1 Recognizing and Managing Testosterone Deficiency J. Bruce Redmon, M.D. Professor Division of Endocrinology Departments of Medicine and Urologic Surgery
2 Disclosure Information I have no financial relationships to disclose. I will discuss off label use and/or investigational use in my presentation.
3 Outline Evaluate men for testosterone deficiency Summarize current data on risks/benefits of testosterone treatment Identify options for management of testosterone deficiency in various clinical situations
4 Testosterone Deficiency Secondary Hyperprolactinemia-tumor,drugs Sellar/suprasellar tumor Infarction Medication-opiates, MJ Infiltrative-sarcoidosis, histiocytosis hemochromatosis,hypophysitis Chronic illness, malnutrition Congenital-Kallmans Iatrogenic Surgery, XRT Idiopathic GnRH H P LH -- Free T SHBG-T Primary Congenital Klinefelter Trauma Infection Iatrogenic-XRT,chemo Idiopathic Autoimmune -? T T SHBG - aging, hyperthyroidism, hepatitis, estrogens, anticonvulsants - obesity, hypothyroidism, nephrotic syndrome androgens Alb-T Total Testosterone
5 Testosterone and Aging
6 Testosterone and Aging Total T SHBG Free T DHT
7 Normal Testosterone Framingham Heart Study Young healthy men Mean/Median 700 ng/dl (FT 14 ng/dl) 2.5 th 350 (FT 7) 1 st 280 (FT 5-6) Univ Washington very healthy older men Mean 420 ng/dl; 20% < 300 ng/dl EMAS Late onset hypogonadism 3 sexual symptoms-libido, AM erections, ED T < 320 ng/dl and FT < 6.4 ng/dl
8 NEJM 9/12/13
9 T Levels and Effects Baseline T ng/dl Incr body fat < 350 Decr lean mass < 200 Decr leg strength < 45 (female levels) Decr sexual desire < 200 Decr erectile function < 200
10 Clinical Trials
11 Randomized Trials of Testosterone Therapy in Older Men Study Snyder Sih Amory Nair T Trials (1999) (1997) (2004) (2006) (2016) N Age (yrs) Duration 3 yr 1 yr 3 yr 2 yr 1 yr T (ng/dl) Pre/Post 367/ / / / /450 (FT 6/11) Outcomes LBM/FM Strength Physical perf Subjective physical fxn Sex fx, E BMD Body fat Grip strength Memory LBM/FM Grip strength Physical perf BMD Cognitive fxn Anxiety/depression LBM/FM Strength Physical perf QOL BMD Glu tol/is Sexual fxn Physical fxn Vitality
13 The Testosterone Trials Response to 2003 IOM recommendation for short term clinical trials in older men with low T and clinical conditions possibly related to low T. Coordinated set of 7 DB/PC trials. Three main trials Sexual Function, Physical Function, Vitality Four additional Cognitive Function, Anemia, Bone, Cardiovascular Men 65, av T < 275 ng/dl on 2 samples (neither > 300). One year active treatment daily T gel or placebo. Treatment target ng/dl.
14 The Testosterone Trials Screened 51,000 men to enroll 790 (1.5%) main reason insufficiently low T. Baseline Age 72, BMI 31 Av T/FT 230/6 ng/dl; SHBG 30 nm, E2 20 pg/ml. Treatment Av T/FT 450/15 ng/dl; SHBG 30 nm, E2 30 pg/ml.
15 SFT - 1 Outcome
16 IIEF EF Score Baseline Treatment Normal - 21 sildenail wt loss Placebo T
17 PFT - 1 Outcome
18 VT - 1 Outcome
19 Global Responses
20 Adverse Events Deaths Prostate Cancer Incr Hgb MI, Stroke, CV Death P T P T P T P T Year Year Total
21 TOM Trial - 65 and older (av age 74) - Some degree of limited mobility - T ng/dl or FT < 5 ng/dl (av 240/4.5 ng dl) - Aggressive Rx goal ng/dl (av 574 ng/dl) NEJM, 2010
22 Conclusion? If testosterone is low enough and you raise it high enough there may be some (statistical?) benefit? Sexual symptoms may be those most likely to benefit? Short term (1 yr) seems safe (if not too aggressive)?
