Male Sexual Dysfunction: Evaluation,Treatment and the Role of Testosterone. UAPRN Georgia Conference September 24, 2016 Elizabeth H.

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1 Male Sexal Dysfnction: Evalation,Treatment and the Role of Testosterone UAPRN Georgia Conference September 24, 2016 Elizabeth H. Brgess, MD

2 Learning Objectives I. 3 Types of Male Sexal Dysfnction II. III. IV. Focsed H&P Choose labs Primary vs. Secondary Hypogonadism V. Imaging VI. Treatment Options VII. Case Practice

3 3 Types of Male Sexal Dysfnction Decreased libido Erectile dysfnction Ejaclatory dysfnction ( incldes prematre ejaclation, retrograde ejaclation) Gideline on Male Sexal Dysfnction, Eropean Association of Urology

4 3 qestions Libido Morning erections Erections partial or go away too fast?

5 Decreased libido Psychological components partner interactions or conflicts stress, depression Physical Components systemic illness, sleep disorders Medication side effects: especially SSRI s, anti-htn, anti-androgens, finasteride. Alcoholism Low testosterone

6 Erectile Dysfnction Erectile dysfnction the inability to achieve and maintain an erection sfficient for satisfactory sexal intercorse Organic Vasclar, nerologic, hormonal, drg related Psychogenic Performance related isses, anxiety, depression, stress Mixed Affects p to 1/3 of adlt men Common in patients with HTN, ischemic heart disease and diabetes mellits

7 Cases of Erectile Dysfnction vary by onset Nerologic - loss of spontaneos morning erections ( slow onset) Vasclar loss of spontaneos erections (slow onset) [CV disease, Diabetes, PVD...] Psychogenic (sdden onset) Increased life stress Performance anxiety in a new relationship

8 Cases of Erectile Dysfnction Tramatic: after prostatectomy ( sdden onset ) Side effect of medications: thiazides, beta blockers, finasteride ( onset variable ) Hormonal low testosterone ( slow onset ) Interpersonal conflict rarely acknowledged

9 Ejaclation disorders Prematre ejaclation: occrs within one minte of vaginal penetration and reslts in distress for the male. Treat with SSRI. absent ejaclation: side effect of antidepressants and alpha adrenergic antagonists like tamslosin. Retrograde ejaclation: Bladder neck sphincter damage dring prostate srgery. Vacm pmp erection aids. Present with infertility and azoospermia

10 3 qestions Libido Morning erections Erections partial or go away too fast?

11 History Onset and dration > sdden vs. slow onset Relationship to new medication Increased life stress trama Presence of chronic diseases SHIM sexal health inventory for men

12 History Symptoms of low testosterone Low energy fatige decreased libido decreased mscle mass decreased body hair hot flashes gynecomastia Infertility pberty? children?

13 Physical exam General Physical vasclar or nerologic abnormalities, absence of testosterone effect. Femoral plses or brits and peripheral plses Nerologic exam monofilament testing in feet/hands, position sense, vibratory sense at the extremities Hair growth pattern: Body hair, facial hair body habits enchoid?

14 Physical Exam GU exam: Penile plaqes àpeyronie s disease micropenis Testicles small, soft, atrophic? Gynecomastia VF confrontation bitemporal hemianopsia

15 Labs CMP for liver and kidney fnction TSH Lipid profile to assess cardiac disease Fasting glcose, A1C

16 Shold we jst screen for low testosterone? NO Poplation screening is not cost effective. Prse case detection in grops that are high risk Absent libido and spontaneos morning erections Osteoporosis associated fractres HIV associated weight loss Those on chronic narcotics or high dose steroids for prolonged periods Men with small atrophic testes on exam.

