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Hormone Replacement Therapy for Transgenders Do’s and Don'ts Steven M. Brown, MD University of Wisconsin School of Medicin...
A Case Report
<ul><li>What is Hormone Replacement Therapy? </li></ul>
What is a Hormone? <ul><li>Organic compound, secreted by a gland, in minute quantities, into the bloodstream, that has a r...
Endocrinology 101 Glands:  Groups of cells which  specialize in the secretion of hormones <ul><li>Some important glands </...
Additional glands <ul><li>Thyroid  </li></ul><ul><li>Pancreas </li></ul><ul><ul><li>Insulin </li></ul></ul><ul><li>Hypotha...
The “sex glands” <ul><li>Ovaries </li></ul><ul><ul><li>Progesterone </li></ul></ul><ul><ul><li>Estrogen </li></ul></ul><ul...
Chemical origins of sex hormones <ul><li>Derived from cholesterol </li></ul><ul><li>Chemical structures of estrogen, proge...
Chemical origins of sex hormones
Changes which occur in puberty <ul><li>Pre-wired biological clock, probably in the hypothalamus, coincides with practical ...
Why Use Hormone Replacement? <ul><li>Change physical appearance to maximize consistency between physical identity and inte...
What are some of the  obstacles to HRT? <ul><li>Patient issues </li></ul><ul><ul><li>Ambivalence, “coming out” issues, fea...
What are some of the  obstacles to HRT? <ul><li>Health care provider issues </li></ul><ul><ul><li>Lack of education </li><...
Who Prescribes  Hormone Replacement? <ul><li>Primary care physician </li></ul><ul><ul><li>Internist </li></ul></ul><ul><ul...
Who SHOULDN’T  Prescribe Hormones <ul><li>Yourself </li></ul><ul><li>Family </li></ul><ul><li>Friends </li></ul><ul><li>In...
Where Transgenders  Get Hormones <ul><li>“ Black Market </li></ul><ul><li>Friends </li></ul><ul><li>Mexico </li></ul><ul><...
SOME IMPORTANT WARNINGS <ul><li>NEVER use hormonal medication prescribed for another person </li></ul><ul><li>DON’T self-m...
SOME MORE WARNINGS <ul><li>Don’t double dose </li></ul><ul><li>Don’t alter regimen without supervision </li></ul>
An HRT “Do” <ul><li>A clinician should collaborate with a mental health specialist who has extensive experience with the d...
Harry Benjamin International  Gender Dysphoria Association: <ul><li>Requirements for HRT in adults </li></ul><ul><ul><li>A...
Some important principles <ul><li>There is a lot of misinformation, especially on the Internet </li></ul><ul><li>Hormone t...
Reproductive options <ul><li>To give opportunity to obtain children who are genetically “their own” </li></ul><ul><li>Sper...
“Real-Life Test” Pros and Cons <ul><li>Pros </li></ul><ul><ul><li>HRT can cause permanent changes including sterility and ...
Purposes of Feminizing Hormones <ul><li>Induce the development of female secondary sexual characteristics </li></ul><ul><l...
An important principle— have realistic expectations
Feminizing Hormones DO NOT <ul><li>Cause the voice to increase in pitch.  </li></ul><ul><li>Dramatically reduce facial hai...
Some important DO’s <ul><li>DO review risks and benefits before starting any hormones </li></ul><ul><li>DO be sure that th...
Some important DO’s <ul><li>DO have regular medical checkups (every 2-3 months) </li></ul><ul><li>DO watch your blood pres...
Some important DO’s of Doctoring <ul><li>DO see a reputable doctor for your care </li></ul><ul><li>DO get regular check-up...
Some important DON’TS <ul><li>DON’T go out on your own for meds </li></ul><ul><li>DON’T alter your medication regimen </li...
Effects of Feminizing Hormones on Males <ul><li>Effects vary from patient to patient—familial, genetic tendencies </li></u...
Effects of Feminizing Hormones on Males <ul><li>Breast development  </li></ul><ul><ul><li>can take years, begins after 2-3...
Effects of Feminizing Hormones on Males <ul><li>Loss of ability to ejaculate/maintain erection (variable) </li></ul><ul><l...
Effects of Feminizing Hormones on Males <ul><li>Decreased testicular size (mostly flaccid) </li></ul><ul><li>The prostate ...
Effects of Feminizing Hormones on Males <ul><li>Decreased facial/body hair </li></ul><ul><ul><li>Body hair lightens in tex...
Cutaneous Effects of Feminizing Hormones on Males <ul><li>Redistribution of body and facial fat </li></ul><ul><ul><li>Face...
Effects of Feminizing Hormones on Males <ul><li>Sensory changes </li></ul><ul><ul><li>Heightened sense of touch </li></ul>...
Effects of HRT on  Metabolism in MTF’s <ul><li>Metabolism decreases </li></ul><ul><ul><li>Given a caloric intake and exerc...
Other effects of hormones <ul><li>Reduced risk of Alzheimer’s </li></ul><ul><li>Improved memory </li></ul>
Effects of Feminizing Hormones on Males <ul><li>Loss of muscle mass </li></ul><ul><li>Loss of strength </li></ul><ul><li>E...
Changes in Sexual Orientation <ul><li>“Of 20 transsexuals of various types that were interviewed, 6 heterosexual male-to-f...
Risks of Feminizing Hormones — Some General Principles <ul><li>Complete risks in transsexuals is not known </li></ul><ul><...
Risks of Feminizing Hormones <ul><li>Blood clots— </li></ul><ul><ul><li>12% over age 40 </li></ul></ul><ul><ul><li>Usually...
Risk factors for Venous Thromboembolism <ul><li>Surgery </li></ul><ul><li>Trauma (major or lower extremity) </li></ul><ul>...
Reducing the Risk of Blood Clots <ul><li>Smoking cessation </li></ul><ul><ul><li>Pharmacologic support </li></ul></ul><ul>...
Risks of Feminizing Hormones <ul><li>Fluid retention </li></ul><ul><li>Prolactin </li></ul><ul><ul><li>14%, in one study d...
The Cardiac Risks of Feminizing Hormones <ul><li>Most studies have and are being done in biologic women </li></ul><ul><li>...
Estrogens and the Heart <ul><li>Current studies </li></ul><ul><ul><li>Women’s Health Initiative  </li></ul></ul><ul><ul><u...
Hormones and the Heart <ul><li>JAMA:  July 17, 2002  </li></ul><ul><ul><li>“Risks and Benefits of Estrogen Plus Progestin ...
Hormones and the Heart <ul><li>What is the risk-benefit ratio in post-menopausal women? </li></ul><ul><ul><li>Decreased ho...
Reducing the Odds of  Cardiac Complications <ul><li>If there’s a history or strong family history of heart attack, coronar...
Risks of Feminizing Hormones <ul><li>Gallstone disease </li></ul><ul><li>Liver disease (low risk) </li></ul><ul><li>Weight...
Risks of Feminizing Hormones <ul><li>Cancer risk </li></ul><ul><ul><li>Fibroadenoma—the most common breast tumor </li></ul...
Contraindications to HRT in FTM Patients <ul><li>Absolute </li></ul><ul><ul><li>History of thromboembolism or thrombotic t...
“DO” Get Appropriate Monitoring <ul><li>Follow-up exams every 2 – 3 month </li></ul><ul><ul><li>Breast exam </li></ul></ul...
Appropriate laboratory monitoring <ul><ul><li>Liver function tests </li></ul></ul><ul><ul><li>Lipid profile </li></ul></ul...
Monitoring changes <ul><ul><li>Estrogen levels </li></ul></ul><ul><ul><li>Testosterone levels (especially in pre-ops) or i...
MTF Monitoring—Johns Hopkins
Other Tests Which Can Be Followed <ul><li>Calcium and phosphorus (skeletal health) </li></ul><ul><li>Bone densitometry eve...
Testosterone levels <ul><li>300-1000 ng/dl  genetic males </li></ul><ul><li>5-85 ng/dl genetic females </li></ul>
Estrogen levels <ul><li>Levels may be misleading secondary to insensitivity of assays </li></ul><ul><li>Dosing is more com...