23 Management Issues Men on T treatment who may not need it. Men on T who want to have children. Monitoring therapy.
24 Dec yo man with dx of hypogonadism recently on T Rx with severe oligospermia and desire to conceive.
25 Oct 2011 Eval of ED Easy fatigue, decr strength/endurance Father with hx of hypogonadism. Pertinent (-) Libido not low Not sad, grumpy No decrease in ability to play sports Doesn t fall asleep after dinner No deterioration in work performance BMI 32, atrophic L testis
26 Lab tests T 274 ng/dl ( ) FT 7.5 (9-30) SHBG 12 nm (13-89) LH 3.2 miu/ml ( ) FSH 1.8 (1 10) Testicular US nl size testes Dx of hypogonadism
27 Started on daily transdermal T Rx. T levels over next year on Rx, Nl Hgb (15 16 range), LH suppressed
28 Summer married Aug 2013 wished to conceive T 928, LH < 0.2 Semen analysis volume 2 ml, no sperm Stopped T. Sept 2013 SA 2.5 ml, no sperm Oct 2013 SA 1 ml, 1 mil/ml
29 Dec 2013 came to see us. Continued off T More problems maintaining erections No HA, change in vision,breast sx No medications, drug use BMI 27, nl BP, nl virilized, VF full, no gynecomastia, testes L 12 ml, R 15-20, nl consistency. Assessment Suppression of HPG axis by exogenous T; question dx of hypogonadism.
30 Recc: Recheck labs now assuming low: Wait let HPG axis recover on its own, might take a few more months. Clomiphene citrate to stimulate axis, speed recovery. ED -? Relationship to T status, use PDI.
31 Labs T 456, SHBG 28, LH 2.5 SA 3.5 ml, 52 mil/ml
32 MacIndoe, JIM 1997 HPG Axis Recovery
33 Bagatell, 1993 JCEM Recovery of Spermatogenesis
34 30 yo man dx idiopathic hypogonadotropic hypogonadism on T therapy, wishes to conceive. Sx fatigue, mood swings, anxiety, depressed mood; more recently ED, decr libido. T levels ( ); SHBG 30,LH 1.4; MRI pituitary - normal. Started on T cypionate injections. Five mos later pt/wife wish to conceive.
35 Seen in our clinic on T Rx approx 5 mos. Three prev pregnancies (two with current partner), most recent 3 yrs ago. Exam nl virilization; testes nl size. T 1320, LH, FSH < 0.1 on therapy. Semen analysis 4.5 ml, est 20 immotile sperm total in sample. Trial of clomiphene 12.5 mg daily.
36 One month T 706, LH months SA 2.8 ml, 6.7 mil/ml, 79% motility. Shortly after wife pregnant. After first trimester stopped clomiphene. 2 months later T = 662, LH months later T = 306, LH 1.7.
37 Clomiphene Citrate Mixed estrogen agonist/antagonist. Stimulates gonadotropins. Off label use in men. Typical doses mg a day.
38 Testosterone Response to Clomiphene Testosterone (ng/dl) Pre Post Clomiphene Citrate 12.5 mg daily
39 Aromatase Inhibitors
40 Weight Loss and Testosterone Levels Corona, Eur J Endocrin, 2013
41 Testosterone Treatment Options
42 Testosterone Therapy Options Intramuscular T esters T enanthate, T cypionate, mg/1-3 wks T undecanoate, 750 mg/10 weeks Transdermal patch once daily Transdermal gel/spray once daily Buccal preparation twice daily Nasal gel three times daily Subcutaneous testosterone pellets, 3-6 mos
43 Variability in T Treatment Levels Swerdloff JCEM 2015
45 Monitoring Therapy Improvement in symptoms are they better? Monitor hemoglobin or hematocrit. Prostate monitoring (?) Signs of excess treatment acne, breast development. Sleep apnea? Dexa
46 Conclusions Unequivocal hypogonadism is uncommon, generally easy to diagnose as to etiology and treatment appears warranted (if the patient wants it). Most men endocrinologists see for possible hypogonadism probably aren t hypogonadal or have mild idiopathic hypogonadotropic hypogonadism of uncertain clinical significance. We have an increasing number of modalities to treat hypogonadism. The challenges are to better understand the risks/benefits of treatment, how to identify men who benefit from treatment and how to appropriately monitor men on treatment.
