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Victors of battle ate the organs (brain, heart, gonads) of enemies thinking thatthey contained important powers. Modern endocrinology has refined this into pillform

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In 1889, a Harvard professor Brown-Sequard

(neurologist, physiologist) who then lived in Paris,

injected under his skin a "rejuvenating elixir” from a

concoction he derived from guinea pig and dog

testicles.

He reported when aged 72 years in the Lancet 1889

“…a radical change took place in me….I fully regained my old powers….Mylimbs…showed a decided gain of strength. With regard to the facility of intellectuallabour,…a return to my previous ordinary condition became quite manifest duringand after the first two or three days of my experiments.”

The effects were not at all long lasting and probably had a lot to do with the placebo effect.

longevity of humans

New formulations of

Testosterone

Pharmaceutical marketing strategy

The public knowledge through the

web and media

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Markers of aging

Andropause refers to an age related decline in Serum

Testosterone levels to below the normal range for young men

that results in a clinical syndrome of androgen deficiency

andros = man + pauein =to cause to cease

(men = month)

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Menopause Andropause

Oestrogen Androgen

Universality Not all

Obvious Symptoms Less clear-cut

Easy to Diagnose Surrounded by Controversy

Rapid onset Gradual onset

Unlike estrogen levels in

women, which fall relatively

abruptly, testosterone levels

in men decline gradually over

several decades in most but

not all men - the average rate

is 110 ng/dl per decade -

making Andropause a

syndrome much less distinct

than menopause40 60 80

Bo

ne

De

ns

ity

An

dro

ge

n/E

2

Age (years)

I II III

Menopause

Male

Female

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Andropause refers to an age related decline in Serum

Testosterone levels to below the normal range for young men

that results in a clinical syndrome of androgen deficiency

True Andropause must be extremely rare = it must theoretically meanthat there is anatomic (e.g. surgical or medical castration, trauma) orphysiological cessation of testicular activity.

Practically most people take andropause to refer to the decline inandrogen observed in some as an ageing process.

Similar terminologies include Androgen Deficiency of the Aging Male(ADAM), Late Onset Hypogonadism (LOH), Symptomatic Late OnsetHypogonadism (SLOH)

Free testosterone

declines with age 70-80 year

olds have about ½ the free

testosterone of 20-30 year

olds

Testosterone must be

interpreted in relation to LH

Purifoy FE, Kiipmans LH, Mayes DM Hum Biol 1981; 53:499

Bremner WJ, Vitiello V, Prinz PN J Clin Endocrinol Metab 1983;56:1278

Vermeulen A: Clinical review 24: androgens in the aging male. J Clin Endocrinol Metab 73:221, 1991

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Purifoy FE, Kiipmans LH, Mayes DM Hum Biol 1981; 53:499

Bremner WJ, Vitiello V, Prinz PN J Clin Endocrinol Metab 1983;56:1278

Vermeulen A: Clinical review 24: androgens in the aging male. J Clin Endocrinol Metab 73:221, 1991

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Testosterone

Free (0.5-3%)

SHBG Bound (~60%)

Albumin Bound (~38%)

Total testosterone is available in most labs -test is automated,

consistent, easy to perform and inexpensive. In the large majority of

cases, the test is satisfactory for initial evaluation. Where there is

sex hormone binding globulin (SHBG) (including healthy aging),

the results may be misleading.

Free testosterone measures the fraction of testosterone that

is unbound to albumin & globulin should be the most accurate

index of a man’s androgenicity, providing the assay is

performed using equilibrium dialysis or ultracentrifugation.

However, these methodologies are cumbersome and costly,

demand expertise, and are rarely performed. Most

laboratories carry out a ‘free testosterone’ test using a RIA

which is automated, cheaper and notoriously inaccurate.

To avoid the inaccuracy & expense of free testosterone determination, Vermeulen et al

devised a method for measuring free testosterone based on a formula using the serum

levels of total testosterone and SHBG (accessible on the Internet

www.issam.ch/freetesto.htm). Studies have shown this method to be as accurate (as a

measure of metabolically active testosterone in peripheral blood) as either free

testosterone or bioavailable testosterone assays.

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FreeTestosterone

Albumin

Sex Hormone Binding Globulin

Total TestosteroneBioavailableTestosterone

Albumin BoundTestosterone

SHBG BoundTestosterone

SHBG seen in•Obesity•Hypothyroidism•Androgen (steroid) use•Cushing disease•(Polycystic ovary syndrome)

SHBG seen in:•Liver disease•Hyperthyroidism•Anorexia nervosa•Steroid/Oestrogen use•Ageing•Hypogonadism•(Pregnancy)

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Impotence should not be equated with Androgen deficiency. One

can occur without the other. (Androgen deficiency is rarely a cause of impotence).

PROBLEMS

free vs

total

Testosterone

Symptoms

of hypogonadism

vs

Sexual

dysfunction

Timing of

measurement

What is normal

for what

age ?

Measurement of

testosterone in

with(out)

gonadotrophins

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Have an indication –not a routine !!