Administration of Hormones <ul><li>Orally  (estrogens, progesterones, androgens) </li></ul><ul><ul><li>Advantage: convenie...
Administration of Hormones <ul><li>Sublingual </li></ul><ul><ul><li>Dissolve under the  tongue </li></ul></ul><ul><ul><ul>...
Administration of hormones <ul><li>Skin patches </li></ul><ul><ul><li>Advantage:  </li></ul></ul><ul><ul><ul><li>Convenien...
Dosing of HRT in Male to Females <ul><li>No generalized agreement </li></ul><ul><li>General principles </li></ul><ul><ul><...
Taking Just One Class of Medications <ul><li>Anti-androgens alone </li></ul><ul><ul><li>Serious bone density loss </li></u...
Common anti-androgens <ul><li>Cyproterone acetate (Androcur®, Cyprostat®) (antigonadotropic) </li></ul><ul><ul><li>Not ava...
Androgen receptor antagonists <ul><li>Flutamide (Eulexin) </li></ul><ul><ul><li>Androgen receptor antagonist </li></ul></u...
Antiandrogens <ul><li>Spironolactone  </li></ul><ul><ul><li>Weak androgen receptor antagonist </li></ul></ul><ul><ul><li>D...
GnRH Agonists <ul><li>Act on pituitary </li></ul><ul><ul><li>Overstimulating pituitary </li></ul></ul><ul><ul><li>Then des...
A word about herbals <ul><li>Not benign—potential for liver injury </li></ul><ul><li>Still a medication and self-medicatin...
Common estrogens <ul><li>Estradiol valerate (Estrace®) </li></ul><ul><ul><li>Equivalent to natural 17   -estradiol </li><...
Common estrogens <ul><li>Ethinylestradiol (Estinyl®) </li></ul><ul><ul><li>Slowly metabolized by the liver, resulting in g...
Common estrogens <ul><li>Conjugated natural estrogens (Premarin®) </li></ul><ul><ul><li>From urine of pregnant mares </li>...
Common estrogens <ul><li>Estraderm® patches </li></ul>50-100 µg/day tramdermally
Common progestogens <ul><li>Anti-androgenic </li></ul><ul><li>Not feminizing alone </li></ul><ul><li>Enhances feminization...
Medroxyprogesterone acetate  Provera® <ul><li>Good safety record </li></ul><ul><li>May be slightly virilizing—may be metab...
Natural Progesterone <ul><li>Micronized progesterone </li></ul><ul><li>Progesterone USP </li></ul><ul><li>Prometrium </li>...
Common HRT in the United States <ul><li>Estrogen preparations </li></ul><ul><ul><li>Conjugated estrogens (Premarin) 2.5-5....
Failure to Respond <ul><li>In no changes are seen (including “tender nipples”) within 2-3 months </li></ul><ul><li>  or </...
FTM Hormone Replacement <ul><li>Females respond quite well to hormone replacement as adolescents and as adults </li></ul><...
Why is FTM easier than MTF? <ul><li>In FTM, addition of androgens excites androgen receptors which are there but dormant <...
Effects of Masculinizing Hormones on Females <ul><li>Acne </li></ul><ul><li>Male pattern baldness  </li></ul><ul><li>Incre...
Effects of Masculinizing Hormones on Females <ul><li>Enlarged clitoris (3-8 cm) with increased libido—can become overly, p...
 
Effects of Masculinizing Hormones on Females <ul><li>Fertility decreases--menstrual cycle becomes irregular then stops, us...
Male hormones DO NOT <ul><li>Significantly decrease the size of the breasts. </li></ul><ul><ul><li>However, they may softe...
Risks of Masculinizing Hormones <ul><li>Ovarian cancer—long-term exposure to endogenous and exogenous androgens are associ...
Risks of Masculinizing Hormones <ul><li>Reduced HDL cholesterol (bad) </li></ul><ul><li>Reduced LDL particle size (bad) </...
Risks of Masculinizing Hormones <ul><li>Water and sodium retention </li></ul><ul><li>Decreased carbohydrate tolerance </li...
Testosterone and the Liver <ul><li>Testosterone-induced hepatotoxicity  </li></ul><ul><ul><li>Increased liver enzyme level...
Contraindications of HRT in FTM’s <ul><li>Absolute </li></ul><ul><ul><li>Pregnancy </li></ul></ul><ul><ul><li>Active subst...
Common Androgen Replacement <ul><li>Injectable testosterone </li></ul><ul><ul><li>Testosterone enanthate 100-400 mg IM eve...
Other androgen replacement <ul><li>Testosterone pellets (Testopel) </li></ul><ul><ul><li>6 -12 pellets under the skin ever...
Drug Interactions of Testosterone <ul><li>Drugs which decrease levels of testosterone levels: </li></ul><ul><ul><li>Phenob...
Progesterone Treatment in FTM’s <ul><li>Short-course progesterone therapy to  </li></ul><ul><ul><li>Induce menstrual perio...
FTM Monitoring—Johns Hopkins
Some FTM Do’s  <ul><li>Prior to hormone therapy , consider hysterectomy and bilateral salpingo-oophorectmy  </li></ul><ul>...
Some FTM Don’ts <ul><li>Don’t buy too many shoes—your feet will grow </li></ul><ul><li>More is not better </li></ul>
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Hormone Replacement Therapy for Transgenders Do's and Don't's

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  • Being Transexual/Transgender is a gift one that takes a life-time to really appreciate only because it takes so long for the journey, and for some it takes a life time..I have been TS for 75 years and I'm still in transistion whether I fulfill my journey is now less important as I love the fact I was given the chance to experience it....
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  • 'true transexual' ' Passsing' 'transgenders' ' good for facial feminization surgery'
    this writer is living in the past. not every trans person wants surgery. using the terms 'passing' & 'transgenders' really shows a lack of understanding of trans people. lastly 'true transexual??' really? doesn't the writer understand what's really going on? there's a huge variety of trans people. everyone has different needs and goals. there's no such thing as a true transexual.. this writer should stop quoting harry benjamin or ray blanchard. so outdated. oh gosh!! i keep reading. 'Increased female type sex drive/ attraction to men??' wow… this is an awful article.
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  • i disagree with the author when it comes to feel more calm only with hormones. I know a lot of transgenders that do no achieve passing feminization and that causes extreme dysphoria. one does not feel extremely satisfied just by taking hormones.
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  • DON'T: Say, 'transgenders'
    DO: Say, 'transgender people', 'trans* people'
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  • Lots of males and females live lives that range from feelings of general discomfort, or knowing that part of them is missing and trying to find this, or are simply going crazy in bodies that lack positive correlation with their brains. Transgendered should be in the same category as intersex, and such a physiological condition. No transsexual ever chooses this. Such confusion anxiety and horrendous feelings are not lifestyle choices. Medicinal disciplines incorrectly think that gender expression is gender identity, and this is untrue, but they only offer terrifyingly invasive surgery: Who would cause lifestyles choices that cause life-threatening illnesses and drug side-effects, post-surgical complications, and loss of support and contact with loved ones and likely loss of employment and safety when walking down the street: None of these are lifestyle choices, which means that TG/TS is not a lifestyle choice.
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  • The risk factors referred to the last couple slides are listed here in no particular order. These risk factors are generally cumulative (from Geerts, reference number 11: Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999;353:1167-1173.) For example, patients with fractures of the hip are at particularly high risk for VTE because of their usual advanced age, the presence of a proximal lower extremity injury as well as its operative repair, and the frequent marked reduction in mobility for weeks after surgery.
