Hormone Therapy

Medicine Summaries

Here are my thoughts regarding the use of Axiron, which is a testosterone formulation that is used in testosterone replacement therapy (TRT).

Low testosterone levels can cause a lack of energy, lack of stamina, depression, and a low sex drive. These issues can be improved by taking supplemental testosterone.





1. The top graph is from the online Lilly Prescribing Information.
2. The second graph is my modified treatment of the Lilly graph.
3. Conclusion - My exrerience
4. Axiron anomalous readings
5. TRT Graphs Compared
6. TRT Products Compared

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The above graph was copied exactly from page 8 of the Axiron prescribing information at pi.lilly.com/us/axiron-pi.pdf.
1. The graph is for Day 7 after 6 days of dosing.
2. Every dose is taken at the same time each day.

Issues
1. The TIME of dosing is not specified, NOR is the time of measurement.

2. Dose Level 4, the top dosing level of 120 mg, is not shown, probably because it is extremely similar to the 90 mg dosing. This is implied due to the similarity of the 60 and 90 mg dosing. One may infer that the 120 mg dosing is closer to the 90 mg dosing, than the 60 mg dosing is to the 90 mg dosing.

3. The prescribing information states - "... steady-state serum concentrations are achieved by approximately 14 days of daily dosing." Yet, the graph shows data for the SEVENTH day. Why doesn't it show the data for the 14th day? Intended obfuscation? Or just a lack of attention to detail?

4. The T levels at zero dose time for hour 0 is NOT IDENTICAL to the 24-hour dose time. These two levels MUST BE IDENTICAL, FOR THE GRAPH TO MAKE SENSE. For a "steady-state" dosing scenario, where the same dose is taken every day at the same time, then the ending level of day 14 MUST be the same as the starting level of day 15. There can be no "magical jump" from a higher level to a lower level, at the same instant of time. This fact alone completely blows the credibility of the entire graph. How can we believe ANY of the numbers, with such an obvious error?

Lilly needs to fix their information. The Androderm graph exhibits the same anomaly - impossible by definition. The Testim graph is marginal, as well. The graphs shown for Androgen are more accurate BY DEFINITION, since the levels shown are the same for the last day of the week, and the first day of the following week - the very definition of "steady-state" in this discussion.

5. The 20-hour data is anomalous. No explanation is given. What secondary effect can explain the weird increase at hour 20? This phenomenon is not exhibited in most of the graphs of competing products (more on this shortly).

6. "There is considerable variation in the half-life of testosterone as reported in the literature,
     ranging from 10 to 100 minutes". This is a factor of 10 uncertainty, a full order of magnitude.
     Even using 100 minutes, serum levels reach 1.56% after 6 half-lives (600 minutes, or just 10 hours).

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I recreated and modified the Axiron dosing graph from the Axiron prescribing information. I did this to illustrate issues I have with the official Lilly graph (Figure 1) found at the top of the page.

1. The graph is for Day 7 after 1 week of dosing.
2. Every dose is taken at the same time each day.
3. Mean testosterone levels (without dosing) are shown for the ages of 30, 40, 50, 60, 70, 80 and 90. This data came from http://www.mens-hormonal-health.com/normal-testosterone-levels.html. Note that the lowest dosing level is inadequate for ANY patient, since the levels do not even achieve the mean levels of a 90-year-old man.

Issues
1. Dose level 4, 120 mg, is not shown.
2. The T levels at zero dose time for hour 0 is NOT IDENTICAL to the 24-hour dose time. THESE TWO LEVELS MUST BE IDENTICAL, FOR THE GRAPH TO MAKE SENSE. d1, d2 and d3 must not exist.
3. The 20-hour data is anomalous. No explanation is given. Without any explanation, I have normalized the data, to where I believe it logically should be, based upon normal decay.

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Conclusion - My Experience
After using 2 bottles of Axiron, one at the 30 mg dosing level, and one at the 60 mg dosing level, I observed NO EFFECT whatsoever. As a minimum, I expected increased energy. Something does not add up here. At $300 per bottle (price after trial), I would expect SOME kind of result. Perhaps some dancing girls.