17 How often is low testosterone the problem? 20% of men in their 60s will have hypogonadism 30% of men in their 70s will have hypogonadism Not all erectile dysfnction, decreased libido, loss of mscle mass, depression or decreased sense of well being is related to low testosterone. Critical Update of the 2010 Endocrine Society Clinical Practice Gidelines for Male Hypogonadism: A Systemic Analysis. Mayo Clin Proc Agst 2015:90(8):

18 Labs: Testosterone testing Serm total testosterone before 8am ( AACE before 10am) If serm total testosterone is below normal on lab reference, confirm by repeating the total testosterone Free testosterone if yo sspect SHBG problem àshbg decreased in obesity and increases with age Check LH, if testosterone is confirmed as low. Consider prolactin, free t4 if testosterone <150

19 Imaging: q=mri+pictre+of+pititary+macroadenoma&view=detailv2&id=36a2ef1459b801b85d2307edd1e8759ce5c65 31B&selectedindex=4&ccid=RaAkw4R3&simid= &thid=JN.BoR2WemaHt2Rc625B%2FJg &mode=overlay&first=1 If more than one pititary hormone is low, àmri

20 Pititary macroadenoma q=mri+pictre+of+pititary+macroadenoma&view=detailv2&id=36a2ef1459b801b85d2307edd1e8759ce5c6531b&select edindex=4&ccid=raakw4r3&simid= &thid=jn.bor2wemaht2rc625b%2fjg&mode=overlay&first=1

21 Etiology of low testosterone If there is indication for checking testosterone, and low vales fond and confirmed, DETERMINE CAUSE Not enogh to find a low testosterone and jst treat. Need to give patient an explanation for why the testosterone is low.

22 Hypogonadism Primary vs. Secondary

23 Both Primary and Secondary Hypogonadism case Loss of sperm prodction Loss of testosterone prodction Primary (testes): FSH and LH elevated, testosterone low Secondary (pititary or hypothalams): FSH and LH low or inappropriately normal and testosterone low.

24 Hypothalamic Pititary Axis X X

25 Hypogonadism? Prevalence 4 to 35% in men with Erectile Dysfnction. One stdy of 422 men with ED Hypogonadism 19% Hypothyroidism (hypogonadotropic hypogonadism) or hyperthyroidism (increased SHBG) in 6% Hyperprolactinemia 4% Drgs that raise prolactin inhibit fsh/lh and lead to hypogonadotropic hypogonadism

26 Common drgs that raise prolactin Haloperidol, risperidone Amitriptyline, sertraline, floxetine, paroxetine, bspirone, alprazolam Metoclopramide Verapamil Morphine Ranitidine, cimetidine Ther Clin Risk Manag Oct; 3(5):

27 Evalation and Treat History Physical Exam Labs Now what?

28 First case 50 yo male with BMI of 25 presents complaining of erectile dysfnction Libido low, morning erections occr bt not as often, + fatige and low energy, erections for intercorse are partial Thinks he has thyroid problems or low testosterone Physical exam > 1+ DP/PT plses, o/w normal GU: testes not soft, 20cc volme. Labs drawn at 1:30pm

29 Labs Testosterone 248mg/dl ( normal 300 to 1000) (other assays se ng/dl) Tsh is 2.5 IU/ml Shold we treat? Remember time of day, confirm x 1 and if consistently low, check LH.

30 First case Repeat testosterone was 400 ng/dl at 8am. Trial of phosphodiesterase inhibitor given with adeqate response Meds reviewed and HCTZ changed to alternate agent.

31 Medications can case Erectile Dysfnction Most common drgs associated with ED are anti-htn meds Thiazides and Beta blockers Chronic narcotics -case sppression of FSH/LH Side effects of finasteride/ssri s. Sometimes better to adjst meds vs adding another

32 FDA approved treatments PDE inhibitors: if nerologic or vasclar etiology sspected. Can help libido. Sildenafil/Viagra, Vardenafil/Levitra, Tardenafil/Cialis ( longest acting ), Avanafil Contraindicated with nitrates Cation with alpha blockers se low dose Side effects of nasal congestion, priapism, vision / hearing changes

33 Sildenafil citrate is an inhibitor of cgmp specific phosphodiesterase type-5 (PDE5) in smooth mscle, where PDE5 is responsible for degradation of cgmp. Sildenafil citrate increases cgmp within vasclar smooth mscle cells reslting in relaxation and vasodilation. In patients with erectile dysfnction, sildenafil citrate enhances the effect of nitric oxide (NO) by inhibiting PDE5 in the corps cavernosm. When sexal stimlation cases local release of NO, inhibition of PDE5 by sildenafil citrate cases increased levels of cgmp reslting in smooth mscle relaxation and inflow of blood to the corps cavernosm

34 If oral PDE inhibitor fails Second line Alprostadil sppositories in rethral meats May case brning discomfort Third line Intracavernosal injections of alprostadil Can be painfl Forth line Penile implant Erect aid vacm pmp if pt s can t take meds.

