I thought we tried to stay on topic and help elucidate the mechanism by which your SHBG and E2 may have been markedly lowered. What was your baseline SHBG? Not much more I can add and I’ll stop clogging up your thread. Running a T/SHBG/sensitive E2 panel right now would be insightful. Have you considered doing this?
I would argue yes, it is possible. I’ll leave all the neurotransmitter signalling, complicated stuff out of this. Aren’t you curious what your T, SHBG and E2 are right now?
Where are you baseline labs? Where are your labs after adding AI? Labs after adding Test+AI+oxandrolone? Best practice is to pull labs methodically after making one change at a time and understand you need to wait at least 5 half lives before taking new bloodwork for the concentration of drug to reach steady state. Then there’s the induction period between when the drug reaches new concentration and when your body makes adjustment (e.g., like HCT that takes up to 3 months to adjust to new Testosterone level). In reality with something like test, the effects take even longer than 5 half lives and up to a year to fully manifest in the body.
In your case, I’d be curious what my blood work looked like after a few weeks. Oxandrolone works very quickly on the liver (few days to a week). Sometimes there’s a price to pay for that ripped physique depending on how quickly you want to get it, and the way you go about it, and how much muscle you want to carry along with lowered BF.
I watched a video today where the guy claimed Oxandrolone did attach to SHBG, but he didn’t offer anything to back that up. But he’s pretty knowledgeable.
If the ED is from the anavar—and I’m generally dubious of this, although it’s happened to enough guys to make me think it’s possible—then simply ceasing to take it would solve the problem.
Did you have issues with e2 at 80? I’m not going back and reading all the comments to see if this was mentioned, sorry. If you had no issues and you started using adex it could very well be related to that.
I believe the template above pulls oxandrolone data from this paper:
The sex steroid binding protein (SBP) which binds androgens circulating in the blood of man has been examined to determine the structural requirements for high affinity binding. SBP was purified partially and the ability of each of more than 150 steroids to compete with [3H]dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) for binding to SBP was assessed.
Binding was enhanced by reduction of the Δ4 double bond to 5α-dihydro, addition of a methyl group at C-4 and in one case unsaturation at C-14, 15. Affinity was always reduced by modifications of the C-17β hydroxy. Binding was also severely decreased by deletion of the keto moiety at C-3; however, relatively high affinity was retained by an alcohol or an unsubstituted pyrazole group at C-3. Certain alpha surface substitutions such as 17α-ethinyl had limited effects on binding; whereas, other modifications such as 7α-methyl or 17α-methyl caused significant reduction in binding. Most modifications at C-2, 6, 9 or 11 also impaired affinity, and the 5β steroids had reduced affinity.
It is unclear whether anabolic steroids act on skeletal muscle via the androgen receptor (AR) in this tissue, or whether there is a separate anabolic receptor. When several anabolic steroids were tested as competitors for the binding of [3H]methyltrienolone (MT; 17 β -hydroxy-17 α -methyl-4,9,11-estratrien-3-one) to the AR in rat and rabbit skeletal muscle and rat prostate, respectively, MT itself was the most efficient competitor. l α -Methyl-5 α -dihydrotestosterone (l α -methyl-DHT; mesterolone) bound most avidly to sex hormone-binding globulin (SHBG) [relative binding affinity (RBA) about 4 times that of DHT]. Some anabolic-androgenic steroids bound strongly to the AR in skeletal muscle and prostate [RBAs relative to that of MT: MT > 19-nortestosterone (NorT; nandrolone) > methenolone (17 β -hydroxy-l-methyl-5 α -androst-l-en-3-one) > testosterone (T) > l α -methyl-DHT]. In other cases, AR binding was weak (RBA values < 0.05): stanozolol (17 α -methyl-5 α -androstano[3,2-c]pyrazol-17 β -ol), methanedienone (17 β -hydroxy-17 α -methyl-l,4-androstadien-3-one), and fluoxymesterolone (9 α -fluoro-11 β -hydroxy-17 α -methyl-T). Other compounds had RBAs too low to be determined (e.g. oxymetholone (17 β -hydroxy-2-hydroxymethylene-17 α -methyl-5 α -androstan-3-one) and ethylestrenol (17 α -ethyl-4-estren-17 β -ol). The competition pattern was similar in muscle and prostate, except for a higher RBA of DHT in the prostate. The low RBA of DHT in muscle was probably due to the previously reported rapid reduction of its 3-keto function to metabolites, which did not bind to the AR [5 α -androstane-3 α ,17 β -diol and its 3 β -isomer (3 α - and 3 β -adiol, respectively)]. Some anabolic-androgenic steroids (only a few synthetic) bound to SHBG (l α -methyl-DHT >> DHT > T > 3 β -adiol > 3 α -adiol = 17 α -methyl-T > methenolone > methanedienone > stanozolol). The ratio of the RBA in rat muscle to that in the prostate (an estimate of the myotrophic potency of the compounds) was close to unity, varying only between about 0.4 and 1.7 in most cases. The present data indicate that 1) the existence of a putative anabolic receptor distinct from the AR must be questioned, 2) many anabolic steroids interact with the AR (generally with lower RBA than NorT or T), 3) some steroids with anabolic-androgenic activity in vivo do not bind to the AR, and must have an indirect mechanism of action ( e.g. via biotransformation to active compounds, by influencing the metabolism of other steroids, or by displacing them from SHBG). ( Endocrinology114: 2100, 1984)
You can gather here that many of the 17-AA derivatives of DHT do not bind strongly (very weakly) to SHBG.