  • Transcript of "Hormone Replacement Therapy for Transgenders Do's and Don't's"

    1. 1. Hormone Replacement Therapy for Transgenders Do’s and Don'ts Steven M. Brown, MD University of Wisconsin School of Medicine [email_address]
    2. 2. A Case Report
    3. 3. <ul><li>What is Hormone Replacement Therapy? </li></ul>
    4. 4. What is a Hormone? <ul><li>Organic compound, secreted by a gland, in minute quantities, into the bloodstream, that has a regulatory effect on the metabolism of tissue or organs at a site different than the site of secretion </li></ul><ul><li>Alter the metabolism of cells or the synthesis and secretion of other substances (“tropic hormones”) </li></ul><ul><li>Bind to receptors (specific proteins) to “turn on” functions in target tissues </li></ul>
    5. 5. Endocrinology 101 Glands: Groups of cells which specialize in the secretion of hormones <ul><li>Some important glands </li></ul><ul><ul><li>Pituitary </li></ul></ul><ul><ul><ul><li>Anterior pituitary </li></ul></ul></ul><ul><ul><ul><ul><li>Growth hormone </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Thyroid stimulating hormone </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Adrenocorticotropic hormone (ACTH) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>FSH </li></ul></ul></ul></ul><ul><ul><ul><ul><li>LH </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Prolactin </li></ul></ul></ul></ul>
    6. 6. Additional glands <ul><li>Thyroid </li></ul><ul><li>Pancreas </li></ul><ul><ul><li>Insulin </li></ul></ul><ul><li>Hypothalamus </li></ul><ul><li>Parathyroid glands </li></ul><ul><li>Adrenal glands </li></ul><ul><ul><li>Cortisol </li></ul></ul><ul><ul><li>Testosterone </li></ul></ul><ul><ul><li>Estrogen </li></ul></ul><ul><ul><li>Aldosterone </li></ul></ul>
    7. 7. The “sex glands” <ul><li>Ovaries </li></ul><ul><ul><li>Progesterone </li></ul></ul><ul><ul><li>Estrogen </li></ul></ul><ul><ul><li>Regulate reproduction, bone metabolism, regulation of blood cholesterol, breasts, skin </li></ul></ul><ul><li>Testes </li></ul><ul><ul><li>Testosterone </li></ul></ul><ul><ul><li>Regulates reproduction, musculature, bone metabolism, cholesterol levels, red blood cell production </li></ul></ul>
    8. 8. Chemical origins of sex hormones <ul><li>Derived from cholesterol </li></ul><ul><li>Chemical structures of estrogen, progesterone, testosterone vary slightly </li></ul><ul><li>Testosterone is a metabolite of progesterone </li></ul><ul><li>Estrogen is a metabolite of testosterone </li></ul><ul><li>Production is governed by negative feedback loops </li></ul><ul><li>Present in males and females in differing concentrations </li></ul>
    9. 9. Chemical origins of sex hormones
    10. 10. Changes which occur in puberty <ul><li>Pre-wired biological clock, probably in the hypothalamus, coincides with practical reproductive considerations </li></ul><ul><li>Hypothalamus releases Leutinising Hormone-Releasing Hormone (LHRH). </li></ul><ul><li>LHRH passes down nerve endings, stimulates pituitary gland </li></ul><ul><li>In girls, around age 10 to 13, FSH and LH are produced—starts the cyclic activity of the ovaries in the production of estrogen </li></ul><ul><li>In boys, ages of 10 and 14 years, FSH and LH “switch on” testicular function in males (FSH triggers sperm production), LH triggers testosterone production </li></ul>
    11. 11. Why Use Hormone Replacement? <ul><li>Change physical appearance to maximize consistency between physical identity and internal gender identity </li></ul><ul><li>Assist in “passing” </li></ul><ul><li>Create better skin and hair patterns for subsequent cosmetic surgery such as facial feminization </li></ul><ul><li>Assist FTM transgenders with “beard growth” </li></ul><ul><li>For emotional well-being </li></ul>
    12. 12. What are some of the obstacles to HRT? <ul><li>Patient issues </li></ul><ul><ul><li>Ambivalence, “coming out” issues, fears of violence, fears of rejection, discrimination, social stigmatization </li></ul></ul><ul><ul><li>Not transsexual or not intensely transsexual </li></ul></ul><ul><ul><li>Financial considerations “social and economic marginalization” </li></ul></ul><ul><ul><li>Access to health care </li></ul></ul><ul><ul><li>Mistrust of medical establishment </li></ul></ul><ul><ul><li>Ability to have sustained follow-up and monitoring </li></ul></ul><ul><ul><li>Medical/behavioral contraindications </li></ul></ul><ul><ul><ul><li>Underlying disease states </li></ul></ul></ul><ul><ul><ul><li>Unfavorable family history </li></ul></ul></ul><ul><ul><ul><li>Unfavorable lifestyle (tobacco, alcohol) </li></ul></ul></ul>
    13. 13. What are some of the obstacles to HRT? <ul><li>Health care provider issues </li></ul><ul><ul><li>Lack of education </li></ul></ul><ul><ul><li>Lack of clinical experience </li></ul></ul><ul><ul><li>Relative paucity of studies </li></ul></ul><ul><ul><li>Unanswered questions </li></ul></ul><ul><ul><li>Personal discomfort </li></ul></ul><ul><ul><li>Serious complications </li></ul></ul><ul><ul><li>Fear of litigation </li></ul></ul><ul><ul><li>Off-label administration of medications </li></ul></ul>
    14. 14. Who Prescribes Hormone Replacement? <ul><li>Primary care physician </li></ul><ul><ul><li>Internist </li></ul></ul><ul><ul><li>Family Practitioner </li></ul></ul><ul><ul><li>“Gender dysphoria” clinic </li></ul></ul><ul><li>Endocrinologist </li></ul><ul><li>Gynecologist </li></ul><ul><li>Urologist </li></ul><ul><li>SRS Surgeon </li></ul><ul><li>Psychiatrists </li></ul>
    15. 15. Who SHOULDN’T Prescribe Hormones <ul><li>Yourself </li></ul><ul><li>Family </li></ul><ul><li>Friends </li></ul><ul><li>Internet “buddies” </li></ul><ul><li>“Urgent care” physicians </li></ul><ul><li>“On-line” doctors </li></ul><ul><li>“On-line” pharmacies </li></ul>
    16. 16. Where Transgenders Get Hormones <ul><li>“ Black Market </li></ul><ul><li>Friends </li></ul><ul><li>Mexico </li></ul><ul><li>Internet </li></ul><ul><li>Local pharmacy </li></ul>
    17. 17. SOME IMPORTANT WARNINGS <ul><li>NEVER use hormonal medication prescribed for another person </li></ul><ul><li>DON’T self-medicate </li></ul><ul><li>Use caution in purchasing hormones from “Black market sources”, the Internet, foreign countries, mail order houses and vendors who can “get it or you” </li></ul><ul><ul><li>Medication may be impure </li></ul></ul><ul><ul><li>May be contaminated </li></ul></ul><ul><ul><li>Temptation to bypass appropriate monitoring </li></ul></ul>
    18. 18. SOME MORE WARNINGS <ul><li>Don’t double dose </li></ul><ul><li>Don’t alter regimen without supervision </li></ul>
    19. 19. An HRT “Do” <ul><li>A clinician should collaborate with a mental health specialist who has extensive experience with the diagnosis of such patients to avoid mistreatment with hormones or sex-reversing surgical procedures </li></ul>
    20. 20. Harry Benjamin International Gender Dysphoria Association: <ul><li>Requirements for HRT in adults </li></ul><ul><ul><li>Age 18 or older </li></ul></ul><ul><ul><li>Demonstrable knowledge of what hormones can and cannot do </li></ul></ul><ul><ul><li>Knowledge of social benefits and risks </li></ul></ul><ul><ul><li>Documented real-life test for at least 3 months before HRT </li></ul></ul><ul><ul><li> or </li></ul></ul><ul><ul><li>Period of psychotherapy of duration specified by a mental health professional (usually 3 months) </li></ul></ul><ul><ul><li>A letter from the mental health professional to the prescribing physician </li></ul></ul><ul><ul><li>www.hbigda.org. </li></ul></ul>Standards of Care:
    21. 21. Some important principles <ul><li>There is a lot of misinformation, especially on the Internet </li></ul><ul><li>Hormone therapy remains somewhat “hit and miss” </li></ul><ul><li>“ Individual results will vary”, especially for MTF </li></ul><ul><li>Extremely important to let any treating physician and pharmacist know of all your medications to avoid “drug-drug” interactions and to reduce potential complications </li></ul><ul><li>Need to keep spouse/significant others informed </li></ul>
    22. 22. Reproductive options <ul><li>To give opportunity to obtain children who are genetically “their own” </li></ul><ul><li>Sperm banking prior to HRT for MTF </li></ul><ul><li>FTM’s banking of ovarian tissue or oocytes </li></ul><ul><li>Embryo banking </li></ul>Gender reassignment and assisted reproduction, Human Reproduction 16: 612-614 (2001)
    23. 23. “Real-Life Test” Pros and Cons <ul><li>Pros </li></ul><ul><ul><li>HRT can cause permanent changes including sterility and gynecomastia. RLT may confirm that transitioning is the right choice </li></ul></ul><ul><li>Cons </li></ul><ul><ul><li>HRT makes it easier to pass and easier to attempt RLT </li></ul></ul><ul><ul><li>Most people who would consider hormones are pretty sure of what they want by that time </li></ul></ul><ul><ul><li>HRT is “diagnostic” itself—true transsexuals will feel calmer and relieved upon starting HRT; if not truly transsexual, changes will cause worsening anxiety </li></ul></ul>
    24. 24. Purposes of Feminizing Hormones <ul><li>Induce the development of female secondary sexual characteristics </li></ul><ul><li>Anti-androgen treatment to reduce the effect of endogenous male sex hormones </li></ul>
    25. 25. An important principle— have realistic expectations
    26. 26. Feminizing Hormones DO NOT <ul><li>Cause the voice to increase in pitch. </li></ul><ul><li>Dramatically reduce facial hair growth in most people. There are some exceptions with people who have the proper genetic predisposition and/or are less than a decade past puberty. </li></ul><ul><li>Change the shape or size of bone structure. However, they may decrease the bone density slightly. </li></ul>
    27. 27. Some important DO’s <ul><li>DO review risks and benefits before starting any hormones </li></ul><ul><li>DO be sure that this is what you really, really want…permanent changes can occur within weeks </li></ul><ul><li>DO be patient </li></ul><ul><li>DO eat healthy and exercise </li></ul><ul><li>DO reduce alcohol intake (reduce stress on liver) </li></ul>
    28. 28. Some important DO’s <ul><li>DO have regular medical checkups (every 2-3 months) </li></ul><ul><li>DO watch your blood pressure </li></ul><ul><li>DO take a good multi-vitamin/mineral supplement to help be sure the body has everything it needs for new development </li></ul><ul><li>DO give the body time to adjust </li></ul><ul><li>Use the lowest hormone dosage that affords the desired changes. </li></ul><ul><li>DO make sure you are not allergic to Provera tablets before you use Depo-Provera sustained release intramuscular injection </li></ul><ul><li>DO drink fluids, watch potassium intake if taking spironolactone </li></ul>
    29. 29. Some important DO’s of Doctoring <ul><li>DO see a reputable doctor for your care </li></ul><ul><li>DO get regular check-ups </li></ul><ul><li>DO be honest and up front with your doctor about all medications </li></ul><ul><li>DO make a list of questions prior to each visit—don’t be afraid to ask questions </li></ul><ul><li>EDUCATE your doctor, especially if you disagree </li></ul><ul><li>DO keep records of all changes—physical and emotional, and SHARE them with your doctors </li></ul><ul><li>SEE your doctor for any discharge from breasts </li></ul>
    30. 30. Some important DON’TS <ul><li>DON’T go out on your own for meds </li></ul><ul><li>DON’T alter your medication regimen </li></ul><ul><li>DON’T BUY hormones on the Internet or through Mexico </li></ul><ul><li>DON’T BELIEVE everything you read on the Internet, including web pages, bulletin boards, and chat rooms </li></ul><ul><li>DON’T let your weight get out of control </li></ul><ul><li>DON’T smoke </li></ul><ul><li>DON’T taking the maximum planned dosage of all hormones at once </li></ul><ul><li>DON’T take pre-operative dosages of hormones for more than about 3 years </li></ul>
    31. 31. Effects of Feminizing Hormones on Males <ul><li>Effects vary from patient to patient—familial, genetic tendencies </li></ul><ul><li>Younger patients generally obtain and more rapid results </li></ul><ul><li>Noticeable changes within 2-3 months </li></ul><ul><li>Irreversible effects within 6 months </li></ul><ul><li>Feminization continues at a decreasing rate for two years or more, often with a “spurt” of breast growth and other changes after orchidectomy </li></ul>
    32. 32. Effects of Feminizing Hormones on Males <ul><li>Breast development </li></ul><ul><ul><li>can take years, begins after 2-3 months </li></ul></ul><ul><ul><li>final size about 1 to 2 cup sizes less than close female relatives </li></ul></ul><ul><ul><li>less satisfactory results in older patients </li></ul></ul><ul><ul><li>Only one-third more than a “B”-cup </li></ul></ul><ul><ul><li>45% don’t advance beyond an “A” </li></ul></ul><ul><ul><li>growth not always symmetric </li></ul></ul><ul><ul><li>Larger male thorax “dilutes” effect </li></ul></ul><ul><ul><li>enhanced by progesterone </li></ul></ul><ul><ul><li>nipples expand </li></ul></ul><ul><ul><li>areolae darken </li></ul></ul>clevelandplasticsurgery.com
    33. 33. Effects of Feminizing Hormones on Males <ul><li>Loss of ability to ejaculate/maintain erection (variable) </li></ul><ul><li>Fertility and “male sex drive” drop rapidly—this may become permanent after a few months </li></ul><ul><li>Increased female-type sex drive/attraction to men </li></ul>
    34. 34. Effects of Feminizing Hormones on Males <ul><li>Decreased testicular size (mostly flaccid) </li></ul><ul><li>The prostate shrinks but does not disappear and prostate cancer is still possible (although risk is reduced) </li></ul><ul><li>DO HAVE REGULAR PROSTATE EXAMINATIONS </li></ul><ul><li>Decreased penis size, scrotal size (25% within first year), sometimes requiring the patient to stretch by hand to maintain adequate donor material for SRS </li></ul><ul><li>Spontaneous erections suppressed within 3 months (but not totally eliminated) </li></ul>
    35. 35. Effects of Feminizing Hormones on Males <ul><li>Decreased facial/body hair </li></ul><ul><ul><li>Body hair lightens in texture and color, frequently disappears </li></ul></ul><ul><ul><li>Cessation of male pattern baldness </li></ul></ul><ul><ul><li>Limited regrowth of scalp hair which has been lost </li></ul></ul><ul><ul><li>Improvement in thickness and texture of scalp hair </li></ul></ul><ul><ul><li>Enhanced action of 2% or 5% minoxidil (Rogaine ® ) </li></ul></ul><ul><ul><li>Not much effect on distribution of facial hair </li></ul></ul><ul><ul><ul><li>Enhanced effect of electrolysis </li></ul></ul></ul><ul><ul><ul><li>Decreased rate of growth </li></ul></ul></ul>