35 ED and CV disease Endothelial dysfnction common pathway Consider CV evalation before initiating therapy for sexal dysfnction Assess whether low, medim or high risk Medim and High risk patients may need stress test/cv evalation Nitrates contraindicated with PDE inhibitors

36 Second case Obese 70 yo male with BMI 48 presents with erectile dysfnction Testosterone at 3pm 200ng/ml normal ng/ml Repeat at 8am was 180ng/ml Repeat with free and total testosterone and LH total testosterone 150 ( low) free testosterone 90 ( normal ), WHY? LH 6 ng/ml (normal).

37 SHBG Sex hormone binding globlin abnormalities occr for varios reasons Decreased in obesity ( makes a total testo seem low) Increases with age ( makes a total testo seem normal) Can increase with liver diseases like hepatitis C. This patient had normal free testosterone and is not hypogonadal. What else can happen to androgens in obese patients?

38 Obesity and Aromatization

39 Case 3 - Older Veteran 66 yr old fond to have low testosterone level on evalation for erectile dysfnction. Wife died several years before and he is interested in dating again. total testosterone was 156 at 8:51 am Repeat total testosterone was 117 at 9:23am FSH 3.3 and LH 2.3 ng/ml ( low normal )

40 Case 3 contined Repeat with total testosterone 145 (low) and free testosterone 22 (low) Prolactin normal at 5.1 TFT s normal

41 Case 3- contined PMHx: BPH and chronic prostatitis. +sleep apnea and has CPAP bt doesn t se MEDs: Takes 40mg of oxycontin SR BID for back and knees. Prescribed for years. takes finasteride and terazosin If I miss a dose, I can t pee. Social: fathered two children. Normal pberty.

42 Physical Exam Bp 130/68, hr 87, temp 98.3, resp 16 BMI 32 VF intact Mild gynecomastia ~3-4 cm bilaterally, nontender GU: normal phalls, testes 12cc volme and soft, atrophic

43 Assessment and Plan Hypogonadotropic hypogonadism Physical exam c/w hypogonadism Prolactin, TFTs, liver, kidney, blood sgar normal. FSH and LH inappropriately low/normal for low total and free testosterone levels MRI recommended He declines. Can t lie still b/c of back pain. Denies HA, n/v, VF cts

44 Assessment Hypogonadotropic Hypogonadism Chronic narcotics likely playing a significant role. Common case of hypogonadotropic hypogonadism. Testosterone?

45 Testosterone? Endocrine Society Clinical Practice Gideline for Testosterone Replacement in Men 2010 Controversial in this patient for several reasons Untreated sleep apnea BPH that reqires 2 meds and is symptomatic if he forgets to take meds. >65 and risk for increased CAD.

46 Critical Update of the 2010 Endocrine Society Clinical Practice Gideline for Male Hypogonadism Mayo Clinic Proc. Agst 2015:90(8): Reconfirmed: Only treat with clear hypogonadal symptoms and testosterone levels <200. Contradindications to reconsider: Untreated sleep apnea and LUTS Another look at CV disease and testosterone se in men over 65 Other grops that might benefit from testosterone: Patients with type 2 diabetes Metabolic syndrome Compensated CHF

47 Contraindication to reconsider: ntreated sleep apnea Untreated sleep apnea: Hoyos et al RCT on 67 middle aged obese men. Treated with IM testosterone x 18 weeks. Only saw increased O2 desat at 7 weeks, not at final end point. No increase in apnea. (Clin Endocrinology (Oxf) ;77(4): ) Hildreth et al RCT in healthy hypogonadal males, treated with Testosterone gel. No increase in Epworth Sleepiness Score or daytime hypoxemia. (JCEM 2013;98(5): ) Critical Update of the 2010 Endocrine Society Clinical Practice Gidelines for Male Hypogonadism: A Systemic Analysis. Mayo Clin Proc Agst 2015:90(8):

