|
Use, misuse and abuse of androgens
Ann J Conway, David J Handelsman,
Douglas W Lording, Bronwyn Stuckey, Jeffrey D Zajac
on behalf of the Endocrine Society of
Australia
[Abstract] Full Text [PDF]
Position Statement
The Endocrine Society of Australia consensus guidelines for androgen
prescribing
Abstract
- Use of androgens - Misuse
of androgens - Abuse of androgens - Key
references
Abstract
- Androgen replacement therapy (ART) is
usually life-long, and should only be started after androgen deficiency
has been proven by hormone assays. The therapeutic goal is to maintain
physiological testosterone levels.
- Testosterone rather than synthetic
androgens should be used.
- Oral 17-alkylated
androgens are hepatotoxic and should not be used for ART.
- There is no indication for androgen
therapy in male infertility. Although androgen deficiency is an uncommon
cause of erectile dysfunction, all men presenting with erectile
dysfunction should be evaluated for androgen deficiency. If androgen
deficiency is confirmed, investigation for the underlying pathological
cause is required.
- Contraindications to androgen therapy are
prostate and breast cancer. Precautions include using lower starting doses
for older men and induction of puberty. Intramuscular injections should be
avoided in men with bleeding disorders. Androgen-sensitive epilepsy,
migraine, sleep apnoea, polycythaemia or fluid overload need to be
considered. Competitive athletes should be warned about the risks of
disqualification.
- ART should be initiated with intramuscular
injections of testosterone esters, 250 mg every two weeks. Maintenance
requires tailoring treatment modality to the patient's convenience.
Modalities currently available include testosterone injections, implants,
or capsules. Choice depends on convenience, cost, availability and
familiarity. [ Incorrect dosage initially published. Correction made 8
March 2000. ART should be initiated with intramuscular injections of
testosterone esters, 250 mg twice weekly.]
- There is no convincing evidence that, in
the absence of proven androgen deficiency, androgen therapy is effective
and safe for older men per se, in men with chronic non-gonadal
disease, or for treatment of non-specific symptoms. Until further evidence
is available, such treatment cannot be recommended.
-
Androgens are hormones that are based on
the structure of testosterone, the major male sex hormone, and are
capable of developing and maintaining masculine sexual characteristics
(including the genital tract, secondary sexual characteristics, and
fertility) and the anabolic status of somatic tissues. All androgens
have similar biological effects because they all act through the
single androgen receptor. Their effects in different tissues are
diversified by metabolism of testosterone to its active metabolites by
the enzymes 5
reductase (which converts testosterone to 5-dihydrotestosterone,
an androgen with enhanced potency acting on the androgen receptor) and
aromatase (which converts testosterone to
oestradiol, which acts on the oestrogen receptor).
Use of adrogens
The main medical use of androgens (Box
1) is as androgen replacement therapy (ART) for established androgen
deficiency.1-3 Classical
androgen deficiency occurs in about 1 in 200 men, due to testicular
disorders that directly reduce testosterone output, or
hypothalamic-pituitary disorders that reduce pituitary luteinising hormone (LH)
secretion, which is the main drive to testosterone production by the
interstitial (Leydig) cells of the testes. Although classical androgen
deficiency is relatively easy to recognise, diagnosis of less severe
androgen deficiency can be more difficult. Owing to its subtle and variable
clinical features, the diagnosis may easily be missed, denying patients
simple and effective medical treatment with often striking subjective
benefits.
Potential extensions of classical
indications to partial androgen deficiency remain to be fully evaluated for
clinical safety and efficacy. These indications include age, androgen
deficiency secondary to a chronic medical condition or its treatment,
hormonal male contraception, and postmenopausal symptoms.4-6
Until more definitive objective evidence is available regarding the safety
and efficacy of prescribing androgens for these indications, they remain
suitable for carefully monitored, controlled clinical research trials, but
not for routine medical treatment.
