How to Have Sex in a Canoe: Oar Maintenance and Troubleshooting Francisco J

4/1/2019

How to have sex in a canoe: Oar maintenance and troubleshooting Francisco J. Garcia MD, FRCSC Clinical Assistant Professor, University of Saskatchewan Consultant in Urology, Specialist in Andrology and Sexual Medicine Follow: @drfjgarcia Email: [email protected]

Objectives:

• Be familiar with the domains of male sexual dysfunction (MSD) • Be able to identify common disorders of each sexual domain • Be able to educate patients on their disorder/dysfunction • Be able to initiate 1st line therapies for common MSD diagnoses • Be familiar with erectile dysfunction as a cardiac marker • Be familiar with anatomical diseases of the penis • Be familiar with low testosterone diagnosis, risks and therapy

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Domains of sexual function

• Desire • Orgasm • Ejaculation • Erectile function • Anatomy

Image source: Google Images

Orgasmic dysfunction

• Delayed orgasm • Painful orgasm • Hypo‐orgasmia • Anorgasmia • Persistent Genital Arousal Disorder

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Ejaculatory Dysfunction

• Premature ejaculation • Delayed Ejaculation • Painful Ejaculation • Retrograde Ejaculation • Anejaculation

Image source: Google Images

Erectile Dysfunction

• Arteriogenic • Anatomic • Neurogenic • Endocrine • Psychologic

Image source: testshock.com

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Anatomic

• Peyronie’s Disease • Congenital Penile curvature • Penile fractures • Iatrogenic/self‐inflicted

Desire • TDS/ADAM/Hypogonadism • Psychological • Situational • Iatrogenic (medication/treatment related) • Metabolic disease (Cardiac, Metabolic syndrome, diabetes, thyroid disease, etc)

Image source: Google Images

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Erectile dysfunction

• Lessons to learn: • ED is not luxury diagnosis • Asking about it is not only relevant but crucial to your practice • Every erectile problem is ultimately fixable. • “I’ve yet to meet a penis I can’t make erect.”

Created by: Dr. F. Garcia

How to save a life as a penis doctor...

• Penis as the barometer of cardiac health • Dorsal penile arteries – lumen 1‐2 mm • Coronary arteries – lumen 2‐4 mm • A man’s penis and its function is important and changes are often noticed – but ignored. • Am I just trying to justify sexual medicine?

Created by: Dr. F. Garcia

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Can sexual medicine save lives?

• 133 T2DM men with confirmed silent CAD on angio and 127 T2DM men with negative stress EKG, 48 hr ambulatory ECG and stress echo • IIEF‐5 questionnaires to both groups • More ED in those with silent CAD then in those without (33% vs 5%) • ED most potent predictor of silent CAD (vs HDL, apolipoprotein a, LDL, smoking, and microalbuminuria): OR 14.8; 95% CI (3.8‐56.9) • Ok – so maybe its important to diabetics.... Created by: Dr. F. Garcia

ED as the “canary in the coal mine” • Erectile dysfunction: • Is associated with angiographic CAD in 19% of those presenting with presumed vascular ED • European Urology 48 (2005) 996–1003 • Decreased rigidity is predictive of 6 year myocardial event in Danish population (OR 1.2 moderate, 2.6 severe) • International Journal of Impotence Research (2008) 20, 92–99 • US study (n=10,000) showed that ED diagnosis has an OR 1.45 of CVEs at 10 years, and new ED diagnosis has an OR of 1.25 of CVE • JAMA, December 21, 2005—Vol 294, No. 23 • Has a 65% relative risk increase of CVE and stroke at 10 years • European Urology 48 (2005) 512–518 • Severity predicts CAD severity – OR 2.2 for severe ED • J Sex Med 2009;6:3425–3432 • Younger age at diagnosis increases OR of events: • 20‐29: OR 7.6, 30‐39: OR 7.4, 40‐49: OR 3.4, 50‐59: OR 2.2 • J Sex Med 2010;7:192–202 Created by: Dr. F. Garcia

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ED and CVD Meta‐analysis

• Framingham Risk Score on ED patients: • Moderate and severe ED have 65% and 43% increased risk of CVD and stroke respectively • ED alone doesn’t outcompete FRS, but may be as effective in identifying those at risk • Duplex ultrasound of the penis: If patient has abnormal EKG and PSV < 35, 50% sens, 100% spec, 100% PPV, and 60% NPV to identify ischemic heart disease.

