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by Patrick Arnold
Pat is responsible for launching several major product and innovation in the prohormone industry
through LPJ Research and
Ergopharm, including the first to release androstenedione, 1-AD, 6-OXO, 4-androstenediol, and 19-norandrostenediol. In addition, he is responsible for bringing innovative delivery systems to the prohormone market including HPB cyclodextrin, bioadhesive technology for sustained release, and sustained release sprays.
Publication Date: June 7, 1999
Subject: Who Uses HPBCD Cylcodextrin?
Hey Pat,
What cyclodextrin is BTG using for their oral Testosterone?
The only companies that are carrying HPBCD cyclo-prohormones to
date are OSMO, Supertech, and Kaizen. All other cyclodextrins on the
market are inferior beta-cyclo complexes that were put out because
they were cheap and easy to do so. And they profit from my article
and the valid research done only on HPBCD and therefore applicable
only for HPBCD
Subject: Unesterified Testosterone?
Do you think unesterified testosterone in oil is a "bad idea"
since it is eliminated from the body very quickly.
The half life of an intrvenous steroid ester is probably about
the same as the same steroid in the free state. However minute
amounts of long chain lipophilic steroid esters may linger around
longer in the body as they can incorporate into the fat quite well.
This is NOT related to half life.
Esters in oil have a longer half life because their solubility
partition
coefficieint more favors them staying in the oil than leaching out
into
the bodily fluids. Free testosterone is so poorly oil soluble it
much
more prefers the bodily fluids to the oil so it leaches out very
fast
Would this type of preparation be inferior to an aqueous
suspension (slower or faster clearance)?
yes, suspensions were designed as time release formulations and
they truly do work that way. however i think the level of release is
very fast at first and then drops of very quickly making it not so
great
Subject: Re: Prohormone Test Results
There seens to be some evidence that prohormones may cause a
drop in testosterone levels a few hours after administration. Is
this drop due to rebound or normal daily fluctuation?
I have little doubt that to a certain extent it is a rebound. It
happens with all steroids that work fast, damn its not a secret if
you ever read any real literature.
But like I said before, (concerning sex hormones in general) the
total fall from the rebound usually is not enough to compensate for
the overall rise you get from the exogenous spike. Especially at
high
dosages.
I would expect the same situation with prohormones as with what is
well known (and i have just told your) with the actives themselves.
Certainly with the diols. The situation with androstenedione (given
that its conversion rate to test is low, activity in its unconverted
form is low, and rate of aromatization is very high) may not be
quite as pretty though
Subject: Norandro and low test
Dear Mr. Arnold,
After 20 days of norandros (300 mg SS norandrodiol and 300 mg HDT
norandrostenedione a day) I had a blood test. This was my hormonal
profile:
Testosterone: 333 mg/dl
Cortisol: 21,35 ug/ml
LH: 5,48 mUI/ml
FSH: 1,75 mUI/ml
I had not a blood test before the use of prohormones but I'm
21 and I can't believe that my testosterone is that low. Then, since
I have taken prohormones around the clock (at 8am,12am,4pm,19pm,
22pm) I am quite sure that this was
the reason for my low test (and my very good gains). What do you
think ? Could you suggest me a safe "prohormones schedule" and some
supplements to improve my hormonal profile (low testosterone - high
cortisol levels) ?
Thank you very much.
MI.
Your low testosterone level is not strikingly low, but still it is
on the
low end of normal for someone your age. Your LH is still quite
normal however which is strange although your FSH is below normal.
The normal LH coupled with sub-normal testosteorne indicates that
the nors may be interfering with bio-synthesis of testosterone at
the leydig cells (testes).
Then again I can't make any sort of speculation without knowing
what your blood levels of hormones were before your cycle.
What I would have expected would be a suppressed LH and testosterone
level. Your dosages were substantial. I would have liked to see what
your free test and estrogens were too.