Pharmacological applications of androgens usually represent second-line therapy where more specific treatments
are not yet available or have failed.
Androgen treatment can evoke a strong
placebo response. In men without genuine androgen deficiency, this placebo
effect invariably wanes with time, leading to confusion and dissatisfaction
with treatment. In addition, once androgen therapy has commenced, the
biochemical changes can cloud further interpretation of results for months.
Therefore, androgen replacement therapy should be commenced only after
androgen deficiency is clearly established.2,3
Diagnosis of
androgen deficiency 1-3
Diagnosis of androgen deficiency involves the
recognition of appropriate clinical features, with confirmation by
biochemical testing. Important clinical features required to evaluate
testicular function include reproductive history (including pubertal
development), fertility status, changes in sexual function and body hair
growth, known testicular pathology, drug use, and occupation. Physical
examination should record androgenisation (secondary sexual characteristics,
especially body hair distribution, musculature and gynaecomastia) and testis
volumes (by orchidometry).
Serum LH, follicle-stimulating hormone and
testosterone levels should be measured, on at least two separate days and
preferably in the morning, to minimise the effects of random and laboratory
fluctuations and diurnal rhythms. Direct measurements of free testosterone,
if available, may help establish the diagnosis of androgen deficiency, but
require extensive validation. Indirect measurements of free testosterone,
such as the free androgen index (testosterone/sex hormone binding globulin [SHBG]
ratio), correspond poorly with direct measurements and lack empirical
validation as a diagnostic test.
Additional tests that may be required to
identify underlying disorders include karyotyping, pituitary radiology and
measurement of prolactin levels, serum ferritin levels, iron saturation and,
increasingly, genetic diagnosis.
Androgen deficiency is
unlikely in men with mean testis volume > 20 mL without atrophy, with a
plasma testosterone level consistently above 20 nmol/L, or presenting with
erectile dysfunction and a plasma testosterone level consistently above 8
nmol/L (Box 2). Where the diagnosis is not
clear, referral to a clinical endocrinologist with experience in this area
is recommended.1
Androgen
replacement therapy 1-3
ART is indicated to rectify androgen
deficiency of any cause sufficient to cause clinical consequences. After
puberty, there is no age limit to ART. Androgen-deficiency effects may
manifest as changes in one or more androgen-sensitive functions; for
example, psychosexual function, or loss of anabolic effects on bone, muscle,
blood-forming marrow and other androgen-responsive tissues. Apart from
decreased spermatogenesis, ART can rectify all clinical features of androgen
deficiency, which usually respond within 1-2 months of starting therapy,
although the full effect may take longer.
Dosage: Standard ART is either
testosterone enanthate (Primoteston in castor oil; Schering) or mixed
testosterone esters (Sustanon in arachis oil; Organon) as 250 mg in 1 mL oil
at 14-day intervals. Deep intramuscular injections are usually given into
the upper and outer quadrant of the buttock, although some patients prefer
the deltoid or lateral thigh muscle sites. Few men can manage self-injection
with the viscous oil vehicle.
For all ART, testosterone and its esters
should be used in preference to synthetic androgens, because of their
established safety and efficacy, as well as ease of dose-titration and assay
monitoring.
Lower starting doses may occasionally be
needed, especially in previously untreated elderly men and during first
induction of puberty. Less frequent dosing intervals (eg, every three weeks)
are occasionally necessary for those unable or unwilling to have standard
dosage, but are accompanied by more extreme peaks and troughs in blood
testosterone levels, which may exaggerate symptom fluctuations. [Incorrect
dosage initially published. Correction made 10 March 2000. Less frequent
dosing intervals (eg, thrice-weekly)]
An inadequate clinical response raises
doubt about androgen deficiency as the cause of recalcitrant symptoms.