Good point. Thanks for reminding me why I shouldn’t post on here . It’s like peeing in the ocean. Oh well back to another hobby. @unreal24278 is so much more patient with his scholarship. You guys are in good hands.
Plus @iron_yuppie recommendations so much more practical, if you do something and it hurts/bad, stop doing it. Thanks, that’s what I should have recommended. You are always pragmatic.
I almost always read through everything, but I just didn’t have the energy to go back and find his e2 reading. Don’t take my laziness today as a reflection of the very good and important stuff you post here.
Look at blood work before change (no baseline labs were shared). Pull blood work now. Once you understand the effect of oxandrolone on SHBG and Test MCR, then perhaps consider lowering/removing AI. OP said his BF is dropping so that may help his aromatization. Given he shared an E2 (sensitive/non-sensitive of 80 pg/mL with or without exogenous T?) he may already have started with a lowish SHBG. No idea since no blood work was shared.
Taking AI with oxandrolone seems like a bad idea unless you know exactly what you are doing/have regular blood and have a specific goal clearly outside of long term longevity. Given oxandrolone effect on HDL, oxandrolone for any intermittent/long term use is problematic.
Complete conjecture since no lab results and anything I say is to be discounted since I am not an MD. Does that help?
Thanks yes. I’m asking because I finished a Var addition to TRT about 3 weeks ago. Everything is ok but libido not as good as usual and morning wood not as frequent. My first thought is higher E2 but the studies you posted cast a different light on it. Really interesting reading thanks as it’s not what I would have expected.
My pleasure and good luck to you. I am getting a system warning that I’ve posted too much in this thread so I will take a break. This is hard stuff to figure out given biological variability and hardest stuff I’ve worked on (and I work on hard stuff for a living :-))
I always pull a lot of blood work so I can learn how my body reacts when I make a change. Much of this stuff is counterintuitive to what is often repeated which I find fascinating. My general advice after studying this is run from any provider who tells you to try and drop your SHBG (I’m sure there is always some clinical exception).
HDL-c drops solidly across the dosages but authors make no mention of Lp(a), which dropped significantly. I have no confidence in betting HDL vs Lp(a) effects in driving pro-atherogenic risk up vs down.
I am not sure how we can come to a conclusion on if Var makes FT higher or lower while on exogenous test with this data since the test subjects did not take exogenous test. We know Var will lower test production, which is another variable.
Wanted to show you the effect of oxandrolone on SHBG. You are correct the results for Total T are confounded since subjects weren’t taking exogenous Test and did experience some reduction in LH/supression.
That’s why I tagged you in the other post since I know you are interested in this. In reality, elimination rate for testosterone should be a function of free T not total T. Hence, free T is a function of your exogenous dosage (since elimination half life is about 8 days for TC as an example). Here’s the logic (full credit to @cataceous you can search for over there):
The issue with this study is that they are basing MCR on total T rather than free T. The standard equation used is:
Production_rate = MCR * Hormone_concentration
But as I argued above, the proportionality applies to free testosterone, not total. So the equation should be:
The reason it might appear to work anyway is because at constant SHBG, free T is nearly proportional to total T. So you get:
Production_rate = MCR * f(SHBG, T) ~= MCR * f1(SHBG) * T = MCRx * T
The problem is that their measured clearance rate, MCRx, is actually dependent on both the underlying metabolism (MCR) and SHBG. Unfortunately they don’t separate out the two, which potentially weakens their conclusions. The results are further muddied by the drop in SHBG—mainly in younger men—over the course of the experiment. It’s frustrating, because they did measure free testosterone, apparently by an accurate method, along with baseline and final SHBG values—so they did have the raw data needed to separate out the various effects.
