The Medical Management of Transgendered Patients

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Outline. Case PresentationClinical QuestionsBackgroundGender Reassignment TherapyHormonal TherapySex Reassignment SurgeryCase Wrap-Up. Case Presentation. Stephanie is a 45 y/o transsexual woman who presents to your WH clinic to establish care with you her new PCP. She would like you to start prescribing her estrogen pills.PMH: HTNPSH: sex-reassignment surgery in 2001.

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The Medical Management of Transgendered Patients

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1. Jo-Anne Suffoletto, MD VA Womens Health Update March 13th, 2009 The Medical Management of Transgendered Patients

2. Outline Case Presentation Clinical Questions Background Gender Reassignment Therapy Hormonal Therapy Sex Reassignment Surgery Case Wrap-Up

3. Case Presentation Stephanie is a 45 y/o transsexual woman who presents to your WH clinic to establish care with you her new PCP. She would like you to start prescribing her estrogen pills. PMH: HTN PSH: sex-reassignment surgery in 2001

4. Case Presentation (cont.) NKDA Meds: Ethinyl estradiol 100 g po day Spironolactone 100 mg po bid SH: nonsmoker, occ. EtOH She has been living as a woman for 10 yrs.

5. Clinical Questions: What type of estrogen should she be on and at what dose? How does this compare to regular HRT for women? What are the risks of hormonal therapy? What type of routine follow-up/screening will she need?

6. Background: Transgender Identities Cross dresser = Transvestite Androgyne bigender, gender-fluid, non-gendered Intersexed physically ambiguous genitalia, CAH Transsexual a person who desires to live and be accepted as, a member of the sex opposite to that assigned at birth

7. Background: Sex and Gender

8. Transsexualism Individuals who experience themselves as being of the opposite sex, despite having the biological characteristics of 1 sex (MtF, FtM) Persistent discomfort with their anatomical sex Desire to live permanently in the social role of the opposite gender Desire sex reassignment surgery (SRS) There is a continuum of expression

10. Background Prevalence of transsexual people 1 in 11,900 males 1 in 30,400 females

11. Five Parts of Gender Reassignment Therapy Diagnostic assessment Psychotherapy Real-life experience in desired role Hormones of desired gender Surgery to change genitalia and other sex characteristics

12. Gender Reassignment Therapy Various Paths Are Possible hormones?real-life experience?surgery real-life experience?hormones?surgery hormones?breast surgery?real-life experience

13. Gender Reassignment Therapy Aims of Hormonal Therapy: To reduce the hormonally-induced secondary sex characteristics of the original sex To induce the secondary sex characteristics of the new sex

14. Sites of Action for Hormone Rx

15. Eligibility Criteria for Hormone Therapy 1. Age =18 years 2. Knowledge of what hormones medically can/cannot do and their social benefits and risks 3. Either: a. Real-life experience = 3 months b. Psychotherapy usually a minimum of 3 months 4. Letter of Recommendation

16. Readiness Criteria 1. Further consolidation of gender identity during the real-life experience or psychotherapy 2. Progress made in mastering other identified problems leading to improving or continuing stable mental health 3. Likely to take hormones in a responsible manner

17. Setting Realistic Expectations for Hormone Therapy Things that feminizing hormones cannot change: Previous effects of androgens on the skeleton, ie. height, size/shape of hands, feet, jaws and pelvis, cannot be reversed Beard density is not slowed by cross-sex hormone administration

18. Setting Realistic Expectations for Hormone Therapy Breast development Starts almost immediately After 2 yrs, no further development expected Most effective in an androgen-deprived state Fat redistribution Thinning and softening of body hair Atrophy of the testes and prostate

19. Clinical Questions: What type of estrogen should she be on and at what dose? How does this compare to regular HRT for women? What are the risks of hormonal therapy? What type of routine follow-up/screening will she need?

20. Commonly used Estrogen Preparations Ethinyl estradiol 50-100 g/day Potent Inexpensive Highest thrombotic risk 17-estradiol valerate 2-4mg po qday Lower thrombotic risk 17-estradiol 100 g/day transdermally twice per week Lowest thrombotic risk ***goal to titrate dose to achieve total testosterone level < 25 ng/dL***

21. Clinical Questions: What type of estrogen should she be on and at what dose? How does this compare to regular HRT for women? What are the risks of hormonal therapy? What type of routine follow-up/screening will she need?

22. Perspective: How do these regimens compare to regular HRT?

23. Estrogen: Does More = Better? Small, observational, case-control study Ethinyl estradiol doses of 500 g/day demonstrated the same amount of testosterone suppression as ethinyl estradiol 100 g/day However, breast growth was enhanced with the higher estrogen doses

24. Suppression of Androgen Action: Inhibition of testosterone secretion or action: reduction in libido improvement of acne decrease in erections

25. Suppression of Androgen Secretion & Action Cyproterone acetate 50mg po bid Androgen receptor antagonist and progestational agent -> suppresses gonadotropin secretion High thrombotic risk when used in combo with estrogen Used in Europe Medroxyprogesterone acetate 5-10mg/day Progestational agent Less effective than cyproterone Spironolactone 100mg po bid Androgen receptor antagonist Least effective of the three

26. Clinical Questions: What type of estrogen should she be on and at what dose? How does this compare to regular HRT for women? What are the risks of hormonal therapy? What type of routine follow-up/screening will she need?