Created by: Dr. F. Garcia

• Calcium scores: • Negatively correlate with SHIM/IIEF‐5 scores • ED patients had increased risk of highest quartile of calcium and volume compared to controls (OR 3.68) • Biomarkers: • ED correlated with hs‐CRP, phopholipase A2, HgbA1c and microalbuminuria

Created by: Dr. F. Garcia

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Created by: Dr. F. Garcia

Can an ED diagnosis be useful in primary care?

• Symptoms of ED appear 2‐3 years before CAD symptoms and 2‐5 years before CAD events • Opportunity for intervention?!?

Created by: Dr. F. Garcia

8 4/1/2019

Fine...perhaps an important signal, but why

bother treating it?• Because sex is fun... • Most relationships are forged with a component of sexuality • Why is the development of an asexual relationship considered acceptable as the relationship matures? • SF‐36 • SF‐36 of erectile dysfunction: 43.6 +/‐ 15 • SF‐36 of treated ED: 74.4 +/‐ 13

Created by: Dr. F. Garcia

Not just important to the men... • Worse QoL in the partners of those with ED

Created by: Dr. F. Garcia

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How do we investigate it?

• History and Physical Examination • Gradual/rapid onset, situtational/generalized, pelvic surgery/rads/trauma, voiding dysfunction, meds, diseases, degree of bother, failed txs, hypogonadal symptoms, etc. • Blood work • Cardiac profile • Screen for diabetes, cholesterol, etc • Hormone profile x 2 • Imaging • Duplex ultrasound of the penis. ** • Testing • “test dosing”

Created by: Dr. F. Garcia

How to treat it?

* Insured service in all provinces except in SK Created by: Dr. F. Garcia

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Abridged treatments

• If abnormal T, symptomatic and appropriate candidate, strongly consider T replacement • PDE5‐Is • On demand full dose prn • Can attempt double dosing • Attempt a month of daily dosing before declaring PDE5‐I resistant • If T is low and PDE5‐I resistant, correct T and rechallenge • Unless a specific reason, move to intracavernosal injection therapy.

Created by: Dr. F. Garcia

Intracavernosal injection therapy

• Multiple compounded therapies available. • Trimix (prostaglandin e1, papaverine, phentolamine) • Standard • Plus • Forte • Ultra • Bimix (Papaverine and phentolamine) • Standard • Plus • Quadmix (Trimix + atropine) • Quintmix (Quadmix + forskolin)

Created by: Dr. F. Garcia

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ICI troubleshooting • Penile pain/Throbbing • Usually due to alprostadil/prostaglandin dosing. Reduce or remove from the mixture • Penile curvature at injection site • Patient not varying the location of injection. Avoid that location and should self resolve • Priapism • Present to emergency department if persists for more than 4 hours. Often responds quickly to intracavernosal phenylephrine. • Bleeding • Patient likely injured a superficial vessel. Visibly confirm no vessels before insertion of needle • Urethral bleeding • Missed the cavernosal body and injected the urethra/spongiosum • Unable to visualize penis for injection • Adipositypractice with a mirror (this takes lots of practice but is doable) or partner injection • Visual defect/disabilitypartner injection or consider penile implant

Technique • Draw up correct dose (takes some teaching to do depending on solution) • Lateral injection into corporal cavernosal body • BURY the needle (1/2” 30 g) • Challenges? • Obesity • Needle phobias

Image source: Menshealthinstitute.ca Created by: Dr. F. Garcia

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Impact of ED correction outside the bedroom

• Improvements in confidence and self esteem • Althof, S. E. et al. J. Gen. Intern. Med. 21, 1069–74 (2006). • Increases in non‐sexual touching and intimacy • SMSNA 2014 – unpublished data

Created by: Dr. F. Garcia

Peyronie’s Disease • 3‐9% of the male population • Benign, incurable disease • Can prevent intromission during sexual encounters, and associated with ED • Variability in curve number, direction, severity and arc contribute to the “embarrassment” barrier to allow study • Pts often complain of length loss and changes in rigidity

Created by: Dr. F. Garcia

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The many shapes...