I don’t think “we” have concluded anything . Just trying to give you data and tools to come to your own conclusions. If you really want to hold me to higher standard, then you would ding me for using Vermeulen method to calculate free T in examples I shared way up above. So let’s re-run the numbers using Tru-T method:
So using this newest calculator that reports much better agreement with equilibrium dialysis free T measurement, I’d conclude I lost ground on free T when using oxandrolone with exogenous Test. Notice the previous method I used above (Vermeulen) would indicate I basically broke even.
Best thing to do would be repeat all of this using LC/MS for Total Test and measure free T using equilibrium dialysis.
I am very happy to conclude that oxandrolone (not Var!) dropped my SHBG dramatically and also TT when using Test exogenously. Only issue would be if oxandrolone interfered with RIA method for testosterone. With the particular machine used, I don’t think this was the case and if it had then it would have inflated the number anyway which would make actual TT while taking oxandrolone even lower. Make sense?
Here’s a nice thread with member comparisons. Just wanted to add this since I think the jury is still out on whether Tru-T really better with a portion of the male population.
Table 3 has avg HDL at baseline designated at 1 mmol/l with a standard deviation of ± 0.4. Avg depression in HDL is 0.5 with a standard deviation of 0.4. One could extrapolate from this data that a certain subset of patients had abysmally low HDL (0.1-0.2) following treatment with oxandrolone. This would align with the bloods people post up when on oxandrolone, stanozolol, chlorodehydromethyltestosterone and other non aromatising c17-aa anabolic androgenic steroids. Generally speaking, there is data indicative that lipid profile alteration may not be entirely dose dependent for oxandrolone, rather it may be a byproduct of use at any dose high enough to elicit an anabolic effect.
increased postheparin hepatic lipase expression (effects HDL metabolism), cholestasis etc likely contribute to the dramatic effects seen on HDL/LDL ratios with c17-aa AAS, I could be wrong though, I’m not an expert (and oxandrolone isn’t particuarly hepatotoxic)… I get irritated when I see people using stanozolol + trenbolone as on paper it looks like the perfect combination for inducing heart disease.
“To test this hypothesis, we treated these two men and two controls with the oral androgen stanozolol (6 mg/d) for 2 weeks. Consistent with other reports, HL activity increased a mean of 277% in controls with a concomitant decrease in HDL cholesterol (49%), HDL2 cholesterol (90%), HDL3 cholesterol (16%), and apo A-I (41%) and no change in apo A-II. Although stanozolol failed to induce HL activity in the HL-deficient man, HDL cholesterol, HDL2 cholesterol, and apo A-I were reduced a mean of 20%, 48%, and 32%, respectively. In contrast to controls, HDL3 cholesterol (46%) and apo A-II (14%) increased in HL-deficient subjects. Stanozolol treatment also increased LPL activity (124% +/- 86%, n = 4) and decreased lipoprotein(a) ([Lp(a)] 66% +/- 3%, n = 3) in the three men with detectable levels.”
"The mean total postheparin lipolytic activity increased 100 per cent during oxandrolone treatment (p < 0.05). This change was caused mainly by postheparin hepatic lipase, whose activity increased on the average more than 2.5 times (p < 0.001). The change in postheparin plasma-lipoprotein-lipase activity was insignificant. A highly significant correlation(r = + 0.87, p < 0.01) was observed between the activities of postheparin hepatic lipase and phospholipase A1 before and during oxandrolone treatment. No relation was observed between serum triglyceride level and various postheparin lipase activities, or between the changes induced by oxandrolone in the level of serum lipids and the activities of postheparin lipases.”
Literature pertaining to anabolic steroids/atherosclerosis makes it seem somewhat likely that a distinct relationship does exist between AAS use and accelerated atherogenesis. I don’t believe the decrease in lp(a) mediated by androgen use eliminates the prospect of enhanced atherogenesis.
There are numerous ways in which AAS abuse could lead to myocardial infarction, all of which could be considered as being interlinking risk factors. Coronary calcification, the development of atherosclerosis, haematological alteration (increased blood viscosity/hyper-coagulability mediated via increased HCT/RBC count, platelet aggregation, increased TXAC2 receptor density etc), hypertension mediated vascular damage/endothelial dysfunction (20-hete production and subsequent RAAS activation) and rarely… coronary vasospasm. Interestingly quite a few reports exist within relation to stanozolol in particular inducing coronary vasospasm.
