SHBG Too Low!

[James]

I have suffered from low SHBG for many years presenting with low testosterone and complete sexual dysfunction (since teens.)

The main side effect is hyperandrogenism and estrogen dominance.

No doctors have been able to suggest a way to increase the production of SHBG to normals levels or to determine why hepatic synthesis of SHBG is being suppressed.

I'd like to challenge the Ray Peat crowd to suggest a mechanism that may be creating this lifelong affliction.

I am male, and the hypogonadism and low SHBG have been present since my early teens. This is not a disease of old age or diet.

 

[Blossom]

It still could be diet even at a fairly young age. Mine (SHBG) has always been high so I'm looking forward to my test results on a Peat style approach. Confussion reigns in the mainstream but from what I've read high SHBG is supposedly related to hyperthyroidism. I don't believe myself hyperthyroid due to hypo symptoms. I would consider learning more about thyroid while optimizing diet to reduce stress hormone production and help metabolism just to begin with. After all medicine has nothing to offer as far as I can tell.

 

[TKWW]

High protein diets elevate SHBG. High carbohydrate diets and elevated blood glucose lower SHBG. In males elevated estrogen can also associated with elevated SHBG. Try altering the macro nutrient mix placing greater emphasis on protein. Monitor blood glucose levels eith the goal of an 80 fasting level or lower. Employ insulin sensitizing nutrients (chromium, cinnamon extract, vanadyl sulfate, etc.) Resveratrol is a natural aromatase inhibitor to help control estrogen as is green tea extract. Avoid alcohol consumption which also ramps up aromatase activity and increases estrogen production in fat cells.

 

[unexamined_whimsy]

James, what are your vital statistics? Are you diabetic/what are your blood sugar levels? It would be helpful if you could also post measurements of your T-axis (LH, FSH, E2, TT, fT etc).

What manifestations of hyperandrogenism do you have? In men (unlike women), it's unlikely being both estrogen dominant and hyperandrogenic since both hormones are approximately antagonistic.

As alluded to earlier, thyroid supplementation is usually a pretty reliable way of bringing up SHBG and increasing total testosterone levels. Thus, you should get your thyroid metabolism assessed and keep a log of your temperature and pulse rate. In my own experience TT went slightly above the physiological reference range on supplementing thyroid. SHBG followed suit, depressing my Bio-T slightly.

 

[James]

I am now 32, 172 lbs at 16% bodyfat and 6'2" tall.

Here's a TRT-induced sample of the hyperandrogenism:

testosterone, total: 852 [260-1000] ng/dl
testosterone, % free: 3.42 [1.0-2.7] %
testosterone, free: 290.9 [20-210] pg/ml

FT has has been up to 4.3%. Lowest ever measured was 2.74%. It is always out of lab range because of the low SHBG.

If TT is increased through HRT, the FT% does not change and the excessive FT spills over into E2.

From this chronic imbalance, I experience sexual dysfunction (impossible to have intercourse,) hair loss and shedding, strong mood swings and gynecomastia present since early teens, despite a wiry thin frame.

Here is my hypogonadal reference state:

testosterone, total: 185 [260-1000] ng/dl
testosterone, % free 3.07 [1.0-2.7]%
testosterone, free 56.8 [50-210] pg/ml

Notice how FT% was high when I had low TT. Expected. However, when TT increased due to HRT, FT% went even higher instead of lower!

 

[unexamined_whimsy]

I am now 32, 172 lbs at 16% bodyfat and 6'2" tall.

Here's a TRT-induced sample of the hyperandrogenism:

testosterone, total: 852 [260-1000] ng/dl
testosterone, % free: 3.42 [1.0-2.7] %
testosterone, free: 290.9 [20-210] pg/ml

FT has has been up to 4.3%. Lowest ever measured was 2.74%. It is always out of lab range because of the low SHBG.

If TT is increased through HRT, the FT% does not change and the excessive FT spills over into E2.

From this chronic imbalance, I experience sexual dysfunction (impossible to have intercourse,) hair loss and shedding, strong mood swings and gynecomastia present since early teens, despite a wiry thin frame.

