|
|
 |
| ANDROPAUSE
- THE MALE MENOPAUSE |
| |
|
Types
Of Androgen Hormone |
| Androgen
Hormone Replacement Therapy (HRT) |
| Medication |
Administration |
Type
Of Compound |
Product
(Manufacturer)
Picture Denotes Products With Product Information Sites
|
| Short
Acting Testosterone |
Injected
Into The Muscles |
Testosterone
(in Aqueous suspension)
|
Testosterone
Aqueous (Generic)
Testandrol® (Redur Co.)
Testandro® (Redur Co.)
Histerone® 100 (Roberts Hauck)
Tesamone® (Dunhall) |
| Testosterone
Propionate (in oil) |
Testosterone
Propionate (Generic) |
| Long-acting
Testosterone
 |
Injected
Into The Muscles |
Testosterone
Enanthate (in oil) |
Testosterone
Enanthate (Generic)
Andro® L.A. 200 (Forest
Laboratories)
Andropository®-200 (Rugby)
Delatestryl® (BioTechnology General)
Durathate®-200 (Roberts Hauck)
Everone® 200 (Hyrex) |
| Testosterone
Cypionate (in oil) |
Testosterone
Cypionate (Generic)
depAndro® (Forest Laboratories)
Depotest® (Hyrex)
 Duratest®
(Roberts Hauck) |
| Injected
implants |
Testosterone
Pellets |
Testopel®
(Bartor Pharmacal) |
| Testosterone
Transdermal Systems
 |
Patch
on the scrotum |
Patches
& Gel
 |
 |
| Patch
on the arm, back, or upper buttocks |
|
| Patch
on the back, abdomen, upper arms, or thighs |
 |
| Gel
applied to skin |
 |
| Methyltestosterone
 |
Pill
taken orally or placed under tongue |
Pills
or Tablets |
Methyltestosterone
(Generic)
Android® (ICN Pharm)
Oreton® Methyl (Schering-Plough)
Testred® (ICN Pharm)
 |
| Fluoxymesterone |
Pill
taken orally |
Fluoxymesterone
(Generic)
 |
|
|
Treatments
Options |
| 
About
5% of hypogonadal men in the United States receive testosterone
replacement therapy (TRT)] -- the treatment of choice in symptomatic
men with a documented diagnosis of andropause. Therapeutic
goals are to diminish or relieve the adverse effects of hypotestosteronemia
and to restore libido, sexual function, and a sense of well-being.
Hormonal supplementation also appears to improve bone mass,
muscle mass, cognitive function and strength in older men.
Careful patient screening and follow-up are important, however,
as testosterone replacement has been associated with several
serious adverse effects. Testosterone, converted to dihydrotestosterone
in the prostate, is directly linked to benign prostatic hyperplasia,
to increased levels of prostate-specific antigen (PSA), and
to the growth of prostate cancer, if present (an absolute
contraindication for testosterone replacement; occult prostate
cancer may be exacerbated by testosterone.
Still, sleep apnea may worsen in patients who are given testosterone.
Exogenous testosterone may also put elderly men at increased
risk of erythrocytosis (increased red cells) which could be
use advantageously in individuals with anemia.. Other potential
adverse effects are hepatotoxicity (with oral methyltestosterone),
gynecomastia (breast tissue formation), infertility, and aggressive
behavior (especially when physiologic doses are exceeded) |
|
Testosterone
Replacement Options |
The
ideal for testosterone replacement therapy is to maintain physiologic
levels of testosterone, Sex hormone binding globulin and testosterone
metabolites, dihydrotestosterone and estradiol. The circadian
cycle produced by normally functioning testes is
best approximated by testosterone transdermal patches or gel.
Transdermal
preparations and testosterone gel.
Applied ideally at bedtime, both transdermal patches and
testosterone gel achieve peak androgen levels in the early
morning. This will mimic normal diurnal variation. Transdermal
patches are available in scrotal and non-scrotal products.
Non-scrotal patches and testosterone gel are applied to
the shoulder, the upper arm, or the abdomen. In our practice
we favor the use of the transdermal gel compounded into
a 10 or 15% concentrations so only ½ to 1 ml needs
to be applied. We prefer the use of gels made with a propylene
glycol or lecithin pluronic organogel base since penetration
is greater and level peaks are more prolonged.