Rarely, an inadequate clinical response may require increased dosage. If
suboptimal symptomatic benefit is supported by biochemical evidence of
inadequate maintenance of androgen levels (low trough testosterone levels
with or without persistently supranormal LH levels in primary hypogonadism),
the same dose may be injected at 10-day intervals. Persistently inadequate
responses indicate that unresponsive symptoms are not due to androgen
deficiency; further escalation in dose or frequency is not warranted. Men
with mild or partial androgen resistance due to androgen-receptor mutations
may benefit from high-dose androgen therapy.
As the underlying disorders are almost
always permanent, life-long ART after the age of puberty is usually
necessary. Long term therapeutic compliance depends on an acceptable
regimen. Crossover studies indicate that patients strongly prefer the stable
testosterone levels and smoother clinical effects provided by implants
or transdermal formulations, compared with the wide fluctuations in
testosterone levels and symptoms during intramuscular testosterone ester
injections. Thus, although ART should commence with injections, alternative
modalities (Box 3) may improve compliance.
Factors to consider include cost, convenience, availability, familiarity
with alternatives, and tolerance for frequent injections.
Monitoring: Monitoring of ART is
mainly to ensure effective androgen replacement by a regimen tailored to the
patient's needs, aiming to maintain adequate therapeutic compliance by
continuation of treatment. Serial clinical observation of clinical
well-being and major symptoms of androgen deficiency, together with limited
numbers of hormonal assays, is usually adequate. Restoration of sexual
function has a low threshold for androgen action, so adequate libido and
potency is a necessary, but not sufficient, indication of clinically
adequate androgen replacement.
Blood hormone assays have limited utility
in optimising an ART regimen at the start of treatment and in evaluating
androgen replacement. Trough blood testosterone levels (ie, before the next
scheduled dose) within the eugonadal reference range can be a valuable guide
to the adequacy of parenteral androgen replacement, but random blood
testosterone levels are not useful for monitoring with either oral or
injectable testosterone. In men with hypergonadotropic hypogonadism,
suppression of blood LH levels into the eugonadal reference range indicates
adequate ART, whereas persistent non-suppression of LH after 3-6 months of
regular treatment indicates inadequate dosage or compliance. In
hypogonadotropic hypogonadism, blood gonadotropin levels are uninterpretable.
Serial evaluation of bone density (especially vertebral trabecular bone) by
dual-photon absorptiometry at 1-2-year intervals may be useful in evaluating
the adequacy of long-term androgen effects on bone. Other biochemical
indices of androgen action, such as haemoglobin, SHBG, and high density
lipoprotein cholesterol levels, reflect only supraphysiological effects and
are too insensitive for routine monitoring of ART.
Androgen deficiency is protective against
prostate disease, and ART may restore the risks to those equivalent to, but
no more than, eugonadal men of similar age. Screening of men receiving ART
for cardiovascular and prostate disease need be no more intensive than for
men of similar age not on ART.
Precautions and
side effects 14-17
Adverse effects of androgen treatment are
uncommon. Virilisation may occur with androgen therapy in women or children;
androgen therapy in these settings requires expert management. Truncal acne
and hair growth, weight gain, gynaecomastia and male-pattern hair loss may
be observed, and should be managed symptomatically. Certain side effects are
characteristic of specific therapeutic modalities (eg, discomfort from
intramuscular injections, extrusion of subdermal implants, gastrointestinal
disturbance from oral testosterone undecanoate). Polycythaemia may occur
disproportionately often in older men treated with testosterone ester
injections. In addition, certain testosterone formulations have distinctive
effects due to their pharmacokinetic features (eg, reduced levels of SHBG,
high density lipoprotein cholesterol and other hepatic proteins due to
supraphysiological hepatic testosterone exposure). This may be due to
injectable testosterone esters (via high peak blood testosterone
concentrations) or oral testosterone undecanoate (via high first-pass portal
testosterone concentrations), whereas more steady formulations (transdermal,
implants) exhibit fewer or no such effects.
