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Published on : Jul 28, 2021 | Views : 2155 | Downloads : 7

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Adult Male Hypogonadism Amy Neumeister, MD FACP
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Objectives: Adult Male Hypogonadism Screening Diagnosis/Differential Treatment Adverse events & safety monitoring
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Sperm Inhibin Normal Male Reproductive Axis GnRH FSH LH Hypothalamus Pituitary Seminiferous Tubule Leydig Cell Aromatase 5  reductase Estradiol DHT Testes T E
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Diagnosis of Hypogonadism Failure of testes to produce Physiologic levels of testosterone Normal number of spermatozoa Primary = testes failure Secondary = pituitary or hypothalamic failure Dual defects are possible (less likely)
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Treatment of Hypogonadism Depends on the Cause Primary hypogonadism Generally permanent Replace testosterone unless contradindicated Fertility cannot be regained Secondary hypogonadism Distinguish cause Evaluate for other hormone deficiencies first Use testosterone + gonadotropins for fertility
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Definition of Androgen Deficiency (AD) Consistently low testosterone Associated signs/symptoms Evidence based review of literature Data is weak at best
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Don’t Screen Every Man for Low T Don’t look for low T in men seeking care for unrelated reasons Does not meet any criteria for general screening No trials of efficacy or cost-effectiveness Mortality impact of untreated low T unknown
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Who to Screen for AD Men who ask about it based on symptoms Case finding in men with high prevalence clinical disorders Even in these groups, data on risk/benefits of T replacement is unavailable-limited
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**Adapted from Morley JE, et al. Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism. 2000;49(9):1239-1242. The ADAM Questionnaire
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Symptoms/Signs of AD in Men Incomplete sexual development, eunuchoidism  Sexual desire & activity  Spontaneous erections Breast discomfort, gynecomastia  Body hair (axillary & pubic),  shaving Very small or shrinking testes (esp < 5 ml) Inability to father children, low/zero sperm counts  Height, low-trauma fracture, low BMD  Muscle bulk & strength Hot flushes, sweats
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Less Specific Symptoms/Signs of AD  energy, motivation, initiative, aggressiveness, self-confidence Feeling sad or blue, depressed mood, dysthymia Poor concentration and memory Sleep disturbance, increased sleepiness Mild anemia Normochromic, normocytic, in the female range Increased body fat, BMI Diminished physical or work performance
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Conditions with a High Prevalence of Low T (Screening Suggested) Sellar mass, radiation to sella, other sellar disease On meds that affect T production or metabolism Glucocorticoids, ketoconazole, opioids HIV-associated weight loss ESRD and maintainence hemodialysis Moderate to severe COPD Osteoporosis or low trauma fracture (esp if young) Type 2 diabetes mellitus Infertility
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Relevant Medical History Puberty and sexual development Past/present major illnesses Past/present nutritional deficiency All prescription & nonprescription drugs Relationship problems Sexual problems Major life events Related family history Recent changes in body (breasts) Testicle problems
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Physical Exam Amount of body hair Breast exam for enlargement/tenderness Size and consistency of testicles Size of the penis Signs of severe & prolonged AD Loss of body hair Reduced muscle bulk and strength Osteoporosis Smaller testicles
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Guidelines on Screening Initial screen = morning total testosterone Levels are highest in the morning Normal T is generally 300-1000 ng/dl Confirmation = repeat morning total T Free or bioavailable T in some Do not screen during acute or subacute illness Illness, malnutrition, and certain medications may temporarily lower testosterone
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History and Physical (Symptoms and Signs) Exclude reversible illness, drugs, nutritional deficiency Do you suspect altered SHBG? Low T Morning Total T Normal T, LH+FSH Not Hypogonadism Follow up Normal T Repeat T Check LH+FSH If altered SHBG Use free or bio T Semen analysis if fertility issue
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Testosterone Circulates Mostly Bound to Sex Hormone Binding Globulin What lowers SHBG Moderate obesity Nephrotic syndrome Hypothyroidism Use of Glucocorticoids Progestins Androgenic steroids What raises SHBG Aging Hepatic cirrhosis Hyperthyroidism Anticonvulsants Estrogens HIV infection
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Confirmed low T (Total < 300 ng/dl) OR Free or Bio T < normal (Free T <5 ng/dl) Low T Low or normal LH+FSH Prolactin, iron sats Other pituitary hormones Low T High LH+FSH Karyotype Klinefelter Syndrome Other Testicular Insult Secondary Hypogonadism Primary Hypogonadism MRI in certain cases
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Case 52 y/o male with HTN asks for Viagra after 2 years of low libido BP 150/99 Slight gynecomastia, nl GU exam T low, FSH &LH low, Prolactin very high What is the best next step?
