The persistent estrogen vicious cycle?


New member
From a theoretical analysis of literature, it seems a vicious cycle could be created between estrogen and androgens whereby estrogen rises to a level that can create a block of 5-alpha-reductase and a raise in SHBG, thus creating a persistent hypogonadism state.

We know that raising estrogen, raises SHBG, and SHBG binds more firmly to T than E (3). So it takes a lot of SHBG to neutralize E - but spike in SHBG ends up significantly binding up bio-available T.

So, it seems like if you can raise your estrogen to a certainly tipping point, you could create an environment where: most of your T is bound up, and thus very little T is running through 5-alpha-reductase (5AR), which means low DHT.

Adding insult to injury, it's been measured that high Progesterone or E can apparently suppress 5AR (1,4, weak reference dealing with dietary estrogens 2), which would further limit DHT and other 5AR-ized metabolites and also would encourage your T to aromatize. The evidence is weak and honestly more strongly demonstrated with Soy (2) - but it has been demonstrated.

It just seems like the stack is in favor of a persistent lock into high estrogen once it happens.

This forum has a strong knowledge of these areas, so I just wanted to ping this knowledge base to find out if this a known phenomenon. Is this something that is guarded against in the body building world? Is there a trigger or conditions that would create something like this? Maybe specific metabolites of estrogen? Or is this not likely to happen?

1. "Effects of sex steroids on skin 5***945;-reductase activity in vitro,"
2. "Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids," J Endocrinol 1995.
3. "Steroid-Protein Interactions II," p. 200 - this book is citing: "Sex-Hormone-Binding Globulin is an Oestrogen Amplifier" - Burke & Anderson, 1972.
4. "Altered Balance Between the 5***945;-Reductase and Aromatase Pathways of Androgen Metabolism During Controlled Ovarian Hyperstimulation
With Human Menopausal Gonadotropins,"
Are you talking about someone who is Natty or someone who is using AAS? The HPTA works differently in each of these situations.
Thank you Megatron for your reply.

The primary context may be in between synthetic and natural circumstances. I'm from the propeciahelp group - which is composed of men seemingly locked in a persistent hypogonadal state after taking and quitting Finasteride. Even though there are hundreds (maybe thousands) of us, no one knows why.

For those who post lab results on that forum, it is very common to exhibit a pattern of high estrogen (typically some metabolite) and high SHBG. It has also been published that PFSers have low DHT too (1) - citation #1 also documents high E in the forms of 17a-estradiol and 17b-estradiol in PFS.

I'm just trying to make sense of this fingerprint: High SHBG and high E as well as low DHT. Certainly my last post tries to link these patterns, but only this group would know if these things are linked in practice. And if real, how to break this cycle.

1. "Neuroactive Steroid Levels are Modi***64257;ed in Cerebrospinal Fluid and Plasma of Post-Finasteride Patients Showing Persistent Sexual Side Effects and Anxious/Depressive Symptomatology,";jsessionid=FB26548A2502E3F7DF850E26B5444874.f01t04?userIsAuthenticated=false&deniedAccessCustomisedMessage=
I'm going to preface this with the fact that I haven't dug too deeply into 5-alpha-reductase inhibitors as I do not personally have an issue with hair loss. However, with that said, I am pretty familiar with the basics of how the HPTA works, and that there are several mechanisms in place that will trigger it to become suppressed.

As Propecia is an "antiandrogen", it works by binding to endogenous steroids (including testosterone) and more importantly in this case progesterone. Normally this wouldn't be an issue as estradiol is derived from testosterone, but as it has an inverse relationship with progesterone, estradiol is increased as testosterone is decreased. This creates a cascading effect as the body (the hypothalamus) SCREAMS for more testosterone, and subsequently increases estradiol through aromatization.

As far as I know this is the only widespread class of drugs that can actually use the progesterone pathway to force a release of GNRH (which tells the pituitary to release more leutinizing hormone) - creating such a terrible imbalance. This is why 5AR drugs have warnings about gynecomastia and testicular atrophy. I have read a few cases in which the dose is in fact high enough to overcome the progesterone/prolactin relationship - causing lactation on top of gyno and hypogonadism.

It's less of an issue for folks on exogenous hormones as they already have an open feedback loop (the main mechanism in which hypogonadism occurs), and the hypothalamus is taken out of the equation. As the loop is open, estradiol is far easier to control via inhibitors, and SHBG is lowered by an inverse relationship with androgens and its direct relationship with estradiol.

At either rate, hypogonadism is a very real potential outcome if enough time is spent in such a state. I don't know of any methods to counteract the indiscriminate inhibition of ALL androgens, but as I normally tell folks who want to have hair (when prone to MPB) and use AAS - they have to pick one or the other.

My heart goes out to those that got more than they bargained for, but sadly until new classes of drugs become available to reach the same ends, I don't see an alternative.

My .02c :)
I just want to clarify the when Halfwit says "open" feedback loop he means that it is broken and not functioning properly. "Closed" would mean the feedback loop is functioning properly.
Is this something that is guarded against in the body building world? Is there a trigger or conditions that would create something like this?

The HPTA doesn't work properly when one uses exogenous Testosterone. The body senses that it has enough testosterone so it stops making its own. The pituitary stops producing LH and FSH when estrogen levels and/or androgen levels become elevated. There are receptors to detect both.

It should also be noted that when the body has high levels of testosterone it aromatizes it into estrogen. Normally these high estrogen levels would cause the HPTA to produce less testosterone; but someone taking testosterone is getting it exogenously so the HPTA is already shut down. The only way that someone taking exogenous Testosterone can contol estrogen is by using an Aromatase Inhibitor.

So yes, AAS users must guard against high estrogen levels by utilizing AI's.

As for SHBG levels, someone running a test cycle and controlling estrogen with an AI normally doesn't have to worry about it because their testosterone levels are so high it "overwhelms" SHBG. Free T levels will be high as a result. Please note that there are ways to lower SHBG (e.g. managing the thyroid but that is an different conversation).