Male Androgen Replacement Mitchell Sorsby, MD June 19, 2010. QUESTION # 1 Which of the following is not a symptom associated with low T levels? a) decreased libido b) erectile dysfunction c) depression
Late onset Hypogonadism Dr KhooSay Chuan Department of Urology Penang General Hospital Late onset hypogonadism(loh) Definition LOH age associated testoteronedeficiency syndrome (TDS) Male menopause, andropause,
Effects of Hormone Therapy on the Metabolic Syndrome and Cardiovascular Disease Micol S. Rothman, MD Associate Professor of Medicine Endocrinology, Diabetes and Metabolism Clinical Director Metabolic Bone
Testosterone Therapy in Men An update SANDEEP DHINDSA Associate Professor of Medicine Director, Division of Endocrinology and Metabolism, Saint Louis University, St. Louis, MO Presenter Disclosure None
GUIDELINES ON Male Hypogonadism G.R. Dohle, S. Arver,. Bettocchi, S. Kliesch, M. Punab, W. de Ronde Introduction Male hypogonadism is a clinical syndrome caused by androgen deficiency. It may adversely
Androgen Replacement Therapy in the Aging Male Thomas J. Walsh, MD, MS Department of Urology University of California, San Francisco Objectives 1. List 3 effects of androgens on normal male physiology.
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.31 Subject: Testosterone Topical Page: 1 of 9 Last Review Date: September 23, 2016 Testosterone topical
Authoriser: Moya O Doherty Page 1 of 7 BIOCHEMICAL TESTS FOR THE INVESTIGATION OF COMMON ENDOCRINE PROBLEMS IN THE MALE The purpose of this protocol is to describe common tests used for the investigation
Point-Counterpoint: Late Onset Hypogonadism (LOH) We are Under-diagnosing and Treating Men with LOH LOH is a Non-existent Disease ~ Robert E. Donohue, MD Late Onset Hypogonadism LOH: underdx. & undertx
Evaluation and Treatment of Primary Androgen Deficiency Syndrome in Male Patients Jeff Unger, MD Director Chino Medical Group Diabetes and Headache Intervention Center Chino, California January 16, 2008
Laboratory Investigation of Male Gonadal Function Dr N Oosthuizen Dept of Chemical Pathology UP 2010 1 Figure 1. Hypothalamic-pituitary pituitary-testicular testicular axis 2 Testosterone (T) measurement
Alternative management of hypogonadism Tamoxifen Emmanuele A. Jannini, MD Tor Vergata University of Rome ITALY firstname.lastname@example.org What hypogonadism is? What hypogonadism is? It is an empty glass The two
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.33 Subject: Testosterone Injection Implant Page: 1 of 10 Last Review Date: March 17, 2017 Testosterone
Endocrine Update 2016 Mary T. Korytkowski MD Division of Endocrinology University of Pittsburgh Disclosure of Financial Relationships Mary Korytkowski MD Honoraria British Medical Journal Diabetes Research
TUE Application for Testosterone Physician Worksheet Attention Physicians - USADA will not process Therapeutic Use Exemptions (TUE) for the use of testosterone unless all of the requirements for documentation
1. Medical Condition Hypogonadism in men is a clinical syndrome that results from failure of the testes to produce physiological levels of testosterone (testosterone deficiency) and in some instances normal
Male Menopause: Disease or Pseudoscience? March 4, 2015 story: FDA to require warning on labels of testosterone products. 3-30-2015; web William E. Winter, MD University of Florida Departments of Pathology
Aromatase Inhibitors in Male Infertility: The hype of hypogonadism? BEATRIZ UGALDE, PHARM.D. H-E-B/UNIVERSITY OF TEXAS COMMUNITY PHARMACY PGY1 03 NOVEMBER 2017 PHARMACOTHERAPY ROUNDS Disclosures No conflicts
Diagnosis and Clinical Evaluation of Hypogonadism in Adult Patients with Obesity and Diabetes Adrian Dobs, M.D., M.H.S. Professor of Medicine and Oncology The Johns Hopkins University School of Medicine