What I would suggest is using the prohormones that do not aromatize
directly (the diols) as well as forms which by pass liver first pass
(and therefore the enhanced aromatization that takes place in the
liver). Products such as these would include diol transdermal
products as well as hydroxypropyl-beta-cyclodextrin complexed diols
such as Cyclo-Diol(TM) and Cyclo-Nordiol(TM).
Subject: Transdermal Versus Cyclodextrin Delivery
Pat:
I'd like to commend you for offering your advice. 2 quick questions:
1. If you could pick transdermal or cyclodextrin delivery which
would be your choice?
that is like apples and oranges. One raises your levels very high
but for a brief period of time. One raises your levels only
moderately but over a long period of time. I do not know which would
give the most results.
It also would depend on how much gel you rub on and how many times a
day you took the cyclo.
Taking both during a cycle might be quite more effective than either
one alone too
2. Are the Sports One products beta-cyclodextrin or
hydropropylbetadextrin.
Beta-cyclodextrin
Subject: Problems with high dosages of Androstenediol?
Dear Pat,
Has there been any serious side effects associated with very
high dosages of 4-androstenediol (2,500 to 4,500 mg per day) not the
usual androgenic effects; but liver or cardiac problems?
None have been publically reported, and I know of none personally.
Subject: Beard?
Dear Pat,
I would know, if you had a product to give me more beard (only
androgenic effetc)
This sounds like a silly question but I have heard that topical DHT
(dihydrotestosterone) gel has been used successfully to fill in weak
spots on peoples facial beards. I have also heard that testosterone
gels also can be effective.
As far as non-prescription alternatives go an androdiol, or to a
lesser extent androstenedione gel, should be expected to be somewhat
effective.
There is much 5-Alpha reductase in the skin and alot of the
prorhormone should convert locally to DHT. I would rub the gel on
two to three times daily in the trouble spots for a few weeks. I
would also try to keep your face well shaven and moisturized so the
gel penetrates most effectively.
However do not use any moisturizer or after shave on your face
for one hour before and after applying the gel.
Good luck
Subject: Show Me Proof on Cyclodextrin Prohormones!
Hey Pat,
I refuse to believe this cyclodextrin prohormone thing will be
effective at all. I think it is just a high tech scam, these short
term high increases probably do nothing to your body. Show me some
real medical proof that this stuff can do something
OK, I can make parallels to published respected studies using
testosterone instead of 4-androstenediol as the complexed (in HPBCD)
steroid.
We know that 4-androstenediol shares similar androgenic and anabolic
activities to testosterone (128% as androgenic, 95% as anabolic,
Acta Endocrinologica, 42 (1963) 245-253). Regardless of conversion.
This is its activity upon injection, which by passes the liver and
gets directly into the system in much the same way a sublingual dose
would.
So check these studies out, they should be directly applicable to
4-AD cyclo complexes.
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J Clin Endocrinol Metab 1996 Oct;81(10):3654-62
Sublingual testosterone replacement improves muscle mass
and strength, decreases bone resorption, and increases bone
formation markers in hypogonadal men--a clinical research center
study.
Wang C, Eyre DR, Clark R, Kleinberg D, Newman C, Iranmanesh A,
Veldhuis J, Dudley RE, Berman N, Davidson T, Barstow TJ, Sinow R,
Alexander G, Swerdloff RS
Department of Medicine, Harbor-University of California-Los Angeles
Medical Center, Torrance 90509-2910, USA.