Here is my hypogonadal reference state:

testosterone, total: 185 [260-1000] ng/dl
testosterone, % free 3.07 [1.0-2.7]%
testosterone, free 56.8 [50-210] pg/ml

Notice how FT% was high when I had low TT. Expected. However, when TT increased due to HRT, FT% went even higher instead of lower!

Increased androgens secondary to TRT is straightforward but overall you appear to have been suffering from hypoandrogenism since your teens.

You need to determine the nature of hypoandrogenism; is it a low LH level, or rather a lack of testicular sensitivity ? If your SHBG was depressed before TRT, I would strongly suspect hypothyroidism and thus you should get your thyroid related blood work asap. If the decrease of SHBG is secondary to TRT, that is only to be expected since androgens reduce SHBG in general.

If your case is one of lower testicular sensitivity it might be worth reducing your TRT dose to target an optimal free-T number, and/or considering transdermal application - that preferentially converts to DHT, a substrate that cannot convert to estrogen, once applied on scrotal skin. However, remember that TRT is a very slippery slope and often good lab numbers for the T-axis don't translate to the expected benefits. Beyond that, do your research and go to a well-regarded TRT specialist, since TRT requires very experienced hands.

On the other hand, if your thyroid axis is found wanting, and given that you are young, there is every chance your T-metabolism can be normalized with thyroid supplementation. However, LH and ultimately T production takes many months to normalize after a relative shutdown so you will need to be patient. Till then you must be careful to avoid PUFA, get enough zinc and minimize your exposure to stress.

A third possibility for your low T levles is a hyperprolactinemia due to pituitary dysfunction. This can be easily treated by dopamine agonists that should reverse the hypogonadism in a matter of months.

For getting rid of gynecomastia, you need to distinguish between pseudo and actual gynecomastia. If it's the former, fixing the T/E2 ratio should fix it in a matter of months. With the latter you can apply topical DHT (andractim). However, the topical DHT must only be used once your total T is above 500, since topical DHT reduces TT, and you want to avoid a total shutdown.

Edit: FT% is just the amount of f-T relative to TT. Your f-T in absolute terms was low prior to TRT as expected.

 

[James]

You need to determine the nature of hypoandrogenism; is it a low LH level, or rather a lack of testicular sensitivity ? If your SHBG was depressed before TRT, I would strongly suspect hypothyroidism and thus you should get your thyroid related blood work asap. If the decrease of SHBG is secondary to TRT, that is only to be expected since androgens reduce SHBG in general.

SHBG was depressed before HRT. It's the root cause of my secondary hypogonadism, since it doubles estrogen feedback. Clomid proves this. When I use clomid to hide E2 from the hypothalamus, T restores to 700 ng/dL.

I have high TSH, but also high T3 and T4! RT3 is also elevated.

I currently take 50 mcg of T3 per day, but it seems to do nothing. My temperature while I type this, after having taken all 50 mcg of daily T3 (split in 12.5 mcg doses) is only 97.7.

 

[Kenobi]

I recommend progest-E to you because not only does it increase SHBG, but it also reduces testosterone's conversion into estrogen. It's odd that you have elevated thyroud hormones but low SHBG, thyroxine (T4) increases SHBG. Maybe you actually have a progesterone deficiency.

 

[James]

I recommend progest-E to you because not only does it increase SHBG, but it also reduces testosterone's conversion into estrogen. It's odd that you have elevated thyroid hormones but low SHBG, thyroxine (T4) increases SHBG. Maybe you actually have a progesterone deficiency.

Interestingly, I had just started on a progesterone, but the dose was unmetered. This led to elevated progesterone on my lab test.

Well, let me just show you...

Medications:
T3 30mcg/day
T 40mg 3x/wk,
anastrozole 0.5mg 3x/wk,
? progesterone transdermal nightly (unmetered - a quarter sized blob)


TSH 3.55 (0.450-4.50)
FT4 1.34 (0.82 - 1.77)
FT3 3.3 (2.0-4.4)
RT3 16.2 (9.2-24.1)
Progesterone 3.6 (0.2-1.4) HIGH
SHBG 17 (18-55.9) LOW

I switched to 5mg/gm compounded transdermal cream after seeing that. I recommended it to my doctor based on Peat's information that it might combat by high DHT/E2... and it did:

DHT 45 (30-85)
E2 8.9 (7.6 - 42.6)

Are you sure it is T4 that increases SHBG? I thought it was T3. That's why I take T3.

