AXIRON® (testosterone) solution for topical use CIII [package insert]).

Transcript AXIRON® (testosterone) solution for topical use CIII [package insert]).

Managing Hypogonadism in the Primary Care Setting

Dr Michael Gillman

St Andrews Hospital Specialist Suites, Wickham Terrace Mater Private Clinic, South Brisbane Shore Street West Medical Centre, Cleveland 1

Hypothalamic – Pituitary – Testicular Axis

Primary Testicular Failure

• Klinefelters • Bilat Orchidectomy • Radiotherapy, Chemotherapy • Cryptorchidism • Testicular Injury • Orchitis • Age • Co-Morbid conditions particularly Diabetes, Metabolic Syndrome 3

Secondary ( Hypogonadotrophic )

• Pituitary Tumours • Haemachromatosis • Thalassaemia • Sleep apnoea • Other acute or chronic illness affecting hypothalamic-pituitary-testicular axis • Substance abuse ( steroids and opiates ) 4

Presentation (1)

Often picked up incidentally • Reduced sense of general wellbeing; • Energy Loss; • Fatigue; • Low mood or depression; • Irritability; • Poor concentration; • Poor memory; 5

Presention Continued

• Decreased Libido • Failure to conceive • Sexual Dysfunctions • Losing strength and muscle mass 6

Further History

• History of onset • Past Medical and Surgical History • Social and Lifestyle History • Family History • Sexual History • Ask about symptoms of sleep apnoea • Ask about LUTS 7

Examination

• Height Weight and Waist Circumference • Testicular examination • Breast Examination • Body Hair distribution • Muscle Mass • DRE • General examination BP Heart chest abdomen etc 8

Investigations

• FBC, E/LFTs, HDL/LDL, serum ferritin, TSH, serum testosterone, PSA ( Total T more reliable than free T ) • If Testosterone is low repeat along with LH and PRL • Take total T between 8 to 10 a.m.

  The patient should be fasting as glycaemic load can distort the results Avoid prior exhaustive physical exercise (e.g. jogging) as this may influence the testosterone levels • ? Sleep Study if suggested by history • BMD 9

What level of T is hypogonadism?

• Australia: PBS guidelines - Approved indications for authority: • Androgen deficiency in ageing confirmed by

males 40 years and older

without pituitary or testicular disorders other than

x2 early morning total T < 8nmol/L or 8 -15 nmol/L with high LH (>1.5 times upper limit of normal for young men)

• Androgen deficiency in males with

established pituitary or testicular disorders

•

Androgen deficiency in males under 18 years of age

: Micropenis, pubertal induction, or constitutional delay of growth or puberty

Handelsman (2004)

What are the correct levels for Diagnosis?

•

Australia <8 nmol/L

•

US <10.4 nmol/L

•

Europe <12 nmol/L

Management

• Diet, exercise and waist loss • • T levels may be restored by weight loss with a diet and exercise program Attempt weight loss along with TRT and if successful, assess need to decrease or cease TRT (3 to 6 months for function to return) • Correct other risk factors and co morbid conditions; 12

Management

• Examine for contraindications for TRT: • • Prostate or breast cancer Erythrocytosis ( HCT > 55% ) • • • Sleep apnoea Severe LUTS Cardiac failure ( Potential for oedema and raised HCT )

If Decide to treat

• Explain the probability that this will be long term therapy • Explain infertility consequences • Commence with short acting topical 14

TRT – Topical

(less likely to have negative effects on lipids, less likely to cause polycythaemia)

Androderm patch

(testosterone + absorption enhancers)

Testogel

(testosterone) Transdermal patch 2.5 & 5 mg – apply 10 p.m. back, arm, shoulders, abdomen, buttocks, thighs - 1 week between sites

Mimics normal circadian rhythms

Check T level in a.m. after p.m. patch applied

Contact dermatitis 10-60% , visibility, poor adherence, difficulty achieving adequate T concentrations

50mg testosterone in a 5 g sachet Apply daily in a.m. - 5 to 10 g/day - titrate dose by 2.5 g increments after day 7 (max 10g = 100mg T) Apply to shoulders, arms, abdomen - wash hands Allow to dry 3 - 5 mins

Steady state serum T over 24 hours Lack of visibility and less skin irritation Dosage flexibility

Take T level 6 to 8 hours after application

Skin transfer - cover or bathe (4 - 6 hours after application)

Follow up at six weeks

• Assess total T level and adjust dose • Ask about side effects, voiding symptoms • Side effects: • • Male pattern hair loss Worsening of sleep apnoea • • • • • Acne and oily skin Gynaecomastia Fluid retention and oedema Polycythaemia Testicular shrinkage and decreased sperm count 16

TRT - imi injections

Reandron 1000

(T undeconoate)

imi not for men with bleeding disorder or on anticoagulants

4 ml deep gluteal imi slowly @ 0 and 6 weeks (loading dose) then every 10 to 14 weeks (x4 per year) Check T level @ 30 weeks prior to injection 4 Titrate dose by altering timing of injections - administer more often if T level is below normal

Trough levels within normal range More stable levels of energy, mood and libido Less polycythaemia Primosteston depot Reandron 1000 every 3 months

@ 3 months, 6 months then annually

• Assess response to Rx • Assess Total T level • Hb and HCT (>54%) • LFT, lipids, voiding symptoms • Sleep apnoea • Weight, WC and BMI • Breast examination • DRE and PSA – assess velocity • (BMD each 2 years) 18

Axiron Not yet approved for use in Australia or New Zealand

This information is provided in response to your request and is intended for your scientific and/or educational purpose and is not intended for promotional use. This material is copyrighted by Lilly USA, LLC with all rights reserved.

Background

♦ Aim of testosterone topical solution clinical program was to develop a topical solution that would restore total testosterone levels to the normal range (300-1050 ng/dL) • Applied using an applicator • Applied to a discrete anatomical location (underarm)

Data on file, Lilly Research Laboratories, AXSEP2010A

Delivery System

♦ The design hypothesis for this delivery system was that the solution would be applied onto the skin of the axilla by use of the flexible silicone applicator ♦ The product is applied via a metered-dose pump which is used to deliver a consistent amount of testosterone solution to the applicator system, which is then used to apply the dose to the axilla

Data on file, Lilly Research Laboratories, AXSEP2010F

Delivery System

 Testosterone topical solution is available as a metered-dose pump containing 110 mL of solution  The pump is capable of dispensing 90 mL of solution in 60 metered pump actuations  One pump actuation delivers 30 mg of testosterone in 1.5 mL of solution