[email protected]
To study the effects of androgen replacement therapy on muscle
mass and strength and bone turnover markers in hypogonadal
men, we administered sublingual testosterone (T) cyclodextrin (SLT;
5 mg, three times daily) to 67 hypogonadal men (baseline
serum T, < 8.4 nmol/L) recruited from 4 centers in the U.S.:
Torrance (n = 34), Durham (n = 12), New York (n = 9), and
Salem (n = 12). Subjects who had received prior T therapy were
withdrawn from injections for at least 6 weeks and from oral
therapy for 4 weeks. Body composition, muscle strength, and serum
and urinary bone turnover markers were measured before
and after 6 months of SLT. We have shown previously that this
regimen for 60 days will maintain adequate serum T levels and
restore sexual function. Total body (P = 0.0104) and lean body mass
(P = 0.007) increased with SLT treatment in the 34
subjects in whom body composition was assessed. There was no
significant change in total body fat or percent fat. The increase in
lean body mass was mainly in the legs; the right leg lean mass
increased from 8.9 +/- 0.3 kg at 0 months to 9.2 +/-0.3 kg at 6
months (P = 0.0008). This increase in leg lean mass was associated
with increased leg muscle strength, assessed by leg press (0 months,
139.0 +/- 4.0 kg; 6 months, 147.7 +/- 4.2 kg; P = 0.0038). SLT
replacement in hypogonadal men led to small, but significant,
decreases in serum Ca (P = 0.0029) and the urinary
calcium/creatinine ratio (P = 0.0066), which were associated with
increases in serum PTH (P = 0.0001). At baseline, the urinary type I
collagen-cross linked N-telopeptides/creatinine ratio [75.6 +/- 7.9
nmol bone collagen equivalents (BCE/mmol] was twice the normal adult
male mean (41.0 +/- 3.6 nmol BCE/mmol) and was significantly
decreased in response to SLT treatment at 6 months (68.2 +/- 7.7
nmol BCE/mmol; P = 0.0304) without significant changes in urinary
creatinine. Serum skeletal alkaline phosphatase did not change. In
addition, SLT replacement caused significant increases in serum
osteocalcin (P = 0.0001) and type I procollagen (P = 0.0012). Bone
mineral density did not change during the 6 months of SLT treatment.
We conclude that SLT replacement
therapy resulted in increases in lean muscle mass and muscle
strength. Like estrogen replacement in hypogonadal
postmenopausal females, androgen replacement therapy led to
decreased bone resorption and urinary calcium excretion.
Moreover, androgen replacement therapy may have the additional
benefit of increasing bone formation. A longer term study for
several years duration would be necessary to demonstrate whether
these changes in bone turnover marker levels will result in
increased bone mineral density decreased fracture risks, and reduced
frailty in hypogonadal men.
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J Clin Endocrinol Metab 1996 Oct;81(10):3578-83
Testosterone replacement therapy improves mood in hypogonadal men--a
clinical research center study.
Wang C, Alexander G, Berman N, Salehian B, Davidson T,
McDonald V, Steiner B, Hull L, Callegari C, Swerdloff RS
Department of Medicine, Harbor-UCLA, Torrance 90509. USA.
[email protected]
The effect of testosterone (T) replacement on changes in mood was
studied for 60 days in 51 hypogonadal men. All patients were
withdrawn from their prior T replacement for at least 6 weeks
before enrollment. Of these patients, 18 received T enanthate 200 mg
im every 20 days, 16 received sublingual T cyclodextrin
(SLT) at a dose of 2.5 mg three times daily, and 17 received SLT at
a dose of 5.0 mg three times daily. The total treatment period was
60 days. The patients were asked to respond to a questionnaire on 7
consecutive days before the start of treatment and on 7 consecutive
days before their visits to the clinic on days 21, 41, and 60 of
treatment. The following mood parameters were assessed using a
7-point Likert rating scale: angry, alert, irritable, full of pep
(energy), sad/blue, tired, friendly, nervous, and well/good. When
compared with the baseline period, T replacement led to significant
decreases in anger (P= 0.0045), irritability (P = 0.0009), sadness
(P =0.0033), tiredness (P = 0.0035), and nervousness (P = 0.0291),
and significant improvement in energy level (P = 0.0020),
friendliness (P = 0.0072), and sense of well-being (P = 0.024) in
all subjects as a group. Analyses of the area under the curve (AUC)
