Total testosterone (TT) concentration = fT + bioactive T + SHBG bound T.

(Orv Hetil 1998 Aug 23;139(34):2021-4 [Serum and salivary testosterone
levels in erectile dysfunction]. )

Second Step: Blood and Saliva test kit from Diagnostech. Measure
T/fT/E/DHT/LH/DHEA/SHBG/Cortisol (C) in serum and T/E/DHT/DHEA/C in
saliva. (Male Hormone Panel costs $20 per hormone) . Since decreased serum
levels of testosterone (T) do not necessarily predict good outcome of
testosterone treatment for erectile disorder, only high levels of
luteinizing hormone (LH) and low values of the fT/LH ( free
testosterone/LH) ratio consistently emerged as significant correlates
and/or predictors of effective treatment.

Interpretation: Levels of LH above 7.5 IU/L or the fTs/LH ratio equal to
or below 0. 133 or fT/LH below 0.87 in patients with erectile disorder
suggest that testosterone supplementation may be effective. Mean fT, DHT,
E2 and SHBG remain on the constant level until the age of 65 yr. In men
66--80 yr old fT and DHT were found to be significantly lower, whereas E2
and SHBG were elevated when compared with men age 36--55 yr. An age
dependent increase of SHBG is an important cause of the increase in E2 in
men 56--80.

(Maturitas 1980 Jul;2(2):109-18. Interrelationships between sex
hormone-binding globulin and testosterone, 5 alpha-dihydrotestosterone and
oestradiol-17 beta in blood of normal men.
Bartsch W )

( Arch Sex Behave 1997 Oct;26(5):495-504 . Testosterone treatment in men
with erectile disorder and low levels of total testosterone in serum.
Rakic Z, Starcevic V, Starcevic VP, Marinkovic J

Note: High levels of estrogen, prolactin and SHBG or a deficiency in any of
the other hormones ie. DHT or DHEA may also indicate an age-related
reason for erectile dysfunction and should be referred to an
endocrinologist due to complexity and possible pituitary problems or
tumors.

(J Endocrinol 1977 Jul;74(1):1-9. The influence of oestradiol on the
metabolism of androgens by human prosthetic tissue. Bard DR, Lasnitzki I
Arch Sex Behav 1990 Jun;19(3):223-34. Effects of androgen treatment in
impotent men with normal and low levels of free testosterone. Carani C,
Zini D, Baldini A, Della Casa L, Ghizzani A, Marrama P
[1625] Comparison of Various Assays to Measure testosterone in Males across
the Lifespan.
John E Morley, Ping Patrick, HM P Perry, III Geriatric Medicine, Saint
Louis University; GRECC, St. Louis VA , Medical Center, St. Louis, MO (
presented at Endo2000 in Toronto).

Third Step: Digital rectal exam (DRE) and PSA plus biopsy should be
performed on all patients over 50 before starting treatment with T
replacement. If results are normal or no pathology is detected ( ie. PSA
4.0 and neg. biopsy). If PSA is above 4.0 do a Free PSA.

Interpretation: New Data: Low Testosterone Levels in Men May Mask Presence
of Prostate Cancer-Two standard screening tests for prostate cancer may be
unable to detect the presence of the disease in a significant number of
middle aged-men with low levels of the male hormone testosterone, according
to a new study in the December 18 Journal of the American Medical
Association (JAMA) by researchers at Beth Israel Deaconess Medical Center.
Since testosterone can cause growth of an unsuspected prostate tumor, the
study authors recommend that men age 50 and older who are considering
testosterone replacement therapy have a biopsy first since a digital rectal
exam (DRE) or PSA (prostate specific antigen) test alone may miss the
presence of early, hard-to-detect cancers. Free PSA is a much more
sensitive indicator of cancer vs. BPH.