Oral synthetic androgens that have a 17-alkyl
substituent (oxandrolone, fluoxymesterone, danazol) are inherently
hepatotoxic, causing cholestatic hepatitis, peliosis hepatis and hepatic
tumours. Other classes of synthetic androgen, such as 19-nortestosterone
derivatives (nandrolone, MENT) and the 1-methyl androgens (mesterolone,
methenolone), are not hepatotoxic.
Absolute contraindications to androgen
therapy are prostate or breast cancer in men. Androgen therapy should be
started in men over the age of 40 only after exclusion of undiagnosed
prostate disease. Precautions are required for:
- older men starting androgen treatment,
where it may precipitate urinary obstruction or unfamiliar increases in
libido;
- pubertal boys, in whom excessive dosage
may accelerate epiphyseal closure, leading to shortened final stature;
- parenteral androgen therapy in men with
bleeding disorders;
- competitive athletes, who may be
disqualified;
- androgen-sensitive epilepsy, migraine,
sleep apnoea or polycythaemia; and
- cardiac or renal failure or severe
hypertension susceptible to fluid overload from sodium and fluid
retention.
Misuse of androgens
Medical misuse of androgens involves
prescription with no acceptable medical indication. Some common examples of
misguided prescribing of androgens in the absence of established androgen
deficiency include:
Male infertility: There is no
indication for androgen therapy in male infertility. The only likely
consequence is an adverse effect of suppressing spermatogenesis.
Male sexual dysfunction or impotence: Androgen
deficiency (with or without hyperprolactinaemia) is an uncommon (< 5%)
cause of men presenting with erectile dysfunction. In such men, excluding
androgen deficiency as a readily treatable underlying cause is essential. In
the unusual event of severe androgen deficiency presenting with erectile
dysfunction, the underlying cause needs to be identified, and plans for
life-long ART need to be established.
"Male menopause" or "andropause":
There is still no evidence that the modest decreases in circulating
blood testosterone levels which commence during mid-life have any clinical
importance. The risks and benefits of androgen supplementation for partially
androgen-deficient older men require further evaluation by
placebo-controlled studies. Androgen treatment may be inappropriate,
wasteful, and involve placebo effects. Terms such as "male
menopause" and "andropause" are misleading; they have little
place in meaningful medical or scientific discourse.
Elderly men (> 65 years):18
There is no basis for androgen therapy based on age per se. Further
controlled clinical trials are needed to evaluate the potential role of
androgen supplementation in ageing. While some preliminary
placebo-controlled studies suggest short-term benefits for muscle, bone and
quality of life, findings are not yet consistent and the identification of
appropriate treatment objectives and target subgroups, as well as overall
analyses of risks, benefits and costs, are lacking. Specifically, it remains
to be determined whether androgen supplementation has significant and
sustained clinical benefits in older men with low-normal plasma total
testosterone and normal LH levels. At present, there is no basis for
androgen treatment outside properly designed clinical trials.
Treatment of non-specific symptoms: There
is no basis for androgen therapy based on symptoms in the absence of
established androgen deficiency. In addition to the unproven safety and
efficacy, the placebo effect of androgen injections may be confusing to both
doctor and patient. When placebo effects wane, further confusion and
dissatisfaction with treatment may be expected.
Abuse of androgens
Illicit use of androgens19-24
("anabolic steroids") depends largely on obtaining androgens
without legal prescription to be used in the absence of any medical
indication. Illicit androgen use became epidemic over the past four decades,
since androgens were reportedly first used in elite competitive power
sports. A recent placebo-controlled study has shown that high-dose androgen
administration does improve muscle size and strength in healthy eugonadal
men. Whether these changes enhance athletic performance, whether they are
sustained, and whether they apply to older men remains to be clarified.
Medical prescription appears to support
only a small proportion of illicit androgen use, but such activity has been
formally ruled as a breach of professional standards by medical boards in
most States and by the Royal Australasian College of Physicians. Highly
motivated young men can be very sophisticated in manipulating and pressuring
general practitioners while attempting to obtain prescriptions for
androgens. The doctor is often led to believe that other practitioners are
prescribing androgens for young men, and that he or she is being uncaring or
negligent by not acceding to the patient's wishes. We recommend that general
practitioners resist these pressures.
