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ABUSE OF ANABOLIC STEROIDS & CARE OF TRANSGENDER PATIENTS

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Presentation on theme: "ABUSE OF ANABOLIC STEROIDS & CARE OF TRANSGENDER PATIENTS"— 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 Objectives 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

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

5 52% 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 Beaver KM et al. Am J Public Health 2008
Prevalence of AAS Use in the US National Longitudinal Study of Adolescent Health Over 20,000 7th -12th 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) Aggressive act within the past 12 months: AGE NON-USERS USERS 12-17 38% 83% 18-34 13% 36% Property crime within the past 12 months: AGE NON-USERS USERS 12-17 27% 80% 18-34 11% 23% P < 0.01 for all Yesalis CE et al. JAMA 1993

12 Testosterone, Exercise and Strength
STUDY: Randomized controlled trial SUBJECTS: 43 men aged 19-40 90-115% 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 Bhasin S, et al. N Engl J Med 1996

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

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

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

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

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

18 Urhausen A et al. J Steroid Biochem 2003
Physiological Effects of AAS In male bodybuilders and powerlifters, 15 Ex-abusers age 38 ± 7; weight 90 ± 10 kg 17 Abusers age 31 ± 5; weight 96 ± 10 kg HORMONES EX-ABUSERS ABUSERS Testosterone 421 ± 121 1641 ± 1001 SHBG 32 ± 15 5 ± 5 Estradiol 25 ± 8 124 ± 91 LH 3.2 ± 1.3 0.2 ± 0.2 FSH 5.1 ± 1.9 0.5 ± 1.1 P <0.001 for all Urhausen A et al. J Steroid Biochem 2003

19 Urhausen A et al. J Steroid Biochem 2003
Physiological Effects of AAS In male bodybuilders and powerlifters, 15 Ex-abusers age 38 ± 7; weight 90 ± 10 kg 17 Abusers age 31 ± 5; weight 96 ± 10 kg HORMONES EX-ABUSERS ABUSERS Testosterone 421 ± 121 1641 ± 1001 SHBG 32 ± 15 5 ± 5 Estradiol 25 ± 8 124 ± 91 LH 3.2 ± 1.3 0.2 ± 0.2 FSH 5.1 ± 1.9 0.5 ± 1.1 P <0.001 for all Urhausen A et al. J Steroid Biochem 2003

20 Urhausen A et al. J Steroid Biochem 2003
Physiological Effects of AAS In male bodybuilders and powerlifters, 15 Ex-abusers age 38 ± 7; weight 90 ± 10 kg 17 Abusers age 31 ± 5; weight 96 ± 10 kg HORMONES EX-ABUSERS ABUSERS Testosterone 421 ± 121 1641 ± 1001 SHBG 32 ± 15 5 ± 5 Estradiol 25 ± 8 124 ± 91 LH 3.2 ± 1.3 0.2 ± 0.2 FSH 5.1 ± 1.9 0.5 ± 1.1 P <0.001 for all Urhausen A et al. J Steroid Biochem 2003

21 Urhausen A et al. J Steroid Biochem 2003
Physiological Effects of AAS In male bodybuilders and powerlifters, 15 Ex-abusers age 38 ± 7; weight 90 ± 10 kg 17 Abusers age 31 ± 5; weight 96 ± 10 kg HORMONES EX-ABUSERS ABUSERS Testosterone 421 ± 121 1641 ± 1001 SHBG 32 ± 15 5 ± 5 Estradiol 25 ± 8 124 ± 91 LH 3.2 ± 1.3 0.2 ± 0.2 FSH 5.1 ± 1.9 0.5 ± 1.1 P <0.001 for all Urhausen A et al. J Steroid Biochem 2003

