Male hypogonadism - uroleb.orguroleb.org/sites/default/files/male hypogonadiam.pdf · Male...
Transcript of Male hypogonadism - uroleb.orguroleb.org/sites/default/files/male hypogonadiam.pdf · Male...
Maher ABDESSATER M.D PGY IV Urology « Notre Dame des Secours » University Medical Center
Male hypogonadism
Under the supervision of Prof. Raghid EL KHOURY
Defini&on
• Male hypogonadism is a clinical syndrome caused by inadequate testosterone (T) produc&on (androgen deficiency) that is accompanied by a decline in sperm produc&on by the testes.
• N.B: Diminished spermatogenesis with normal T produc&on causes male infer&lity without manifesta&ons of androgen deficiency.
1-‐ ETIOLOGY AND PATHOLOGY
Role of testosterone for male health
E0ology • Disrup&on of one or several level of the hypothalamic-‐pituitary-‐gonadal axis:
• the testes (primary hypogonadism) • the hypothalamus & pituitary (secondary hypogonadism) • the hypothalamus/pituitary and gonads (hypogonadism in adult men) • androgen target organs (androgen insensi&vity/resistance)
Mixed dysfunc5on of hypothalamus/pituitary and gonads
Combined primary and secondary tes&cular failure Low testosterone levels and variable gonadotrophin levels. Gonadotrophin levels depend on the predominant primary or secondary failure. Also known as late-‐onset hypogonadism and age-‐related hypogonadism
Male hypogonadism due to defects of androgen target organs
• Primarily rare defects
• Will not be further discussed
• AR defects with complete, par&al and minimal androgen insensi&vity syndrome – Reifenstein syndrome – bulbospinal muscular atrophy (Kennedy disease) – 5a-‐reductase deficiency
• The classifica&on of hypogonadism has therapeu&c implica&ons.
• In secondary hypogonadism: hormonal s&mula&on with hCG and FSH or alterna&vely pulsa&le GnRH treatment can restore fer&lity
• Combined forms of primary and secondary hypogonadism can be observed in ageing men, mostly obese, with a concomitant age-‐related decline in testosterone levels
E.A.U guidelines
2 -‐ DIAGNOSTIC EVALUATION
Hypogonadism is diagnosed on the basis of persistent signs and symptoms related to androgen deficiency and assessment of consistently low testosterone
levels (at least on two occasions) with a reliable method
• Signs and symptoms: – Age on onset – Dura&on – Severity of the deficiency
• Reference ranges: – 12.1 nmol/L for total serum testosterone – For free testosterone 243 pmol/L
• In men aged 40-‐79 years – 8 nmol/L for decreased sexual thoughts – 8.5 nmol/L for erec&le dysfunc&on – 11 nmol/L for decreased morning erec&ons – 13 nmol/L for diminished vigour
Total testosterone level of < 8 nmol/L (280 ng/dL) or Serum testosterone in the range of 8-‐11 nmol/L and free testosterone < 220 pmol/L (34 pg/ml)(morning)
• Hypogonadism is not always evident by low testosterone levels.
• For example, men with primary tes&cular damage oben have normal testosterone levels but high LH.
• Subclinical or compensated form of hypogonadism àhypogonadal in the future.
History-‐taking and ques0onnaires • Early onsetà primary hypogonadism
– minimal pubertal development – lack of development of secondary sex characteris&cs – eunuchoid body
• Adult-‐onset hypogonadism: sexual dysfunc&on, obesity and loss of vigour. Assess and exclude systemic illnesses, signs of malnutri&on and malabsorp&on, ongoing acute disease.
• Pharmacological treatments: – cor&costeroids – abuse of drugs
• Marihuana • Opiates • Alcohol
– previous treatment or use of testosterone – abuse of anabolic steroids.
Physical examina&on • BMI • waist-‐hip ra&o • body hair • male padern • hair loss • gynaecomas&a and tes&cular size(orchidometer or US)
• Structural examina&on of the penis & DRE of the prostate.
E.A.U guidelines
3 -‐ Clinical consequences of hypogonadism
The clinical consequences of hypogonadism are determined by the age of onset and the severity of hypogonadism
Prenatal androgen deficiency • First 14 WOG: testosterone à virilisa&on of
the external male genitalia.
• Androgen deficiency or resistance due to deficient AR or LH receptor func&on
àhypospadias, female external genitalia with intra-‐abdominal tes&s. Diagnosed at an early age: clearly abnormal external genitalia.
Prepubertal onset of androgen deficiency
• At puberty, rising gonadotrophin àincrease tes&cular volume & ac&va&on of spermatogenesis & testosterone secre&on à male secondary sex characteris&cs
• Delayed puberty: absence of tes&cular enlargement at the age of 14
• Does not necessarily indicate the presence of a disease.
• If severe , hypogonadism is evident (Table 4) and diagnosis and treatment are fairly straighforward.
