Hormone replacement therapy (male-to-female)Many transgender men and women seek hormone therapy as part of the transition process. Exogenous testosterone is used in transgender men to induce virilization and suppress feminizing effrcts. In transgender women, exogenous estrogen is used to help feminize patients, and anti-androgens are used as adjuncts to help suppress masculinizing features. Guidelines jale to help providers choose appropriate candidates for hormone therapy, and act as a what is anabolic steroids side effects for choosing treatment regimens and managing surveillance in these patients. Cross-sex hormone therapy has been shown to have positive physical and psychological male to female hrt side effects on the transitioning individual and is considered a mainstay treatment for many patients.
Hormone therapy for transgender patients
Many transgender men and women seek hormone therapy as part of the transition process. Exogenous testosterone is used in transgender men to induce virilization and suppress feminizing characteristics. In transgender women, exogenous estrogen is used to help feminize patients, and anti-androgens are used as adjuncts to help suppress masculinizing features.
Guidelines exist to help providers choose appropriate candidates for hormone therapy, and act as a framework for choosing treatment regimens and managing surveillance in these patients. Cross-sex hormone therapy has been shown to have positive physical and psychological effects on the transitioning individual and is considered a mainstay treatment for many patients.
Bone and cardiovascular health are important considerations in transgender patients on long-term hormones, and care should be taken to monitor certain metabolic indices while patients are on cross-sex hormone therapy.
Transgender individuals experience discord between their self-identified gender and biological sex. Transgender men are individuals who were assigned female at birth but identify as men, and transgender women are individuals who were assigned male at birth but identify as women. While research in this area is sparse, the current evidence points toward a biologic etiology for transgenderism.
These data come from studies examining children with congenital genitourinary anomalies who were assigned gender at birth 1 , 2 , as well as postmortem cadaveric studies 3. Estimation of prevalence of transgenderism has historically been challenging. The most recent estimates in the United States have been reported from survey studies, and range from 0.
The number of transgender individuals seeking cross-sex hormone therapy has risen over the years 6. The administration of exogenous virilizing hormones is considered medically necessary for many transgender individuals 7. Many transgender men seek therapy for virilization and the mainstay treatment is exogenous testosterone. Transgender women desire suppression of androgenic effects and often use anti-androgen therapy with feminizing exogenous estrogens. The purpose of this review is to present updates on the current hormonal regimens used by transgender patients, to discuss the safety and efficacy of these treatments, and to provide a summary of the current data that exist on both their short- and long-term effects.
Both the World Professional Association for Transgender Health WPATH and the Endocrine Society have created transgender-specific guidelines to help serve as a framework for providers caring for gender minority patients. These guidelines are mostly based on clinical experience from experts in the field. Guidelines for hormone therapy in transgender men are mostly extrapolations from recommendations that currently exist for the treatment of hypogonadal natal men and estrogen therapy for transgender women is loosely based on treatments used for postmenopausal women.
This test required patients to live full-time as their self-affirmed gender for a predetermined period of time usually 12 months before starting cross-sex hormones. The recommendation was intended to help patients transition socially. As a result, the updated guidelines do not require this step, and instead, the societies recommend that patients transition socially and with medical therapy at the same time 7 , 8.
WPATH recommends that hormone therapy should be initiated once psychosocial assessment has been completed, the patient has been determined to be an appropriate candidate for therapy, and informed consent reviewing the risks and benefits of starting therapy has been obtained. Per WPATH, a referral is required by a qualified mental health professional, unless the prescribing provider is qualified in this type of assessment.
The criteria for therapy include: This fourth criterion can sometimes be the most challenging to interpret. Many patients may have concurrent mood disorders related to their gender dysphoria, and experienced providers may have success alleviating the severity of these symptoms by allowing the patient to begin the medical transition process.
Later in this review I discuss the effects hormones have on quality of life and perception of personal well-being. This is a key concept and should be considered when patients are being evaluated for hormone therapy initiation.
Patients with comorbid psychiatric conditions should be closely monitored and mental health support remains paramount for these patients. Testosterone therapy is used to suppress female secondary sex characteristics and masculinize transgender men. The therapy used resembles hormone replacement regimens used to treat natal men with hypogonadism and most of the preparations are testosterone esters. Current formulations for testosterone are presented in Table 1.
These are usually administered weekly, but if higher doses are needed to reach adequate physiologic levels, the dosing interval can be extended to every 10 to 14 days. Before a patient is started on testosterone, a baseline hematocrit and lipid profile should be obtained, as these indices will change over time. In addition, if a patient is at significant risk for osteoporosis, a baseline bone mineral density should be obtained 9. Most providers start testosterone therapy with half the anticipated dose needed to reach maximum virilization in a patient.
Studies exist looking at dose-response with regard to virilization once testosterone is initiated. Therefore, while higher doses may achieve desirable effects sooner, the risks associated with fast titration need to be assessed, and patients should be aware that testosterone effects eventually become the same over the intermediate-term.
Once implanted, the pellets slowly release testosterone for a long-acting androgenic effect. They are approved for the treatment of primary hypogonadism and hypogonadotropic hypogonadism. Our group recommends that patients first be started on an alternative form of testosterone until maximum virilization is achieved and maintenance dosing is then necessary. Patients may then be transitioned to the implanted pellets.