    36. 36. Cutaneous Effects of Feminizing Hormones on Males <ul><li>Redistribution of body and facial fat </li></ul><ul><ul><li>Face looks more “feminine”—reduced angularity, fuller cheeks </li></ul></ul><ul><ul><li>Redistribution of fat from waist to hips and buttocks </li></ul></ul><ul><li>Skin softer/smoother/thinner, more translucent, less greasy </li></ul><ul><li>Skin sometimes becomes excessively dry </li></ul><ul><li>Improvement in spots and acne </li></ul><ul><li>Redistribution of fat to hips and buttocks </li></ul><ul><li>Brittle fingernails </li></ul><ul><li>Increased susceptibility to scratching and bruising </li></ul><ul><li>Tactile sensation becomes more intense </li></ul><ul><li>Oil and sweat glands become less active, resulting in dryer skin, scalp, and hair </li></ul>
    37. 37. Effects of Feminizing Hormones on Males <ul><li>Sensory changes </li></ul><ul><ul><li>Heightened sense of touch </li></ul></ul><ul><ul><li>Increased sense of smell </li></ul></ul><ul><li>Emotional changes </li></ul><ul><ul><li>More labile </li></ul></ul>
    38. 38. Effects of HRT on Metabolism in MTF’s <ul><li>Metabolism decreases </li></ul><ul><ul><li>Given a caloric intake and exercise regimen consistent with pre-hormonal treatment </li></ul></ul><ul><ul><ul><li>Weight gain </li></ul></ul></ul><ul><ul><ul><li>Decreased energy, </li></ul></ul></ul><ul><ul><ul><li>Increased need for sleep </li></ul></ul></ul><ul><ul><ul><li>Cold intolerance </li></ul></ul></ul>
    39. 39. Other effects of hormones <ul><li>Reduced risk of Alzheimer’s </li></ul><ul><li>Improved memory </li></ul>
    40. 40. Effects of Feminizing Hormones on Males <ul><li>Loss of muscle mass </li></ul><ul><li>Loss of strength </li></ul><ul><li>Estrogen prevents bone loss after testosterone deprivation </li></ul>Long-term follow-up of bone mineral density and bone metabolism in transsexuals treated with cross-sex hormones, Clinical Endocrinology, 48: 347-354
    41. 41. Changes in Sexual Orientation <ul><li>“Of 20 transsexuals of various types that were interviewed, 6 heterosexual male-to-female transsexual respondents reported that their sexual orientation had changed since transitioning from male to female…three of the respondents claimed that the use of female hormones played a role in changing their sexual orientation.” </li></ul><ul><li>Daskalos CT. Changes in the sexual orientation of six heterosexual male-to-female transsexuals. Arch Sex Behav. 1998;27:605-614 </li></ul>
    42. 42. Risks of Feminizing Hormones — Some General Principles <ul><li>Complete risks in transsexuals is not known </li></ul><ul><ul><li>Most studies are performed in biological women </li></ul></ul><ul><ul><li>Limited research regarding risks </li></ul></ul><ul><ul><li>Safety data and Food and Drug Administration approval do not acknowledge the use of hormones in transsexuals </li></ul></ul><ul><ul><li>All administration is thus “off-label” </li></ul></ul><ul><ul><li>Mortality not necessarily increased </li></ul></ul>
    43. 43. Risks of Feminizing Hormones <ul><li>Blood clots— </li></ul><ul><ul><li>12% over age 40 </li></ul></ul><ul><ul><li>Usually start in the veins of the legs </li></ul></ul><ul><ul><li>Can break off and block blood supply to the lungs—a FATAL complication (pulmonary embolism) </li></ul></ul><ul><ul><li>20-fold increased risk in MTF’s </li></ul></ul><ul><ul><li>Risk increased with oral vs. transdermal estrogens </li></ul></ul><ul><ul><li>Central retinal vein occlusion has been reported </li></ul></ul>Mortality and morbidity in transsexual subjects treated with cross-sex hormones, Clinical Endocrinology, 47: 37-342 (1997)
    44. 44. Risk factors for Venous Thromboembolism <ul><li>Surgery </li></ul><ul><li>Trauma (major or lower extremity) </li></ul><ul><li>Immobility, paresis </li></ul><ul><li>Malignancy </li></ul><ul><li>Cancer therapy (hormonal, chemotherapy, or radiotherapy) </li></ul><ul><li>Previous venous thromboembolism </li></ul><ul><li>Increasing age </li></ul><ul><li>Pregnancy and postpartum period </li></ul><ul><li>Estrogen therapies </li></ul><ul><li>Selective estrogen receptor modulators </li></ul><ul><li>Acute medical illness </li></ul><ul><li>Heart or respiratory failure </li></ul><ul><li>Inflammatory bowel disease </li></ul><ul><li>Nephrotic syndrome </li></ul><ul><li>Myeloproliferative disorders </li></ul><ul><li>Paroxysmal nocturnal hemoglobinuria </li></ul><ul><li>Obesity </li></ul><ul><li>Central venous catheterization </li></ul><ul><li>Inherited or acquired thrombophilia </li></ul><ul><li>Varicose veins </li></ul><ul><li>Smoking </li></ul>Geerts et al. CHEST 2004:338S-400S. Risk Factors are Cumulative
    45. 45. Reducing the Risk of Blood Clots <ul><li>Smoking cessation </li></ul><ul><ul><li>Pharmacologic support </li></ul></ul><ul><ul><li>Relaxation therapy </li></ul></ul><ul><ul><li>Behavioral therapy </li></ul></ul><ul><li>Discontinue HRT for 3-6 weeks prior to any major surgery, including SRS </li></ul><ul><li>Review HRT with surgeon and anesthesiologist prior to minor surgery </li></ul><ul><li>Discontinue HRT in injuries which result in immobilization </li></ul>
    46. 46. Risks of Feminizing Hormones <ul><li>Fluid retention </li></ul><ul><li>Prolactin </li></ul><ul><ul><li>14%, in one study developed elevations </li></ul></ul><ul><ul><li>Pituitary enlargement can sometimes require surgery </li></ul></ul><ul><li>Hypertension </li></ul><ul><ul><li>May vary with hormone regimen </li></ul></ul>Mortality and morbidity in transsexual subjects treated with cross-sex hormones, Clinical Endocrinology, 47: 37-342 (1997)
    47. 47. The Cardiac Risks of Feminizing Hormones <ul><li>Most studies have and are being done in biologic women </li></ul><ul><li>Much evidence suggests that estrogen lowers cholesterol levels, and raises HDL (good cholesterol) </li></ul><ul><li>Increases triglycerides, blood pressure, subcutaneous and visceral fat </li></ul><ul><li>Decreased LDL particle size (bad) </li></ul><ul><li>Decreased insulin sensitivity (bad) </li></ul>
    48. 48. Estrogens and the Heart <ul><li>Current studies </li></ul><ul><ul><li>Women’s Health Initiative </li></ul></ul><ul><ul><ul><li>27,500 enrollees without CAD to test estrogen or estrogen plus progestin post-hysterectomy </li></ul></ul></ul><ul><ul><li>Women’s Angiographic Vitamin and Estrogen </li></ul></ul><ul><ul><li>Women’s Estrogen/Progestin and Lipid Lowering Hormone Atherosclerosis Regression Trial (WELL-HART) </li></ul></ul>
    49. 49. Hormones and the Heart <ul><li>JAMA: July 17, 2002 </li></ul><ul><ul><li>“Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women” </li></ul></ul><ul><ul><ul><li>16,608, ages 50-79 studied </li></ul></ul></ul><ul><ul><ul><li>Received placebo or Premarin ® plus Provera ® </li></ul></ul></ul><ul><ul><ul><li>Study stopped after 5.2 years because of significantly increased risk of cancer in treatment group </li></ul></ul></ul><ul><ul><ul><li>Reduced risk of colorectal cancer and hip fractures </li></ul></ul></ul><ul><ul><ul><li>Increased risk of coronary artery disease, pulmonary embolism, stroke </li></ul></ul></ul>