Created by: Dr. F. Garcia

Natural Hx

• Acute phase (6‐24 mo) • 15 resolve/45 stabilize/40 worsen • Chronic phase • Associated conditions • Tympanosclerosis • Dupuytren’s • Ledderhosen’s • Paget’s • Associated with hypogonadism (30% by TT, 75% by FT) • Role of T as an inflammatory mediator • Importance of T in maintenance of viscoelastic properties of the tunica

Created by: Dr. F. Garcia J Sex Med 2009;6:1729–1735

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My assessment of PD

• Hx • Hx of trauma with intercourse • Onset of pain and curvature • Does the pt have photos • Psychosexual hx • Hearing loss/plantar contracture/dupuytren’s • P/E • Palpate the plaque • Examine for contractures (hand/foot) • Ix • Duplex U/S OR Standard U/S • Hormone profile, CBC, lytes, BUN, Cr

Created by: Dr. F. Garcia

Oral management

• Oral therapies • Potaba • Vitamin E • L‐carnitine • PTX • Colchicine* • Some evidence when acute • Tamoxifen • PDE5‐Is ** • U/S evidence of scar resolution and curve improvement

Created by: Dr. F. Garcia

15 4/1/2019

Traction Therapy • “Stretch” therapy has a long successful history with joint contractures • Difficulty in stretching flaccid penile plaque • Mechanical forces on neighbouring fibroblasts promote scar remodelling • Oldest therapy • Allows patient participation

Created by: Dr. F. Garcia

Intralesional treatments • Verapamil • 10 mg in 10 cc q 2wk x 6‐12 txs • Interferon • Collagenase (Xiaflex)* FDA approval • Others • Steroids...etc.

Created by: Dr. F. Garcia

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My “aggressive conservative” approach • Parallel trimodal therapy • Daily Cialis (5 mg or 2.5 mg) • Improved erectionsplaque stretching • Antifibrotic effect • Intralesional therapy • Mechanical disruption of scar • Scar remodelling • Traction therapy • Mechanical stretch of scar (open up disrupted plaques) • Fibroblast remodelling with mechanical transduction • 1‐2cm length gain with diligent use • Patient empowerment • Results? • Approx 40‐60% of men have response enough to avoid surgical intervention • Average curve correction of 15‐45 degrees.

Created by: Dr. F. Garcia

Surgery

Surgical Options Consent Issues • Plication • Penile length/shape changes • Intracorporal incision • Sensation changes • Grafting • Curve complications • Implantation • Erectile dysfunction

Created by: Dr. F. Garcia

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Intracorporeal incision

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IC‐Incision results

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Grafting

• Reserved for most severe and complex curves • Significant risk of sensation changes (and anorgasmia) d/t elevation of neurovascular bundle • Risk of ED d/t disruption of veno‐occlusive mechanisms • Importance of post‐operative traction use!

Created by: Dr. F. Garcia

Index Case • 59 yo M • Symptoms: complains of low energy x 3 years, decreased libido, soft erections for 5 years. Used to walk the golf course and needs a cart now. Wife says he’s been more “crusty with a short fuse” for a few source: Google Images years now. • PMHx – T2DM, Depression • Meds – Metformin, Celexa • P/E – obese male, waist circumference = 50 inch • Soc: last child moved to college a year ago • FHx – his dad died of an MI at 60 • Ix: Testosterone = 11.3 nmol/L

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Low Testosterone/Hypogonadism

• Real scarcity of descriptive statistics • Different definitions of different societies • Inter‐assay variability • Non‐specific nature of historical symptoms • MMAS estimates at 12.3/1000‐person years, or approximately 481k new cases/yr in American men age 40‐69. • Boston Aging Community health study estimates incidence at 5.6% in men age 30‐70, supported by an Australian study, the European Male Aging Study.

Testosterone

• Synthesized from cholesterol • Principal steroid produced by testis • Cyclical regulation via LH pulses, inhibin and activin • Biological half‐life, 2‐4 hours • Exists in free and bound forms • Bound to albumin (reversible) or Sex Hormone Binding Globulin (Irreversible) • High variability in CAG repeats in T receptor, high variability in sensitivity of receptor

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Free (0.5‐3%)

Albumin SHBG Bound Bound (~60%) (~38%)

Testosterone Synthesis

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Testosterone regulation • Regulated through the HPG axis • Negative and positive feedback • Multiple modulators to GnRH secretion

Image source: Campbell’s Urology 9th Edition

Testosterone Rhythms

Image source: Campbell’s Urology 9th Edition

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Symptoms?