• The major challenge – Differen&ate from a cons&tu&onal delay in puberty
– when to start androgen treatment.
Adult-‐onset hypogonadism • Testosterone deficiency, with clinical symptoms or
signs in a person who has had normal Secondary sex characteris&cs.
• Depending on the underlying cause of hypogonadism, the decline in gonadal func&on may be gradual and par&al.
• Signs and symptoms may be obscured by the physiological phenotypic varia&on.
• Mul&factorial e&ology, and can also be found in men with completely normal testosterone levels.
• Confirma&on of a clinical suspicion by hormonal tes&ng is mandatory
• Threshold level is near the lower level of the normal range for plasma testosterone levels in young men, but wide varia&on exists.
E.A.U guidelines
4 -‐ DISEASE MANAGEMENT
Testosterone treatment aims to restore testosterone levels to the physiological range in men with consistently low levels of serum testosterone and associated
symptoms of androgen deficiency. The aim is to improve QoL, sense of well-‐being, sexual func&on, muscle strength and bone mineral density.
Benefits of treatment
SEVERAL STUDIES
Hypogonadism and fer&lity issues
• Exogenous testosterone reduces endogenous testosterone by nega&ve feedback on the hypothalamic-‐pituitary-‐gonadal axis.
• If secondary hypogonadism + fer&lity issues, hCG trt should be considered, especially in men with low gonadotrophins.
• hCG s&mulates testosterone produc&on of Leydig cells.
• Normal physiological serum levels: standard dosage of 1500-‐5000 IU IM or SC twice weekly.
• In pa&ents with secondary hypogonadism & fer&lity issues, hCG is combined with FSH treatment (150 IU 3 X weekly i.m. or s.c.) to induce spermatogenesis.
E.A.U guidelines
5-‐ Risk factors in testosterone treatment
Physicians are oben reluctant to offer TRT especially in elderly men due to the poten&al risk of this therapy: on the prostate, cardiovascular risks and sleep apnoea
Many studies
E.A.U guidelines
6-‐
Monitoring of pa0ents receiving TRT • Regular follow-‐up & careful monitoring of changes in
clinical manifesta&ons
• Effects of TRT on sexual interest may already appear aber 3 weeks of trt, and reach a plateau at 6 weeks
• Changes in erec&le func&on and ejacula&on: up to 6 months
• Effects on QoL & depressive mood is detectable within 1 month, but the maximum effect may take longer
E.A.U guidelines
Bone density Bone mineral density (BMD) should be monitored only in men whose BMD was abnormal before ini&a&on of TRT. An increase in lumbar spine BMD may already be detectable aber 6 months of TRT and may con&nue for 3 more years
TRUE HYPOGONADISM
A Case to consider
A moderately obese 58 Y.O man Erec&le dysfunc&on (ED) DM II à peripheral neuropathy and stage 2 CKF, HTN, DLP, and asthma. Past 3 years: erec&ons poorly sustained and penile rigidity insufficient to complete sexual intercourse, despite normal sexual desire Excessive fa&gue, reduced physical ac&vity and a 10 kg weight gain over the past year.
• Medica&ons: meformin, insulin, acetaminophen with codeine, hydrochlorothiazide, atenolol, lisinopril, simvasta&n, niacin, and inhaled salmeterol and flu&casone.
• A recent asthma exacerba&on was treated with a pulse and tapering doses of prednisone over 2 weeks.
• He smokes 1 pack of cigaredes daily but no longer drinks alcohol. There is no history of coronary artery disease, prostate or bladder surgery, or genitourinary trauma.
• BP 124/84 mmHg, regular pulse 64/min, R.R 14/min, BMI 35
• His mood is mildly depressed. He has normal skin thickness; mild frontal balding; & normal axillary, chest, and pubic hair.
• A 3-‐cm nontender, palpable breast &ssue is detected bilaterally.
• Lung and C.V exam are unremarkable.
• Despite moderate central adiposity, his abdomen is without striae.
• His penis appears normal.
• Tes&cular volumes are: 30 mL on the right and 35 mL on the leb (by orchidometer).
• His prostate is mildly enlarged without palpable nodules.
• Hair loss is evident on his lower extremi&es, and dorsalis pedis and posterior &bial pulses are absent to palpa&on.
• He has reduced vibratory sensa&on in both feet, but intact sensa&on to a 10-‐g monofilament. Thigh muscle bulk is reduced, though thigh strength is normal
Laboratory evalua&on • Normal CBC • HbA1c 8.3% • fas&ng glucose of 198 mg/Dl • es&mated glomerular filtra&on rate of 62 mL/min/1.73 m2 • total cholesterol, 200 mg/dL ; triglycerides, 366 mg/dL ; HDL 30 mg/dL ; LDL 97 mg/dL
• albumin, 3.2 g/dL • urine protein excre&on, 1022 mg/24 • TSH 0.89 IU/L • PSA, 1.6 ng/mL • total T, 248 ng/dL
QUIZ