Fortunately, most people appear ultimately
to lose interest in this form of drug abuse.
|
Background and evidence basis of
recommendations
The Endocrine Society of Australia (ESA)
Consensus Guidelines for Androgen Prescribing were written on behalf
of the Endocrine Society of Australia. The ad hoc Writing Committee
commissioned by the ESA's Council was Dr A J Conway, Professor D J
Handelsman (Chair), Associate Professor D W Lording, Dr B Stuckey, and
Associate Professor J D Zajac. The draft guidelines were extensively
circulated for comment to active members of the ESA with clinical
expertise or interests in male reproductive endocrinology. Comments
were incorporated into the final document, which was ratified by the
ESA's Council. Androgen therapy, in regular clinical use for over 60
years, is one of the oldest hormonal regimens in modern therapeutics.
As a long established standard and effective form of hormone
replacement for many decades, placebo-controlled studies are
unavailable and now unacceptable. Consequently, the NHMRC Quality of
Evidence Ratings for these recommendations are those appropriate to an
expert committee reviewing all available evidence from controlled
experimental and observational studies as well as clinical experience.
|
Key references
- Diagnosis and management of androgen
deficiency
- Behre HM, Yeung CH,
Nieschlag E. Diagnosis of male infertility and hypogonadism. In: Nieschlag
E, Behre HM (eds): Andrology: Male Reproductive Health and Dysfunction.
Berlin:Springer, 1997: 87-111.
- Plymate SR. Male
Hypogonadism. In: Becker KL (ed): Principles and Practice of
Endocrinology and Metabolism. 2nd ed. Philadelphia: J B Lippincott
Company, 1995: 1056-1082.
- Nieschlag E, Wang
C, Handelsman DJ, et al (eds) (1992). Guidelines for the use of androgens
in men. Geneva, Special Programme of Research, Development and Research
Training in Human Reproduction of the World Health Organisation.
Male contraception
- Cummings DE,
Bremner WJ. Prospects for new hormonal male contraceptives. In: Bremner WJ
(ed): Clinical Andrology. Philadelphia: W B Saunders Company, 1994:
893-922.
- Handelsman DJ.
Contraception in the male. In: DeGroot LJ (ed): Endocrinology. 3rd
ed. Philadelphia: W B Saunders, 1994: 2449-2458.
Androgen therapy in systemic disease
- Liu PY, Handelsman
DJ. Androgen therapy in non-gonadal disease. In: Nieschlag E, Behre HM (eds):Testosterone:
Action, Deficiency and Substitution. 2nd ed. E Nieschlag, Behre HM (eds), Berlin,
Springer-Verlag, 1998.
Comparative pharmacology of androgen
formulations
- Bals-Pratsch M,
Langer K, Place VA, Nieschlag E. Substitution therapy of hypogonadal men
with transdermal testosterone over one year. Acta Endocrinologica
1988; 118: 7-13.
- Behre HM,
Oberpenning F, Nieschlag E. Comparative pharmacokinetics of androgen
preparations: application of computer analysis and simulation. In:
Nieschlag E, Behre HM (eds): Testosterone: Action, Deficiency and
Substitution. Berlin: Springer-Verlag, 1990: 115-135.
- Cantrill JA, Dewis
P, Large DM et al. Which testosterone replacement therapy? Clin
Endocrinol (Oxf) 1984; 24: 97-107.
- Conway AJ, Boylan
LM, Howe C, Ross G, Handelsman DJ. A randomised clinical trial of
testosterone replacement therapy in hypogonadal men. Int J Androl
1988; 11: 247-264.
- Handelsman DJ,
Conway AJ, Boylan LM. Pharmacokinetics and pharmacodynamics of
testosterone pellets in man. J Clin Endocrinol Metab 1990; 71:
216-222.