• Low Libido • Low energy/fatigue • Weakness • Lost height • Anhedonia • Mood/personality changes • Erectile dysfunction • Physical performance deterioration • Somnolence • Cognition changes

Metabolic consequences of hypogonadism

Depression No libido Personality changes Cognitive decline

Increased lipids Cardiac events Gynecomastia

Metabolic Obesity syndrome/Insulin resistance Testicular atrophy

Muscle loss Bone loss

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Consequences of untreated low T

• Sexual dysfunction • Diabetes** • Metabolic syndrome** • Decreased max. exercise capacity • Obesity • Psychological effects • Osteoporosis • Decreased muscle mass • Lower quality of life • Increased mortality rate • Increased cardiovascular risk** Image source: Google Images

Diabetes?!? • Unpublished abstract from SMSNA 2015 • Correction of T in hypogonadal men reduces HgbA1c in diabetic and non‐diabetic men

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Mortality and Diabetes?

1.000 TT>10.4 nmol/l • Mortality 17% vs 9% 343‐312* 0.975 TT≤10.4 nmol/l • Approximately 600 238‐197* 0.950 diabetic men • 0.925 Observational study • Muraleedharan V, et 0.900 Cumulative Survival al. Eur J Endocrinol. P=0.009 0.875 HR=2.02 (1.2‐3.4) 2013

0 20 40 60 80 Survival (months)

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Cardiac markers

Overall Mortality?

Mortality 10.3% (Treated) vs 20.7% (Untreated)

Shores MM et al, J Clin Endo Metab, 2012.

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Testosterone and cardiac comorbidities

• Hypogonadal men with CHF (meta‐analysis) • Improves exercise capacity • Greater improvements as compared to conventional treatments (ACE‐Is, Cardiac Resynch, alpha blockers) • Toma M, et al. Circ Heart Fail. 2012;5:315‐21. • Testosterone therapy in hypogonadal men with angina significantly improved time to ischemic threshold vs. Placebo • Malkin CJ, et al. Heart. 2004;90:871‐6.

Approach to diagnosis of low T

• Signs and symptoms suggestive of Low Testosterone • Morning testosterone blood draw (between 8 am and 11 am) • If normal, consider other causes • If abnormal or borderline, repeat with full bloodwork

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Definitions

• Cdn Endo Soc • Low total T (300 ng/dL [US] or 10.4 nmol/L) • Measured twice • Both morning samples (before 11 am) • AND Symptoms • If total T borderline AND symptoms, consider adding free T calculations • SMSNA • Same as above, but can attempt “trial of therapy” for 3‐6 months if symptoms and borderline low T • Saskatchewan Laboratories reference range? • 5.6‐28.0 nmol/L

Definitions

• ISSAM (International Society for the Study of the Aging Male): Symptoms + • Two measures of TT < 12.1 nmol/L • If > 12.1 nmol/L, free T can be calculated • Free T < 200 pmol/L (0.2 nmol/L) is positive • If > 12.1 nmol/L, normal %free and ++ symptoms, can consider 3‐6 month trial of therapy based on clinical judgement.

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Meds that affect T synthesis/levels (Adapted from ISSM) • Ketoconazole – complete synthesis inhibition • Cimetidine (Tagamet) • Spironolactone (Aldactone) • Serotinergic antidepressants • Chemotherapy • Chronic opoid use – via beta‐endorphin secretion • Statins (affect may be insignificant)

Image source: Google Images

Low T high risk groups • Type 2 diabetes • Metabolic syndrome • HIV‐associated weight loss • Treatment with opioids, glucocorticoids or ketoconazole • Osteoporosis or low trauma fracture at a young age • End‐stage renal disease and maintenance hemodialysis • Chronic obstructive pulmonary disease • Infertility • Sellar region mass, disease, radiation or trauma • Use of street drugs • Liver disease 1. Morales et al. CUAJ. 2010;4:269‐75.

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More than just a number

What comprises my Low T workup?

• Basics: • CBC, lytes, BUN, Cr • LFTs • AST, ALT, ALP, GGT • Cardiovascular • HgbA1c, Lipid profile, +/‐ uric acid • Endocrine • T, E2, FSH, LH, SHBG, Prolactin • Tumour Marker ‐ PSA • DEXA (selected patients) Image source: Adobe Stock

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Normal T, what else to consider?