The number of pellets to be implanted depends upon the minimal daily requirements of testosterone needed to reach physiologic levels. Each pellet is cylindrical in shape and contains 75 mg of testosterone and six pellets may be implanted with each pass of the insertion device that is provided with the kits.
Two pellets should be inserted for every 25 mg of parenteral testosterone needed weekly. The pellets are placed in a fatty area under the skin. Most commonly, the upper gluteal region or hip is used as a site for implantation. The effects of the pellets may last up to 6 months, but most patients require re-implantation every 3 to 4 months.
Hormone therapy for transgender women is intended to feminize patients by changing fat distribution, inducing breast formation, and reducing male pattern hair growth Estrogens are the mainstay therapy for trans female patients. Through a negative feedback loop, exogenous therapy suppresses gonadotropin secretion from the pituitary gland, leading to a reduction in androgen production Estrogen alone is often not enough to achieve desirable androgen suppression, and adjunctive anti-androgenic therapy is also usually necessary.
Ethinyl estradiol used to be the mainstay of most estrogen-directed therapies. This is no longer the case, as clinical evidence has showed a strong relationship between ethinyl estradiol and the incidence of deep venous thrombosis As a result, there are strong recommendations against the use of ethinyl estradiol in transgender patients 8. See Table 2 for dosing recommendations.
No studies have examined the efficacy of the different formulations specific to transgender hormone management. After the age of 40, transdermal formulations are recommended as they bypass first pass metabolism and seem to be associated with better metabolic profiles There are no unanimous recommendations for the use of anti-androgens.
Options are also listed in Table 2. Spironolactone is one of the most common medications used to suppress endogenous testosterone in trans female patients. The biggest risk associated with spironolactone is hyperkalemia, and this should be closely monitored. GnRH agonists can be very expensive, and are not always a good option for patients. Progestins are used by some providers, but should be used with caution as there is a theoretical risk of breast cancer associated with long-term exogenous progesterone use Many trans men seek maximum virilization, while others desire suppression of their natal secondary sex characteristics only.
Within three months of initiating testosterone therapy, the following can be expected: Later effects include deepening of the voice, atrophy of the vaginal epithelium, and increased clitoral size. Male pattern hair loss also can occur over time as a result of androgenic interaction with pilosebaceous units in the skin Some patients find this favorable as it may be considered masculinizing.
However, patients should be made aware of the potential side effects on sexual functioning that can be associated with these medications, and they should be counseled that no data exist on the use of these medications in transgender men In most female-to-male patients unless testosterone is administered during the peri-pubertal period , there is some degree of feminization that has taken place that cannot be reversed with exogenous testosterone.
As a result, many transgender men are shorter, have some degree of feminine subcutaneous fat distribution, and often have broader hips than biologic males The following changes are expected after estrogen is initiated: The extent of these changes and the time interval for maximum change varies across patients and may take up to 18 to 24 months to occur.
Use of anti-androgenic therapy as an adjunct helps to achieve maximum change. Longitudinal studies also show positive effects on sexual function and mood 16 , There is biologic evidence that may explain this. SERT expression has been shown to be reduced in individuals with major depression These types of data are preliminary, but do point to the important role of hormone therapy in patients who suffer from gender dysphoria.
Hormone therapy may even have a positive effect on physiologic stress as well. They found that after starting cross-sex hormones, both perceived stress and cortisol were significantly reduced. This finding also has important implications for treatment. Patients on testosterone should be monitored every 3 months for one year and then every 6 to 12 months thereafter.
Hormones should be carefully monitored to avoid a prolonged hypogonadal state if dosing is too low, which can lead to significant losses in bone mineral density; and to avoid exposures to supraphysiologic levels, which could have significant physiologic and metabolic effects Sex steroids—testosterone and estradiol—are necessary to maintain bone health in men and women, respectively.
They are responsible for bone growth and turnover, and hypogonadal states in both males and females can result in clinically significant bone loss. Testosterone has a direct role in bone health maintenance, but the steroid is also aromatized peripherally to estradiol, which has a very important role as well Testosterone also has an important role in increasing muscle mass, which further helps with bone health preservation. Studies have looked at bone health in transgender men on long-term testosterone therapy.
Exogenous testosterone appears to have an anabolic effect on cortical bone and when dosed at physiologic levels, is adequate enough to avoid issues with bone demineralization in transgender patients Transgender women may be at higher risk for bone loss despite estrogen use This is likely a result of anti-androgen use, and therefore, providers should consider stopping anti-androgen therapy if and when patients undergo orchiectomy with or without genital confirmation surgery.
Screening for bone loss should be performed per the guidelines for the general population, unless a patient has baseline low bone mineral density, or is at risk for osteoporosis tobacco use, alcohol abuse, previous fractures, eating disorder, family history of osteoporosis.
Patients at risk should be screened sooner and more regularly. It is not clear whether use of exogenous testosterone increases the risk of cardiovascular disease in transgender men. Some studies have shown that testosterone has a negative effect on indices that may increase the risk of cardiovascular events. For instance, Gooren and Giltay 28 showed that long-term testosterone use reduced high-density lipoprotein cholesterol and increased triglycerides as well as inflammatory markers.