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Best next step? A) Prescribe Viagra B) Testosterone replacement C) MRI pituitary D) Neurosurgery consult
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When Should You Get a Pituitary MRI? Severe secondary hypogonadism T <150 ng/dl Symptoms/signs of tumor mass HA, visual impairment, visual field defect Persistent hyperprolactinemia Panhypopituitarism Cost-effectiveness is unknown Don’t bother with a CT
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Should You Get a DXA? Recommend DXA in men with Severe androgen deficiency Low trauma fracture Cost-effectiveness is unknown
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Goals of Testosterone Therapy Improve/maintain secondary sexual characteristics Improve libido and erections Increase energy and well-being Improve muscle mass and strength Improve bone mineral density
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Who Should be Treated with T? Men with low T & signs/symptoms of AD Men with low testosterone & low libido Men with low testosterone & erectile dysfunction After evaluation of underlying causes of ED And consideration of other treatment for ED
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Who Else Should be Treated with T? Men with low testosterone, HIV infection & weight loss Short-term treatment For weight-maintenance, lean body mass, & muscle strength Men with low testosterone & taking high dose glucocorticoids Short-term treatment For lean body mass and bone mineral density
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What About Older Men? Recommend against offering T to all older men with low T Treat men with consistently low T and clinically significant symptoms After explicit discussion of pros and cons Task force disagreed on T level below which T should be offered to older men with symptoms Depends on the severity of symptoms Some T<300 Some T<200
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Case 75 y/o male had a lower thoracic vertebral fracture after falling on a wet floor Non-smoker, non-drinker, 1 glass milk/day Poor energy Libido and erections “not what they used to be” T low x 2, LH and FSH “normal” Anemic, normal calcium & phos DXA T-score at L-spine -2.6, at femur -1.9 What is the best treatment course?
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Best treatment? A) Nasal calcitonin B) Bisphosphonate C) Testosterone replacement D) Calcium and Vitamin D E) Testosterone & bisphosphonate
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Who should NOT receive testosterone therapy?
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Contraindications to Testosterone Therapy Breast or prostate cancer Lump/hardness on prostate exam by DRE PSA >3 ng/ml that has not been evaluated for prostate cancer Severe untreated BPH (AUA/IPSS >19) Erythrocytosis (hematocrit >50%) Hyperviscosity Untreated obstructive sleep apnea Severe heart failure (class III or IV)
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Testosterone for the Following Reasons May be Harmful To improve strength/athletic performance For physical appearance To prevent aging
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How Do You Give Testosterone? Start at standard dose Check levels Therapeutic target Serum testosterone in mid-normal range for healthy, young men Target in older men Considerable disagreement among experts Total T in the lower part of the normal range for younger men 400-500 ng/dl
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Nongenital Transdermal Patch Mimics normal diurnal rhythm Less increase in hemoglobin than IM shots Start at 1-2 x 5 mg nightly to the skin of the back, thigh, or upper arm Away from pressure areas Some men need 2 patches Skin irritation/redness/rashes
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Testosterone Gel Starting dose 5-10 grams daily Skin tolerates it well Potential transfer to others by skin contact Cover the application site Wash hands with soap and water after application Wash skin before skin-to-skin contact with others T levels maintained when skin washed 4-6 hours after application
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Testosterone Enanthate or Cypionate Injections (IM) T levels are supraphysiologic, then gradually drop to hypogonadal range Peaks and valleys Fluctuation of mood or libido Relatively inexpensive if self-administered Start at 75-100 mg IM weekly Or 150-200 mg IM every other week Pain at injection site Excessive erythrocytosis (esp in older pts)
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Buccal, Bioadhesive T Tablet Normalizes T and DHT 30 mg to buccal mucosa twice daily q12h Gum-related adverse events in 16% Gum irritation Examine gums and oral mucosa for irritation Alteration in taste