The new study may have serious implications for men with sexual
dysfunction since the male hormone testosterone is commonly used to treat
this condition, an increasingly common medical problem as men age. Dr.
Morgentaler and his colleagues studied 77 men with low levels of
testosterone and found that 11 of the men had prostate cancer. Needle
biopsies under transrectal ultrasound guidance were used to detect the
cancers. All the cancers were found in men who had normal DRE and PSA,
according to Morgentaler. All the men in the five-year, retrospective study
had been referred to Beth Israel Deaconess Medical
Center.

The researchers believe that low testosterone levels falsely lower PSA and
shrink prostate cancers, so that these tumors are more difficult to detect.
The PSA test is an easy blood test to administer that is used to detect and
monitor problems of the prostate. It is estimated that prostate cancer
will be diagnosed in more than 318,000 men this year, according to the
American Cancer Society.

JAMA , 1996 Dec,17."Occult Prostate Cancer in Men with Low Serum
Testosterone Levels." Abraham Morgentaler, MD,

J Urol 1999 Sep;162(3 Pt 1):719-21. An assessment of the clinical relevance
of serum testosterone level determination in the evaluation of men with low
sexual drive. Ansong KS, Punwaney RB

Fourth Step: Treatment for hypogonadal men using either 1/2 or 1 gram of
TestoCreme¨ applied to non-genital hairless skin along the back, inner
arms, ribs, inner thighs or chest rubbed into a small area with a diamter
of about 3". Younger patients ( <40 yrs) should receive the higher dose
initially.

Interpretation: The choice of dose is dependent on age of the patient and
severity of T deficiency. TestoCreme delivers about 10% of the T dose to
the blood stream and results are stable for up to 24hrs. Daily 8AM
treatment or 8PM application is adequate.

Fifth Step: Monthly follow up for the first three months and then
quarterly thereafter is adequate for monitoring, then annually with a
hemoglobin and hematocrit each year. Natural T can be used safely in large
doses by men who are deficient. Physiologic doses present no apparent
health risks.

Note: It does not take much hormone to exceed the recommended physiologic
dosage. Monitoring by a physician and regular blood or saliva tests are
important. Results for Saliva Testing for men and women are found in the
addendum at the end of this summary.

Other options for supplemental hormone therapy include : Androgel,
Testogel, and of course, the original Testoderm¨patch, the first patch
delivery system of natural testosterone. Testoderm delivers 5mg of
testosterone daily and is applied to the back.
Androderm¨ is a very similar preparation containing 5 mg of testosterone
which can be applied anywhere on the body. Usually two patches are required
for most men. Since the normal physiologic pattern is to have higher levels
of hormone in the morning, these patches are applied each morning and
results in a surge of hormone within a few hours of application.


Addendum: Testocreme¨ was developed by myself and my local pharmacist, Dana
Gordon, in 1997 and does not appear to have any negative side effects when
used in physiologic doses. The cream contains 100 mg. of micronized
testosterone per gram . There have been no unusual changes in PSA levels or
prostate size in our patients ( hypogonadal men). The proper dosage is
critical for good results and to avoid problems. All Testocreme¨ products
must be prescribed and monitored by a physician trained in hormone
balancing.

Review of NB abstracts from the Endo2000 meeting in Toronto:

[1625] Comparison of Various Assays to Measure testosterone in Males
across the Lifespan.John E Morley, Ping Patrick, HM P Perry, III Geriatric
Medicine, Saint Louis University; GRECC, St. Louis VA
Medical Center, St. Louis, MO