Anabolic steroids may also increase homocysteine (data conflicting). Hyperhomocystemia is strongly correlated with the development and progression of cardiovascular disease as homocysteine interferes with the structural formation of arteries (or rather interferes with the building blocks that make up arteries). Androgen receptors are present throughout the body, including vascular smooth muscle. Vascular calcification noted in bodybuilders may be mediated via direct effect induced via AR binding.
“we addressed the hypothesis that exogenous androgen treatment induces vascular calcification. Immunohistochemical analysis revealed expression of androgen receptor (AR) in the calcified media of human femoral artery tissue and calcified human valves. Furthermore, in vitro studies revealed increased phosphate (Pi)-induced mouse vascular smooth muscle cell (VSMC) calcification following either testosterone or dihydrotestosterone (DHT) treatment for 9 days. Testosterone and DHT treatment increased tissue non-specific alkaline phosphatase (Alpl) mRNA expression. Testosterone-induced calcification was blunted in VSMC-specific AR-ablated (SM-ARKO) VSMCs compared to WT. Consistent with these data, SM-ARKO VSMCs showed a reduction in Osterix mRNA expression. However, intriguingly, a counter-intuitive increase in Alpl was observed. These novel data demonstrate that androgens play a role in inducing vascular calcification through the AR. Androgen signalling may represent a novel potential therapeutic target for clinical intervention.”
“Six of the 7 calcium scores were >90th percentile.“
CRP also tends to be elevated within AAS users compared to controls. Higher CRP/homocystine is associated with systemic inflammation/oxidative stress, both of which serve as factors towards inducing a pro-atherogenic environment. Oxidative stress induced via AAS is also an important factor when accounting for the cardiac damage induced (myocardial apoptosis, subsequent fibrosis). Other mechanisms off the top of my head in relation to cardiac damage include direct AR mediated injury, enhanced capsase-3 activity, hypertension mediated LVH, excess sympathetic nervous system stimulation (also contributes towards arrhythmia/SCD)
Coronary plaque volume associated with cumulative years of anabolic-androgenic steroid exposure (taken from this study Cardiovascular Toxicity of Illicit Anabolic-Androgenic Steroid Use - PMC). I’d have to plug in each dot point individualistically to find the correlation co-efficient, but I’m not doing that. From eyeballing there appears to be a weak-moderately strong correlation between use/the development of atherosclerosis. When comparing mean plaque scores to controls the P value was significant.
Exposure to supra physiologic concentrations of androgens within themselves intrinsically induces oxidative stress, both at rest and during exercise (exacerbated response). AAS mediated medical pathology is multi-faceted. It isn’t just lipid profile alteration one needs to worry about in terms of atherosclerosis progression, there are a number of variables of which will contribute towards the risk of stroke, myocardial infarction and sudden cardiac death.
If we look here (another deca study) The Anabolic Androgenic Steroid Nandrolone Decanoate Disrupts Redox Homeostasis in Liver, Heart and Kidney of Male Wistar Rats - PMC Nandrolone appears to alter redox homeostasis within the heart (focusing on the heart). Nandrolone appears to increase NOX expression within the heart. Over expression of NOX leads to ROS imbalance, ROS imbalance induces a favourable environment for the development of atherosclerosis. Rodents obviously have differing metabolic/elimination pathways compared to humans, but I believe we have enough data to go on suggesting a direct relationship between prolonged AAS exposure and atherosclerosis. Some of the mechanisms by which AAS accelerate plaque build up aren’t solely related to dyslipidemia and many variables are interlinked with one another (hypertension can induce LVH, as can direct AR binding within cardiac myocytes etc).
I haven’t covered much, there’s a LOT to write up about when delving into AAS induced aetiology. I should state while many of these mechanisms may seem scary (and they are) but in practicality the human body can generally endure and bounce back from quite a bit of abuse.
In short, HDL vs Lp(a) isn’t enough to drive atherogenic risks down when taking into account all the other variables at hand
People also need to start talking about AAS mediated neurotoxicity and the studies (on humans) indicative of AAS mediated enhanced glutamate turnover, beta amyloid accumulation etc. Mechanisms behind proposed neurotoxicity are numerous, from NDMA receptor overactivation to dopaminergic neurotoxicity… This is something that needs to be talked about more often.
. It’s like peeing in the ocean. Oh well back to another hobby. 
. Just trying to give you data and tools to come to your own conclusions. If you really want to hold me to higher standard, then you would ding me for using Vermeulen method to calculate free T in examples I shared way up above. So let’s re-run the numbers using 
