31 PEDs testosterone

UNIVERSITY

PEDs
Testosterone: A base of
understanding to AAS
action and cycle design


Lesson Overview
Testosterone, Estrogen, & DHT
AAS Mechanism of Action
Role of Hormone Receptor
Androgen to Estrogen Ratio
Role of Estrogen
Role of DHT
Why Testosterone as a Base/First Cycle?
Dose Response Relationship of Testosterone
How Long is a Cycle?
Initial Cycle Progression Framework


Testosterone, Estrogen, and DHT
In males, testosterone is the
primary sex hormone, ~510mg produced per day.
In females, estrogen is the
primary sex hormone.
Testosterone ~0.5g per day.
In both sexes, testosterone
can be aromatized into
estrogen and/or 5alphareduced into
Dihydrotestosterone (DHT)

Androgen receptor
activation & upregulation
Decreased SHBG
Aromatization to Estrogen

AAS
Mechanisms
of Action

Gh/Igf-1 increase
IGF binding protein
decrease
Increase IGF1
receptors
Increased Beta-adrenergic
receptors on fat cells

Increased
Protein
Synthesis
Increase
Satellite Cell #
&
differentiation

Increased
lipolysis

5-alpha reduced to DHT
Increased creatine
phosphate and
glycogen stores
Glucocorticoid receptor antagonist

Increased
Strength

Decreased
Protein
Degradation


Hormone Receptor
Testosterone is a starting point to understand how our own natural
androgen reacts in the body and lead to understanding other
androgen derivatives

Testosterone (T) and Estrogen (E) are similar in chemical structure and
main mechanism of action is via the androgen (AR) or estrogen
receptor (ER) in cells.
T and E can diffuse into
cell

Enzyme
biotransformation may
occur
Binds to hormone
receptor and forms

complex
Gene transcription
occurs leading to specific
actions to be carried out
by cell


Testosterone to Estrogen Ratio
The AR complex will effect different genes than the ER complex and can have opposing roles.
Each hormone will react differently in its target tissue whether skeletal muscle, scalp,
prostate, heart, or breast tissue.
The AR might upregulate a gene while the ER might downregulate it.
Examples:

Skin: androgens increase sebum production while estrogens decrease it, hence more acne
vulgaris with high dosed androgen cycles.
Breast tissue: Androgens oppose the effects of estrogens on breast tissue growth, hence
why Drostanolone was used in breast cancer treatment.

Plasma Proteins: Androgens decrease SHBG, Estrogens increase it
Hair: Androgenic alopecia, while estrogen promotes hair growth

This gives us understanding of effects of altered ratios of androgens to estrogens as they
balance one another.


Estrogen Neuroprotective
Supraphysiological doses of T increase neurotoxicity, however
physiological T is neuroprotective. (Orlando 2007)
If an aromatase inhibitor is given with low/normal T levels the

neuroprotective effects are diminished.
Estrogen is neuroprotective when balanced with testosterone.
Nandrolone and Stanozolol given alone are neurotoxic likely due to lack of
17B-estradiol conversion.
Supraphysiological doses have shown high deposition of amyloid-beta
plaque in brain tissue, same plaque associated with Alzheimer’s and
Dementia (Kaufman, 2019)
AAS induced oxidative stress reduces amyloid-beta elimination from
brain.
Studies in humans have shown decreased cognitive attention in users on
steroids vs off


Estrogen Cardioprotective
12-week study (Freidel 1990)
IM 280mg Test E +
250mg testolactone 4x
daily

IM 280mg Test E w/o AI

PO 40mg
Methyltestosteron
e

Serum Testosterone
(ng/dl)

1155

1155

432

Serum Estradiol (pg/ml)

19

68

19

HDL reduction

25%

Nonsignificant

35%


Estrogen Libido and Erections and Body Fat
Low and High estrogen can cause ED with estrogen modulating
testosterone
Penile tissue is dense with ER and stimulated can have an antiapoptotic effects on the endothelium cells
Hypothalamus and pre-optic area are high in ER and aromatase and
regulate libido. Estrogen impacts serotonin levels

(Finklestein 2013) found that the administration of testosterone with
and without aromatase inhibitors markedly impaired sexual function

when aromatization was inhibited.
Increasing testosterone in subjects decreased body fat, but the effect
was negated with use of an aromatase inhibitor


Estrogen and Muscle Mass
Estrogen and Glucose
Estrogen increases Glucose 6-phosphate dehydrogenase in skeletal
muscle, G6PD increases post exercise to enhance glucose uptake and
recovery. This effect is diminished when an AI is used and estradiol is
over suppressed.
Estrogen and GH/IGF-1 Axis
Estrogen increases GH and IGF-1 levels
In men given 300mg of test e vs 300mg test e + 20mg tamoxifen, the
tamoxifen group IGF-1 was suppressed (Weissberger 1993)
300mg of test e vs 300mg of nandrolone decanoate showed the
nandrolone to have less IGF1 levels likely due to the lack of
aromatization into estrogen. (Hobbs 1993)
”Steroid Fatigue” estrogen promotes wakefulness and alertness