Controversy exists over the utility of various assays to determine
whether or not older men are hypogonadal. We studied 50 healthy males age
28 to 90 years of age. In each subject, we measured testosterone (T),
bioavailable T (BT), free T by dialysis (FTD), free T by centrifugation
(FTC), free T (analog) assay (FTA), and free androgen index (FAI).
testosterone did not significantly decline with aging (r=-.13). SHBG
increased significantly with age (r=.50, p<0.001). BT (-.74) and FTC
(-.59) showed the most significant decline with age. FTD (-.38), FTA
(-.43), and FAI (-.29) also declined significantly with age. BT and FTC
showed the best correlation with FTD (both 0.67). T (0.48), FAI (0.49),
and FT (0.35) also correlated with FTD. Sensitivity and specificity of BT
to predict hypogonadism by FTD was 85.7% and 66.9% respectively. Similarly, the
sensitivity and specificity of FTD to predict hypogonadism by BT was 50%
and 92.3%. Based on the data reported here, we conclude that FTD, BT, and
FTC are equivalent assays to predict hypogonadism. Other assays appear less
accurate. T is a poor assay for detecting the age-related decline in
testosterone because of the increase in SHBG.

[1628] testosterone Administration to Older Men for Six Months Increases
Skeletal Muscle Strength, Net Muscle Protein Balance, and the Expression
of Intramuscular IGF-I Transcripts.
Randall J Urban, Charles Gilkison, Jie Jiang, Taylor Marcell, Kevin Tipton,
Melinda Sheffield-Moore, Cathy W Yeckel, Steven Lieberman, Arny A Ferrando
Departments of Internal Medicine and Surgery, The University of Texas
Medical Branch, Galveston, TX

Testosterone enanthate was administered to healthy, older men (60 y
and older) for six months in a double-blinded, placebo controlled study.
testosterone was adjusted so that the treatment group maintained mean
trough testosteroneconcentrations of 625 ng/dL while the placebo group had
a mean of 337 ng/dL. Effects of testosterone on skeletal muscle were
determined from a global perspective (muscle strength, volume, and body
composition), physiologic perspective (stable isotope infusions), and
molecular perspective (rt-PCR of anabolic-related genes). No significant
changes in the placebo group occurred for any of the above parameters.
Older men who received testosterone showed an increase in muscle strength
in both the lower (quadriceps and hamstring) and upper (triceps and
biceps) extremities after 1 and 6 months as determined by 1-RM
measurements. Muscle volume as determined by MRI increased significantly
(9%) after 6 months of testosterone. Per cent body fat (DEXA) decreased
and fat free mass (K-40) increased after 6 months of testosterone. Stable
isotope infusion showed an increase in net muscle protein balance at 1 and
6 months during testosterone administration. Intramuscular IGF-I
transcripts as determined by rt-PCR were increased after 1 and 6 months of
testosterone, while expression of the androgen receptor increased at 1
month, but returned to baseline at 6 months. In conclusion, testosterone
administration to older men has significant beneficial effects on muscle metabolism. Determining the mechanisms mediating these effects will result
in the development of treatment paradigms that maximize the anabolic
benefit while minimizing side-effects.

[1944] testosterone Supplementation Increases Growth Hormone
Secretion in Older Men.
Angela Gentili, Thomas Mulligan, Michael Godschalk, John Clore, Jim
Patrie, Ali Iranmanesh, Johannes Veldhuis Medical College of
Virgina/Virginia Commonweath Unversity and Hunter Holmes McGuire VA
Medical Center, Richmond; Salem VA Medical Center, Salem; University of
Virginia, Charlottesville, VA

