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Hormone Replacement Therapy for Transgenders Do's and Don't's


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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> </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>
  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) 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>