Estrogen Low or High?
Testosterone normal range males: 300-1000 ng/dL
Estradiol normal range males: 20-55pg/mL
Signs of Low Estrogen:
Fatigue
No sex drive and erectile dysfunction
Fat accumulation
Depression and Irritability
Forgetfulness

Signs of High Estrogen:
Libido present and erectile dysfunction
Nipple sensitivity, breast swelling (gynecomastia)
Water retention
Elevated blood pressure
Night sweats


Saturation Point of Aromatase Enzyme
Increasing dosages of testosterone lead to an increased T/E2 ratio
Higher test dosages lead to higher estrogen levels, but to a lesser
magnitude.
At a dosage that appears around 400-600mg of testosterone per week
the aromatase is enzyme is highly saturated and the E2/T ratio is much
less. (Lakshman, 2010)


Dihydrotesosterone (DHT)
Testosterone is converted to DHT via 5 alpha reductase enzyme and is
3-4x as potent as testosterone.
The enzyme is present in high amounts of the skin, scalp, prostate,
liver, and nervous system
This accounts largely for the androgenic side effects from AAS.

DHT being very androgenic is not very anabolic in skeletal muscle
tissue.
Skeletal muscle contains the enzyme 3α -hydroxysteroid dehydrogenase (3α-HSD) which breaks down DHT to a much weaker androgen


DHT Benefits

Strong role in organization and function of nervous system
Neuromuscular system is of primary importance for contraction of
skeletal muscle and hence why many strength athletes are in favor of AAS
that are DHT derivative for strength but not size.
Graded dosing of testosterone (25,50,125,300,600mg) with or without
Dutasteride had not difference in fat free mass gain. 600mg group 7.1kg
vs 8.1kg (not significant, but still 2.2lbs of fat free mass) (Bhasin 2012)
This interaction secondarily will impact muscle gain, as it impacts muscle
performance.

5 alpha reductase inhibitors like dutasteride and finasteride increase
occurrence of erectile dysfunction and low libido (Trost, 2013)
DHT and metabolites modulate estrogen
1. Antagonist of ER binding the to gene response element
2. Offset androgen/estrogen ratio


Why Testosterone First Cycle and Base?
Main purpose is to maintain a physiological amount of estrogen and
DHT that might otherwise by nonexistent using another AAS.
Testosterone allows for a bioidentical compound our bodies are used
to managing with E2 and DHT levels in conjunction
We know estrogen is protective for the brain, heart, penis, skin, and
needed for muscle growth, a baseline amount needs to be present.
A non aromatizing DHT derivative (anavar, masteron, primobolan)
although anabolic, will shutdown exogenous test levels and limit
estrogen levels significantly (poor health and gains)
An aromatizing drug like nandrolone, has low estrogen conversion and
also 5 alpha reduces to DHN, a weak version of DHT. Many report
sexual issues without a base of testosterone. Also nandrolone is highly

suppressive and not appropriate for a first cycle.


Testosterone Dosing
There is a dose response relationship with testosterone and muscle
gain. 25,50,125,300 and 600mg of testosterone enanthate for 12 week
in healthy young men, nonresistance trained
The 125, 300, and 600mg group gained 3.4, 5.2, and 7.9kg of fat free
mass, respectively (Bhasin 2001).
100-200mg testosterone is considered TRT levels. This should be
based on your initial baseline labs for: T, E2, LH, FSH.

A first starting cycle would start at 200-300mg of testosterone per
week w/o Aromatase Inhibitor
Remember we want to gain the biggest result from the smallest dose
needed and least health impact before moving up in dosage.


How Long is a Cycle?
Time course to maximize effect, but also limit detrimental effects
Will depend on pharmacodynamics of test ester used, genomic and
nongenomic effects, genetic polymorphisms and steroid metabolism.

We can gain insight looking at the time course of effect of test
replacement in hypogonadal men (Saad 2011).

Start of
TRT

3 wks

6 wks

12 wks

20 wks

24wks

52 wks

In literature we see maximal effects in muscle and strength at 12-20
weeks of testosterone therapy, giving validation to the idea of cycle
length of 12 weeks.
This cycle duration should be based on your goal, level, health
markers, and phase. Also consideration for Blast/Cruise/PCT.


Initial Cycle Progression
An initial cycle progression would be to increase testosterone dosages
until you need to combat high estrogen levels.

For many this will depend on you on genetic predisposition to
aromatization.
You can increase testosterone dosage 100-150mg per cycle as needed
to continue making muscular gain up until an aromatize inhibitor
would be needed.
This might be 300-600mg of testosterone per week for many
At this point rather than an AI, it would be time add in other
compounds to bring about anabolism and offset estrogen.

Some may also face more androgenic sides from DHT conversion, this
might also need consideration for cycle design with compounds less
effected by 5 alpha reductase.


Summary
The proper ratios of testosterone, estrogen and DHT are essential for
optimal health
Estrogen is not “bad” males need it for the brain, heart, penis and
skeletal muscle. We need a ratio in accordance with that of
testosterone.
If testosterone is supraphysiological, estrogen can be as well, as long
as no symptoms of high estrogen are present.
A first cycle should be a testosterone base and subsequent cycles
should be a tapered-up testosterone dosage to a point estrogen
control is needed.
Monitor labs and health markers and document to establish response
to each dosage of testosterone used.


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