of baseline serum T levels before T replacement showed significant
positive correlations between serum T (AUC) and friendliness (r =
0.29, P < 0.05) and sense of well-being (r = 0.27, P < 0.05), and
significant negative correlations with nervousness (r = -0.27, P <
0.05), irritability (r = -0.29, P < 0.05) and tiredness (r = -0.28,
P < 0.05). Similar correlations were found between serum
dihydrotestosterone (DHT) and some of the mood parameters. After T
replacement in the hypogonadal men, these correlations between AUC
of serum T levels and the positive and negative mood scores
disappeared. These results were corroborated in a subsequent study
in which 30 hypogonadal men were supplemented with SLT 5 mg three
times daily for 6 months. The patients were less nervous (P =
0.0025) and more alert (P = 0.0004), friendly (P = 0.042), and
energetic (P = 0.0001) during the 6-month treatment period compared
with baseline. We conclude that T replacement therapy in hypogonadal
men improved their positive mood parameters, such as energy,
well/good feelings, and friendliness and decreased negative mood
parameters including anger, nervousness, and irritability, and
direct correlations between serum T and DHT with mood scores were
only observed in the baseline period when serum androgen levels were
below the normal range. The latter observation suggests that once a
minimally adequate serum T/DHT level was achieved by T replacement
therapy, further increases in serum T/DHT levels did not further
contribute to the improvement in mood variables.
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J Clin Endocrinol Metab 1995 Dec;80(12):3567-75
Pharmacokinetics, bioefficacy, and safety of sublingual
testosterone cyclodextrin in hypogonadal men: comparison to
testosterone enanthate--a clinical research center study.
Salehian B, Wang C, Alexander G, Davidson T, McDonald V, Berman N,
Dudley RE, Ziel F, Swerdloff RS
Department of Medicine, Harbor-UCLA Medical Center, Torrance 90509,
USA.
We studied and compared the pharmacokinetics and bioefficacy of two
doses of sublingual testosterone cyclodextrin (SLT; 2.5 and 5.0 mg,
administered three times per day) with testosterone enanthate (TE;
200 mg) given once every 20 days by im injections over a 60-day
study period in 63 hypogonadal men. After SLT administration, serum
testosterone (T) levels peaked at 20 min and then fell, reaching
baseline levels by 360 min. The calculated half-lives were 60.3 +/-
7.5 and 68.8 +/- 5.0 min after a single dose of 2.5 and 5.0 mg SLT,
respectively. The mean area under curve (AUC) of serum T was
computed over 20-day periods for the 3 treatment groups. The mean
net AUC of serum T after TE administration was about 4- and 2-fold
higher than that in the 2.5 and 5 mg groups over the last 20 days.
Serum estradiol and dihydrotestosterone followed the same pattern as
serum T. Serum estradiol to T ratios decreased after T replacement
in all 3 groups, whereas serum dihydrotestosterone to T ratios were
not significantly changed by T treatment. Suppression of serum LH
and FSH levels was more marked in the patients treated with TE than
in those given SLT. Similarly, serum sex hormone-binding globulin
levels showed significant decreases with androgen replacement only
in the TE and SLT 5.0 mg range groups. There were no significant
adverse effects based on comprehensive physical examinations, urea,
electrolytes, and renal or liver function tests. Hematocrit levels
increased in the TE-treated group, but remained slightly lower than
baseline levels in the SLT groups. Serum high density lipoprotein
cholesterol showed a small, but significant, decrease with time of
treatment in all groups. Despite the differences in the AUC of serum
T levels achieved by different androgen replacement therapies, all
patients showed significant improvements in sexual motivation and
performance, with no significant difference between the treatment
groups. We conclude that SLT may be a useful addition to the
currently available injectable and transdermal delivery systems for
treatment of hypogonadal men. Because of the ease of administration,
rapid reversibility of effects, and lower AUC of serum T levels
achieved compared to those of TE injections, SLT may be especially
suitable for treatment of boys with delayed puberty and older men
with androgen deficiency.
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