a criterion for femaleto-male breast surgery; a year of feminizing therapy is encouraged prior to male-to-female mammoplasty for best cosmetic results [1].
The WPATH criteria for proceeding with pelvic procedures are the same as those for breast procedures with the added criteria of one year of cross hormone therapy, and specifically for metoidioplasty/phalloplasty/ vaginoplasty, a year of living in the desired gender role.

Female-to-male SRS
Masculinizing chest surgery for transmen commonly involves a mastectomy through either a peri-aereloar or inframammary incision.The decision of which technique to use usually revolves around surgeon experience, breast size and skin elasticity [32,33].The overall complication rate in these procedures is around 12%, the reoperation rate around 4%.The most common complications include the formation of a hematoma or seroma, nipple necrosis, contour irregularity, and scarring [34].Pelvic surgery for transmen usually involves a hysterectomy, bilateral salpingo-oopherectomy, creation of a phallus (described below), vaginectomy, scrotoplasty, urethroplasty and placement of testicular and penile implants.A metoidioplasty is when the clitoris is used to create a phallus after it is released form the clitoral hood.A phalloplasty is the creation of a phallus using tissue from the thigh or forearm.An alternative to a phalloplasty is a metoidioplasty procedure.This involves the lengthening of the hypertrophied clitoris (from masculinizing cross hormone therapy) and releasing it from its suspensory ligaments [39].This creates a smaller phallus from local tissue.The urethra may be transplanted into the phallus after adequate lengthening [36].The scrotum can be created from labia majora flaps at the same time as the metoidioplasty and vaginectomy.Testicular implant insertion is usually delayed for a few months after surgery.Patient who undergo a metoidioplasty can achieve erections without a prosthesis.Metoidioplasty is associated with less complications, better patient aesthetic satisfaction, more orgasmic sensations, and higher patient report of standing micturition [40]

Male-to-female SRS
Feminizing augmentation mammoplasty for transwomen involves the placement of an implant either below the subcutaneous tissue or under the pectoralis muscle [41].Feminizing cross hormone therapy is recommended prior to breast augmentation; some experts recommend at least 6 months [42].Complications associated with breast augmentation include hematomas, seromas, infections, ruptured implants, implant malpositioning, and aesthetic complications [43,44].
Pelvic surgery for transwomen includes orchiectomy, creation of labia majora and minora from the scrotal sac, and creation of a neovagina.The neovagina is created either by penile skin inversion vaginoplasty (most common technique) or bowel vaginoplasty, where a segment of the cecum or rectum is used to create the self-lubricating walls of the neovagina [17,45].The clitoris is created form the glans penis, and the prostate is usually left in place to avoid unnecessary surgery and urinary complications [46].Vaginal dilation is necessary postoperatively to prevent loss of vaginal length and girth.Complications from these procedures include wound dehiscence, urethral stenosis, infection, hematoma and seroma formation, fistula formation, [47].Cancers have also been documented in the neovagina, namely adenocarcinoma in bowel neovaginas and squamous cell carcinomas in penile inversion neovaginas [48].Some expert recommend screening endoscopy of the colon and neovagina, as well as assessment for symptoms such as postcoital bleeding and bloody discharge with biopsies [48,49].Since no major sensory nerves are transected during the creation of the neovagina, most patients remain orgasmic after the procedure [50].

Conclusions
While today's gynecologist may not be the physician prescribing cross hormone therapy or performing transgender surgery, she/he will likely care for a transgender patient at some point.Familiarization with some level of transgender health specifics is fast becoming a necessary fund of knowledge for every gynecologist.Of course, it is entirely up to the individual physician whether to simply learn the basics such as screening recommendations, or to delve deep into a more comprehensive knowledge of cross hormone therapy and the fundamental understanding of transgender surgeries.Being aware of this advancing field will allow the gynecologist to offer the best care to her/his transgender patients.

Figure 2 :
Figure 2: UCSF Feminizing Cross Hormone Therapy and Monitoring Protocol

Figure 3 :
Figure 3: Endocrine Society Masculinizing Cross Hormone Therapy and Monitoring Protocol

Figure 4 :
Figure 4: UCSF Masculinizing Cross Hormone Therapy and Monitoring Protocol

Table 1 :
Terms to Know TransgenderPeople whose gender identity and/or gender expression differs from their assigned sex at birth Cisgender, non-transgender People whose gender identity and gender expression align with their assigned sex at birth Transwoman/transwomen Someone who was identified male at birth but who identifies and portrays her gender as female Transman/transmen Someone who was identified female at birth but who identifies and portrays his gender as maleBigenderedVariations other than the traditional, dichotomous view of male and female.People who self-refer with these terms may identify and present themselves as both or alternatively male and female gender, as no gender, or as a gender outside the male/female binaryNon-binaryTransgender or gender nonconforming person who identifies as neither male nor female Gender non-conforming People whose gender expression is (1) neither masculine nor feminine or (2) different from traditional stereotypic expectations of how a man or woman should appear or behave

Table 2 :
Transwomen Cancer Screening Guidelines * Transwomen are believed to have lower risk of prostate cancer from estrogen therapy and orchiectomy

Table 3 :
Transmen Cancer Screening Guidelines *Unless history of CIN II/III.In that event, continue screening for 20 years after hysterectomy **If HIV positive, then first pap smear should be within first year of dx *** Consider using pediatric speculum with lubrication, oral benzodiazepine pre-examination or vaginal estrogen for a week prior to collection surgery.For transgender men, preservation of fertility may include oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation.

Table 4
summarizes SRS procedures for transmen and