• Depression • Hypothyroidism • Sexual dysfunction (low libido/ED) from other causes • Osteoporosis • Cardiovascular disease • Metabolic syndrome • Diabetes • Anemia • Low relative T

Source: Google Images

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S&S suggestive of TDS/ADAM or complication of low T

Hx & P/E, am Total T>12 nmol/L Testosterone (TT)

TDS unlikely, consider T <10.4 nmol/L T 10.4‐12 nmol/L other causes

Repeat TT with Alb, SHBG, FSH, LH, E2, PRL, LFTs and CBC. % free >2%

Clinical suspicion of TDS T <10.4 nmol/L % free < 1% % free 1‐2% extremely high, other causes ruled out

Confirmed TDS Consider Trial of TRT for 3‐6 mo TRT 63

Free Testosterone

• Some variability in definitions • Free T < 200 pmol/L (0.2 nmol/L) • Free T < 2% • Etc. • Unless using equilibrium dilution (very expensive and rarely done), better to calculate. • Need SHBG

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Elevate SHBG Decrease SHBG OCPs/Estrogen Anabolic steroids Pregnancy PCOS Hyperthyroidism Hypothyroidism Cirrhosis Cushing’s Syndrome Anorexia Nervosa Obesity Anticonvulsants Acromegaly

Contraindications to TRT

• CHF NYHA class III or IV* • Hematocrit elevated and uninvestigated (>55%) • Elevated PSA uninvestigated • Abnormal DRE uninvestigated • Prostate cancer** • Breast cancer • Sleep Apnea – untreated • Severe LUTS

Source: Google Images

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How to pick a T replacement method? • 5 main considerations: • Availability • Safety/tolerability • Efficacy • Patient Preference • Cost/Insurance coverage

Source: Google Images

Options for replacement • Fertility preservation • Oral: clomiphene citrate 50 mg PO OD • Injection: T IM injection with 500 IU of HCG 3x/wk • No fertility preservation • Oral: Andriol © • Injection: Depot‐Testosterone ©, Delatestryl © • Patch: Androderm © • Gels: Androgel ©, Testim © • Topical solution: Axiron ©

Source: Google Images

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Andriol ©

• BID dosing • Issues with absorption • First pass effect of liver

6 ― 80 mg Fed ― 80 mg Fasted

(ng/mL) 4

2 Mean T Concentration

0 0 2 4 6 8 10 12 14 16 18 20 22 24 Time (hours) 69

Injections • Depot‐Testosterone © (100mg/mL) and Delatestryl © (200mg/mL) • IM injections, patient or partner can be taught to inject • Depot‐T © : inject q2wk; Delatestryl © : inject q1‐4 wk • Volume accepted by IM sites? • Deltoid – 3 mL • Gluteus – 3 mL • Vastus lateralis – 2 mL • Most likely covered by insurance plans • Cheapest – cost approx $50/5mL vial • Highest rates of hematological side effects • No accidental contact concerns

Source: Google Images

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Topicals

• Androderm ©– approximately 65% site reactions (from mild to blistering) • Gels: • Testim ©– resealable tube • Androgel ©– sachet/pump • Both cost about $100‐150/mo • Preserves diurnal variation in testosterone • Easy to apply – must wait for it to dry • Advised to apply to chest and shoulders • Risk of accidental exposures • Low risk of hematologic side effects

Formulations of T Summary

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How to follow? • 1 month • Expect no symptom improvement • CBC, LFTs, T, FSH, LH, E2, SHBG, PSA • 3 month • May see sexual and psychological symptoms improve • CBC, LFTs, T, FSH, LH, E2, PSA • 6 month • Should see major improvements in sexual and psychological symptoms (if not, consider other diagnoses) • May begin to see improvements in muscle mass, adiposity and body compisition • CBC, LFTs, T, Lipids, HgbA1c, FSH, LH, E2, PSA • Continue q6 mo x 2 then q 1 yr if no issues • Expect benefits in muscle mass by 12‐18 mo • Expect benefits in bone mineral density at 24‐36 months

Complications

• Main concern is erythrocystosis • If hgb >180 or hct > 55%, consider intervention • Do not necessarily need to stop T therapy • Phlebotomize 1‐2 u pRBC and recheck CBC • Major risk is MI and stroke due to erythrocytosis if left untreated. • If an infrequent problem, recommend regular donations • If frequent, may need to consider dose adjustments, or change formulations • LFTs? • Important in oral T administration

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Pitfalls/advice

• Some patients are good at self injection, others are not. • Measure injection testosterones midway between injections (day 7 or 8 for a 14 day cycle) • Measuring LH and FSH can be a useful measure of compliance in TRT (should be suppressed) • Encourage your patient to donate blood whenever possible • Discourage topical therapies for patients with young children • Try to target 18‐23 nmol/L • Don’t be afraid to switch modalities • Avoid compounded hormones when possible

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Testosterone and cardiac risk... • JAMA, November 2013...