27. Observed mortality in 816 MtF transsexuals treated with estrogens and anti-androgens and Standardized Mortality Ratio (SMR)

28. Observed mortality in 816 MtF transsexuals treated with estrogens and anti-androgens and Standardized Mortality Ratio (SMR)

29. Complications of Hormone Therapy Venous thromboembolism Cardiovascular risk? Prolactinoma Breast Cancer Prostate Cancer

30. Observed morbidity in 816 MtF transsexuals treated with estrogens and anti-androgens, and Standardized Incidence Ratio (SIR)

31. Venous Thromboembolism Retrospective, morbidity and mortality data from Free University in Amsterdam (1997) Reported a 20-fold increased incidence of DVT 21 of the 36 cases occurred within the 1st year of hormone treatment 20 of the 21 cases occurred in oral estrogen users

32. Venous Thromboembolism Substantial decrease in risk as compared to 1989 data from the same institution: In 1989, 45-fold increased incidence of DVT/PE with oral ethinyl estradiol + cyproterone combination therapy Pts with DVT/PE were older (>40) 138 pts had used transdermal estradiol for >1yr and had a much lower incidence of DVT/PE

33. Venous Thromboembolism Based on the 1989 study the authors changed their clinical practice and began to use transdermal estradiol for all pts >40 yrs Subsequent groups have recommended that transdermal estradiol be the first-line agent for all age groups based on these data

34. Cardiovascular Risk 1989 & 1997 Morbidity and Mortality data demonstrate lower than expected incidence rates of MI in MtF transsexuals Biomarker data 1 small study 20 young, non-obese MtF transsexuals were given combination oral ethinyl estradiol 100 + cyproterone 100 mg/d (no controls) Conflicting results: Increased HDL, Decreased LDL good Increased TG, visceral fat, HTN and decreased LDL particle size and insulin sensitivity - bad

35. Complications of Hormone Therapy Venous thromboembolism Cardiovascular risk? Prolactinoma Breast Cancer Only case reports. Prostate Cancer

36. Sex Reassignment Surgery: Eligibility criteria Legal age of majority in the patient's nation =12 months of continuous hormonal therapy =12 months of successful continuous full time real-life experience Psychotherapy throughout the real-life experience Demonstrable knowledge of the cost, required lengths of hospitalizations, likely complications, and post-surgical rehabilitation requirements of various surgical approaches; Awareness of different competent surgeons.

37. Sex Reassignment Surgery: Readiness criteria 1. Demonstrable progress in consolidating ones gender identity 2. Demonstrable progress in dealing with work, family, and interpersonal issues resulting in a significantly better state of mental health

38. Sex Reassignment Surgery (SRS) Orchiectomy Penectomy Vaginoplasty Clitoroplasty Labiaplasty Penile skin inversion, pedicled rectosigmoid transplant, or free skin graft to line the neovagina

39. Sex Reassignment Surgery (SRS) Other surgeries that may be performed to assist with feminine appearance: Tracheal shaving Suction-assisted lipoplasty of the waist Rhinoplasty Facial bone reduction Face-lift Blepharoplasty

40. Transsexuals pre- and s/p SRS Pts must stop their hormone therapy 4 weeks prior to elective surgery due to increased DVT/PE risk After SRS pts should no longer require progestational agents for additional anti-androgen effects They can resume hormonal therapy at regular HRT doses after SRS once they are fully mobile. Castrated pts who do not continue long-term HRT are at risk for developing osteoporosis

41. Follow-up and Screening

42. Back to Our Patient Stephanie is a 45 y/o transsexual woman who presents to your WH clinic to establish care with you her new PCP. She would like you to start prescribing her estrogen pills. PMH: HTN PSH: sex-reassignment surgery in 2001 NKDA Meds: Ethinyl estradiol 100 g po day Spironolactone 100mg po bid

43. Back to our patient Switch to transdermal 17-estradiol 50 g/day (lower HRT dosing) Cont. spironolactone Screening: PSA, lipids, LFTs, testosterone (baseline level), prolactin level, Breast exam, mammogram, DEXA

44. Acknowledgement Thank you to Melanie Gold, D.O. for providing me with additional resources.

45. References Asscheman H, Gooren LJ, et al. Metabolism. 1989; 38:869-73. Elbers JM,Giltay EJ, et al. Clin Endocrinology (Oxf). 2003; 58:562-71. Standards of care for gender identity disorders, 6th version. The Harry Benjamin International Gender Dysphoria Association. 2001. Van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf) 1997; 47:337-42. Van Kesteren PJ, Lips P, Gooren LJ et al. Long-term follow-up of bone mineral density and bone metabolism in transsexuals treated with cross-sex hormones. Clin Endocrinol (Oxf) 1998; 48:347. Moore E, Wisniewski A, Dobs A. Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse events. J Clin Endocrinol Metab 2003; 88:3467. http://theemergencesite.com/Tech/TechIssues-TransGender-Chart.htm www.gendersanity.com www.wpath.org www.uptodate.com - Treatment of transsexualism. 2007.

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