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 low T associated with: diffuse sexual (e.g., erectile dysfunction), physical (e.g. loss of vigor and frailty) and psychological (e.g., depression) symptoms. AKA: male menopause or climacterium, andropause and partial androgen deficiency of the ageing male (PADAM)
Definition LOH is a clinical and biochemical syndrome associated with advancing age and characterized by symptoms and a deficiency in serum T levels (below the young healthy adult male reference range)
Trend and problem T replacement therapy has become a popular option for its therapy Doubling between 2005-2010. This trend occurs without solid scientific evidence of the benefits and risk of treatment
Etiopathogenesis Several mechanism postulated: Primary testicular changes Altered neuroendocrine regulations of leydig cell function Increase SHBG binding capacity Decreased adrenal androgen secretion
Associated factor reduce T Chronic Disease; HTN, DM, Cardiac, hepatic, renal, COPD, arthritis Medication Steroids, opiods : altered LH secretory dynamics High BMI; BMI >30 kg m 2 is, on average, 30% lower than that of a man with BMI <25 kg m 2
BMI @ T
Diagnosis (biochemical) Definition of low T in ageing man: based on at least two measurements from morning blood samples taken in standardized conditions, i.e., before 10:00 hours. Proper age-dependent reference ranges for T do not exist
Measurement Total testosterone= Tightly bound T (SHBG) + Weakly bound T (albumin and other protein) Free (unbound) Bioavalable T = Free + Weakly bound T The EMAS study observed that free T improved the LOH diagnosis especially at borderline levels of total T (see below). According to this study; a total T <8 nmol l 1 is sufficient for the diagnosis gray zone of 8 11 nmol l 1 then free T <220 pmol l 1 strengthens the diagnosis.
Diagnosis (clinical) Questionnaire Ageing Male Symptom Score (AMS) Androgen Deficiency in Aging Men (ADAM) Massachusetts Male Aging Study not recommended for the diagnosis of LOH because of their poor specificity
European Male Ageing Study Definition and prevalence of symptoms and relationship to total and free testosterone.
Diagnosis and Treatment Algorithm
Treatment In adult-onset hypogonadism Testosterone Replacement Therapy (TRT) may improve symptoms, but many hypogonadal men are sick and/or obese, and weight reduction, lifestyle modification and good treatment of comorbidities are more important than just TRT.
Contraindication of T Prostate cancer Male breast cancer Severe sleep apnoea Male infertility-active desire to have children Haematocrit > 0.54% Severe lower urinary tract symptoms due to benign prostatic hyperplasia Severe chronic cardiac failure/new York Heart Association Class IV
Testosterone Preparation
Recommendation
Risk BPH Increase in volume Need to monitor PSA; raise in the first 3/12 then remains plateau. Within reference range Prostate Ca Permisive rather than causal factor Cardiovascular risk Deficiency and excees: unfavaourable lipid profile: increase cardiovascular risk Hypogonadal man with angina and chronic hearth failure showing benefit from normalisation of testosterone level. Polycytemia More with IM T Liver impairment Only with alkylayted T preparation. Other side effect: Acne, hirsutism, mood changes, sleep apnea
Follow up
Conclusion Def: LOH = Clinical + Biochemical Diagnosis: Clinical: European Male Ageing Study (Sexual/Physical/Psychological) Biochemical: at least two measurements gray zone of 8 11 nmol l 1 then free T <220 pmol l 1 strengthens the diagnosis. Rx: Weight reduction, lifestyle modification and good treatment of comorbidities are more important than just TRT. TRT: Benefits, risk, formulation, follow-up