Created by: Dr. F. Garcia

• No T: 681+420+486 = 1587 events • Divided by 7486 pts = 21.2% • T: 67+23+33 = 123 events • Divided by 1223 pts = 10.1%

Created by: Dr. F. Garcia

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Statistical methods

Created by: Dr. F. Garcia

Excluding events

Created by: Dr. F. Garcia

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Then...

• Whoops: • Authors claimed excluded group was actually a magnitude of 10 lower (just over 100 pts) • Authors identified that there were over 100 patients included in the no testosterone arm that were female • Given methodological and validity concerns, over 30 different societies from around the world have asked for a formal retraction • Not done. Article still available but heavily edited from original version

Created by: Dr. F. Garcia

My ICI recipes

• Trimix (Prostaglandin E1, Papaverine 22.5 mg/mL, Phentolamine 0.83 mg/mL) – 5 mL bottle. Prostaglandin dose • Regular 8.3 mcg/mL • Plus 20 mcg/mL • Forte 40 mcg/mL • Ultra 60 mcg/mL • Quad mix – any of the above recipes with Atropine 0.1 mg/mL • Bimix (Papaverine/Phentolamine) – 5 mL bottle • Regular 27.1 mg/mL & 0.83 mg/mL • Light 13.05 mg/mL & 0.83mg/mL • Super 30 mg/mL & 2 mg/mL

41 How to have sex in a canoe – oar maintenance

Fast facts

‐ Domains of male sexual dysfunction: Desire, Orgasm, Ejaculation, Erectile function, Anatomical o Orgasmic dysfunction: Delayed, Painful, Hypo, Anorasmia, PGAD o Ejaculatory Dysfunction: Premature, Delayed, Painful, Retrograde, Anejaculation o Erectile dysfunction: Arteriogenic, Anatomic, Neurogenic, Endocrine, Psychogenic o Anatomic dysfunction: Penile curvature (Congenital, Peyronie’s), Penile fractures, self‐inflicted o Desire: Low Testosterone, Psychological, Situational, Iatrogenic, Metabolic ‐ Erectile dysfunction is an early marker for cardiovascular disease and provides an opportunity for intervention and education with a patient symptom as a motivator to have proactive lifestyle and medication interventions ‐ Moderate and severe ED have 65% and 43% increased risk of CVD and stroke respectively ‐ Treatments for ED o Oral PDE5‐Is: on demand full dose, double dosing, daily tadalafil, check Testosterone and correct o ICI: Customized mix (Prostaglandin E1, Papaveirne, Phentolamine) – several strengths. High reliability, very easy patient uptake o VED: Oldest therapy, reusable. Unpopular due to “hinge” effect, discolouration and pain ‐ Peyronie’s disease o 3‐9% of men, a smaller percentage have significant enough disease to hamper/prevent intromission o Limited role for oral therapies o Traction therapies require significant dedication, 30‐60 minutes daily for 3mo+ for 10‐15 degree correction. Main adjunct to other therapeutic options. o Intralesional approaches may be effective but have long time courses and require commitment o Surgical therapies can be effective but require a detailed consent due to consequences and side effects ‐ Low Testosterone – estimated at 5% of the male population age 30‐70 o Diagnosis requires symptoms and biochemical confirmation (2 AM Testosterone samples 2‐4 wks apart drawn before 11 am) o Consequences of untreated low T: ED, obesity, osteoporosis, lower QoL, increased cardiovascular risk, increased mortality, metabolic syndrome, poor glycemic control o Sexual symptoms and fatigue won’t improve before 3 mo, and should improve by 6 mo o Symptoms are vague – have a broad differential if the therapy isn’t successful o S/E of Testosterone replacement: Sleep apnea, erythrocytosis, LUTS, acne, infertility o Fertility preserving and non‐preserving options exist o Oral therapies are difficult to use and ultimately ineffective o Monitor with regular blood work (minimum CBC, LFTs, T)