|
| AndroGel®
is available by prescription in indivivdual packets
unfortunately it comes in only a testosterone 1% concentration
requiring anywhere from 5 to 15 ml to be used. Also without
a prescription plan this replacement will cost around
$150 month. |
| Oral
preparations. Products that are currently available
are all rapidly metabolized by the liver. This makes achieving
satisfactory ("circadian-like") serum androgen
levels difficult. Prolonged use may lead to hepatotoxicity
and to unsatisfactory alterations in lipid profiles. In
Europe a form of oral testosterone "undecanoate"
is available commonly known as (Adriol/Androxon). This
version of testosterone is based in oil and is sealed
in a capsule to be taken orally. According to the manufacturer,
this method bypasses the liver and enters the body as
a fat through the lymphatic system. In theory this reduces
liver toxicity but it also reduces it's effectiveness. |
|
 Testosterone
Fused Pellets. Fused testosterone pellets, which
are inserted in the buttocks with a simple pellet inserter
that takes around 5 minutes. This procedure requires
just some local anesthesia and no sutures. In general
the pellets last for around 4 months before they are
completely absorbed and then new pellets need to be
inserted. Due to the very steady release of this type
of testosterone you don't have many problems with estrogen
aromatization, lowering of HDL or secondary polycthemia.
This is probable the best options for long-term replacement
in my opinion.
|
Abstracts:
Pharmacokinetics
and pharmacodynamics of subcutaneous testosterone
implants in hypogonadal men.
Pharmacokinetics
and pharmacodynamics of testosterone pellets in man.
Which
testosterone replacement therapy?
Author:
Conway, AJ, Boylan, LM, Howe, C, Ross, G, Handelsman,
DJ
Affiliation: Andrology Unit, Royal Prince Alfred Hospital,
Sydney, Australia.
Title: Randomized clinical trial of testosterone replacement
therapy in hypogonadal men.
Source: International Journal of Andrology, 1988 Aug,
11(4):247-64.
Subjects: Major Subjects (MeSH): Hypogonadism--drug
therapy Testosterone--therapeutic use
Other Subjects (MeSH): Clinical Trials Estradiol--blood
FSH--blood LH--blood Random Allocation Sex Hormone-
Binding Globulin--metabolism Testosterone--pharmacokinetics
Abstract:
We have compared the pharmacokinetics and pharmacodynamics
of the three commonly used testosterone formulations
in a prospective, randomized cross-over clinical trial.
Plasma free and total testosterone and their ratio
(proportion of unbound testosterone), sex hormone-binding
globulin (SHBG), oestradiol, LH and FSH were measured
in 15 hypogonadal men (nine hyper- and six hypogonadotrophic)
who underwent, in a randomized sequence, three treatment
periods each separated by an intervening washout period.
The treatments were: (i) intramuscular injection of
250 mg mixed testosterone esters at 2-weekly intervals,
(ii) oral testosterone undecanoate 120 mg bd, and
(iii) subcutaneous testosterone pellets (6 x 100 mg).
Pellet implantation gave the most prolonged effect
with free and total testosterone levels being elevated
for up to 4 months. This was accompanied by prompt
and sustained suppression of plasma LH and FSH, an
increase in plasma levels of oestradiol but no change
in SHBG levels. In contrast, intramuscular injections
induced marked but reproducible week-to-week fluctuations
in free and total testosterone, which resulted in
a small decrease in plasma SHBG levels, less marked
suppression of LH and FSH and a smaller increase in
plasma levels of oestradiol. Oral testosterone undecanoate
produced the most variable plasma levels of free and
total testosterone with a peak in the first treatment
week and a fall thereafter and, despite maintenance
of testosterone levels within the physiological range,
there was no significant suppression of plasma levels
of LH and FSH, and oestradiol levels were unchanged
but levels of SHBG and total cholesterol were decreased.
Free testosterone levels were increased disproportionately
during testosterone treatment as the proportion of
unbound testosterone was increased by all three treatments.
All three testosterone preparations lowered plasma
levels of urea and all were without biochemical or
haematological toxicity. Reported sexual function
was better maintained and side-effects were fewer
with parenteral compared with oral treatments. The
marked decrease in SHBG and cholesterol levels during
oral testosterone undecanoate, when compared with
parenteral treatments, occurred despite lesser androgenic
effects (suppression of gonadotrophin levels and reported
sexual function), which suggests that the liver is
exposed to excessive androgenic load via the portal
vein during oral treatment with testosterone esters.
It is concluded that testosterone pellets give the
closest approximation to zero-order (steady-state)
delivery conditions for up to 4 months after a single
insertion.
Print Access: Locations and holdings (PE): All, All
UC, UCB, UCD, UCI, UCLA, UCR, UCSC, UCSD, UCSF, CDL,
STAN, Greater Bay Area, Northern California, Greater
Los Angeles, San Diego/Inland Empire
Author: Zacharin, MR, Warne, GL
Affiliation: Department of Endocrinology and Diabetes,
Royal Children's Hospital, Parkville, Victoria, Australia.
Title: Treatment of hypogonadal adolescent boys with
long acting subcutaneous testosterone pellets.