Overview of Reproductive Endocrinology I have no conflicts of interest to report. Maria Yialamas, MD Female Hypothalamic--Gonadal Axis 15 4 Hormone Secretion in the Normal Menstrual Cycle LH FSH E2, Progesterone,
4 4:4pm Testosterone Therapy: Examining the Evidence SPEAKER Culley Carson, MD Presenter Disclosure Information The following relationships exist related to this presentation: Culley Carson, MD: Consultant
Disorders of Growth and Puberty: How to Recognize the Normal Variants vs Patients Who Need to be Evaluated Paul Kaplowitz, M.D Pediatric Endocrinology. VCU School of Medicine Interpretation of Growth Charts
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.08.37 Subject: Testosterone Powder Page: 1 of 11 Last Review Date: September 18, 2015 Testosterone powder
John Sutton, DO, FACOI, FACE, CCD Carson Tahoe Endocrinology Carson City, NV KCOM Class of 1989 Gonadal Physiology and Disease 3 No Disclosures Gonadal Axis Hypothalamic-pituitary-gonadal Feedback mechanisms
Philip S. Zeitler MD. PhD Division of Endocrinology Children s Hospital Colorado Aurora, Colorado Primary testicular failure Central hormones responsible for onset of puberty are normal The testis itself
Options for Treatment of Hypogonadism in Men Desiring Fertility Preservation Natan Bar-Chama MD Director Male Reproductive Medicine and Surgery The Mount Sinai School of Medicine New York NY American Association
LABioMed Harbor-UCLA Medical Center Division of Endocrinology and Metabolism Reversible Contraceptive Method for Men Niloufar Ilani, M.D. Endocrine Fellow Introduction Unintended pregnancy remains a major
Reproductive Health and Pituitary Disease Janet F. McLaren, MD Assistant Professor Division of Reproductive Endocrinology and Infertility Department of Obstetrics and Gynecology email@example.com Objectives
ANDROGEN DEFICIENCY A GUIDE TO MALE HORMONES A BOOKLET IN THE SERIES OF CONSUMER GUIDES ON MALE REPRODUCTIVE HEALTH FROM First published in July 2003 by Andrology Australia 5th Edition, December 2015 Copyright
PATHOPHISIOLOGY OF SEX HORMONES R. Mohammadi Biochemist (Ph.D.) Faculty member of Medical Faculty CHOLESTEROL IS THE PRECURSOR OF STERIOD HORMONES Cholesterol Pregnenolone 17-OH 17βHSD Pregnenolne DHEA
Klinefelter Syndrome: A Near Miss in a Child with Congenital Hypothyroidism Mandi Cafasso, RN, DNP, CPNP Cincinnati Children s Hospital Medical Center April 28, 2017 Minneapolis, MN PENS Conference Objectives
One Day Hormone Check Patient: EMILY TEST DOB: January 18, 1948 Sex: F MRN: 0000000004 Order Number: J5070009 Completed: March 07, 2014 Received: March 07, 2014 Collected: March 07, 2014 Alec Smart, ND
Late Onset Hypogonadism Toh Charng Chee Hospital Selayang Introduction Although suppressed serum testosterone (T) is common in ageing men, only a small proportion of them develop the genuine syndrome of
Common Issues in Management of Hypothyroidism Family Medicine Refresher Course April 5, 2018 Janet A. Schlechte, M.D. Disclosure of Financial Relationships Janet A. Schlechte, M.D. has no relationships
16 YEAR-OLD OBESE FEMALE WITH OLIGOMENORRHEA Katie O Sullivan, MD Adult/Pediatric Endocrinology Fellow University of Chicago ENDORAMA Thursday, September 4th, 2014 Disclosures No financial interests. Will
Pharmacy Policy Class: Transgender Hormonal Treatment for Adults Line of Business: Medi-Cal Effective date: February 15, 2017 Revision date: February 15, 2017 This policy has been developed through review
Take-Home Messages: Androgens Anthony J. Bella MD, FRCSC Greta and John Hansen Chair in Men s Health Research Division of Urology, Department of Surgery University of Ottawa SUMMARY SLAMS Symposium Clinical
SPECIAL ARTICLE Adult-Onset Hypogonadism Mohit Khera, MD, MBA, MPH; Gregory A. Broderick, MD; Culley C. Carson III, MD; Adrian S. Dobs, MD, MHS; Martha M. Faraday, PhD; Irwin Goldstein, MD; Lawrence S.
