Testicular Atrophy

Testicular atrophy is a reduction in testicular size with loss of spermatogenic and sometimes endocrine function.

The normal adult testis has a volume of about 15 to 25 mL, and a volume under 12 mL, or a difference of over 20% from the other side, is considered abnormal.

It causes infertility and, when extensive, testosterone deficiency. It may be unilateral from a local injury, or bilateral from a systemic or endocrine cause.

Pathophysiology. Seminiferous tubule germ cells are lost first, then peritubular fibrosis develops, and later Leydig cells are lost.

Causes:

• Vascular and inflammatory: torsion, orchitis (mumps), epididymo orchitis, trauma and surgical injury to the cord (hernia repair, hydrocelectomy, varicocelectomy).
• Developmental: cryptorchidism, congenital hypoplasia and Klinefelter syndrome.
• Local: varicocele (volume loss over 20% in adolescents), large hydrocele and radiotherapy.
• Hormonal: exogenous testosterone and anabolic steroids, hypogonadotropic hypogonadism (including Kallmann syndrome and pituitary disease), GnRH analogues and opioids.
• Systemic: cirrhosis, chronic kidney disease, haemochromatosis, sickle cell disease, HIV, chemotherapy (alkylating agents), spinal cord injury and ageing.
• Drugs: spironolactone, ketoconazole and alcohol.

A small, soft testis, noticed by the patient or at examination, with infertility or low sperm count. Androgen deficiency features when both testes are affected: reduced libido, erectile dysfunction, fatigue, hot flushes, loss of body hair, gynaecomastia, reduced muscle mass and low bone density. Ask about previous torsion, mumps, undescended testis, hernia surgery, steroid use and chemotherapy.

• Testicular volume by Prader orchidometer, and by ultrasound with volume calculated as length x width x height x 0.71.
• Scrotal Doppler ultrasound: size, echotexture, microlithiasis, varicocele and exclusion of a tumour (a small testis carries a higher cancer risk).
• Morning total testosterone, repeated once if low (under 8 nmol/L, about 230 ng/dL, is low, and 8 to 12 nmol/L is borderline), sex hormone binding globulin, LH, FSH, prolactin and oestradiol.
• Semen analysis on two samples. Karyotype and Y chromosome microdeletion testing when azoospermia or severe oligospermia is found.
• Iron studies (ferritin, transferrin saturation), liver and renal function, HIV test, and bone density for long standing hypogonadism.

Differential diagnosis.

• Normal size asymmetry
• Retractile or ascended testis
• Klinefelter syndrome
• Hypogonadotropic hypogonadism
• Vanishing testis syndrome
• Testicular tumour
• Hydrocele hiding the testis
• Congenital hypoplasia

• Treat the cause: stop exogenous testosterone, anabolic steroids and gonadotoxic drugs (spermatogenesis often recovers within 3 to 24 months), treat iron overload and chronic illness, and reduce opioids.
• Adolescent varicocele with testicular volume loss over 20%: varicocelectomy.
• Hypogonadotropic hypogonadism with fertility wanted: human chorionic gonadotrophin 1500 to 5000 IU subcutaneously or intramuscularly two to three times weekly, adding recombinant FSH 75 to 150 IU three times weekly after 3 to 6 months if sperm do not appear, for up to 12 to 24 months.
• Testosterone deficiency (confirmed on two morning measurements, with symptoms) when fertility is not wanted: testosterone gel 50 mg daily, or testosterone undecanoate 1000 mg intramuscularly at 0 and 6 weeks, then every 10 to 14 weeks, titrated to a mid-normal level of about 12 to 25 nmol/L. Contraindications: prostate or breast cancer, haematocrit over 54%, untreated severe sleep apnoea, uncontrolled heart failure, and desire for fertility.
• Fertility: sperm banking when sperm are present, and micro-dissection testicular sperm extraction with intracytoplasmic sperm injection in azoospermia.
• Bone health: calcium and vitamin D, bone density scan, and a bisphosphonate for osteoporosis.
• Painful non-viable testis after torsion or infection: orchidectomy. A testicular prosthesis can be offered for cosmetic reasons.
• Surveillance: yearly scrotal ultrasound for men with cryptorchidism or microlithiasis, and teach testicular self-examination.

Monitoring. Testosterone, haematocrit and PSA (men over 40) at 3, 6 and 12 months after starting testosterone, then yearly, with blood pressure and lipids. Semen analysis every 3 months during gonadotrophin therapy.

Referral and escalation. Refer to urology, andrology or endocrinology for bilateral atrophy, abnormal hormones or infertility. Urgent referral for a new mass or rapid loss of volume.