Source: Archives of Disease in Childhood, 1997 Jun,
76(6):495-9.
Language: English Publication Type: CLINICAL TRIAL;
JOURNAL ARTICLE
Subjects: Major Subjects (MeSH): Hypogonadism--drug
therapy Testosterone--administration & dosage
Other Subjects (MeSH): Bone Development--drug effects
Delayed-Action Preparations Drug Implants Emotions
FSH--blood Growth--drug effects Hypogonadism--blood
Hypogonadism--physiopathology LH--blood Penis--
growth & development Puberty--drug effects Testosterone--blood
Testosterone--therapeutic use
Abstract:
AIMS: Long acting subcutaneous testosterone pellets
are of proved efficacy for the treatment of hypogonadal
men, but have not been reported as a treatment modality
in adolescent boys. Pharmacodynamic studies of subcutaneous
testosterone release have shown prolonged normalisation
of testosterone levels for at least four months. Administration
of a long acting, safe, effective, and convenient
form of treatment is desirable when life-long treatment
is indicated.
PATIENTS AND METHODS: Eighteen boys (aged 13.9-17.5
years at the start of treatment)-seven with primary
hypogonadism, nine with secondary hypogonadism, and
two boys being treated with testosterone for tall
stature--were given testosterone pellets (8-10 mg/kg)
every six months for 18 months. Height, weight, pubertal
status, and psychosocial parameters were assessed
and follicle stimulating hormone, luteinising hormone,
testosterone, prolactin, and lipids were measured
at 0, 1, 3, 6, 12, and 18 months. Bone age was measured
at 0 and 12 months.
RESULTS: In all boys growth velocity continued appropriately
for bone age. Puberty continued to progress in all
boys and in two boys the amount of virilisation exceeded
that seen with previous treatment with intramuscular
testosterone. After testosterone administration, follicle
stimulating hormone and luteinising hormone suppressed
incompletely in the boys with primary hypogonadism.
Serum testosterone ranged from 4.3 to 26.7 nmol/l
at three months to less than 10 nmol/l at six months
after implantation. Prolactin and lipid levels were
normal throughout the study. By report, there was
an improvement in mood and emotional wellbeing. No
pellet extrusions occurred in a total of 156 pellet
insertions.
CONCLUSIONS: All boys preferred this mode of testosterone
administration to intramuscular injections. Long acting
subcutaneous testosterone pellets are safe, efficacious,
well tolerated, and convenient, and result in normal
physical growth and improved psychological outlook
in adolescent hypogonadal boys.
|
|  Intramuscular
Preparations - Though
not comfortable and inconvenient, the intramuscular
injection is the most cost-effective and most commonly
used method of testosterone replacement therapy. Yet
its pharmacokinetic peaks and valleys may cause fluctuations
in mood and sexual function. Long-acting intramuscular
preparations such as testosterone cypionate or testosterone
enanthate achieve a peak serum level at approximately
72 hours post injection and decline thereafter. I have
found that for best results with minimizing peaks and
trough variations is to use injections of smaller doses
at shorter invertals usually between 7 and 10 days.
Short-acting preparations such as testosterone propionate
have a short half-life (approximately 12 to 24 hours)
and must be administered every other day to achieve
satisfactory serum testosterone levels; they are rarely
used and are more painful on injection. Ultra long acting
preparation of blended testosterone suspension, which
last up to 3 weeks, are not available in the United
States
|
Follow-up
During testosterone replacement, follow-up is important. Total
and free serum testosterone levels and estradiol levels should
be checked at 8 weeks, then every six to 12 months; at three
months, lipid levels and hematocrit should be checked. Every
six months, a digital rectal examination should be performed,
PSA levels checked, and treatment efficacy and adverse effects
if any reviewed. In
Summary
Proper
work-up and diagnosis of male hypogonadism and/or andropause
/ androgen deficiency in aging men (ADAM) are important aspects
of health care in aging men. The goal for clinicians is to
determine whether symptoms resulting from falling serum testosterone
levels are age- or disease-related. Among several available
testosterone replacement options, transdermal gel preparations
or testosterone pellets best approximate physiologic androgen
levels. However, use of exogenous androgens carries a risk
of adverse effects, making careful patient selection and monitoring
essential. |
BACK
TO TOP OF PAGE
Disclaimer: The
information contained on this website has not been evaluated by the
FDA. This information is not intended to treat, diagnose, cure or
prevent any disease. All material provided in the Dr. Brizel's web
site is provided for educational purposes only. Always seek the advice
of your physician or other qualified health care provider with any
questions you have regarding a medical condition, and before undertaking
any diet, exercise or other health program. ©2002,
All Rights Reserved, Center For Clinical Age Management, Inc.
|