48 Contraindication to reconsider: elevated LUTS score LUTS score >19 on International Prostate Symptom Score qestionnaire = contraindication to TRT in 2010 recommendations from Endocrine Society. Severe LUTS has been an exclsion criterion Tan et al RTC of 114 hypogonadal men treated with IM testosterone for 48 weeks. 14.9% had severe LUTS symptoms measred by IPSS. NO difference in symptoms between treated and placebo arms. Small improvement in LUTS symptoms in the treatment arm. ( p=0.54 ) (BJU Int. 2013;111(7): ) Strict contraindication? Critical Update of the 2010 Endocrine Society Clinical Practice Gidelines for Male Hypogonadism: A Systemic Analysis. Mayo Clin Proc Agst 2015:90(8):

49 Testosterone and CV Disease: MAYO 2015 Update Most data is from large retrospective cohort stdies VA 8709 patients increased CV otcomes in testosterone treated patients. Finkle evalated database of 55,593 men for acte MI within 90 days of filling a testosterone prescription. Fond positive association in yonger men with known heart disease and in older men. Medicare database with 6355 men. Fond men at highest risk for MI had a relative redction in risk on testosterone 2015 FDA Safety Annoncement: possible increased MI and CVA risk with TRT se CAUTION High qality trials are needed to address CV morbidity and mortality associated with TRT.

50 Contraindications to Testosterone replacement therapy ( TRT ) Breast cancer Prostate cancer Transgender female to male with + pregnancy History of DVT or PE

51 Cancer and testosterone Absolte contraindication in active breast and prostate cancer patients. Testosterone is not thoght to case prostate cancer. BUT, it can increase prostate and breast cancer growth Discssions with Oncology and Urology late relapses of prostate cancer are common with or withot hormonal treatment Concern abot increased vasclar thrombosis Wold this be higher in cancer patients? BAD IDEA- even in those who are cred

52 Grops not addressed in 2010 gidelines: Type 2 DM and Metabolic Syndrome Does T help inslin sensitivity? Conflicting evidence on inslin sensitivity in Diabetics BLAST stdy in UK = RCT 190 symptomatic hypogonadal men with type 2 DM treated with IM testosterone x 30 weeks Modest improvement in a1c (-0.18) No change in inslin sensitivity, inslin levels or inflammatory markers overall. Testosterone treated grop had improved BMI, weight, waist circmference, sexal fnction and symptoms of hypogonadism improved at 30 weeks.

53 Grops not addressed in 2010 gidelines:type 2 DM and Metabolic Syndrome TIMES2 RCT with 220 symptomatic hypogonadal men with type 2 DM or Metabolic Syndrome. Testo gel for 12 months. Inslin sensitivity improved in first 6 months. BUT, no difference in a1c, fasting lipids, glcose levels or BMI. HDL was significantly decreased BLAST (+) and TIMES2 (-) are conflicting. Men with type 2DM data inconclsive.

54 Hypogonadal Metabolic Syndrome patients Cold they benefit from testosterone treatment? MOSCOW trial: 184 hypogonadal men with metabolic syndrome, treated with IM testosterone x 30 weeks. Lost weight ( kg), decreased BMI ( -1.32kg/m2), decreased waist circmference by 6cm, decreased CRP to 19 for TRT vs. 38 for placebo. Inslin sensitivity and lipid profile not significantly different at 30 weeks. Men with metabolic syndrome data sggests potential benefits. Interesting, bt needs more stdy.

55 Contraindication to testosterone: compensated CHF? Often an exclsion criterion No new data for decompensated CHF NO TESTOSTERONE Stot et al 41 hypogonadal men with stable CHF ( NYHA avg.score = 2.5 +/- 0.5 ) Improved O2 ptake Improved leg strength Critical Update of the 2010 Endocrine Society Clinical Practice Gidelines for Male Hypogonadism: A Systemic Analysis. Mayo Clin Proc Agst 2015:90(8):

56 Back to case 3: Wold yo treat with testosterone?

57 Confirmed hypogonadal patients Testosterone cypionate or enanthate 200mg IM every 2 weeks 100mg IM weekly Testosterone patch 4mg patch, apply new patch daily to nonscrotal skin Testosterone gel 2 pmps to sholders, arms, chest, back. Cover with cloth, flly absorb. Shower before coming into contact with another person if gel applied in last few hors.

