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ABUSE OF ANABOLIC STEROIDS & CARE OF TRANSGENDER PATIENTS Michael S. Irwig, M.D. Associate Professor of Medicine Division of Endocrinology & Metabolism.

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Presentation on theme: "ABUSE OF ANABOLIC STEROIDS & CARE OF TRANSGENDER PATIENTS Michael S. Irwig, M.D. Associate Professor of Medicine Division of Endocrinology & Metabolism."— Presentation transcript:

1 ABUSE OF ANABOLIC STEROIDS & CARE OF TRANSGENDER PATIENTS Michael S. Irwig, M.D. Associate Professor of Medicine Division of Endocrinology & Metabolism

2 Disclosures

3 Review the use and abuse of androgens and anabolic steroids Discuss the morbidity and mortality of anabolic steroid use Review the endocrine and surgical protocols for transgender patients Discuss the morbidity and mortality in transgender patients Objectives

4 Anabolic Androgenic Steroids (AAS) PRACTICAL ISSUES Underground labs Imports from foreign countries Law enforcement – drug trafficking Safety – what is the actual dose? Sterility Counterfeit and bogus drugs DEFINITION Doping - The use of a drug or blood product to improve athletic performance.

5 The Goldman Dilemma QUESTION POSED TO ELITE ATHLETES: “Would you take an illegal performance enhancing drug that was undetectable and guaranteed you would win an Olympic gold medal, if it would kill you in five years?” 52%

6 Anabolic Androgenic Steroids (AAS) 17α alkylated substitutions There is no known mechanism to remove these substitutions; hence unique metabolites are present in the blood and urine Esterifications The longer the carbon chain ester, the more non-polar (fat-soluble) and greater half life Steroid nucleus

7 Legitimate Uses of AAS Osteoporosis: Tibolone - androgen, estrogen and progestin systems ↑ bone mineral density Hematopoietic: Anemia of end-stage renal disease (ESRD) erythropoietin dependent and independent Aplastic anemia Fanconi anemia Growth: Constitutional delay of growth and puberty Muscle wasting disorders: AIDS and cancer

8 Effects of Anabolic Steroids Muscle Hypertrophy: ↑ muscle fiber diameter ↑ lean body mass Positive nitrogen balance Retention of potassium, phosphates and sulfates Blood Volume: ↑ red cell mass Glucocorticoid Receptor Antagonists: Inhibit catabolism Central Nervous System: Function of androgen receptors in the brain is unclear

9 Prevalence of AAS Use in the US National Longitudinal Study of Adolescent Health Over 20,000 7 th -12 th grade students in 1994 Nationally representative sample 7 years of follow-up data Personal interviews & questionnaires RESULTS Lifetime use was 2.6% (M) and 0.9% (F) Previous year use was 2.3% (M) and 0.4% (F) Beaver KM et al. Am J Public Health 2008

10 Prevalence of AAS Use in the US National Household Survey on Drug Abuse (1991) 32,594 respondents aged 12 and older randomly selected response rate was 84% personal interviews & questionnaires RESULTS Lifetime use was 0.9% (M) and 0.1% (F) Median age of first use = 18 years old As compared to those who did not report use, those who used AAS were also more likely to have used illicit drugs Yesalis CE et al. JAMA 1993

11 Prevalence of AAS Use in the US National Household Survey on Drug Abuse (1991) Yesalis CE et al. JAMA 1993 Aggressive act within the past 12 months: Property crime within the past 12 months: AGENON-USERSUSERS %83% %36% AGENON-USERSUSERS %80% %23% P < 0.01 for all

12 Testosterone, Exercise and Strength Bhasin S, et al. N Engl J Med 1996 STUDY: Randomized controlled trial SUBJECTS: 43 men aged % of ideal body weight no competitive sports in past year GROUPS:placebo with no exercise, T with no exercise, placebo with exercise, T with exercise DESIGN:4 wk control, 10 wk treatment, 16 wk recovery standardized diet (kcal, protein) controlled, supervised strength training 3/wk

13 Testosterone, Exercise and Strength Bhasin S, et al. N Engl J Med 1996

14 Adverse Effects of AAS in Both Sexes Acne Infertility Anovulation Amenorrhea Testicular atrophy Oily skin

15 Voice deepening Larynx enlarges Vocal cords stiffen Adverse Effects of AAS in Women Clitoromegaly Male pattern balding Breast atrophy