Differential Diagnosis of Cushing s Syndrome Cushing s the Diagnostic Challenge Julia Kharlip, MD and Caitlin White, MD Endocrinology, Diabetes and Metabolism Perelman School of Medicine at the University
ISPUB.COM The Internet Journal of Gynecology and Obstetrics Volume 8 Number 1 A Therapeutic Scheme For Oligospermia Based On Serum Levels Of FSH And Estradiol P Sah Citation P Sah. A Therapeutic Scheme
Assessing Adrenal Function in Ill, Hospitalized Patients Bruce Redmon, MD Division of Endocrinology, Diabetes and Metabolism Disclosures Very surprised when I received an email two weeks ago disclosing
Infertility FINANCIAL DISCLOSURE I HAVE NO FINANCIAL INTEREST IN ANY OF THE PRODUCTS MENTIONED IN MY PRESENTATION Bryan K. Rone, M.D. University of Kentucky Obstetrics and Gynecology I AM RECEIVING COMPENSATION
PCOS across the Lifespan: An Update on Diagnosis and Management Heather Gibson Huddleston, MD Assistant Professor University of California San Francisco PCOS: Overview Most common endocrine disorder reproductive
ADRENAL INSUFFICIENCY? FATIGUE? Sajeev Menon MD Endocrinologist KCIM OBJECTIVES Review primary and adrenal insufficiency including clinical and laboratory findings To appropriately interpret the results
Male Hypogonadism More than just a low testosterone? KM Pantalone Endocrinology Conflicts of Interest None to declare Case 1 A 54 year old man is referred for evaluation of low testosterone The patient
Review Article Off label therapies for testosterone replacement Lorenzo DiGiorgio 1, Hossein Sadeghi-Nejad 2 1 Division of Urology, Rutgers New Jersey Medical School, Newark, NJ, USA; 2 Hackensack University
Fertility in the 21 st Century Dr Leigh Searle Fertility Specialist, Obstetrician, Gynaecologist FRANZCOG, PGDipOMG, MBChB Dr Kate Van Harselaar Fertility Specialist, Obstetrician and Gynaecologist Overview
Polycystic Ovarian Syndrome: Treatment Goals and Options Marc Cornier, MD Division of Endocrinology, Metabolism and Diabetes Colorado Center for Health and Wellness University of Colorado School of Medicine
PITUITARY: JUST THE BASICS PART 2 THE PATIENT DISCLOSURE Relevant relationships with commercial entities none Potential for conflicts of interest within this presentation none Steps taken to review and
Case Study 1 Abnormal Uterine Bleeding Case Studies Abigail, a 24 year old female, presents to your office complaining that her menstrual cycles have become a problem. They are now lasting 6 7 days instead
13 y.o male with delayed puberty, and XX chromosomes Stelios Mantis, MD 4-5-12 Initial Clinic Visit CC: 13 2/12 y.o male with a concern for delayed puberty and growth problems. HPI: Complicated past med
Endocrinology Update Dr Colin Johnston Hon Consultant West Herts Trust firstname.lastname@example.org Thyrotoxicosis Symptoms GI symptoms-diarrhoea Fatigue Anxiety Irreg Menstruation Do not be put off the diagnosis
EFFICACY AND SAFETY OF TESTOSTERONE THERAPY FOR LATE-ONSET HYPOGONADISM: AN UPDATE Matthew Ho, PGY-2 Department of Urologic Sciences University of British Columbia OBJECTIVES 1. Review the characteristics
1 How do you diagnose low Testosterone in men? Low Testosterone can be diagnosed if you have 3 or more of the following symptoms: lack of libido fatigue insomnia erectile dysfunction (ED) depression loss
13 th Annual Women s Health Day PCOS Saturday 02/09/2017 Dr Mathias Epee-Bekima O&G Consultant KEMH Learning objectives Perform the appropriate investigations in women where there is a clinical suspicion
GONADAL FUNCTION: An Overview University of PNG School of Medicine & Health Sciences Division of Basic Medical Sciences Clinical Biochemistry BMLS III & BDS IV VJ Temple 1 What are the Steroid hormones?
