Dr. K. Suresh, MD, O

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Dr. K. Suresh, MD, OGAssistant Professor Govt.
M.K. Medical College Hospital, SalemConsultant
Obs Gynaecologist, Salem Poly clinic
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Myth or reality
Androgen Insufficiency in women
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???

• Does androgen deficiency exist in pm women?
• Do Testosterone level reduce after menopause?
• Is androgen and estrogen therapy superior to
  estrogen therapy alone?
• Best means of androgen therapy
• How does androgen therapy be monitored ?

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Bone metabolism

• Aromatisation of androgens to estrogen within the
  bone is essential for maintainence of bone
  mineralisation.
• Morishma et al 1995
• In postmenopausal women androgens levels are
  positively correlated with BMD
• Davidson et al 1983

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Androgens in women

• DHEAS
• DHEA
• ANDROSTENEDIONE
• TESTOSTERONE
• DIHYDROTESTOSTERONE
• Most potent- Testosterone
• Burger et al 2002

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Source and Dynamics Of Androgens
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Role of SHBG

• Major determinant of bioavailability
• Different binding capacity
• DHT, Testosterone, androste, estradiol , estrone
• Testo approx
• 66 bound to SHBG
• 33 bound to albumin
• 1 un bound form

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Androgen insufficiency in women - Definition

• Symptoms of androgen insufficiency
• Presence of decreased bioavailable testosterone
• Normal estrogen status

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Criteria for diagnosing androgen insufficiency

• Symptoms and signs
• poor sense of well being
• impaired sexual function
• unexplained fatigue
• vasomotor instability
• decreased muscle strength
• bone loss
• poor concentration

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Criteria- contd.

• Adequate estrogenisation
• No hot flushes and regular menstrual cycles or
• Receiving estrogen replacement therapy
• Low free testosterone level
• measured by equilibrium dialysis or
• low calculated free testosterone level

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Measuring androgen levels

• Measurement and analysis is problematic
• due to lack of assays with adequate sensitivity
• lack of established normal ranges of Testosterone
  in women
• influence of SHBG

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Measuring androgen levels- contd.

• Free androgen index
• Total T in n mol / L
• SHBG in n mol/ L
• Accurate method
• high performance liquid chromatography
• tandem mass spectrometry
• Davis et al 2003

X
100
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contd

• Blood should be drawn between 8-10 am
• between 8- 20th day of cycle
• Vierhapper et al 2002

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Evidence for beneficial effects of testosterone
therapy
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Mood and well being

• Addition of IM Testosterone to estrogen
  replacement in surgically menopausal women
  resulted in improved well being and increased
  energy levels compared to those who received
  estrogen alone.
• Sherwin et al1988

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Mood and well being contd.

• The use of transdermal testosterone patches 300
  micro gram daily in surgically menopausal women
  over a 12 week period resulted in symptomatic
  improvement in psychological well being index
  scores when compared to placebo.
• Shifren et al 2000

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Mood and well being contd.

• In a randomised placebo controlled cross over
  trial of healthy premenopausal women complaining
  of loss of libido, testosterone cream application
  resulted in improveent in libido, mood and
  general well being.
• Goldstat et al 2003.

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Androgens and sexual function

• 12 wk study on estrogen replaced surgically
  menopause women with decreased libido
  demonstrated significant improvement in sexual
  function with transdermal testosterone.
• Shifren et al2000

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Androgens and sexual function contd.

• Combined treatment with estrogen 50mg and
  testosterone 50mg increased serum testosterone
  concentration and improved all parameters of
  sexual function, measured using the satisfactory
  sabbatsberg sexual self rating scale.
• Davis et al 2003

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Bone metabolism

• In Surgically menopausal women, 2 year duration
  study comparing four regimens
• CEE .625 mg
• CEE 1.25 mg
• CEE .625mg Methyl testo 1.25 mg
• CEE 1.25 mg methyl testo 2.5 mg
• Reported an increase in BMD at the hip and spine
  more with higher dose combination
• Bareth connor et al 1999

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Bone metabolism contd.

• In post menopausal women on long term estrogen
  therapy, treatment with 50mg testosterone implant
  50mg estrogen implants resulted in a 5.7
  increase in BMD at the spine and hip versus no
  change in the group who remained on oral estrogen
  alone.
• Savvas et al 1992

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Take home message

• Clear documentation that androgen production
  declines in women.
• Androgen production is linked to sexual desire,
  bone metabolism, general wellbeing.
• Convincing evidence from well designed and
  sizable clinical trials that restoration of
  androgens approximating physiology of
  reproductive years restores lost sexual desire to
  many.
• It is clear that until the FDA approves,
  physician and their patients will continue to use
  off label, locally compounded products with
  efficacy and undocumented safety.

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Thank You!!