37 PEDs estrogen and prolactin modulation

UNIVERSITY

PEDs
Estrogen and Prolactin
Modulation


Lesson Overview
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AAS Stack Design Review
Estrogen Benefits and Side Effects
Stimulus and Inhibitory Inputs for Gynecomastia
AAS Effects on Gynecomastia
Other Factors as Input Signals
Relationship of Estrogen, Progesterone and Prolactin
Types of Gynecomastia
Aromatase Inhibitor (AI) Review

Selective Estrogen Receptor Modulator (SERM) Review
Health Effects of AI and SERMS
Prolactin Regulation
Effects of High Prolactin Levels and Stimulus for Increase
Dopamine Agonist Withdrawal Syndrome
Framework for Estrogen and Prolactin Management


Overview of Stack Design Framework
IF using the cycle design framework we have established prior. You
should not need to do damage control once your cycle has begun.
Test is our anchor up until you need estrogen control

Then a DHT derivative is implemented to modulate estrogen
Then a 19-nor derivative is implemented to further androgen levels

To get to higher levels of usage if needed or at the later stages of
contest prep you might have brief moments of time needing to
manage estrogen and prolactin.
This should be compounds implemented short term on an as needed
basis if stack design can not be manipulated to further see out our
physique goals


Estrogen Benefits
Neuroprotective
Cardiovascular protective
Needed for Erection and Libido
Regulates Body Fat
Needed for GH/IGF-1 Axis

Needed for insulin sensitivity
Bone Health
Wakefulness and Alertness


Estrogen Low or High?
Testosterone normal range males: 300-1000 ng/dL
Estradiol normal range males: 20-55pg/mL
It will be normal at supraphysiological testosterone levels to have supraphysiological
estradiol levels and that is acceptable if you are asymptomatic for high estrogen.

Signs of Low Estrogen:
Fatigue
No sex drive and erectile dysfunction
Fat accumulation
Depression and Irritability
Forgetfulness
Joint Pain
Signs of High Estrogen:
Libido present and erectile dysfunction
Nipple sensitivity, breast swelling (gynecomastia)
Water retention
Elevated blood pressure
Night sweats


Estrogen via Aromatization


Gynecomastia Imbalance in Inputs

Figure from: Swerdloff 2019


AAS and Gyno Stimulation
Anabolic Androgenic Steroids
Aromatizing Compounds
Testosterone
Nandrolone
Boldenone
Dianabol

Compounds with Progesterone and
Prolactin Stimulation
Nandrolone
Trenbolone

Non-Aromatizing Compounds
Primobolan
Masteron
Anavar
Proviron
Winstrol
Halotestin

Ancillary Compounds
Aromatase Inhibitors
Anastrozole
Exemestane
Letrozole

Selective Estrogen Receptor
Modulators
Compounds with Estrogen Receptor Nolvadex
Interaction

Anadrol
Nandrolone

Dopamine Agonist
Cabergoline
Pramipexole


Other Factors to Consider


Estrogen, Prolactin, Progesterone and Gyno
Estrogen will be primary driving cause for gynecomastia
Prolactin has a permissive role and estrogen is the stimulator for Prolactin increase.
Also the prolactin receptor is expressed minimally in most gynecomastia cases.
(Ferreira 2018)

Constantly assessing and pinching nipples will be a direct stimulus for irritation and
prolactin increase as well.
Progesterone is involved in more of luminal epithelium of the breast, which is cells of
the milk ducts, but does not contribute to the glandular tissue of gyno.
Also we have studies in men receiving 100mg test enanthate with the progestin
levonorgestrel 0.5mg daily for 6 months and no gyno formation. (Bebb 1996)
All in all, main gyno focus should be around estrogen management, however

prolactin should be addressed as it can be increase unrelated to estrogen in
situations.


