Hypogonadism: Role of androgens

Guidelines on the management of sexual problems in men: the role of androgens
British Society for Sexual Medicine

Introduction

The role of androgens in maintaining well-being in men is well established. Low androgen levels in men are chiefly the result of hypogonadism. Hypogonadism (primary or secondary) can occur at all ages, including in elderly men.

Men with erectile dysfunction and/or diminished libido and documented testosterone deficiency are candidates for testosterone therapy. The diagnosis of hypogonadism should be confirmed before any androgen therapy is initiated.

Diagnosis

The diagnosis of treatable hypogonadism requires the presence of symptoms and signs suggestive of testosterone deficiency, as well as biochemical evidence.

The symptom most associated with hypogonadism is low libido. Other manifestations include; erectile dysfunction, absence of morning erections, delayed ejaculation, decreased muscle mass and strength, increased body fat, decreased bone mineral density and osteoporosis, decreased vitality and depressed mood. None of these are specific to the low-androgen state but each may raise suspicion of testosterone deficiency.

Clinical assessment should be made in person by the consulting physician, who should not rely on non-specific unvalidated questionnaires. It may be undertaken over several consultations.

Laboratory testing
The initial assessment of all men with erectile dysfunction and/or diminished libido should include determination of serum testosterone:

a total testosterone level above 12nmol/l (350ng/dl) does not require replacement
patients with serum total testosterone levels below 8nmol/l (230ng/dl) will usually benefit from testosterone treatment
if the serum total testosterone level is between 8 and 12nmol/l, repeating the measurement of total testosterone with sex hormone binding globulin (SHBG) and albumin to calculate free testosterone, or free testosterone by equilibrium dialysis, may be helpful

For total testosterone determination blood should preferably be taken at 9am and certainly between the hours of 7am and 11am, without fasting.

Measurements of serum levels of luteinising hormone will assist in differentiating between primary and secondary hypogonadism, and a determination of serum prolactin level is indicated when the serum testosterone is lower than 5.2nmol/l (150ng/dl) or when secondary hypogonadism is suspected. The prolactin level should be measured to avoid missing a prolactinoma.

Determinations of estradiol, thyroid hormones, cortisol, DHEA, DHEAS, melatonin, GH and IGF-I are not indicated unless other endocrine disorders are suspected, based on the clinical signs and symptoms of the patient.

Treatment
Co-morbidities

Men with diabetes, mellitus, hyperprolactinaemia, metabolic syndrome, severe symptoms of lower urinary tract symptoms, significant erythrocytosis (heamatocrit>50%), untreated obstructive sleep apnoea or untreated severe congestive heart failure, breast or prostate cancer should not be started on treatment with testosterone without appropriate assessment and treatment of these co-morbid conditions.

The use of testosterone in patients with locally advanced or metastatic prostate cancer is absolutely contraindicated. Severe symptoms of lower urinary tract symptoms due to benign prostate hyperplasia represent a relative contraindication.

Types of interventions and treatments

The combination of testosterone and phosphodiesterase-5 inhibitors (PDE5i) treatment should be considered in hypogonadal patients with erectile dysfunction who fail to respond to either treatment alone. It is suggested that men with hypogonadism and erectile dysfunction should be treated with testosterone prior to the introduction of PDE5i.

Preparations of natural testosterone should be used for substitution therapy. Intramuscular, subdermal, transdermal, oral and buccal preparations are safe and effective. The treating physician should have sufficient knowledge and adequate understanding of the pharmacokinetics as well as of the advantages and drawbacks of each preparation. The selection of the preparation should be a joint decision of an informed patient and physician. Risks of transfer should be discussed in advance of starting treatment.

Any adverse events during treatment (especially elevated haematocrit or prostate carcinoma) require rapid discontinuation of testosterone substitution; short-acting preparations may be preferred over long-acting depot preparations in the initial treatment of patients with late-onset hypogonadism.

Follow-up and monitoring

Once patients are on therapy, testosterone levels should be monitored to ensure normal concentrations are being achieved. The aim of therapy should be a total testosterone level of at least 15nmol/l. Sustained supra-physiological levels should be avoided.

Erythrocytosis can develop during testosterone treatment, especially in older men treated with injectable testosterone preparations. Haematological assessment is indicated before treatment, then at 3-4 months and 12 months, and annually thereafter. To keep the haematocrit below 53% (48% if history of thrombosis), dose adjustments and/or periodic venesection may be necessary.

Assessments of treatment outcome and decisions about continuing therapy should be based on improvement in signs and symptoms of testosterone deficiency. Failure to benefit with a reasonable time interval (up to six months is adequate for libido and sexual function, muscle function and improved body fat) should result in discontinuation of treatment. Further investigation for other causes of symptoms is then mandatory.

Hypogonadal older men should be carefully monitored for prostate safely during treatment, at 3-6 months, 12 months and at least annually thereafter. Confirmed PSA increments >1.4ng/ml during one-year period after initiation of testosterone therapy or a PSA velocity >0.4ng/ml per year during sequential PSA measurements for periods of more than two years should warrant a urological evaluation and more intensive future surveillance for prostate cancer. The combined application of PSA and digital prostate examination improves the prostate cancer detection rate over either test alone.

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