Objective: To gain insight in the role of testosterone in the
decreased growth hormone (GH) secretion evident in older men. Design: We
conducted a randomized, double-blind, cross-over study of two doses of
testosterone versus placebo on GH secretion in young and older men.
Intervention: testosterone (100mg and 200mg) IM weekly for three weeks
versus placebo. Measurements: During phase one, 8 young and 8 older men
received in random order: testosterone enanthate 100 mg or 0.5 cc saline
IM weekly for three weeks. Subjects were then admitted to the General
Clinical Research Center
(GCRC). While on the GCRC at 0730, an indwelling catheter was placed in one
forearm vein to collect blood samples every 10 min for 24 hours. In Phase
II, 9 young and 8 older men, were given in random order: testosterone
enanthate 200mg versus 1 cc saline IM weekly for 3 weeks, followed by 24
hours of blood sampling every 10 minutes.
Analysis: To estimate GH secretion, we used an ultrasensitive
chemiluminescence-based GH assay and multi-parameter deconvolution
analysis. All data were analyzed by Two-Way Nested ANOVA. All response
variables other than basal GH were analyzed on the logarithmic scale to
equalize residual variation within all treatment groups.
Results: Low or high dose testosterone had no significant effect on GH
secretion in young subjects, nor did low dose testosterone have a
significant effect in older subjects. However, older men who received high
dose
testosterone had on average: 1) a 2.12 fold increase in mean GH [95% CI
=1.12 - 4.00, (p=0.0265)], 2) a 2.28 fold increase in GH secretory burst
mass [95% CI = 1.32 - 3.91, (p=0.0086)], and 3) a 1.27 fold increase in GH
secretory burst amplitude [95% CI = 1.16 - 3.59 p=0.0202] relative to their
baseline response.
Conclusion: The age-related decline in serum testosterone concentration may
contribute to the concomitant decrease in GH secretion.



[1488] Characterization of a Rat Model in Which to Study the Differential
Control of Gene Regulation by testosterone (T) and 5a-Dihydrotestosterone
(DHT). Tianshu Gao, Michael J McPhaul Internal Medicine, UT Southwestern
Medical Center, Dallas, TX

Testosterone (T) and 5a-dihydrotestosterone (DHT) are the principal
androgens in mammals and mediate a range of processes in males. T is the
major androgen in male plasma and is secreted by the fetal and adult
testis. Circulating DHT is formed principally by the conversion of T to
DHT in specific androgen target tissues by 5a- reductase, although a small
amount is derived from direct secretion by the testis. Although the same
specific androgen receptor protein mediates the effects of T and DHT, the
biological effects of these hormones are not equivalent. DHT formation is
essential for differentiation of the prostate, virilization of the
external genitalia, and for the development of male secondary sexual
characteristics. By contrast, T is required for the regulation of
gonadotropin secretion and is capable of virilizing the Wolffian ducts in
the absence of DHT formation. The differential actions of T and DHT have
been demonstrated pharmacologically in the rat by the use of 5a- reductase
inhibitors.
In order to identify and characterize genes that show a pattern of
expression consistent with selective regulation by T or DHT, we sought to
establish a rat model in which T and DHT levels could be selectively
modulated. One week
following castration, animals were implanted with silicon tubing containing
varying quantities of T or DHT. All T-implanted animals received daily
injections of finasteride (50 mg/kg/day). After the two-week treatment
period, the rats were sacrificed and tissue samples (testis, ventral
prostate, seminal vesicle, adrenal, and epididymis) were weighed and stored
at -80¡C for analysis.
Serum samples were collected just prior to implantation, at the end of the
1st week following implantation, and at the time of sacrifice. At end of
the 2nd week, the serum levels of T were elevated from the castrate levels
(0.09±0.04 ng/ml) to a subnormal range (2.11±0.81 ng/ml) in the rats
implanted with tubing containing 40 mg of T and from the castrated value
(0.07±0.02 ng/ml) to the normal range (4.39±0.51 ng/ml) in the rats
implanted with tubing containing 80 mg of T. Similarly, the serum levels of
DHT were elevated from the castrate levels (<0.02 ng/ml) to a subnormal
range (0.04±0.02 ng/ml) in the rats implanted with tubing containing 15 mg
of DHT and a near normal range (0.08±0.03 ng/ml) in the rats implanted with
tubing containing
30 mg of DHT. These serum hormone levels were paralleled by measurable
differences in the weights of the androgen target tissues that we examined
(see table below).
These experiments demonstrate that we have established a replacement
protocol that permits the selective modulation of serum T and DHT to
physiologic levels over a two-week period in castrate rats. These methods
will permit the identification and study of genes preferentially modulated
by T and DHT in different androgen target tissues.