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Managing Hypogonadism in the Primary Care

SettingDr Michael Gillman

St Andrews Hospital Specialist Suites, Wickham Terrace

Mater Private Clinic, South Brisbane

Shore Street West Medical Centre, Cleveland

Hypothalamic – Pituitary – Testicular Axis

Primary Testicular Failure

•Klinefelters

•Bilat Orchidectomy

•Radiotherapy, Chemotherapy

•Cryptorchidism

•Testicular Injury

•Orchitis

•Age

•Co-Morbid conditions particularly Diabetes, Metabolic Syndrome

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Secondary ( Hypogonadotrophic )

•Pituitary Tumours

•Haemachromatosis

•Thalassaemia

•Sleep apnoea

•Other acute or chronic illness affecting hypothalamic-pituitary-testicular axis

•Substance abuse ( steroids and opiates )

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Presentation (1)

Often picked up incidentally

•Reduced sense of general wellbeing;

•Energy Loss;

•Fatigue;

•Low mood or depression;

•Irritability;

•Poor concentration;

•Poor memory;

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Presention Continued

•Decreased Libido

•Failure to conceive

•Sexual Dysfunctions

•Losing strength and muscle mass

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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

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Examination

•Height Weight and Waist Circumference

•Testicular examination

•Breast Examination

•Body Hair distribution

•Muscle Mass

•DRE

•General examination BP Heart chest abdomen etc

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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

•BMD9

What level of T is hypogonadism?

•Australia: PBS guidelines - Approved indications for authority:• Androgen deficiency in males 40 years and older without pituitary or testicular disorders other than ageing confirmed by 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;

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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

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

Androderm patch

(testosterone + absorption enhancers)

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

Testogel

(testosterone)

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

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TRT - imi injections

Reandron 1000(T undeconoate)

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

imi not for men with bleeding

disorder or on anticoagulants

every 3 weeks every 3 months

Primosteston depot

Reandron 1000

@ 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)

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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

Data on file, Lilly Research Laboratories, AXSEP2010A

♦ 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)

Delivery System

Data on file, Lilly Research Laboratories, AXSEP2010F

♦ 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

Delivery System

AXIRON® (testosterone) solution for topical use CIII [package insert]). Indianapolis, IN: Eli Lilly and Company; 23 Nov 2010

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

Axillary Application

Dosing and Administration

AXIRON® (testosterone) solution for topical use CIII [package insert]). Indianapolis, IN: Eli Lilly and Company; 23 Nov 2010

♦ Recommended daily dose is 60 mg (2 pump actuations)

♦ Apply to the axilla (clean, dry, intact skin)

♦ Do not apply to any part of the body other than the axilla

♦ Apply at the same time each day (preferably morning) following showering/washing

♦ Pump will need to be primed prior to first use

Dosing and Administration

AXIRON® (testosterone) solution for topical use CIII [package insert]). Indianapolis, IN: Eli Lilly and Company; 23 Nov 2010

♦ One (1) pump will dispense 30mg

• If the patient requires a 60mg dose, the application procedure should be repeated for the other axilla

• If the patient requires the 90mg or 120mg dose, after the initial application into each axilla, the skin should be allowed to dry (approximately 3 minutes) prior to repeating an application on the same axilla or to dressing

Dosing and Administration

AXIRON® (testosterone) solution for topical use CIII [package insert]). Indianapolis, IN: Eli Lilly and Company; 23 Nov 2010

♦ After use, the applicator should be rinsed with running water that is room temperature and then patted dry with a tissue

♦ The applicator and cap are then replaced on the bottle for storage

♦ Hands should be washed thoroughly with soap and water immediately after application

Dosing and Administration

AXIRON® (testosterone) solution for topical use CIII [package insert]). Indianapolis, IN: Eli Lilly and Company; 23 Nov 2010

♦ Patients may use antiperspirants/deodorants with testosterone topical solution • underarm antiperspirants or deodorants spray or stick

products may be used 2 minutes prior to dose application as part of normal, consistent, and daily routine

♦ Patients should be advised to avoid swimming or washing the application site until 2 hours following dose application

♦ Patients should cover the axilla application site(s) with clothing (e.g., a shirt) after the solution has dried

Patient Counseling: How to minimize risk of secondary exposure

AXIRON® (testosterone) topical solution [package insert]). Indianapolis, IN: Eli Lilly and Company; 23 Nov 2010

♦ Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from testosterone topical solution treated skin:• Testosterone topical solution should only be applied

to the axilla, not to any other part of the body

• Children and women should avoid contact with the unwashed skin of the axilla or unclothed application sites of men using testosterone topical solution

• Patients should wash their hands immediately with soap and water after application of testosterone topical solution

Take-home messages

•Consider hypogonadism when patients present with typical symptoms and signs

•Diagnose hypogonadism and either treat or refer

•Select patients carefully and monitor closely