16 Serious but Rare Adverse Effects Hepatocellular adenoma and carcinoma Peliosis Hepatis - blood-filled cysts in liver or spleen

17 Cardiovascular Effects of AAS Nieminem MS et al. Eur Heart J 1996 Four cases of serious CVS effects in male weightlifters: 33 yoLV wall thickening and ventricular dilatation 29 yoventricular tachycardia (230 beats/min) cardioversion echo – dilated LV, thickened LV walls; EF 40% 27 yolarge bilateral intraventricular thrombi 31 yocongestive heart failure LV hypertrophy reduced after stopping AAS In male weightlifters, steroids  Left ventricular wall thickness Left ventricular mass End-diastolic volume

18 Physiological Effects of AAS Urhausen A et al. J Steroid Biochem 2003 In male bodybuilders and powerlifters, 15 Ex-abusers age 38 ± 7; weight 90 ± 10 kg 17 Abusers age 31 ± 5; weight 96 ± 10 kg HORMONESEX-ABUSERSABUSERS Testosterone 421 ± ± 1001 SHBG 32 ± 155 ± 5 Estradiol 25 ± 8124 ± 91 LH 3.2 ± ± 0.2 FSH 5.1 ± ± 1.1 P <0.001 for all

19 Physiological Effects of AAS Urhausen A et al. J Steroid Biochem 2003 In male bodybuilders and powerlifters, 15 Ex-abusers age 38 ± 7; weight 90 ± 10 kg 17 Abusers age 31 ± 5; weight 96 ± 10 kg HORMONESEX-ABUSERSABUSERS Testosterone 421 ± ± 1001 SHBG 32 ± 155 ± 5 Estradiol 25 ± 8124 ± 91 LH 3.2 ± ± 0.2 FSH 5.1 ± ± 1.1 P <0.001 for all

20 Physiological Effects of AAS Urhausen A et al. J Steroid Biochem 2003 In male bodybuilders and powerlifters, 15 Ex-abusers age 38 ± 7; weight 90 ± 10 kg 17 Abusers age 31 ± 5; weight 96 ± 10 kg HORMONESEX-ABUSERSABUSERS Testosterone 421 ± ± 1001 SHBG 32 ± 155 ± 5 Estradiol 25 ± 8124 ± 91 LH 3.2 ± ± 0.2 FSH 5.1 ± ± 1.1 P <0.001 for all

21 Physiological Effects of AAS Urhausen A et al. J Steroid Biochem 2003 In male bodybuilders and powerlifters, 15 Ex-abusers age 38 ± 7; weight 90 ± 10 kg 17 Abusers age 31 ± 5; weight 96 ± 10 kg HORMONESEX-ABUSERSABUSERS Testosterone 421 ± ± 1001 SHBG 32 ± 155 ± 5 Estradiol 25 ± 8124 ± 91 LH 3.2 ± ± 0.2 FSH 5.1 ± ± 1.1 P <0.001 for all

22 Physiological Effects of AAS Urhausen A et al. J Steroid Biochem 2003 EX-ABUSERSABUSERS CBC -- Hematocrit44 ± 348 ± 2 -- Erythrocytes5.13 ± ± Leucocytes6600 ± ± Thrombocytes220 ± ± 58 LFTS -- ALT24 ± 1065 ± AST18 ± 1138 ± 27 LIPIDS -- Total cholesterol176 ± ± 39 (NS) -- Triglycerides118 ± 4477 ± LDL-cholesterol103 ± ± 37 (NS) -- HDL-cholesterol43 ± 1117 ± 11

23 Physiological Effects of AAS Urhausen A et al. J Steroid Biochem 2003 EX-ABUSERSABUSERS CBC -- Hematocrit44 ± 348 ± 2 -- Erythrocytes5.13 ± ± Leucocytes6600 ± ± Thrombocytes220 ± ± 58 LFTS -- ALT24 ± 1065 ± AST18 ± 1138 ± 27 LIPIDS -- Total cholesterol176 ± ± 39 (NS) -- Triglycerides118 ± 4477 ± LDL-cholesterol103 ± ± 37 (NS) -- HDL-cholesterol43 ± 1117 ± 11