22 Urhausen A et al. J Steroid Biochem 2003
Physiological Effects of AAS EX-ABUSERS ABUSERS CBC -- Hematocrit 44 ± 3 48 ± 2 -- Erythrocytes 5.13 ± 0.37 5.55 ± 0.41 -- Leucocytes 6600 ± 1800 8800 ± 1700 -- Thrombocytes 220 ± 72 303 ± 58 LFTS -- ALT 24 ± 10 65 ± 55 -- AST 18 ± 11 38 ± 27 LIPIDS -- Total cholesterol 176 ± 37 165 ± 39 (NS) -- Triglycerides 118 ± 44 77 ± 45 -- LDL-cholesterol 103 ± 30 138 ± 37 (NS) -- HDL-cholesterol 43 ± 11 17 ± 11 Urhausen A et al. J Steroid Biochem 2003

23 Urhausen A et al. J Steroid Biochem 2003
Physiological Effects of AAS EX-ABUSERS ABUSERS CBC -- Hematocrit 44 ± 3 48 ± 2 -- Erythrocytes 5.13 ± 0.37 5.55 ± 0.41 -- Leucocytes 6600 ± 1800 8800 ± 1700 -- Thrombocytes 220 ± 72 303 ± 58 LFTS -- ALT 24 ± 10 65 ± 55 -- AST 18 ± 11 38 ± 27 LIPIDS -- Total cholesterol 176 ± 37 165 ± 39 (NS) -- Triglycerides 118 ± 44 77 ± 45 -- LDL-cholesterol 103 ± 30 138 ± 37 (NS) -- HDL-cholesterol 43 ± 11 17 ± 11 Urhausen A et al. J Steroid Biochem 2003

24 Urhausen A et al. J Steroid Biochem 2003
Physiological Effects of AAS EX-ABUSERS ABUSERS CBC -- Hematocrit 44 ± 3 48 ± 2 -- Erythrocytes 5.13 ± 0.37 5.55 ± 0.41 -- Leucocytes 6600 ± 1800 8800 ± 1700 -- Thrombocytes 220 ± 72 303 ± 58 LFTS -- ALT 24 ± 10 65 ± 55 -- AST 18 ± 11 38 ± 27 LIPIDS -- Total cholesterol 176 ± 37 165 ± 39 (NS) -- Triglycerides 118 ± 44 77 ± 45 -- LDL-cholesterol 103 ± 30 138 ± 37 (NS) -- HDL-cholesterol 43 ± 11 17 ± 11 Urhausen A et al. J Steroid Biochem 2003

25  Neuropsychiatric Effects of AAS
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 Su TP, et al. JAMA 1993

26 Psychiatric Effects of AAS
STUDY: Retrospective SUBJECTS: 156 male athletes recruited from gyms; AAS non-users, current users, past users GROUPS: maximum steroid dose (mg per week) low (<300), medium ( ), high (>1000) DESIGN: Structured Clinical Interview for DSM III administered during “on period” and “off steroid” period Pope HG, et al. Arch Gen Psychiatry 1994

27 Psychiatric Effects of AAS
CURRENT PAST NON USERS USERS USERS MEDICAL Testicular length (mm) Gynecomastia (%) ON OFF NON DISORDER STEROIDS STEROIDS USERS Manic episode (%) Hypomanic episode (%) 10* 1 0 Major depression (%) 13* 5 4 Dysthymia (%) Any mood disorder (%) 23* Reverse anorexia (%) * Pope HG, et al. Arch Gen Psychiatry 1994

28 Psychiatric Effects of AAS
WEEKLY STEROID DOSE MANIC EPISODE (%) HYPOMANIC MAJOR DEPRESSION Low (n=12) 8 Med (n=51) 10 6 High (n=25) 16 12 28 P= P=0.003 Pope HG, et al. Arch Gen Psychiatry 1994

29 Psychiatric Effects of AAS
WEEKLY STEROID DOSE MANIC EPISODE (%) HYPOMANIC MAJOR DEPRESSION Low (n=12) 8 Med (n=51) 10 6 High (n=25) 16 12 28 P= P=0.003 Pope HG, et al. Arch Gen Psychiatry 1994

30 Parssinen M et al. Int J Sports Med 2000
Anabolic Steroids Users & Mortality Subjects were suspected users of AAS: 62 male powerlifters who placed 1st-5th 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 Deaths Risk of death Powerlifters 8/62 4.6 ( ) Controls 34/1094 1.0 Deaths: myocardial infarction (3), suicide (3), hepatic coma (1), lymphoma (1) Parssinen M et al. Int J Sports Med 2000