Types Of Gynecomastia
There are three types of gyno: florid, fibrous, and intermediate
Florid is ductal hyperplasia early onset with loose edematous stroma
Fibrous has more stromal fibrosis and fewer ducts this usually forms
once the gyno has been present for over one year.
Intermediate has features of both florid and fibrous.
If breast tissue has gone fibrotic nothing is going to resolve (No AI, No
SERM) only surgery is an option.


Compounds to Address Estrogen
Aromatase Inhibitors
Anastrozole (Arimidex) non-steroidal competitive inhibitor, binds
reversibly to aromatase enzyme.
1mg daily in men, 50% reduction in estradiol
Terminal half life of 47 hours
Once stopped aromatase will aromatize testosterone again
0.25-0.5mg EOD is a starting point for dosing
Letrozole (Femara) non-steroidal competitive inhibitor, binds
reversibly to aromatase enzyme.
1mg daily in men, 50% reduction in estradiol
Terminal half life of 48 hours
Once stopped aromatase will aromatize testosterone again
1.25-2.5mg EOD is a starting point for dosing
After 28 days of letrozole treatment at 2.5 mg daily, estradiol was
reduced by 46 % in young men and 62 % in elderly men (T’sjoen 2005)

Anecdotally reported as strong effect on estradiol, but data doesn’t
support it


Compounds to Address Estrogen
Aromatase Inhibitors
Exemestane (Aromasin) steroidal suicidal inhibitor, bind to aromatase and
deactivates it.
25mg or 50mg daily in men, 60% and 56% reduction in estradiol (25mg
max dosage needed)
Terminal half life of 9 hours
24 hours after one 25mg dose, estrogen levels are reduced by 70-80%;
72 hours later estrogen levels are still 40% below the baseline;
120 hours after initial dose, estrogen levels return to baseline
Mild androgenic effect and lowers SHBG
In postmenopausal breast cancer patients Exemestane suppress estradiol
by 92.2%; Arimidex and Letrozole 90%.
All three commonly used AIs seem to suppress estradiol in men to a
similar degree when taken on a daily basis
Side effects very similar amongst all three, preference to Aromasin for a
suicidal inibitor and prevent estrogen rebound.


Exemestane Versus Anastrozole in Postmenopausal
Women With Early Breast Cancer: NCIC CTG
MA.27—A Randomized Controlled Phase III Trial
(Goss, 2013)
25mg Exemestane
vs 1mg Anastrozole
daily for 5 years

No difference in
breast cancer
outcomes
Exemestane less
lipid effects,
increased bone loss
and LFTs
Both drugs have
toxic effects and
should be used
short term


“For cardiovascular events, pooled data showed that longer durations of
aromatase inhibitor use are associated with a statistically significantly
higher odds of developing such events compared with tamoxifen alone or
a shorter period of aromatase inhibitor use after an initial period of
tamoxifen therapy”
Aromatase inhibitors may have a direct effect on endothelium that may
predispose us to the development of atherosclerosis

This is most apparent with longer durations of aromatase inhibitor use,
suggesting that it is the cumulative exposure to aromatase inhibitors that
is important.
What about a SERM vs AI efficacy?
In a double-blind RCT, prostate cancer patients received either
bicalutamide with a placebo, or in combination with tamoxifen (20 mg
daily) or anastrozole (1 mg daily) for 48 weeks. Gynecomastia developed
in 73 % of patients receiving a placebo, 10 % of patients receiving
tamoxifen, and 51 % of patients receiving anastrozole. As such,

anastrozole seems ill-suited in the prevention of gynecomastia, whereas
tamoxifen appears to be very effective (Boccardo 2005)


Selective Estrogen Receptor Modulator
(SERM)
Tamoxifen Citrate (Nolvadex): Tamoxifen functions as a competitive
antagonist of the estrogen receptor. It does not reduce total estrogen
simply prevents its binding with the ER.
Terminal elimination half- life of about 5 to 7 hours

10-20mg Nolvadex ED for 3-9 months has been shown efficacious for up
to 90% gyno resolution. (Narula 2014)
10mg is likely effective close to physiological normal levels, higher AAS
will require high Tamoxifen.
Minor mentions: Clomid and Raloxifene have minimal data on efficacy for
gyno reduction. Aromatase Inhibitors haves also performed poorly in
reduction of gyno while Nolvadex has shown superior.
If the problem is estrogen as a stimulatory input, Nolvadex blocks the
issue but does not solve it. Not a long-term strategy. This is when stack
modulation comes in place.