24 Physiological Effects of AAS Urhausen A et al. J Steroid Biochem 2003 EX-ABUSERSABUSERS CBC -- Hematocrit44 ± 348 ± 2 -- Erythrocytes5.13 ± ± Leucocytes6600 ± ± Thrombocytes220 ± ± 58 LFTS -- ALT24 ± 1065 ± AST18 ± 1138 ± 27 LIPIDS -- Total cholesterol176 ± ± 39 (NS) -- Triglycerides118 ± 4477 ± LDL-cholesterol103 ± ± 37 (NS) -- HDL-cholesterol43 ± 1117 ± 11

25 Neuropsychiatric Effects of AAS Su TP, et al. JAMA 1993 Symptom scores in the high dose methylT, as compared to the placebo baseline, showed significant increases in POSITIVE MOOD Euphoria Energy Sexual arousal NEGATIVE MOOD Irritability Mood Swings Violent feelings Hostility COGNITIVE IMPAIRMENT Distractibility Forgetfulness Confusion 

26 Psychiatric Effects of AAS Pope HG, et al. Arch Gen Psychiatry 1994 STUDY: Retrospective SUBJECTS:156 male athletes recruited from gyms; AAS non-users, current users, past users GROUPS:maximum steroid dose (mg per week) low ( 1000) DESIGN:Structured Clinical Interview for DSM III administered during “on period” and “off steroid” period

27 Psychiatric Effects of AAS Pope HG, et al. Arch Gen Psychiatry 1994 CURRENTPASTNON USERSUSERSUSERS MEDICAL Testicular length(mm) Gynecomastia (%)24313 ONOFFNON DISORDERSTEROIDSSTEROIDSUSERS Manic episode (%)500 Hypomanic episode (%)10*10 Major depression (%)13*54 Dysthymia (%)020 Any mood disorder (%)23*106 Reverse anorexia (%)7110*

28 Psychiatric Effects of AAS Pope HG, et al. Arch Gen Psychiatry 1994 P=0.010 P=0.003 WEEKLY STEROID DOSE MANIC EPISODE (%) HYPOMANIC EPISODE (%) MAJOR DEPRESSION (%) Low (n=12)080 Med (n=51)0106 High (n=25)161228

29 Psychiatric Effects of AAS Pope HG, et al. Arch Gen Psychiatry 1994 P=0.010 P=0.003 WEEKLY STEROID DOSE MANIC EPISODE (%) HYPOMANIC EPISODE (%) MAJOR DEPRESSION (%) Low (n=12)080 Med (n=51)0106 High (n=25)161228

30 Anabolic Steroids Users & Mortality Parssinen M et al. Int J Sports Med 2000 Subjects were suspected users of AAS: 62 male powerlifters who placed 1 st -5 th in Finnish championships during (doping controls began in 1984) Mean age: 35.1 years Mean weight: 107 kg ( kg weight class) Control group: Random population matched for age from the FINRISK/WHO MONICA study from 1982 Copies of death certificates from DeathsRisk of death Powerlifters8/624.6 ( ) Controls34/ Deaths: myocardial infarction (3), suicide (3), hepatic coma (1), lymphoma (1)

31 Care of Transgender Patients

32 Definitions Gender identity -- self representation as male, female, neither or somewhere in between (genderqueer) Gender role -- sex-typical behavior Sexual orientation -- erotic interests Transsexualism -- a person with normal somatic differentiation who is convinced that he or she is a member of the opposite sex (term coined by Hirschfeld in 1923) Disorders of sex development (DSD; formerly intersex, pseudohermaphrodite, etc) -- congenital conditions with atypical development of chromosomal, gonadal or anatomic sex

33 Prevalence of Transsexualism Van Kesteren PJ, et al. Arch Sex Behav in 30,000 1 in 12,000

34 Etiology of Transsexualism Heylens G, et al. J Sex Med 2012 Central subdivision of the bed nucleus of the stria terminalis important in sexual behavior larger in men than women female-sized in MtF transsexuals not related to hormone therapy Twin Studies – concordant for transsexualism Monozygotic twins: 39% (n=23) Same sex dizygotic twins: 0% (n=21) Zhou JN, et al. Nature 1995

35 ICD-10 Criteria for Transsexualism Hembree WC, et al. J Clin Endocrinol Metab 2009 In 2013, the American Psychiatric Association changed the diagnosis of “gender identity disorder” to “gender dysphoria” in the Diagnostic and Statistical Manual of Mental Disorder (DSM-5)