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
1 in 30,000 1 in 12,000 Van Kesteren PJ, et al. Arch Sex Behav 1996

34 Etiology of Transsexualism
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 Heylens G, et al. J Sex Med 2012

35 ICD-10 Criteria for Transsexualism
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) Hembree WC, et al. J Clin Endocrinol Metab 2009

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” SIGNIFICANT OTHER CHILDREN SELF FRIENDS FAMILY CO-WORKERS

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

39 Voice/Speech Therapy for MtF

40 Binding

41 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 National Center for Transgender Equality 2011

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

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

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

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

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

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

48 Suicide Among Trans Adults
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) Clements-Noelles, et al. J Homosex 2006 Moody C, et al. Arch Sex Behav 2013

49 Hormonal Therapy

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

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

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
M  F F  M Body composition -- Weight -- Total body fat -- Visceral fat NS or Lipids -- Total cholesterol NS -- LDL cholesterol -- HDL cholesterol -- Triglycerides Gooren LJ, et al. J Clin Endocrinol Metab 2008

57 Cardiovascular Risk Factors
M  F F  M Insulin sensitivity -- Fasting insulin NS -- Insulin sensitivity NS or Other -- Systolic & DBP -- Homocysteine Gooren LJ, et al. J Clin Endocrinol Metab 2008

58 Monitoring M  F F  M Total testosterone < 55 ng/dl normal
Estradiol* <200 pg/mL <50 pg/mL Electrolytes Spironolactone Lipids Hematocrit Liver function Prolactin Pap smears If cervix Mammograms DXA If risk factors *Conjugated or synthetic estrogens can not be monitored by blood tests Hembree WC, et al. J Clin Endocrinol Metab 2009

59 Surgical Options

60 M F Surgery 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 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 St. Peter, et al. J Sex Med 2012

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

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
BIMAXILLARY OSTEOTOMIES Becking AG, et al. Clin Plast Surg 2007

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)
local groin flap or a microvascular free flap a neopenile erection can be achieved only if some mechanical device (i.e. rod or inflatable apparatus) is imbedded in the penis Tonseth KA, et al. Tidsskr Nor Legeforen 2010

72 Long Term Follow Up

73 Malignancies Gender Clinic (1975-2006)
started and run by Dr. Louis Gooren, an endocrinologist at Amsterdam’s Vrije University M F N = 2236 F M N = 876 Breast cancer 1 Ovarian cancer 2 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
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 Asscheman H, et al. Eur J Endocrinol 2011

75 Mortality All sex-reassigned persons (n=324) in Sweden from 1973-2003
Population-based register study with random population controls (10:1) matched by birth year and birth sex Dhejne C, et al. PLoS ONE 2010

76 # Events cases/controls Adjusted hazard ratio* (95% CI)
Mortality # Events cases/controls Adjusted hazard ratio* (95% CI) Any death 27/99 2.8 ( ) -- Death by suicide 10/5 19.1 ( ) -- Death by CVD 9/42 2.5 ( ) -- Death by neoplasm 8/38 2.1 ( ) Psych admission 64/173 2.8 ( ) Substance misuse 22/78 1.7 ( ) -- Suicide attempt 29/44 4.9 ( ) Any accident 32/233 1.4 ( ) Any crime 60/350 1.3 ( ) -- Any violent crime 14/61 1.5 ( ) *Adjusted for prior psychiatric morbidity and immigrant status Dhejne C, et al. PLoS ONE 2010

77 Mortality Psychiatric Hospitalizations PRIOR to changing sex
Biological females 4% Biological males FtM 17% MtF 19% 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 Dhejne C, et al. PLoS ONE 2010

78 Conclusions ANABOLIC STEROIDS
In men, use and abuse of anabolic steroids is associated with infertility, gynecomastia, cardiac events, hepatotoxicity, aggression, mood disorders and probably increased mortality TRANSGENDER CARE 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

79 Questions


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