Estrogen and Estrogen Antagonist GH Effects

Figure: Birzniece 2017


Prolactin Regulation

Endocrinol Metab Clin North Am 1992; 21:877


Training alone can
significantly increase
prolactin levels.
Enhanced Bbers had a
further increase in
prolactin but
corresponded with
Estradiol increase
If estrogen is
controlled Prolactin
can likely be controlled


High Prolactin Levels
This has been blamed as the culprit of “deca dick”
High prolactin decrease erection quality and increases the refractory
period between erections
High prolactin can also cause breast lactation

More liable culprit of ED related nandrolone use is test suppression or
inadequate test base, leading to low estradiol (needed for erections)
and higher DHN to DHT (DHT needed for penial vasodilation and
sexual drive)
However high prolactin can happen

Lab work is best to truly test and find the root issue

Prolactin and Dopamine Agonist
Cabergoline: Dopamine receptor agonist, inhibitory input for prolactin
production
3-4 days half life
Headache, nausea vomiting
Constipation, diarrhea
Fatigue, anxiety, depression
Can increase sexual interest and refractory period
Clinically used at an initial dosage on 500mcg per week divided into 2
weekly dosages.
Pramipexole: Dopamine receptor agonist, inhibitory input for prolactin
production
8-12 hour half life
Clinically used at an initial dosage 125mcg 2x daily ED
More frequent occurrence of GI distress and nauseas
Due to side effect and ease of dosage Cabergoline is preferred
Dosing in PM might aid side effect management


Dopamine Agonist Withdrawal Syndrome: Implications for Patient Care
Nirenberg 2013
“While some patients have transient symptoms and make a full
recovery, others have a protracted withdrawal syndrome lasting for
months to years, and therefore may be unwilling or unable to
discontinue DA therapy”


European Academy of Andrology clinical practice guidelines—
gynecomastia evaluation and management 2019

Framework of Action
1. Lab work to assess: Estradiol, Total Estrogen, Prolactin
2. Address the Culprit
1.

High Estrogen
1.
2.
3.

4.
5.

2.

Micro-dose your AAS to prevent large boluses of steroid exposed to aromatase
Lower Aromatizing Compounds (Stimulus) and review AAS for other direct receptor
actions
Modulate androgen to estrogen ratio with Masteron, Primobolan or Proviron
(Inhibitor)
Utilize Tamoxifen Citrate lowest effective dosage as you adjust AAS stack for 7-10
days then reduce dosage 50% every 7-10 days and taper off.
If lowering dosage is not option implement aromatase inhibitor lowest effective
dosage preferable Extremestane. Adjust dosage base on needs and still utilize
Tamoxifen if gyno is present and taper off

High prolactin
1.

2.
3.
4.

Address Estrogen first as this is an input for prolactin stimulation
Lower input of nandrolone or trenbolone, decrease dosage
Add Masteron or Proviron to modulate Prolactin
Dopamine Agonist Last Option: Cabergoline 0.5mg twice per week


When might we deploy these strategies?
Offseason
During peak blast AAS levels in advanced cycle design
AI, SERM, and dopamine agonist should be removed during cruise
periods

Pre-contest
In later stages of prep if estrogen is limiting fat loss and stack design is
unable to be modified.

Later stages of prep if you are removing aromatizing compounds there
is no rationale to increase AI or SERMs.