36 Gender Dysphoria ~ 75% of prepubertal children with gender dysphoria do NOT turn out to be transsexual in adolescence Gender dysphoria can be reliably assessed only after the first signs of puberty Hembree WC, et al. J Clin Endocrinol Metab 2009

37 “Coming Out” SELF CHILDREN SIGNIFICANT OTHER CO-WORKERS FRIENDS FAMILY

38 Real Life Test/Experience Real life test – full time living as a member of the desired sex; It tests: 1)person’s resolve 2)capacity to function in the preferred gender 3)Adequacy of social, economic and psychological support

39 Voice/Speech Therapy for MtF

40 Binding

41 National Center for Transgender Equality 2011 Life as a Transgender Person Injustice at Every Turn: A Report of the National Transgender Discrimination Survey Jaime M. Grant PhD, Lisa A. Mottet JD, Justin Tanis D.Min. N=6450 participants From all 50 states, DC, Puerto Rico and Guam Surveys were online or paper

42 National Center for Transgender Equality 2011 Life as a Transgender Person

43 National Center for Transgender Equality 2011 Life as a Transgender Person

44 National Center for Transgender Equality 2011 Life as a Transgender Person

45 National Center for Transgender Equality 2011 Life as a Transgender Person

46 National Center for Transgender Equality 2011 Life as a Transgender Person

47 National Center for Transgender Equality 2011 Life as a Transgender Person * Underground economy – sex work and/or drugs

48 Suicide Among Trans Adults Moody C, et al. Arch Sex Behav 2013 Clements-Noelles, et al. J Homosex 2006 Risk Factors: Younger age Depression Alcohol/drug treatment Forced sex or rape Gender discrimination Physical gender victimization Protective Factors: Social support from family Social support from friends Optimism Child-rearing concern Suicide resilience (perceived ability, resources or competence)

49 Hormonal Therapy Hormonal Therapy

50 M  F Hormonal Therapy ANDROGEN SUPPRESSION Cyproterone acetate (not in US) mg/d Medroxyprogesterone acetate 5-10 mg/d Spironolactone mg/d Hembree WC, et al. J Clin Endocrinol Metab 2009 GnRH AGONIST Leuprolide 7.5 mg IM monthly Histrelin implant q months Spack NP. JAMA 2013

51 M  F Hormonal Therapy FEMINIZATION Oral E2 2-6 mg/d Transdermal E2 patch mg twice a week Parenteral: E2 valerate5-20 mg IM q 2 weeks or cypionate Avoid Ethinyl E2 which venous thromboembolus PROGESTINS There is no evidence that they add to feminization  Hembree WC, et al. J Clin Endocrinol Metab 2009 Spack NP. JAMA 2013

52 Feminizing Effects Hembree WC, et al. J Clin Endocrinol Metab 2009

53 Hormone Abuse Johns Hopkins University 45% of M  F patients were on treatment that exceeded recommended estrogens There is a stronger potential for abuse with the IM formulations Moore E, et al. J Clin Endocrinol Metab 2003

54 F  M Hormonal Therapy MASCULINIZATION Testosterone esters mg IM q 2 wks Testosterone gels daily g/d Testosterone patches mg/d Subdermal testosterone implants Buccal testosterone Hembree WC, et al. J Clin Endocrinol Metab 2009

55 Masculinizing Effects Hembree WC, et al. J Clin Endocrinol Metab 2009

56 Cardiovascular Risk Factors Gooren LJ, et al. J Clin Endocrinol Metab 2008 M  FF  M Body composition -- Weight -- Total body fat -- Visceral fatNS or Lipids -- Total cholesterolNS -- LDL cholesterolNS orNS -- HDL cholesterol -- TriglyceridesNS or        

57 Cardiovascular Risk Factors Gooren LJ, et al. J Clin Endocrinol Metab 2008 M  FF  M Insulin sensitivity -- Fasting insulinNS -- Insulin sensitivityNS or Other -- Systolic & DBPNS orNS -- Homocysteine     

58 Monitoring M  FF  M Total testosterone< 55 ng/dlnormal Estradiol*<200 pg/mL<50 pg/mL ElectrolytesSpironolactone Lipids ✓✓ Hematocrit ✓ Liver function ✓ Prolactin ✓ Pap smearsIf cervix Mammograms± DXAIf risk factors Hembree WC, et al. J Clin Endocrinol Metab 2009 *Conjugated or synthetic estrogens can not be monitored by blood tests

