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, ADAM (androgen deficiency of the aging male), PADAM (partial androgen deficiency in aging male)
Late onset hypogonadism(loh) 1. Recommendation 1: Definition LOH Clinicaland biochemical syndrome associated with advancing age and characterized by symptoms and a deficiency in serum testosterone levels( below young healthy adult male reference range). This condition may result in significant detriment in the QoLand adversely affect the function of multiple organs
Pathophysiology: Reasons for declining serum testosterone in aging male Reduced testicular response to gonadotrophins (vascular supply to testis; reduced leydigcells; testis less responsive to LH) Decline in hypothalamic pituitary function (pulse freq and amplitude of gonadotropinssecretion reduces ) Age related SHBG : less free serum T on target tissue 1% annual decline after age 30
2. Recommendation 2 : Clinical diagnosis opresence of symptoms and signs suggestive of testosterone deficiency:- Low libido (most common) ED Decreased muscle mass and strength Increased body fat Decreased bone mineral density and osteoporosis Decreased vitality Depressed mood oone or more of these must be corroborated with low serum testosterone
Questionnaires e.g. Aging Male Symptom Score (AMS), Androgen Deficiency in Adult Males (ADAM) are NOT to be used for Dx. (Low specificity)
3. LabarotoryDiagnosis exclude transient cause of low T determine primary or secondary cause (serum LH, prolactin) serum T level taken at 0700 and 1100 (peak 0800) serum total T measured no accepted lower limit of normal total T > 12nmol/l (350ng/dl) no substitution Rx total T < 8nmol/l (230ng/dl) need substitution Rx between 8-12 nmol/l (measure free T level)
4. Assessment of treatment outcome and decision on cont therapy improvement in s&s discont therapy if failure of clinical benefit 5. Body composition 5. Body composition testosterone administration improves body composition (decrease fat mass, increase lean body mass level 1b) secondary benefits : strength, muscle fn, metabolic and CVS
6. Bone density and fracture rate T substitution increase bone density BMD assessment 2 yrs interval Fracture reduction not proven 7. Testosterone and sexual function Might be related to co morbidities (DM, PVD, BOO) ED with low libido and documented low T should be given testosterone therapy (level 2a) Therapeutic synergism of PDE5I with T therapy (level lb) Unclear which one to start first (PDE5I or T) or combination
8. Obesity, Type 2 DM, metabolic syndrome obesity, HPT, dyslipidemia, impaired glucose regulation, insulin resistance obese men 20-64% low T testosterone therapy may have benefit to metabolic status
9. BPH and Prostate Ca No evidence No conclusive evidence T increase risk of BPH/Pca No evidence T will convert subclinical PCa to clinically detectable Pca (level 4) Evidence Evidence suggest T stimulate growth and aggravate symptoms in locally advanced PCa and metastatic PCa(level 2a) Asses PCarisk (age, DRE, PSA, family Hx) before starting T therapy If risk is high while on T perform TRUS Bx Those treated for PCawith LOH, T therapy possible after prudent interval, no clinical or lab evidence of residual Ca, and follow up Uncertain No long term data on prostate ca risk related to T replacement
Testosterone Replacement Goals: Maintain QoL Reduce disability Maintain physiologic concentration of T Reduce side effects Target: Mid-range to lower young adult levels Contraindications: Active prostate or breast cancer or unexplained raised PSA Significant erythrocytosis(hct> 52%), untreated sleep apnoea, untreated CCF Relative: High IPSS Age is not a contraindication
Treatment and Delivery Systems Oral T undecanoate(andriol) commonly used Raises T to mid range level Taken daily with meals >20g fat for T to be absorbed Intramuscular T undecanoate Long acting 3 monthly Stable T level within normal range T enanthate Shorter acting 2-3 weeks; maintain normal average T level First few days results in supraphysioogical peaks and hypogonadal troughs hence roller coaster effects on symptoms
Treatment and Delivery Systems Transdermal Patch (scrotal/non scrotal) or gels form Sustain delivery of T over 24 hrs Normal T level Skin irritation (not with gel) Difficult adjust dose Lower incidence erytrocystosis compare to IM Sublingual/ buccal Subdermalimplants T pellets ; subcutaneous tissue Sustain released about 4-6 mths
Adverse effect and monitoring Contraindications men with PCa, breast cancer high risk of CaP(relative) Low grade PCaGleason <7 ( relative / absolute) erythrocytosis(hct >52%) untreated OSA untreated CCF
Side effects Breast tenderness Gynecomastia Compromised fertility Change in testicle size Skin reactions Fluid retention Acne/oily skin Increased body hair
Summary Diagnosis of LOH = presence of hypogonadal symptoms/ signs + persistent low serum testosterone Before Rx discuss risks/benefits assessment of prostate cancer and other risks Response to Rx must be assessed (no response -withdraw) Goalis to keep T in mid normal range