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Testosterone Pellets 4-6 200-mg pellets implanted subQ Serum T peaks at 1 month and then is sustained in normal range for 4-6 months Requires surgical incision for insertion Infection risk Pellets may spontaneously extrude
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Monitoring T Levels Target the mid-normal range Timing Injections: mid-way between injections Target 350-700 ng/dl, adjust dose or frequency Patch: 3-12 hours after application Gel: after 1-2 weeks of treatment Buccal tab: immediately before next tab
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Safety Monitoring Baseline Testosterone level DRE PSA Hematocrit Follow-up ~3 months then annually Assess improvement/side effects Testosterone level DRE PSA age- and race-appropriate interval Hematocrit If osteoporosis - DXA at 1-2 years
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When to Consult a Urologist Average PSA increase after starting T 0.3 ng/ml in young men, 0.44 ng/ml in older men Increase >1.4 in any 3-6 month period unusual PSA up 1.4 ng/ml in any 1 year PSA >4.0 ng/ml PSA velocity >0.4 ng/ml per year If sequential PSA’s over 2 years Using the PSA after 6 months of T therapy as a reference Abnormality on DRE American Urologic Association or IPSS prostate symptom score of >19
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Hematocrit If >54%  stop T until safe level Evaluate for hypoxia and OSA Then restart at lesser dose Smoking cessation Phlebotomy
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Conclusion Screen symptomatic patients & high risk populations Evaluate for the underlying cause Primary vs. Secondary Treat symptomatic patients with unequivocally low testosterone levels Options: shots, patches, pills, buccal Pt preference, cost, side effects Monitor for adverse events
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Thank You Questions?
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Case 60 y/o male c/o ED, gradual over years Same sexual partner x 25 years HTN & CABG ACE-I and beta blocker Mildly enlarged prostate on DRE Testosterone 310 and 350 (ref 280-880) LH & FSH normal What should you try first?
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What should you try first? A) Psychiatry consult B) IM injections of testosterone C) Decrease beta blocker D) Viagra E) Finasteride
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Case 35 y/o male’s wife called worried about her otherwise healthy husband’s sperm count Trying to conceive x 2 years Decreased sex drive x 1 year – pressure? Exam normal Afternoon T 240 (ref 280-880) Sperm count 15 million (ref >20 million) Best next step?
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Best next step? A) MRI pituitary B) Draw AM testosterone, LH, FSH & repeat semen analysis in 3 days C) Draw LH & FSH D) Scrotal US E) Order strict morphology on semen analysis
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Case 30 y/o WM with DM-1 x 20y presents for infertility DM good control (A1c 7.2%), occasional diarrhea Fair-skinned, completely normal exam Semen analysis - Normal sperm count, decreased motility Testosterone, LH, FSH, prolactin all normal Anemic, MCV low ALT 104, AST 83 TSH and Free T4 normal Best next step?
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Best next step? A) Pituitary MRI B) Scrotal skin biopsy with sequencing of androgen receptor C) Tissue transglutaminase antibodies D) Iron/TIBC/Ferritin E) Sperm antibodies
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Case 35 y/o man presents with infertility & azoospermia Puberty at age 15, normal libido, shaves every other day 72” tall, 180#, gynecomastia, small testes Normal thyroid & phallus T low, LH high, FSH high Best test to establish definitive diagnosis?
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Definitive Diagnosis? A) Scrotal US B) Karyotype C) Ferritin D) LFT’s E) MRI pituitary
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Eunuchoidal body habitus Variable androgenization Long extremities (LS>US) Karyotype: XXY Klinefelter’s Syndrome Klinefelter’s Syndrome
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Klinefelter’s Syndrome Most common endocrine cause of primary hypogonadism FSH always  T variably affected (T  or normal) Fertility rare (in mosaics only) Treatment: T only if needed Will not reverse infertility
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Case 36 y/o man has fatigue, infertility, poor energy x6 months Few morning erections, cannot sustain intercouse Decreased shaving frequency Generalized skin darkening despite no sun exposure 4 months ago random BG was >200, started on DM diet and glipizide Enlarged liver, tan without tan lines Normal thyroid, breast, GU exam Testosterone is low, TSH & Free T4 normal