What are the possibilities?
1. The Axiron formulation may not contain the amount of testosterone specified.
2. Absorption rates (skin permeability) can vary by a large factor.
     Your pores must compete with your deodorant for absorption.
3. The absorption rate is inversely proportional to the amount of material applied.
     The more you add, the less additional effect is obtained - absorption rate is limited.
     At dosing level 3 and 4, white precipitated testosterone goo may be present.
4. The effects of TRT can vary by a large factor. The effect may even be NEGATIVE (see below).

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Do T levels actually get LOWERED by Axiron? Some users say yes.

. Axiron Backwards Effect
Forum User Statement	Date Reported	Dosage	T Level Before Therapy	T Level AFTER Therapy	T Reduction %
anonymous @drugs.com	Sep. 12, 2011	60 mg	430	217	49 %
nevergiveup@ forums.steroid.com	May 13, 2011	60 mg	230	203	12 %
mp @webmd.com	Oct. 26, 2011	60 mg	255	135	47 %
		120 mg	135	109	19 %
lowTbill @webmd.com	Sep. 29, 2011	?	288	288	0 increase
hoosier2211 @anabolicminds.com	Sep. 20, 2011	60 mg	430	217	49 %
yarborg @anabolicminds.com	Sep. 29, 2011	?	295	171	42 %

While many expect to see a doubling of T level, some seem to experience a HALVING.
What's up with that?

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ANDROGEL 1.00 GRAPH from page 15 of androgel_PI.pdf

.Figure 1: Mean (± SD) Steady-State Serum Testosterone Concentrations
on Day 30 in Patients Applying AndroGel Once Daily

Note: Note that the 0 hour and 24 hour readings are identical - as they should be.
         Are we to believe that post-dosing levels are independent of initial levels? Wouldn't this be a factor?
.

ANDROGEL 1.62 GRAPH from page 9 of androgel_1_62_PI.pdf

.Figure 2: Mean (±SD) Serum Total Testosterone Concentrations on Day 7 in Patients Following
AndroGel 1.62% Once-Daily Application of 81 mg of Testosterone (N=33) for 7 Days

Note: Note that there is no indication of testosterone starting level.
          Are we to believe that post-dosing levels are independent of initial levels? Wouldn't this be a factor?
.

AXIRON GRAPH from page 8 of axiron-pi.pdf

.
Figure 1: Mean (±SD) Serum Testosterone Concentrations on Day 7 in Patients Following
AXIRON Once-Daily Application of 30 mg, 60 mg, or 90 mg of Testosterone

Notes: For a "steady-state" situation, the levels at hour 0 MUST be the same as the levels at hour 24.
            This graph is bogus, on the face of it. The graph for days 6 and 8 should be the SAME as for day 7.
            This CANNOT be, if the beginning and ending levels for day 7 are not identical.
.

FORTESTA GRAPH from page 9 of fortesta_pi.pdf

.Figure 1: Mean (±SD) Serum Total Testosterone Concentrations on Day 7 in Patients
Following FORTESTA Once-Daily Application of 40 mg of Testosterone (N=12)

Notes: Why is there the unexplained rise from 12 to 20 hours? What causes that?
            Starting and ending points are not identical, but they are close.
.

TESTIM GRAPH from page 4 of Testim_PI_Medication_Guide.pdf

.Figure 1: Mean Steady-State Serum Testosterone (±SD) (ng/dL) Concentrations on Day 30
in Patients Applying Testim® Once Daily

Notes: There is no aberrant data rise at 20 hours.
            Correspondence between hour 0 and hour 24 is good, as it should be (50 mg).
            Correspondence between hour 0 and hour 24 is poor (100 mg).
            Graphs for day 29 and day 31 should be IDENTICAL. They CANNOT be identical,
            unless the starting and ending points are the same on the graph for day 30.