    50. 50. Hormones and the Heart <ul><li>What is the risk-benefit ratio in post-menopausal women? </li></ul><ul><ul><li>Decreased hot flashes </li></ul></ul><ul><li>How does the risk-benefit ratio differ in transgenders? </li></ul><ul><ul><li>Physical feminization </li></ul></ul><ul><ul><li>Reduced emotional stress </li></ul></ul>
    51. 51. Reducing the Odds of Cardiac Complications <ul><li>If there’s a history or strong family history of heart attack, coronary artery disease, or stroke </li></ul><ul><ul><li>Close supervision by a cardiologist, stress test </li></ul></ul><ul><ul><li>Blood pressure, lipid control, blood thinners </li></ul></ul><ul><li>Estradiol (Estrace ® 1 or 2 mg), a naturally occurring estrogen, is preferred to Premarin ® </li></ul><ul><ul><li>Usual dose is 4 mg daily pre-op, 2 mg daily post-op </li></ul></ul><ul><li>Natural progesterone (Prometrium ® ) does not have the adverse effects of medroxyprogesterone (Provera ® ) on blood cholesterol or blood pressure levels </li></ul><ul><li>Consider daily administration of aspirin 81 mg daily </li></ul><ul><li>Reduce risk factors </li></ul><ul><ul><li>No smoking </li></ul></ul><ul><ul><li>Watch weight </li></ul></ul><ul><ul><li>Watch blood sugar </li></ul></ul>
    52. 52. Risks of Feminizing Hormones <ul><li>Gallstone disease </li></ul><ul><li>Liver disease (low risk) </li></ul><ul><li>Weight gain </li></ul><ul><li>Mood swings </li></ul>
    53. 53. Risks of Feminizing Hormones <ul><li>Cancer risk </li></ul><ul><ul><li>Fibroadenoma—the most common breast tumor </li></ul></ul><ul><ul><ul><li>Influenced by estrogen </li></ul></ul></ul><ul><ul><ul><li>Estrogen receptors present in 28-100% of patients with fibroadenoma </li></ul></ul></ul><ul><ul><li>Breast cancer </li></ul></ul><ul><ul><li>Prostate cancer </li></ul></ul><ul><ul><ul><li>Has been reported </li></ul></ul></ul>
    54. 54. Contraindications to HRT in FTM Patients <ul><li>Absolute </li></ul><ul><ul><li>History of thromboembolism or thrombotic tendency </li></ul></ul><ul><ul><li>History of macroprolactinoma </li></ul></ul><ul><ul><li>History of breast cancer </li></ul></ul><ul><ul><li>Active substance abuse </li></ul></ul><ul><li>Relative </li></ul><ul><ul><li>Coronary artery disease </li></ul></ul><ul><ul><li>Cerebrovascular disease </li></ul></ul><ul><ul><li>Hepatic dysfunction or tumor </li></ul></ul><ul><ul><li>Strong family history of breast cancer </li></ul></ul><ul><ul><li>Cholelithiasis </li></ul></ul><ul><ul><li>Poorly controlled hypertriglyceridemia </li></ul></ul><ul><ul><li>Poorly controlled diabetes mellitus </li></ul></ul><ul><ul><li>Refractory migraine headaches </li></ul></ul><ul><ul><li>Heavy tobacco use </li></ul></ul><ul><ul><li>Uncontrolled hypertension </li></ul></ul>Endocrine Therapy of Transsexualism and Potential Complications of Long-Term Treatment, Archives of Sexual Behavior, 27 : 209-226 (1998)
    55. 55. “DO” Get Appropriate Monitoring <ul><li>Follow-up exams every 2 – 3 month </li></ul><ul><ul><li>Breast exam </li></ul></ul><ul><ul><ul><li>Measurements </li></ul></ul></ul><ul><ul><ul><li>Looking for galactorrhea </li></ul></ul></ul><ul><ul><li>Weight </li></ul></ul><ul><ul><li>Blood pressure </li></ul></ul><ul><ul><li>Testicular size </li></ul></ul><ul><ul><li>Examination of extremities for phlebitis, edema </li></ul></ul><ul><ul><li>Visual fields </li></ul></ul>
    56. 56. Appropriate laboratory monitoring <ul><ul><li>Liver function tests </li></ul></ul><ul><ul><li>Lipid profile </li></ul></ul><ul><ul><li>Renal (kidney) function </li></ul></ul><ul><ul><li>Blood pressure </li></ul></ul><ul><ul><li>Fasting glucose </li></ul></ul><ul><ul><li>Thyroid function </li></ul></ul><ul><ul><li>Blood clotting times (every 6 – 12 months) </li></ul></ul><ul><ul><li>Testosterone levels (<50 ng/dl) in MTF’s </li></ul></ul><ul><ul><li>Prolactin (rule out prolactinoma) </li></ul></ul><ul><ul><li>Breast self-examination </li></ul></ul><ul><ul><li>Prostate examination </li></ul></ul><ul><ul><li>Pregnancy testing (FTM’s) </li></ul></ul>
    57. 57. Monitoring changes <ul><ul><li>Estrogen levels </li></ul></ul><ul><ul><li>Testosterone levels (especially in pre-ops) or if considering antiandrogens in a post-op—can usually be followed o clinical grounds </li></ul></ul>
    58. 58. MTF Monitoring—Johns Hopkins
    59. 59. Other Tests Which Can Be Followed <ul><li>Calcium and phosphorus (skeletal health) </li></ul><ul><li>Bone densitometry every two or three years </li></ul>
    60. 60. Testosterone levels <ul><li>300-1000 ng/dl genetic males </li></ul><ul><li>5-85 ng/dl genetic females </li></ul>
    61. 61. Estrogen levels <ul><li>Levels may be misleading secondary to insensitivity of assays </li></ul><ul><li>Dosing is more commonly made on “clinical grounds” </li></ul>
    62. 62. Administration of Hormones <ul><li>Orally (estrogens, progesterones, androgens) </li></ul><ul><ul><li>Advantage: convenience </li></ul></ul><ul><ul><li>Disadvantage: increased stress on the liver </li></ul></ul>
    63. 63. Administration of Hormones <ul><li>Sublingual </li></ul><ul><ul><li>Dissolve under the tongue </li></ul></ul><ul><ul><ul><li>Better absorption </li></ul></ul></ul><ul><ul><ul><li>Avoid passing through the liver which may stimulate clotting problems </li></ul></ul></ul><ul><li>Injections (estrogens, progesterones, androgens) </li></ul><ul><ul><li>Advantages: </li></ul></ul><ul><ul><ul><li>Preferred in setting of liver disease </li></ul></ul></ul><ul><ul><ul><li>Preferred mode of delivering androgens </li></ul></ul></ul><ul><ul><li>Disadvantages: </li></ul></ul><ul><ul><ul><li>unsteady hormone levels (except for sustained-release preparations in oil or microscopic beads) </li></ul></ul></ul><ul><ul><ul><li>pain </li></ul></ul></ul><ul><ul><ul><li>infection risk from hypodermic needle usage </li></ul></ul></ul>
    64. 64. Administration of hormones <ul><li>Skin patches </li></ul><ul><ul><li>Advantage: </li></ul></ul><ul><ul><ul><li>Convenience </li></ul></ul></ul><ul><ul><li>Disadvantage: </li></ul></ul><ul><ul><ul><li>skin irritation, allergy to adhesive </li></ul></ul></ul><ul><li>Cream (estrogens): </li></ul><ul><ul><li>Advantage </li></ul></ul><ul><ul><ul><li>moister and healthier skin. </li></ul></ul></ul><ul><ul><li>Disadvantage: </li></ul></ul><ul><ul><ul><li>low transfer rate into the body, </li></ul></ul></ul><ul><ul><ul><li>requires frequent spread on very large skin surfaces. </li></ul></ul></ul>
    65. 65. Dosing of HRT in Male to Females <ul><li>No generalized agreement </li></ul><ul><li>General principles </li></ul><ul><ul><li>DON’T mix drugs within categories </li></ul></ul><ul><ul><li>Need drugs from these two categories </li></ul></ul><ul><ul><ul><li>Anti-androgens (discontinued post-operatively) </li></ul></ul></ul><ul><ul><ul><li>Estrogens </li></ul></ul></ul>
    66. 66. Taking Just One Class of Medications <ul><li>Anti-androgens alone </li></ul><ul><ul><li>Serious bone density loss </li></ul></ul><ul><li>Estrogens alone </li></ul><ul><ul><li>Does not lower testosterone levels </li></ul></ul>