58 Monitoring on testosterone Digital prostate exam CBC LFTs Lipids PSA Testosterone level Baseline and 3 to 6 months after treatment starts and then annally Monitor for improvement in symptoms testosterone level goal is mid normal range. Injection measre at midpoint between shots Patch measre 3 to 12 hors after application Gel check anytime once patient on treatment for a week.

59 Monitoring on testosterone Secondary polycythemia most common complication of testosterone treatment Check hematocrit at baseline and then 3 to 6 months after start, then annally. Stop treatment if hct >54% and restart at lower dose once HCT normal. Evalate for hypoxia and sleep apnea.

60 Case 3 Older Veteran Anything else? à Check a bone density Reslts Showed normal spine, hip and back t-score and low FRAX score. Vitamin D ok Recommended repeat bmd in 3-5 years.

61 Effects of Testosterone on Bone Density, Frailty and Mscle Strength Improved spine BMD and hip bt not in all stdies. Overall + trend Effects on risk of fractre in men with osteoporosis not stdied. Inconsistent benefits to mscle strength and physical fnction.

62 Case 4: Yong veteran 32 yo male with h/o hypogonadism, treated since HPI: retrned from Afghanistan 4/1/2010 complaining of ED No sex drive, coldn t maintain an erection Labs checked and told testosterone labs messed p.

63 Case 4 contined No hx of TBI or exposre to IED blast Pberty was a little later than friends arond age 16 or 17. Never fathered children. He and girlfriend weren t sing contraception. No pregnancies.

64 CASE 4 He had infertility workp in 2012 and was told his semen analysis had zero sperm. He is not interested in fertility now. Testosterone treatment fixed his libido and erections. Viagra helps when injection is waning and dose de in a few days. Most recent dose is testosterone 150mg IM weekly

65 Case 4 ROS: mild acne on back, worse in smmer Meds: no other significant meds. Crrent labs: HCT 46.5 PE: VF intact Chaperoned GU exam: testes 20cc volme, not soft, normal phalls

66 2 important points Records didn t show workp for why this 32 year old male is hypogonadal. Before starting testosterone determine if the patient has confirmed hypogonadism and if it is primary or secondary Explore fertility plans. Exogenos testosterone will sppress FSH and LH leading to leydig and sertoli cell dysfnction. This can lead to decreased sperm prodction. Can be permanent.

67 Case 4 evalation Hold testosterone. How long? Months? Check fsh, lh, total testosterone, prolactin, free t4/tsh. His testosterone was 129, LH low normal. Testosterone held a month. MRI negative. Semen analysis azoospermic rare sperm seen. Shold repeat and follow with post collection UA. If sperm present then he also has retrograde ejaclation or other obstrctive process. SSRI or rologist. Hold testosterone for 2 to 3 months and see if axis rebonds.

68 Smmary 3 types of male sexal dysfnction 3 qestions: libido, AM erections, erections partial? Determine etiology of sexal dysfnction Confirm, don t jst treat low testosterone Treatment might reqire removing or changing meds, psychology referrals FDA approved treatments: PDE inhibitors, testosterone Use cation, do no harm.

69 References AACE/ACE Position Statement on the Association of Testosterone and Cardiovasclar Risk. Endocrine Practice 2015;21(No. 9): Critical Update of the 2010 Endocrine Society Clinical Practice Gidelines for Male Hypogonadism: A Systemic Analysis. Mayo Clin Proc Agst 2015:90(8): Gideline on Male Sexal Dysfnction, Eropean Association of Urology Sexal-Dysfnction-2015-v2.pdf Testosterone Therapy in Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Gideline ( JCEM 95; , 2010) Up to Date: reviewed 8/1/2016: Overview of male sexal dysfnction; Clinical featres and diagnosis of male hypogonadism; Treatment of male sexal dysfnction

70 THE END Photo from admireentertainment.com