Medical Management of Adult Transsexual Persons

Emily L. Knezevich, Pharm.D; Laura K. Viereck, Pharm.D; Andjela T. Drincic, M.D.

Pharmacotherapy. 2012;32(1):54-66.

Conclusion

With the increasing recognition of GID, pharmacists will likely encounter patients using hormone therapy to achieve sex characteristics of their identified gender. It is pertinent for pharmacists to be familiar with the standards of care that have been developed to optimize patient safety and outcomes. There are many therapeutic options for the treatment of GID, but they do not come without risks. The risks and benefits of therapy should be appropriately weighed and extensively discussed with each patient desiring cross-sex hormone therapy.

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Table 1. DSM-IV-TR Criteria for Diagnosis of Gender Identity Disorder ^1,2 and ICD-10 Criteria for Transsexualism ⁵
DSM-IV-TR Criteria for Gender Identity Disorder	ICD-10 Criteria for Transsexualism
Diagnosis
Strong and persistent cross-gender identification (not merely a desire for any perceived cultural advantages of being the other sex)	Desire to live and be accepted as a member of the opposite sex, usually accompanied by the wish to make his or her body as congruent as possible with the preferred sex through surgery and hormone treatments
Persistent discomfort with his or her sex or sense of inappropriateness in the gender role of that sex	Transsexual identity has been present persistently for at least 2 yrs
Disturbance is not concurrent with a physical intersex condition	Disorder is not a symptom of another mental disorder or a genetic, intersex, or chromosomal abnormality
Disturbance causes clinically significant distress or impairment in social, occupational, or other important areas or functioning
Symptom manifestations
Stated desire to be the other sex
Frequent passing as the other sex
Desire to live or be treated as other sex
Conviction that he or she has typical feelings and reactions of other sex
Preoccupation with getting rid of primary and secondary sex characteristics (request for hormones, surgery, other procedures to simulate other sex)
Belief that he or she was born the wrong sex

DSM-IV-TR = Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; ICD-10 = International Classification of Diseases, Tenth Revision.

Table 2. Effects of Cross-Sex Hormone Therapy
Time Relative to Starting Therapy	Male-to-Female Effects	Female-to-Male Effects
First 3 mo	Decreased spontaneous erections Decreased libido	Skin oiliness and acne Fat redistribution
After 3–6 mo	Redistribution of body fat Decrease in muscle mass and strength Softening of skin and decreased skin oiliness Breast growth Decreased testicular volume	Cessation of menses Clitoral enlargement Vaginal atrophy
Beyond 6 mo	Decreased terminal hair growth Decreased sperm production Male sexual dysfunction	Scalp hair loss Facial and body hair growth Increased muscle mass and strength Deepening of voice

Although this table demonstrates an expected timeline for changes with cross-sex hormone therapy, maximal effects can take years to develop.

Table 3. Drug Therapy for Management of Male-to-Female Transition in Transsexual Persons
Formulation	Dosage Range	Advantages	Disadvantages
Oral estradiol	2.0–6.0 mg p.o. once/d	Improves physical characteristics, inexpensive, ease of administration	Higher thromboembolic risk
Intramuscular estradiol Estradiol valerate	5–20 mg i.m. every 2 wks	Flexible dosing, higher levels of circulating estrogens	Requires intramuscular injection, longer time to reach steady state, high potential for abuse or overdose
Estradiol cypionate	2–10 mg i.m. every wk
Transdermal estradiol patch	0.1–0.4 mg twice/wk	Ease of application, lower thromboembolic risk	Skin reactions, adhesion problems, slower onset of action
Spironolactone	100–400 mg p.o. once/d	Reduction of testosterone levels	Gynecomastia, hyperkalemia
Finasteride	2.5–5 mg p.o. once/d	Slows male pattern baldness, reduction of testosterone levels	Risk of prostate cancer
Goserelin acetate	3.75 mg s.c. every mo	Reduction of testosterone levels	Gynecomastia, subcutaneous injection

Table 4. Timeline for Laboratory Monitoring of Male-to-Female Patients Receiving Cross-Sex Hormone Therapy ^[1]
Baseline	Every 2–3 Mo After Starting Estrogen for First Year of Therapy	Every 6–12 Mo After First Year of Therapy	Additional Screening^a
Lipids, FPG, CBC, BP, weight, serum estradiol, LFTs, BMD (if osteoporosis risk exists), serum testosterone, hemoglobin, prolactin, PSA, electrolytes,^b coagulation markers (if deep vein thrombosis risk)	Serum testosterone, estradiol, electrolytes,^b CBC, hemoglobin, lipids, FPG (if family history of diabetes mellitus), LFTs, weight, BP	CBC, FPG, LFTs, lipids, BP, weight, serum testosterone, estradiol, electrolytes,^b prolactin	Prostate examination, mammogram

FPG = fasting plasma glucose; CBC = complete blood count; BP = blood pressure; LFTs = liver function tests; BMD = bone mineral density; PSA = prostate-specific antigen.
^aScreening frequency as recommended by the American College of Obstetricians and Gynecologists and the American Cancer Society.
^bFor individuals taking spironolactone, serum electrolytes (especially potassium) should be monitored every 2–3 months during the first year.

Table 5. Testosterone Replacement Products
Formulation	Dosage Range	Advantages	Disadvantages
Testosterone esters (enanthate or cypionate)	100–200 mg i.m. every 2 wks or 50–100 mg i.m. every wk	Improves physical characteristics and serum testosterone levels, inexpensive, longer duration between doses	Requires injection, fluctuations in serum testosterone levels cause cyclic changes in mood
Topical gels and solutions	2.5–10 g/d (25–100 mg testosterone)	Corrects symptoms, flexible dosing, ease of application, well tolerated	Potential for secondary exposure, hypersensitivity, musky odor, highcost
Transdermal patches	1–2 patches^a (testosterone 2.5–7.5 mg) q24 h	Ease of application, mimics diurnal testosterone release	Lower serum testosterone levels, skin irritation likely

^aAvailable as 2.5- or 5-mg patches.

Table 6. Timeline for Laboratory Monitoring of Female-to-Male Patients Receiving Cross-Sex Hormone Therapy ^[1]
Baseline	Every 2–3 Mo After Starting Testosterone for First Year of Therapy	Every 6–12 Mo After First Year of Therapy	Additional Screening^a
Lipids, FPG, CBC, BP, weight, serum testosterone, BMD (if osteoporosis risk exists)	Serum testosterone, estradiol (for 6 mo after cessation of menses), BP,^b CBC, lipids,^b FPG^b (if family history of diabetes mellitus), LFTs, weight^b	CBC, FPG, LFTs, lipids, BP, weight, serum testosterone	Pap smear, mammogram

FPG = fasting plasma glucose; CBC = complete blood count; BP = blood pressure; BMD = bone mineral density; LFTs = liver function tests.
^aScreening frequency as recommended by the American College of Obstetricians and Gynecologists and the American Cancer Society.
^bLaboratory tests that should be performed at regular visits.

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Medical Management of Adult Transsexual Persons

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