Nothing beats a good history and clinical

examination

Measure total testosterone

Measure SHBG and calculate testosterone

free testosterone if borderline low

If T low measure FSH/LH and Prolactin

Distinguish between primary and secondary

causes

DecreasedBone Mass

Decreased MuscleMass & Strength

ErectileDysfunctionDiminished

libido

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Prolonged

Exercise

Recovery

Fatigue

IrritabilityDepression

Inability to

Concentrate

Centripetal

Obesity

Hot Flashes

Decreased Cognitive

Function /Memory

It is more gradual than that experienced by women, but it is just

as real. It often starts as early as age 35. Because it is so

gradual, men often reach their mid-forties or later, living a life that

has accommodated to the loss of youthful energy, mental

sharpness, sex drive, muscle loss and enjoyment of life.

If you tire more easily

If it is more difficult to get and stay in shape

If time to recover after exercise is longer

If you don’t have the same zest for life

If the body is getting soft

If you are eating the same or less and putting on weight

If mental action and reaction has slowed

If the fire has gone out of your sex drive

If you are 35 years of age or older and if you have two or more of these

symptoms... YOU ARE ANDROPAUSAL

www.renewman.com

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….testosterone decline is linked to age-related

changes in healthy men like ↓ muscle tissue

(sarcopenia), osteoporosis, ↑ increase adiposity, ↑

cholesterol, & deteriorating heart function +

psychological & sexual changes…..

…similar to those seen in hypogonadal young men...

We know that such hormonal associations with aging exist for

women, and we can treat them with replacement therapy. We

also know that young men with severe testosterone deficiency

suffer from muscle weakness, osteoporosis and psychosexual

dysfunction, and that these problems lessen or disappear when

such men are given a testosterone supplement.

…. Rx of HIV infected patients and

wasting with androgens have shown

success and suggested the it may prove

useful to combat frailty in aging men

(Grinspoon et al. Ann Intern Med 2000.;133:348-355

Basaria S & Dobs AS reviewed published studies of testosterone

replacement and recommended that “once the diagnosis of

andropause is confirmed testosterone replacement should be

initiated”

Hypogonadism and androgen replacement in elderly men Am J Med 2001;110:563-572

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…..Although hormone replacement therapy for menopause

has become well established, clinical experience with

treatment of andropause remains much less extensive.

Unlike oestrogen levels in women, which fall relatively

abruptly, testosterone levels in men decline gradually—

Andropause a syndrome much less distinct than

menopause….. Testosterone is known to increase bone

mineral density, stimulate libido, increase red cell mass, and

increase lean body mass.

Nevertheless, there is no clear testosterone level at which

all men have symptoms of hypogonadism.

….. Not much data regarding the efficacy of testosterone in elderly, hypogonadal

males. In a retrospective analysis, 45 such subjects, all with testosterone levels

<72 ng/dl, received 200 mg of testosterone enanthate or cypionate i/m q 2 weeks.

One third of the subjects discontinued therapy. Among those completing two

years of treatment, libido was markedly improved, as was the hematocrit.

However, 24% of the treated subjects experienced polycythemia requiring

phlebotomy.

Testosterone replacement has been associated with side effects that include

polycythemia, gynecomastia, edema, BPH, prostate cancer, and CAD.

Hormone's role in preventing disease has not been established by randomized

clinical trials.

For now, therefore, its use in the elderly remains investigational. It should

be administered only for treating specific symptoms attributed to a low

testosterone level.

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Testosterone, aging and survival: biomarker or deficiency

Curr Opin Endocrinol Diabetes Obes 2014, 21:209–216

Clear-cut symptoms

Biochemical Support

Absence of contraindication

When I am not sure I may consider a therapeutic trial in a well informed patient

I would exercise caution in those with Cardiovascular Disease

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Contraindications to Testosterone Replacement

Carcinoma Breast

Carcinoma Prostate

Severe BPH

Improve athletic

performance

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Clinical

• Response to treatment in terms of improvement in signs and symptoms

• Assess for concerns like breast tenderness

• Sexual function improvement

Testosterone

• Testosterone levels should be checked 3-12 hours after application of a transdermal T

• Those on injectable T, nadir testosterone levels should normally be obtained at 3-4 months, (prior to the next injection)

Ancillary

• PSA

• Full Blood count especially Haematocrit

• If treatment is for osteoporosis bone mineral density

Monitoring a patient on replacement testosterone

Adult with suspected

androgen deficiency

History and Examination

(Gonadal/Hypothalmo-pituitary)

Testosterone with LH / FSH (in obese Free

Testosterone) – ideally measure in morning

Look for a reversible factor e.g. Sleep

Apnoea, Pituitary tumour and treat that

Androgen deficiency Replace testosterone if

indicated and no contraindications

Monitor Treatment

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Andropause Exists (maybe not as frequent as hyped)Definition on onset-age still arbitrary

Treatment must be selectiveTreat with caution

Treatment must be monitored

Is low testosterone just part of aging which is inevitable and best left alone

or can we attempt to slow ageing – at what price (social, financial, health ) ??