- Meikle AW, Mazer
NA, Moellmer JF, et al. Enhanced transdermal delivery of testosterone
across nonscrotal skin produces physiological concentrations of
testosterone and its metabolites in hypogonadal men. J Clin Endocrinol
Metab 1992; 74: 623-628.
- Snyder PJ,
Lawrence DA. Treatment of male hypogonadism with testosterone enanthate. J
Clin Endocrinol Metab 1980; 51: 1335-1339.
Safety of androgens
- Alexandersen P,
Haarbo J, Christiansen C. The relationship of natural androgens to
coronary heart disease in males: a review. Atherosclerosis 1996;
125: 1-13.
- Barrett-Connor E.
Testosterone, HDL-cholesterol and cardiovascular disease. In: Bhasin S,
Gabelnick HL, Spieler JM et al (eds): Pharmacology, Biology, and
Clinical Applications of Androgens: Current Status and Future Prospects.
New York: Wiley-Liss, 1996: 215-223.
- Behre HM, Bohmeyer
J, Nieschlag E. Prostate volume in testosterone-treated and untreated
hypogonadal men in comparison to age-matched normal controls. Clin
Endocrinol (Oxf) 1994; 40: 341-349.
- Gooren LJ,
Polderman KH. Safety aspects of androgen therapy. In: Nieschlag E, Behre
HM (eds): Testosterone: Action, Deficiency and Substitution.
Berlin: Springer-Verlag, 1990: 182-203.
Androgen and the ageing male
- Tenover JL.
Androgen therapy in aging men. In: Bhasin S, Gabelnick HL, Spieler JM, et
al (eds): Pharmacology, Biology, and Clinical Applications of
Androgens: Current Status and Future Prospects. New York: Wiley-Liss,
1996: 309-318.
Androgen abuse
- Bhasin S, Storer
TW, Berman N, et al. The effects of supraphysiologic doses of testosterone
on muscle size and strength in normal men. N Engl J Med 1996; 335:
1-7.
- Handelsman DJ,
Gupta L. Prevalence and risk factors for anabolic-androgenic steroid abuse
in Australian secondary school students. Int J Androl 1997; 20:
159-164.
- Lin GC, Erinoff L
(eds). (1990). Anabolic Steroid Abuse. National Institute on Drug Abuse
Research Monograph Series. Rockville, US Department of Health and Human
Services.
- Wilson JD.
Androgen abuse by athletes. Endocr Rev 1988; 9: 181-199.
- Yesalis CE,
Kennedy NJ, Kopstein AN, Bahrke MS. Anabolic-androgenic steroid use in the
United States. JAMA 1993; 270: 1217-1221.
- Young NR, Baker
HWG, Liu G, Seeman E. Body composition and muscle strength in healthy men
receiving testosterone enanthate for contraception. J Clin Endocrinol
Metab 1993; 77: 1028-1032.
Authors' details
Endocrine Society of Australia, Sydney,
NSW.
Ann J Conway, MB BS, FRACP;
David J Handelsman, MB BS, PhD, FRACP;
Douglas W Lording, MB BS, FRACP;
Bronwyn Stuckey, MB BS, FRACP;
Jeffrey D Zajac, PhD, FRACP.
Reprints will not be available from the
authors.
Correspondence: Associate Professor J D Zajac, Department of Medicine,
University of Melbourne, Royal Melbourne Hospital, Parkville, VIC 3050.