    67. 67. Common anti-androgens <ul><li>Cyproterone acetate (Androcur®, Cyprostat®) (antigonadotropic) </li></ul><ul><ul><li>Not available in United States </li></ul></ul><ul><ul><li>Androgen receptor antagonist </li></ul></ul><ul><ul><li>50-150 mg/daily </li></ul></ul><ul><ul><li>Oral or injectable </li></ul></ul><ul><ul><li>Risk of liver damage, thromboembolic disease </li></ul></ul><ul><ul><li>Altered carbohydrate metabolism </li></ul></ul><ul><li>Medroxyprogesterone </li></ul><ul><li>Nilutamide (androgen receptor blocker) </li></ul><ul><li>Finesteride Propecia (testosterone antagonist—decreases DHT) </li></ul><ul><ul><li>5 mg daily </li></ul></ul><ul><ul><li>Reduces male pattern baldness </li></ul></ul>
    68. 68. Androgen receptor antagonists <ul><li>Flutamide (Eulexin) </li></ul><ul><ul><li>Androgen receptor antagonist </li></ul></ul><ul><ul><li>Hepatotoxic </li></ul></ul><ul><ul><li>Reduced blood counts, including platelets </li></ul></ul><ul><ul><li>Hypertension </li></ul></ul><ul><ul><li>Fluid retention </li></ul></ul><ul><ul><li>Depression, anxiety, nervousness, lassitude, insomnia, GI disturbances </li></ul></ul><ul><ul><li>250 mg one to three times daily </li></ul></ul>
    69. 69. Antiandrogens <ul><li>Spironolactone </li></ul><ul><ul><li>Weak androgen receptor antagonist </li></ul></ul><ul><ul><li>Diuretic </li></ul></ul><ul><ul><li>Can cause elevated potassium levels </li></ul></ul><ul><ul><li>Antihypertensive </li></ul></ul><ul><ul><li>100 to 400 mg daily </li></ul></ul>
    70. 70. GnRH Agonists <ul><li>Act on pituitary </li></ul><ul><ul><li>Overstimulating pituitary </li></ul></ul><ul><ul><li>Then desensitizing it to GnRH from hypothalamus </li></ul></ul><ul><ul><li>Used in adolescents to delay puberty or when hormones are withdrawn prior to surgery to reduce reversion to male </li></ul></ul><ul><ul><li>Limited experience </li></ul></ul><ul><ul><li>Drugs: </li></ul></ul><ul><ul><ul><li>Nafarelin acetate nasal spray </li></ul></ul></ul><ul><ul><ul><li>Goserelin acetate injection </li></ul></ul></ul><ul><ul><ul><li>Lupron </li></ul></ul></ul><ul><ul><ul><li>Leunrorelin acetate </li></ul></ul></ul>
    71. 71. A word about herbals <ul><li>Not benign—potential for liver injury </li></ul><ul><li>Still a medication and self-medicating </li></ul><ul><li>Unregulated by FDA </li></ul>
    72. 72. Common estrogens <ul><li>Estradiol valerate (Estrace®) </li></ul><ul><ul><li>Equivalent to natural 17  -estradiol </li></ul></ul><ul><ul><li>May be safer than ethinylestradiol </li></ul></ul><ul><ul><li>Reduced risk of breast cancer and thrombosis although how much risk reduction in high doses of transsexuals is not known </li></ul></ul><ul><ul><li>4-6 mg pre-op in divided doses </li></ul></ul><ul><ul><li>1-2 mg daily post-op </li></ul></ul><ul><ul><li>Best combined with an antiandrogen </li></ul></ul><ul><ul><li>If hot flushes, night sweats appear, switch to ethinylestradiol may be helpful </li></ul></ul>
    73. 73. Common estrogens <ul><li>Ethinylestradiol (Estinyl®) </li></ul><ul><ul><li>Slowly metabolized by the liver, resulting in greater potency and longer half life </li></ul></ul><ul><ul><li>Regarded by many as pre-op drug of choice </li></ul></ul><ul><ul><li>More intense feminizing effects </li></ul></ul><ul><ul><li>50  g twice daily, gradually reduced to 50  g </li></ul></ul>
    74. 74. Common estrogens <ul><li>Conjugated natural estrogens (Premarin®) </li></ul><ul><ul><li>From urine of pregnant mares </li></ul></ul><ul><ul><li>Ethical issues </li></ul></ul><ul><ul><li>More expensive </li></ul></ul><ul><ul><li>5 – 7.5 mg daily pre-op (divided doses) </li></ul></ul><ul><ul><li>1 – 2.5 mg daily post-op </li></ul></ul>
    75. 75. Common estrogens <ul><li>Estraderm® patches </li></ul>50-100 µg/day tramdermally
    76. 76. Common progestogens <ul><li>Anti-androgenic </li></ul><ul><li>Not feminizing alone </li></ul><ul><li>Enhances feminization from estrogen </li></ul><ul><li>May help maintain libido </li></ul><ul><li>May reduce cancer risk associated with estrogens </li></ul>
    77. 77. Medroxyprogesterone acetate Provera® <ul><li>Good safety record </li></ul><ul><li>May be slightly virilizing—may be metabolized into testosterone </li></ul><ul><li>If virilization occurs, switch to dydrogesterone </li></ul><ul><li>Typical dose 5 mg twice daily pre-op for 10 days of the month </li></ul><ul><li>May enhance breast development </li></ul><ul><li>2.5 – 5 mg daily post-op </li></ul>
    78. 78. Natural Progesterone <ul><li>Micronized progesterone </li></ul><ul><li>Progesterone USP </li></ul><ul><li>Prometrium </li></ul><ul><ul><li>Molecular structure closer to the progesterone produced in a natal female's body </li></ul></ul><ul><ul><li>Provera has been linked to depression in trans women </li></ul></ul><ul><ul><li>Less androgenic </li></ul></ul><ul><ul><li>More costly </li></ul></ul>
    79. 79. Common HRT in the United States <ul><li>Estrogen preparations </li></ul><ul><ul><li>Conjugated estrogens (Premarin) 2.5-5.0 mg/day </li></ul></ul><ul><ul><li>Estradiol (Estrace) 2-6 mg/day </li></ul></ul><ul><ul><li>Ethinyl estradiol 0.100-0.300 mg/day </li></ul></ul><ul><ul><li>Estradiol transdermal patches 0.1-0.4 mg twice weekly </li></ul></ul><ul><ul><li>Estradiol valerate 20-40 mg every 2 wk </li></ul></ul><ul><li>Antiandrogens </li></ul><ul><ul><li>Spironolactone 200-400 mg/day </li></ul></ul>
    80. 80. Failure to Respond <ul><li>In no changes are seen (including “tender nipples”) within 2-3 months </li></ul><ul><li> or </li></ul><ul><li>Feminization is very limited over a longer period of time </li></ul><ul><li>Serum testosterone, DHEAS levels to rule out overproduction of androgens </li></ul><ul><li>Referral to an endocrinologist </li></ul>
    81. 81. FTM Hormone Replacement <ul><li>Females respond quite well to hormone replacement as adolescents and as adults </li></ul><ul><li>Experience all the changes that genetic males experience during puberty </li></ul><ul><li>Most of these changes are irreversible </li></ul>
    82. 82. Why is FTM easier than MTF? <ul><li>In FTM, addition of androgens excites androgen receptors which are there but dormant </li></ul><ul><li>Puberty occurs again, but differentiating as a male this time </li></ul><ul><li>In MTF, bodies are already differentiated by the natural presence of androgen </li></ul><ul><li>Males are thus “immune” to further pubertal changes </li></ul>
    83. 83. Effects of Masculinizing Hormones on Females <ul><li>Acne </li></ul><ul><li>Male pattern baldness </li></ul><ul><li>Increased muscle mass and development </li></ul><ul><li>Growth of facial and body hair </li></ul><ul><li>Thickening of vocal cords and deepening of voice (not always reversible), not always down to typical male pitch </li></ul>
    84. 84. Effects of Masculinizing Hormones on Females <ul><li>Enlarged clitoris (3-8 cm) with increased libido—can become overly, painfully sensitive, peaks after 2-3 years </li></ul><ul><li>Atrophy of uterus and ovaries </li></ul><ul><li>Growth spurt, closure of growth plates before puberty </li></ul><ul><li>Increased bone density </li></ul><ul><li>Reduced risk of blood clots </li></ul>Testosterone increases bone mineral density in female-to-male transsexuals: a case series of 15 subjects, Clinical Endocrinology, 61: 560-566 Venous Thrombosis and Changes of Hemostatic Variables during Cross-Sex Hormone Treatment in Transsexual People, J. Clin. Endocrin. Metab. 88: 5723-5729 (2003)
