Male menopause, androgen deficiency and PADAM

Written by Dr John Dean, Specialist in Sexual Medicine, South Devon Healthcare NHS Trust

Physical features include

diminished muscle mass

loss of body hair

abdominal obesity.

Several other effects on body chemistry and metabolism occur, such as:

reduction in high-density lipoprotein (HDL) cholesterol and increase in low-density lipoprotein (LDL) cholesterol, which increases the risk of developing coronary artery disease.

increase in total body fat (because of a fall in the proportion of body weight that is muscle rather than through weight gain).

osteoporosis (a change in bone structure and strength that predisposes the sufferer to fractures, particularly of the wrist, hip and spine).

reduction in red cell volume (a reduction in the proportion of red blood cells to plasma.

What are the consequences of androgen deficiency (PADAM)?

Changes caused by PADAM could potentially affect health in several ways:

increased risk of osteoporotic fracture and cardiovascular disease

reduced general well-being

depression.

cognitive impairment (problems with thought, concentration and memory).

reduced physical strength

sexual problems.

The symptoms, signs and metabolic consequences of androgen deficiency are largely reversible, and can be corrected by replacement therapy.

How is androgen deficiency (PADAM) diagnosed?

No definitive test for PADAM exists. Low blood levels of testosterone alone are insufficient to make the diagnosis. The combination of several different suggestive symptoms and physical signs, together with low blood levels of testosterone, should raise suspicion that PADAM is present.

The problem with measuring testosterone levels

It would be comforting to think that a simple blood test could identify androgen deficiency. Unfortunately, this is not the case.

Widespread disagreement exists over what is the normal range of testosterone levels and what, exactly, should be measured in the blood to assess androgen deficiency.

The existing 'normal' range for total testosterone is based upon statistical analysis of pooled samples from all men, including those who might have PADAM. So 'normal' testosterone levels are not necessarily the same as healthy levels.

Testosterone is released into the bloodstream in pulses, and levels vary through the day (diurnal variation). In general, the testicles release more testosterone in the morning than later in the day.

Blood samples should therefore be taken between 8am and 10am, and at least two separate, consistent results are needed to establish that there is a problem with testosterone levels.

About 60-70 per cent of the total testosterone is tightly bound to a protein, present in the blood, called sex hormone binding globulin (SHBG). This protein-binding is a common way in which hormones are transported in the bloodstream and it is effectively a circulating store of testosterone. The testosterone only becomes active when the link to SHBG is broken, and this is a process which occurs at a certain rate all the time.

Older men produce relatively more SHBG, as do heavy drinkers and men with thyroid disorders, thus reducing the amount of 'free' testosterone.

Another 30-40 per cent of the total testosterone is more loosely bound to another protein, called albumen. Testosterone bound to albumen is also inactive, so free testosterone probably accounts for only 1 to 2 per cent of the total.

Measurement of total testosterone is therefore a poor measure of active testosterone. Free testosterone levels are expensive to measure and are not widely available.

Free Androgen Index (FAI = total testosterone/SHBG x100) is an alternative measure of androgen state that is not as reliable as free testosterone, but is better than relying solely on total testosterone.

All this is confusing for doctors, too!

Treatment

Many doctors do not believe that PADAM exists and will not offer treatment. Others are 'believers' and see it everywhere.

At present, a practical approach is probably the most helpful. If multiple symptoms of PADAM are present and FAI is below normal or in the lower part of the normal range, a 'therapeutic trial' of testosterone supplement therapy for up to three months can be worthwhile.

If there has been no improvement in symptoms, despite a rise in FAI after three months of therapy, then continuation of treatment is probably not worthwhile.

If there is an improvement in symptoms, persevering with treatment is worthwhile for as long as the improvement is maintained. A very high placebo response to treatment probably occurs, so it is important to check that the improvement is maintained over time.

Men receiving testosterone supplements should have regular medical checks every three months for the first year of treatment, which must include a rectal examination of the prostate gland (which sits beneath the bladder producing fluids that nourish and protect sperm) and blood tests. After that period, at least yearly checks are necessary.

Testosterone preparations

Testosterone is available as:

capsules or tablets (eg Restandol, Striant SR)

injections (eg Nebido, Sustanon, Virormone)

patches (eg Andropatch)

implants

gels (eg Testim gel, Testogel).

Capsules do not always provide steady blood levels. Patches are probably the easiest form of testosterone to use, although they are reasonably expensive. All these preparations can be prescribed on the NHS, although a GP would be unlikely to agree to prescribe these mediations for PADAM without a specialist's advice.

Side effects

Headache, weight gain, acne, increased aggression and male-pattern baldness have all been reported with testosterone treatment, but are uncommon if free testosterone levels are maintained within the normal range.

Considerable controversy exists over the effect of testosterone upon the prostate gland. Men with abnormally low levels of testosterone have small prostate glands. Replacement therapy causes the prostate to grow to about the average size predicted for their age.

Current evidence indicates that testosterone does not cause abnormal prostate enlargement (benign prostatic hypertrophy). Testosterone should not be given to men who have symptoms of restricted urine flow (urinary outflow obstruction) due to prostate enlargement.

Testosterone supplements are not thought to cause prostate cancer. However, the hormone does help existing prostate cancers grow and must not be given to men with prostate cancer. If a man lives long enough, he will probably develop prostate cancer (up to 80 per cent of 80-year-old men are found to have prostate cancer at post-mortem examination) so whether testosterone supplements will affect mortality in older men is unknown.

Cholesterol levels and production of red blood cells are affected by testosterone, and must be closely monitored, particularly during the first year of treatment.

Conclusions

The long-term benefit of testosterone supplements in older men with symptoms of PADAM is unclear. However, testosterone is probably worth trying in men with disabling symptoms, provided that they are properly counselled and receive adequate follow up. More research is urgently needed to clarify this controversial area.

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