j.zajac@medicine.unimelb.edu.au
©MJA 2000
|
1: Use, misuse
and abuse of androgens
Use
Physiological (androgen deficiency)1-3
- Classical androgen deficiency
("hypogonadism")
- Age-related partial androgen
deficiency
- Micropenis (neonatal)
- Delayed puberty
- Aged men*
- Androgen deficiency secondary to
chronic disease*
- Induced androgen deficiency
- Hormonal male contraception*
Pharmacological (non-androgen
deficiency) 4-6
- Osteoporosis
- Anaemia due to marrow or renal
failure
- Advanced breast cancer
- Excessively tall stature in boys
Misuse
Inappropriate indications
- In absence of proven androgen
deficiency:
- Male infertility
- Sexual dysfunction/impotence
- "Male menopause",
"andropause"
- Older men (>65 years)
- Non-specific symptoms
|
|
Abuse 19-24
Absence of medical indication
|
|
|
Competitive power sports (athletics,
weightlifting, football, swimming, rowing, boxing)
|
|
|
Bodybuilding
|
|
|
"Body beautiful" subculture
|
|
|
Security, police, armed forces,
professional sports
|
|
* These indications remain to be fully evaluated for safety and
efficacy in controlled clinical trials.
|
Back to text
|
2: Biochemical
evaluation of the diagnosis of androgen deficiency in men with
clinical features consistent with hypogonadism*
|
|
|
|
Testosterone level†
|
Luteinising hormone level†
|
Diagnosis
|
|
|
|
<8 nM
|
High‡
|
Androgen deficiency
(hypergonadotropic hypogonadism§)
|
|
<8 nM
|
Not high
|
Androgen deficiency (hypogonadotropic
hypogonadism§)
|
|
8-15 nM
|
High‡
|
Androgen deficiency (Leydig cell
failure)
|
|
8-15 nM
|
Not high
|
Androgen deficiency not confirmed:
unproven therapeutic benefit of androgen replacement therapy
|
|
>20 nM
|
Any
|
Excludes androgen deficiency
|
|
>30 nM**
|
High‡
|
Androgen resistance
|
|
|
|
*There is necessarily an arbitrary
component to this type of table. It is based on current experience and
should be subject to changes according to further clinical evidence.
†Blood sample classification based on at least two separate morning
blood samples. ‡"High" luteinising hormone level is
defined as > 1.5 times the upper limit of the eugonadal reference
range for young men. §Hypergonadotropic and hypogonadotropic
hypogonadism are also referred to as primary and secondary
hypogonadism, respectively. Compensated Leydig cell failure is a form
of partial androgen deficiency in which androgen replacement is often
beneficial. **Elevated testosterone is defined as above the upper
limit of the eugonadal reference range for young men.
|
Back to text
|
3: Androgen
treatment modalities 7-13
Testosterone implants
- Fused cylindrical pellets of pure
crystalline testosterone that form a subdermal depot
- Provide stable, physiological
levels of testosterone for 4-6 months following a single
implantation of four 200 mg (800 mg) implants
- Implantation uses a trochar and
cannula technique under office sterile conditions, and requires
local anaesthesia
- Main adverse effect is extrusion
of implants via the insertion site 1-2 months after implantation
- Extrusion rate (about 10%) depends
on operator experience and patient's physical activity
- Minor adverse effects related to
the minor office surgery (bleeding, infection) are infrequent
(<5%)
- Should only be used for patients
who have demonstrated satisfactory tolerance of androgen effects
with shorter-acting preparations
Transdermal testosterone
- Administered daily via
androgen-impregnated adhesive skin patches or hydroalcoholic gels
(not yet available in Australia)
Other depot testosterone
formulations
- Newer injectable esters
(testosterone undecanoate, testosterone buciclate)
- Testosterone-laden biodegradable
microspheres
- Both these formulations deliver
stable, physiological testosterone levels for 2-3 months following
injection
Oral testosterone undecanoate
- Useful where parenteral
testosterone is undesirable (eg, bleeding disorders or
anticoagulation) or poorly tolerated
- Administered as 160-240 mg (four
to six 40 mg capsules), divided into 2-4 doses per day
- Second-line formulation for
routine ART, because of frequency of administration, high hepatic
load, gastrointestinal intolerance, and higher cost
|
Back to text
Citation:
MJA 2000; 172: 220-224 an article published on the Internet by The Medical
Journal of Australia <http://www.mja.com.au/>
|
