Low Testosterone — Symptoms, Causes & Treatment | MyMedicPlus

Low testosterone (hypogonadism) is defined as a serum total testosterone below 300 ng/dL (10.4 nmol/L) combined with symptoms of androgen deficiency. It affects 2-6% of adult men and up to 30% of men over 70. Primary hypogonadism originates in the testes; secondary hypogonadism involves the hypothalamic-pituitary axis. Testosterone deficiency (hypogonadism) is defined as consistently low morning testosterone (total testosterone below 10.4 nmol/L or 300 ng/dL on two occasions) combined with symptoms and/or signs of deficiency. It is classified as primary (testicular failure — elevated LH/FSH) or secondary (hypothalamic-pituitary dysfunction — low or normal LH/FSH). Prevalence of symptomatic hypogonadism is approximately 2-6% in men aged 40-70, rising steeply with age, obesity, and comorbidities. Many men remain undiagnosed as symptoms overlap with normal ageing and other conditions.

Primary causes include Klinefelter syndrome, testicular trauma or torsion, orchitis, and chemotherapy or radiation. Secondary causes include pituitary tumors, hyperprolactinemia, obesity, type 2 diabetes, obstructive sleep apnea, chronic illness, opioid use, and anabolic steroid abuse. Age-related decline of 1-2% per year begins after age 30. Primary hypogonadism causes include Klinefelter syndrome (47,XXY — present in approximately 1 in 650 men; most common chromosomal cause of male infertility), orchitis (mumps orchitis causes bilateral testicular atrophy and hypogonadism in up to 30% of post-pubertal men affected), bilateral cryptorchidism, orchidectomy (testicular removal — for cancer, trauma, or torsion), and chemotherapy or radiotherapy. Secondary hypogonadism causes include pituitary adenoma (hyperprolactinaemia suppresses GnRH pulsatility), Kallmann syndrome (anosmia with GnRH deficiency), haemochromatosis (iron deposition in the pituitary), and functional hypogonadism from obesity, opioid use, anabolic steroids, or severe illness.

Reduced libido, erectile dysfunction, decreased muscle mass and strength, increased body fat especially visceral fat, fatigue, depressed mood, irritability, poor concentration, decreased bone density, hot flushes, reduced beard and body hair growth, and small testicular volume are characteristic features. Sexual symptoms are the most commonly reported: reduced libido (loss of sexual interest or fantasy), erectile dysfunction (difficulty achieving or maintaining erections), reduced spontaneous and morning erections, and reduced ejaculatory volume. Somatic symptoms include fatigue, reduced physical stamina, loss of muscle mass, increased body fat (particularly central), reduced body and facial hair, gynaecomastia (breast tissue development from relative oestrogen excess), and sweating or hot flushes in acute hypogonadism. Psychological symptoms — depression, poor concentration, and reduced motivation — are common but often attributed to other causes, delaying diagnosis.

Two morning serum total testosterone measurements (8-10 am when levels peak) are required for diagnosis. If low, measure LH, FSH, and prolactin to classify primary vs secondary hypogonadism. Free testosterone is calculated in obese patients. Bone mineral density, lipid profile, CBC, and PSA are obtained before initiating TRT. Diagnosis requires blood tests taken fasting between 08:00-10:00 (testosterone levels peak in early morning and decline through the day): total testosterone should be confirmed low on two separate occasions before initiating treatment; calculate free testosterone when SHBG is abnormal (obesity lowers SHBG; ageing and liver disease raise it). LH and FSH distinguish primary from secondary hypogonadism. Prolactin should be measured in secondary hypogonadism — elevation requires pituitary MRI to exclude prolactinoma. Additional tests: full blood count, metabolic panel, bone density (DXA scan if established hypogonadism), semen analysis if fertility is relevant.