Menopause Dr Sonia Davison MBBS FRACP PhD Endocrinologist and Clinical Fellow, Jean Hailes for Women s Health Women s Health Research Program, Monash University = the last natural menstrual period depletion
Polycystic Ovary Syndrome (PCOS): Current diagnosis and treatment Anatte E. Karmon, MD Disclosures- Anatte Karmon, MD No financial relationships to disclose 2 Objectives At the end of this presentation,
Hormone Therapy Overview for the Behavioral Health Provider Julie Thompson, PA Fenway Health Continuing Medical Education Disclosure Program Faculty: Julie Thompson, PA Current Position: Physician s Assistant,
Polycystic Ovarian Syndrome (PCOS) for the Family Physician Barbara S. Apgar MD, MS Professor or Family Medicine University of Michigan Ann Arbor, Michigan Important references for PCOS Endocrine Society
Hormonal Control of Human Reproduction Bởi: OpenStaxCollege The human male and female reproductive cycles are controlled by the interaction of hormones from the hypothalamus and anterior pituitary with
Fundamentals of Testosterone Production in Men Dr. HHJ Leliefeld Bruges, Belgium 25-26 September, 2014 PRISM IV Why should we know? Essential for understanding the ratio of diagnosis and treatment of :
Vitamin D and Calcium Therapy: how much is enough DISCLOSURE Daniel D Bikle, MD, PhD Professor of Medicine VA Medical Center and University of California San Francisco Nothing to disclose RECOMMENDATIONS
Infertility Thomas Lloyd and Samera Dean Infertility Definition Causes Referral criteria Assisted reproductive techniques Complications Ethics What is infertility? Woman Reproductive age Has not conceived
Hypogonadism and Testosterone: Who Needs Testosterone Replacement? Mikel Gray, PhD, PNP, FNP, CUNP, CCCN, FAANP, FAAN Professor School of Medicine, Department of Urology School of Nursing, Department of
Male hypogonadism & testosterone replacement therapy Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard Adverse events should also be reported
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.02 Subject: ART Drugs Page: 1 of 7 Last Review Date: September 15, 2017 ART Drugs Description Bravelle
Infertility Dafydd Ywain & Kayleigh Hansen Terminology Epidemiology Aetiology Male infertility Female infertility Conclusion Content Terminology Fecundability The probability of conceiving during a single
Central hemodynamics and prediction of cardiovascular events in patients with erectile dysfunction N.Skliros, N.Ioakeimidis, D.Terentes-Printzios, C.Vlachopoulos Cardiovascular Diseases and Sexual Health
Case 1: 24 yo pregnant female presenting with abnormal TFTs and tachycardia RAJESH JAIN ENDORAMA 3/16/2017 Chief Complaint The ER calls about a 24 year old, 12 weeks pregnant. She presented with tachycardia
HORMONE BALANCE QUESTIONNAIRE FOR MEN Name: Date: Address: City: State: Zip: Home Phone: Cell Phone: Work Phone: Date of Birth: Age: Height: Weight: Primary Care Doctor: Health History Do you have a personal
GENder Education and Care Interdisciplinary Support (GENECIS) Feminizing Medications for Patients with Gender Dysphoria Patient Information and Informed Consent and Assent for Minors Before using medications