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Conference of the European Society of Antiaging Medicine
Monaco March 2007

Dr Perring was invited to speak on the subject of Late Onset Hypogonadism
from which the following has been extracted:

Introduction

We may say that men are driven sexually by three forces:  male hormones, that drive what we call 'libido': sexual desire, the motivation for which in any individual, is psychological and complex; and sexual self-image, the mental view men have of themselves as sexual beings which is psychologically, but also culturally, determined.

In my clinical experience older men often have loss of both libido and desire, while retaining a strong image of themselves as sexual beings.  In the service of this self-image they often welcome the opportunity of medical intervention, as offered within the specialty of anti-aging medicine, to maintain or recover sexual function.

This we do by androgen replacement, following proper assessment and selection of patients, with the addition of chemical aids to erection if necessary.

This presentation will focus on the diagnosis, assessment and safe treatment of testosterone depletion in later life, called Late Onset Hypogonadism.

Definition

The term Late Onset Hypogonadism (LOH), now preferred to Andropause of Male Menopause, is defined by the Society for the Study of the Ageing Male (ISSAM) as 'A clinical and biochemical syndrome associated with advancing  age and characterised by typical symptoms and deficiency in serum testosterone levels'.

Safety First!
The decision to institute testosterone replacement in older men with low testosterone levels must be individualised and accompanied by a detailed discussion of the potential risks and benefits.


Question: 
Which older men should be given testosterone?
Answer:  Those men who are significantly affected by  having low levels of testosterone, who want it and who would benefit from its use.  The risk of developing prostate cancer and other contra-indications to its use should be taken into account.

Clinical Presentation and Diagnosis

Clinically, symptoms of LOH are:

  • Reduced lean body mass, loss of muscle volume/strength

  • Reduced erection strength (also nocturnal erections)

  • Increased visceral fat

  • Reduced bone mineral density (osteopenia/osteoporosis)

  • Fatigue, depression and irritability

  • Reduced cognitive functions and spatial orientation

  • Reduced libido and fantasies

  • Reduced body hair and skin tone/thickness
    (ISSAM 2002)

The depletion of testosterone occurs gradually as measured in the Massachusetts Male Aging Study:
Longitudinal Decline within Subjects by over 10 years:

  • Decline of Total Testosterone by 1.6% pa

  • Decline of Bioavailable Testosterone by 2-3% pa

The incidence of LOH in the Baltimore Longitudinal Study on Aging 1997 was shown to be:

  • 20% in men over 60 years of age

  • 50% in men over 80

The diagnostic criteria for diagnosing LOH biochemically are:

  • Total Testosterone (TT) <12nmol/L (346ng/dL)

  • Free Testosterone Index (TT/SHBG) 41-159%
                                  Or

  • Free Testosterone <250 pmol/L (72pg/mL)

The actions of Androgens on sexual functions in hypogonadal men are central and peripheral:

  • Central Action - increased libido (interest and motivation)

  • Peripheral actions:  There is activation of nitric oxide synthase which regulate activity in cavernosal smooth muscle to promote erection

Androgens and Sexual Function in (young) hypogonadal men:
Testosterone replacement increases

  • Sexual activity

  • Sexual daydreams, thoughts and desires

  • Spontaneous and nocturnal erections

  • Penile rigidity

  • Penile sensitivity
    Orgasm and ejaculation are androgen dependent.

Other actions of androgens include:

  • Maintenance of muscle strength and mass

  • Reduced adipose tissue

  • Maintenance of bone density

  • Action on neurones and neuro-transmitters with effects on verbal fluency, memory and energy

The minimum tests to assess the need for testosterone replacement are:

  • Serum Total Testosterone, Sex Hormone Binding Globulin (SHBG) and Free Testosterone Index (FTI) or Free Testosterone

  • Serum Luteinising Hormone (LH)

  • Serum Prolactin

Optional Hormone tests include:

  • Dehydrotestosterone (DHT), Dihydroepiandrosterone (DHEA), Oestradiol (E2), IGF 1, thyroid and cortisol

Assessment for Hormone Replacement Therapy may also require:

  • Measurement of bone density: Dexascan

  • Assessment of Prostate Function:  Phenotypic or genotypic disease, current urinary symptoms, DRE, prostate specific antigen (PSA)

  • Rectal ultrasound

Testosterone Treatment  (NB 'testosterone' is used as a generic term)

In general a short-acting natural testosterone to be preferred.
The therapeutic goal of treatment is the mid-range level of a young adult male
(TT about 20 nmol/L or SHBG/TT ratio >60)

Specific  forms of testosterone are:

  • Testosterone gel (Testogel) 50mg bd

  • Transdermal Patch:  Testosterone 5mg/d (Andropatch)

  • Buccal Tablets:  Testosterone 30mg (Striant)

  • Orally:  Testosterone undecanoate (Restandol): 80mg twice daily

  • Intramuscular injection: testosterone as proportionate 30mg, phenylpropionate 60mg, isocaproate 60mg, decanoate 100mg (Sustanon): 250mg every two/three weeks

  • Implant:  Testosterone <600mg every 3 months

Follow-up of patients receiving HRT

  • PSA and DRE at 3, 6, 9,and 12months and then annually thereafter

  • Transrectal U/S with biopsy only if above abnormal

  • Hb and hematocrit at 3,6,9,12 months and then annually thereafter

  • Bone density (dexascan) may be advisable 2 yearly

Prostate cancer is not a total bar to later treatment with testosterone following its successful treatment - after one year or later.

Effects of Hormonal Therapy (HT) on Sexual Function

Meta-analysis of male HRT showed testosterone administration is associated with greater improvement in sexual function compared to placebo treatment in men with sexual dysfuntion and low testosterone levels.
Testosterone may also favourably affect partner interactions and intimacy due to an overall increase in sexual desire and sense of well-being, independent of the change in erectile function

Specifically: 
Testosterone restores erectile response in 40 - 60% of hypogonadal patients.
The 'best' treatment is currently testosterone plus a PDE5 inhibitor (e.g. Sildenafil, Vardenafil, Tadanafil) or Prostaglandin E1 (e.g. Caverject).

A Holistic View
For the maintenance of satisfying sex consider the whole person:

  • Hormones and other aids to arousal are only part of a complex social/biological system

  • Consider also lifestyle factors (nutrition, exercise, 'stress') and the relationship of the couple (communication, intimacy and maturation towards autonomy)


 

 

 

 

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