DELATESTRYL
No Testosterone concentration-over-time graph provided in Delatestryl Prescribing Information.
.
Note: You get what you get - no data provided.

TESTOPEL
No Testosterone concentration-over-time graph provided in Testopel Prescribing Information.
.
Note: You get what you get - no data provided.

ANDRODERM from (no page #) at http://pi.watson.com/data_stream.asp?product_group=1200&p=pi

Figure 2 summarizes the pharmacokinetic profiles of total testosterone in 35 patients
completing 28 days of ANDRODERM treatment applied as a starting
dose of 4 mg/day for the initial 14 days followed by a possible dose titration.

Notes:: Again, the starting and ending points do NOT coincide
.            "... followed by a possible dose titration." What kind of jibberish is this?
             The graph MAY be correct, when some undefined titration is employed? I call BS!

.

STRIANT from page 1 of 58816-10_Striant_full_PI_4pager.pdf

.Figure 1: Mean (SD) total testosterone concentration-time curves for two consecutive dosing
intervals at steady-state for both the 12- week study (Study 1) and the 7-day study
(Study 2) of Striant®. (The horizontal dotted lines represent the upper and
lower limit of normal for the normal physiologic range in healthy adult males).

Notes: Applied twice daily
            Striant uses milliliters in their graph - all others use deciliters (100x difference).
            Although the document is named "4pager", it actually contains 2 pages.
            Correspondence between hour 0 and hour 24 is good, as it should be.
           Why do the T levels go down, instead of up? This demands explanation. This says that T levels are REDUCED by Striant!
.

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.
APPLICATION/ NOTES

Drug
store
.com

GELS

Androgel 1.00%
(Abbott)

Topical gel
2-75gm bott.

50 mg
75 mg
100 mg

Abdomen, arms and shoulders
Once a day - 10% absorption rate

PDF
27p

Androgel 1.62%
(Abbott)

Topical gel
50mg packet
1 box=30

1- 20 mg
2- 40 mg
3- 60 mg
4- 80 mg

Abdomen, arms and shoulders
Once a day

PDF
19p

Axiron 2% (Lilly)

Topical
liquid pump
30 mg/ pump
90 pumps

1- 30 mg
2- 60 mg
3- 90 mg
4- 120 mg

Armpit application
Once a day
"sticking spring actuator"
"shallow cup applicator" - spillage

PDF
12p

Fortesta
(Pharbil Waltrop for Endo)

Topical gel pump
10 mg/ pump

40 mg
50 mg
60 mg
70 mg

Apply to inner thighs
Once a day

PDF
17p

Testim 1%
(DPT Labs - Texas)

Topical gel
5 g tubes
30 tubes

50 mg/ tube
100 mg

Arms and shoulders
Once a day - 10% absorption rate
"Messy to apply" - "Unbearable smell"

PDF
28p

INJECTIONS

Andro LA 200,
Delatestryl 200,
Depandro 100,
Depo-Testosterone,
Testosterone Cypionate,
Testosterone Enanthate

Gluteus
Injection
3 vials

-
50 - 400 mg
50 - 400 mg
50 - 400 mg
50 - 400 mg
-

-
Every 2 -4 weeks
Every 2 -4 weeks
Every 2 -4 weeks
Every 2 -4 weeks
"Potency loss near end of the cycle."

$ 263

PDF
8p

IMPLANTS

Testopel (Bartor P.)

Implant
75 mg/ pellet

6 - 12 pellets

Gluteus maximus implants
Every 4 - 6 months

PDF
4p

PATCHES

Androderm (Watson)

Transdermal
Patch
1 box=30 p.

2 mg (was 2.5)

Back, stomach, arms, thighs
Once a day

4 mg (was 5)

6 mg (was 7.5)

Striant (Mipharm-Italy)

Buccal
Gum Patch
60 ea

30 mg

Applied to upper gum
Twice a day

PDF
2p

PILLS

(none in US)

Pills

-

Sufficiently high T levels cannot be achieved through oral dosing, due to the action of the liver.

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-

30

180

90

90

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30

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