Testosterone replacement therapy (TRT) is available as intramuscular injections (testosterone cypionate or enanthate), transdermal gels or patches, subcutaneous pellets, or buccal tablets. TRT improves libido, energy, mood, muscle mass, and bone density. Clomiphene citrate stimulates endogenous testosterone in secondary hypogonadism. Fertility-sparing options are available for men wishing to conceive. Testosterone replacement therapy (TRT) can be delivered via: intramuscular injection (testosterone enanthate 250 mg every 2-3 weeks, or undecanoate 1000 mg every 10-14 weeks — the most reliable delivery method); transdermal gel (testosterone 1-2% gel applied daily to skin — non-invasive but requires skin-to-skin transfer precautions); transdermal patches; or buccal adhesive tablets. Monitor treatment response with total testosterone (aim for mid-normal range, 15-20 nmol/L), haematocrit (do not treat if haematocrit exceeds 0.52), PSA in men over 40, and symptom reassessment at 3-6 months. TRT is contraindicated in prostate cancer, uncontrolled erythrocytosis, severe heart failure, and desire for fertility (consider clomifene or gonadotrophins instead).

See a GP for: persistent symptoms consistent with testosterone deficiency — significant fatigue, reduced libido, erectile dysfunction, mood change, or loss of muscle mass — particularly in middle-aged or older men; men with known risk factors (obesity, type 2 diabetes, chronic renal or liver disease, pituitary disease, or prior chemotherapy/radiotherapy); and all men with unexplained anaemia, low bone density, or fragility fractures at a young age. Two early morning fasting total testosterone levels below 12 nmol/L (with symptoms) are required for diagnosis — a single measurement is insufficient. Seek urgent assessment for: signs of pituitary tumour causing hypogonadotrophic hypogonadism — new headaches, visual field defects (bitemporal hemianopia from macroadenoma compressing the optic chiasm), or galactorrhoea (raised prolactin); or in young men with symptoms of primary hypogonadism (possibly Klinefelter syndrome — warrants karyotyping). Discuss testosterone therapy with a specialist endocrinologist or GP experienced in andrology — monitoring of haematocrit, PSA, lipids, and clinical response is required during TRT.

Untreated testosterone deficiency (hypogonadism) causes progressive systemic complications beyond sexual dysfunction. Bone mineral density decreases by approximately 2-3% annually, leading to osteoporosis and increased vertebral and hip fracture risk — testosterone replacement therapy consistently improves BMD. Skeletal muscle mass declines (sarcopenia) reducing physical strength, functional capacity, and increasing fall risk. Metabolic complications include increased visceral adiposity, insulin resistance, type 2 diabetes risk, and dyslipidaemia. Depression, cognitive impairment, fatigue, irritability, and reduced quality of life are significant manifestations of sustained low testosterone. Anaemia from reduced erythropoiesis (testosterone stimulates erythropoietin and iron incorporation) occurs in moderate-to-severe hypogonadism. Cardiovascular risk is elevated through endothelial dysfunction and arterial stiffness. In Klinefelter syndrome — the most common genetic cause — additional complications include infertility, gynaecomastia, increased breast cancer risk, and autoimmune disease susceptibility.

Maintain healthy weight through diet and exercise, as obesity significantly reduces testosterone via aromatization to estrogen. Manage sleep apnea, limit alcohol, avoid anabolic steroids and opioids, and control diabetes. Regular aerobic and resistance exercise naturally supports testosterone levels. Annual monitoring of testosterone levels is advised during TRT. Prevention is possible for secondary hypogonadism through lifestyle optimisation: weight loss (obesity reduces testosterone by 2-5 nmol/L per 10 kg excess weight — through increased aromatase activity converting testosterone to oestradiol), regular vigorous exercise (resistance and aerobic training raise testosterone by 10-20%), adequate sleep (testosterone secretion peaks during deep sleep — sleep restriction below 5 hours reduces testosterone by 15%), stress management (cortisol inhibits GnRH and Leydig cell function), and avoiding alcohol excess (even moderate alcohol consumption reduces testosterone synthesis). Avoid anabolic steroids — exogenous androgens suppress the HPG axis, causing secondary hypogonadism and testicular atrophy that may be permanent.