    85. 86. Effects of Masculinizing Hormones on Females <ul><li>Fertility decreases--menstrual cycle becomes irregular then stops, usually within 5 months </li></ul><ul><li>Outer skin layer becomes rougher in feeling and appearance </li></ul><ul><li>Prominence of veins </li></ul><ul><li>Fat is redistributed. The face becomes more typically “male” in shape. Fat tends to move away from the hips and toward the waist </li></ul><ul><li>Body odors (skin and urine) change. They become less &quot;sweet&quot; or &quot;musky&quot; and become more &quot;tangy&quot; or &quot;metallic.&quot; </li></ul><ul><li>Emotions change. Aggressive and dominant feelings may increase </li></ul>
    86. 87. Male hormones DO NOT <ul><li>Significantly decrease the size of the breasts. </li></ul><ul><ul><li>However, they may soften somewhat </li></ul></ul><ul><li>Change the shape or size of bone structure </li></ul><ul><li>Grow a penis </li></ul><ul><li>Prevent pregnancy </li></ul><ul><li>Work overnight </li></ul>
    87. 88. Risks of Masculinizing Hormones <ul><li>Ovarian cancer—long-term exposure to endogenous and exogenous androgens are associated with ovarian epithelial cancer </li></ul><ul><li>Steroids increase epidermal growth factors and transforming growth factor (TGF-  ) which promote cancer growth </li></ul><ul><li>Polycystic ovaries </li></ul><ul><li>Endometrial hyperplasia—risk of endometrial cancer </li></ul><ul><li>Breast cancer—breast cells may remain even after mastectomy </li></ul>Ovarian Cancer in Female-to-Male Transsexuals: Report of Two Cases, Gynecologic Oncology 76 : 413-415 (2000)
    88. 89. Risks of Masculinizing Hormones <ul><li>Reduced HDL cholesterol (bad) </li></ul><ul><li>Reduced LDL particle size (bad) </li></ul><ul><li>Increases triglycerides </li></ul><ul><li>Polycythemia (elevated red blood cell levels) </li></ul><ul><li>Increased sweating </li></ul><ul><li>Increased metabolism </li></ul><ul><li>“Hot flashes” </li></ul>
    89. 90. Risks of Masculinizing Hormones <ul><li>Water and sodium retention </li></ul><ul><li>Decreased carbohydrate tolerance </li></ul><ul><li>Obesity and insulin-resistance </li></ul><ul><li>Sleep apnea </li></ul><ul><li>Increased aggressive behavior, hypersexuality (rare) </li></ul><ul><li>Excessive testosterone can convert to estrogen, increase risk of breast cancer </li></ul>
    90. 91. Testosterone and the Liver <ul><li>Testosterone-induced hepatotoxicity </li></ul><ul><ul><li>Increased liver enzyme levels are a frequent occurrence </li></ul></ul><ul><ul><ul><li>occurs in about 15% </li></ul></ul></ul><ul><li>Hepatic adenomas </li></ul><ul><li>Hepatocellular carcinomas </li></ul><ul><li>Peliosis hepatitis—blood-filled cavities in the liver </li></ul>
    91. 92. Contraindications of HRT in FTM’s <ul><li>Absolute </li></ul><ul><ul><li>Pregnancy </li></ul></ul><ul><ul><li>Active substance abuse </li></ul></ul><ul><li>Relative </li></ul><ul><ul><li>History of breast or uterine cancer </li></ul></ul><ul><ul><li>Polycythemia </li></ul></ul><ul><ul><li>Hepatic dysfunction or tumor </li></ul></ul><ul><ul><li>Coronary artery disease </li></ul></ul><ul><ul><li>Hyperlipidemia </li></ul></ul><ul><ul><li>History of violent behavior </li></ul></ul><ul><ul><li>Severe obstructive sleep apnea </li></ul></ul><ul><ul><li>Androgen sensitive epilepsy </li></ul></ul><ul><ul><li>Migraines </li></ul></ul><ul><ul><li>Bleeding disorders (for injected testosterone) </li></ul></ul>Hormone replacement therapy (trans) http://en.wikpedia.org/wiki/Hormone_ re-placement_therapy_(trans)
    92. 93. Common Androgen Replacement <ul><li>Injectable testosterone </li></ul><ul><ul><li>Testosterone enanthate 100-400 mg IM every 2-3 wk </li></ul></ul><ul><ul><li>Testosterone cypionate 100-200 mg IM every 2-3 wk </li></ul></ul><ul><ul><li>Can be self-administered </li></ul></ul><ul><li>Transdermal testosterone </li></ul><ul><ul><li>Testosterone transdermal patches† 2.5-7.5 mg/day </li></ul></ul><ul><ul><li>Testosterone gel 1% (AndroGel)† 2.5-10 g/day </li></ul></ul><ul><ul><ul><li>Risk of inadvertent exposure to others who come into contact with skin </li></ul></ul></ul>EXCESSIVE TESTOSTERONE MAY LEAD TO STROKE AND HEART ATTACK Endocrine Therapy of Transsexualism and Potential Complications of Long-Term Treatment, Archives of Sexual Behavior, 27 : 209-226 (1998)
    93. 94. Other androgen replacement <ul><li>Testosterone pellets (Testopel) </li></ul><ul><ul><li>6 -12 pellets under the skin every three months </li></ul></ul><ul><ul><li>Local anesthetic </li></ul></ul><ul><ul><li>More constant blood levels </li></ul></ul><ul><li>Oral </li></ul><ul><ul><li>Andriol—not available in the US </li></ul></ul><ul><ul><li>Has to pass through liver </li></ul></ul><ul><li>Sublingual/buccal lozenge </li></ul><ul><ul><li>Striant—absorbed through oral mucosa, avoiding liver </li></ul></ul><ul><ul><ul><li>Gum irritation </li></ul></ul></ul><ul><ul><ul><li>Taste changes </li></ul></ul></ul><ul><ul><ul><li>Headaches </li></ul></ul></ul>
    94. 95. Drug Interactions of Testosterone <ul><li>Drugs which decrease levels of testosterone levels: </li></ul><ul><ul><li>Phenobarbital and Dilantin (seizure medicines) </li></ul></ul><ul><ul><li>Rifampin </li></ul></ul><ul><ul><li>Alcohol! </li></ul></ul><ul><li>Drugs which increase levels of testosterone: </li></ul><ul><ul><li>Serzone, Prozac, Paxil (antidepressants) </li></ul></ul><ul><ul><li>Sporanox, Diflucan (antifungals) </li></ul></ul><ul><ul><li>Tagamet </li></ul></ul><ul><ul><li>Biaxin, Zithromax (antibiotics) </li></ul></ul><ul><ul><li>Protease Inhibitors (HIV treatment) </li></ul></ul><ul><li>Testosterone can also alter the effects of other drugs: </li></ul><ul><ul><li>Increase the blood thinning effect of Coumadin </li></ul></ul><ul><ul><li>Decreases the effectiveness of Inderal (propranolol) a blood-pressure medicine </li></ul></ul><ul><ul><li>Increases the effect of some oral medicines for diabetes and can cause dangerously low blood sugar levels </li></ul></ul>
    95. 96. Progesterone Treatment in FTM’s <ul><li>Short-course progesterone therapy to </li></ul><ul><ul><li>Induce menstrual period in first 2 years to shed build-up of endometrial lining (if a hysterectomy has not been performed) </li></ul></ul><ul><ul><ul><li>Reduces spot bleeding </li></ul></ul></ul><ul><ul><ul><li>Decreases risk of uterine cancer </li></ul></ul></ul>
    96. 97. FTM Monitoring—Johns Hopkins
    97. 98. Some FTM Do’s <ul><li>Prior to hormone therapy , consider hysterectomy and bilateral salpingo-oophorectmy </li></ul><ul><ul><li>Eliminates risk of ovarian cancer </li></ul></ul><ul><ul><li>Saves awkward situation of doing a hysterectomy on a masculinized patient </li></ul></ul><ul><li>Stress management </li></ul><ul><li>Giving blood </li></ul><ul><li>Be patient </li></ul><ul><li>PAP smears, pelvic examination if you still have a uterus </li></ul><ul><li>Check bone densitometry </li></ul><ul><li>Endometrial ultrasounds every two years </li></ul><ul><li>Take a calcium supplement </li></ul>
    98. 99. Some FTM Don’ts <ul><li>Don’t buy too many shoes—your feet will grow </li></ul><ul><li>More is not better </li></ul>
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