59 Surgical Options Surgical Options

60 Gonadectomy: Removing the testes makes hormone replacement therapy much easier and reduces the risks associated with high doses of hormones such as estrogens Inquire about thoughts about self-castration St. Peter, et al. J Sex Med 2012 M  F Surgery Skin of the penis  wall of the vagina Skin of scrotum  labia majora After surgery tampon dilators should be used to maintain the depth and width of the vagina

61 Tonseth KA, et al. Tidsskr Nor Legeforen 2010 M  F Surgery

62 M  F Facial Feminization MANDIBULAR ANGLE REDUCTION Becking AG, et al. Clin Plast Surg 2007

63 M  F Facial Feminization MANDIBULAR ANGLE REDUCTION Becking AG, et al. Clin Plast Surg 2007

64 M  F Facial Feminization Becking AG, et al. Clin Plast Surg 2007 BIMAXILLARY OSTEOTOMIES

65 M  F Facial Feminization BIMAXILLARY OSTEOTOMIES Becking AG, et al. Clin Plast Surg 2007

66 M  F Facial Feminization FOREHEAD REDUCTION Becking AG, et al. Clin Plast Surg 2007

67 F  M Surgeries -- Mastectomy Tonseth KA, et al. Tidsskr Nor Legeforen 2010

68 Double Mastectomy ( F  M)

69 F  M Surgeries Metaidioplasty/metaidoioplasty (“clitoral free-up”) -- enlarged clitoral tissue is released from its position and moved forward to more closely approximate the position of a penis -- urethral lengthening procedure to allow the patient to urinate through the penis while standing. Scrotoplasty -- joining the two labia to create a scrotal sac -- Insertion of testicular implants Vaginectomy/colpectomy -- Closure or removal of vaginal cavity Hudson’s FTM Resource Guide

70 Metaidoioplasty (F  M Surgery) Tonseth KA, et al. Tidsskr Nor Legeforen 2010

71 Phalloplasty (F  M Surgery) a neopenile erection can be achieved only if some mechanical device (i.e. rod or inflatable apparatus) is imbedded in the penis local groin flap or a microvascular free flap

72 Long Term Follow Up Long Term Follow Up

73 Malignancies Gender Clinic ( ) started and run by Dr. Louis Gooren, an endocrinologist at Amsterdam’s Vrije University M  F N = 2236 F  M N = 876 Breast cancer1 Ovarian cancer2 Prostate cancer N=3 from other studies (were over age 50 when started E) orchidectomy before 40 prevents development of prostate cancer and BPH Gooren LJ, et al. J Clin Endocrinol Metab 2008

74 Standardized Mortality Ratios Asscheman H, et al. Eur J Endocrinol 2011 Cross sex hormones were started before 1997 Median follow-up was 18.5 years Mortality data from the general population were stratified by age and biological sex

75 Mortality Dhejne C, et al. PLoS ONE 2010 All sex-reassigned persons (n=324) in Sweden from Population-based register study with random population controls (10:1) matched by birth year and birth sex

76 Mortality Dhejne C, et al. PLoS ONE 2010 # Events cases/controls Adjusted hazard ratio* (95% CI) Any death27/992.8 ( ) -- Death by suicide10/519.1 ( ) -- Death by CVD9/422.5 ( ) -- Death by neoplasm8/382.1 ( ) Psych admission64/ ( ) Substance misuse22/781.7 ( ) -- Suicide attempt29/444.9 ( ) Any accident32/ ( ) Any crime60/ ( ) -- Any violent crime14/611.5 ( ) *Adjusted for prior psychiatric morbidity and immigrant status

77 Mortality Dhejne C, et al. PLoS ONE 2010 FtM17% MtF19% Psychiatric Hospitalizations PRIOR to changing sex Biological females4% Biological males4% Sex-reassignment improves gender dysphoria but is not a cure-all Patients often still have psychiatric conditions, social isolation, troubled relationships and be victims of discrimination

78 Conclusions In men, use and abuse of anabolic steroids is associated with infertility, gynecomastia, cardiac events, hepatotoxicity, aggression, mood disorders and probably increased mortality Hormone therapy is associated with weight gain in both sexes but it is unclear if any other medical conditions are increased Several studies show increased mortality in MtFs but the studies are inconsistent in FtMs ANABOLIC STEROIDS TRANSGENDER CARE

79 Questions


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