 

[ddjd]

High protein diets elevate SHBG. High carbohydrate diets and elevated blood glucose lower SHBG. In males elevated estrogen can also associated with elevated SHBG. Try altering the macro nutrient mix placing greater emphasis on protein. Monitor blood glucose levels eith the goal of an 80 fasting level or lower. Employ insulin sensitizing nutrients (chromium, cinnamon extract, vanadyl sulfate, etc.) Resveratrol is a natural aromatase inhibitor to help control estrogen as is green tea extract. Avoid alcohol consumption which also ramps up aromatase activity and increases estrogen production in fat cells.

Why does ray say this then ;
"SHBG should be as high as possible to keep estrogen out of cells, and that it actually enters cells when it is unloaded, unlike albumin."

 

[ddjd]

However, the topical DHT must only be used once your total T is above 500, since topical DHT reduces TT, and you want to avoid a total shutdown.

is it the same for all DHT - i.e. supplementing dht

 

[unexamined_whimsy]

is it the same for all DHT - i.e. supplementing dht

I would imagine so. In any case, there doesnt seem to be a USP grade DHT product that has been tried orally to my knowledge.

It’s probably best to measure your TT levels after a washout period for DHT to know how your body really responds.

 

[ddjd]

Resveratrol is a natural aromatase inhibitor to help control estrogen as is green tea extract

reservatrol is estrogenic

 

[benaoao]

High protein diets elevate SHBG. High carbohydrate diets and elevated blood glucose lower SHBG. In males elevated estrogen can also associated with elevated SHBG. Try altering the macro nutrient mix placing greater emphasis on protein. Monitor blood glucose levels eith the goal of an 80 fasting level or lower. Employ insulin sensitizing nutrients (chromium, cinnamon extract, vanadyl sulfate, etc.) Resveratrol is a natural aromatase inhibitor to help control estrogen as is green tea extract. Avoid alcohol consumption which also ramps up aromatase activity and increases estrogen production in fat cells.

Very good post although I’ve read a number of times that some amino acids raise igf-1 which isn’t desirable in OPs context. Mostly cysteine, methionine. Same old sulfur aminos who can benefit the people who don’t have enough free T I guess.

Fiber also raises SHBG a lot. I’d guess that is the one thing that “saves” whole food vegans (temporarily) because insulin resistance is widespread but barely mentioned. Whereas this + the lack of sunlight are the 2 main causes destroying people’s health IMO.

 

[ddjd]

thyroxine (T4) increases SHBG

not t3?

 

[Jon]

@James estradiol will raise to counter the effects of hyperandrogenism. I have high end estradiol 33pg/mL (35pg/mL being highest normal clinical range) but my test is 818ng/dl (915ng/dl being highest normal clinical range).

Are you taking an anti aromatase? Shbg is most likely not the root of your problems. Unbridled aromatization sounds like a bigger cause.

 

[Jon]

Eat MUFA:

Oleic acid increases hepatic sex hormone binding globulin production in men. - PubMed - NCBI

 

[Hairfedup]

High protein diets elevate SHBG. High carbohydrate diets and elevated blood glucose lower SHBG. In males elevated estrogen can also associated with elevated SHBG. Try altering the macro nutrient mix placing greater emphasis on protein. Monitor blood glucose levels eith the goal of an 80 fasting level or lower. Employ insulin sensitizing nutrients (chromium, cinnamon extract, vanadyl sulfate, etc.) Resveratrol is a natural aromatase inhibitor to help control estrogen as is green tea extract. Avoid alcohol consumption which also ramps up aromatase activity and increases estrogen production in fat cells.

Why do such incredibly high carbohydrate diet cultures (West Africans/Papuan Tribes etc) show such little signs of having low SHBG or attributes/symptoms associated with decreased SHBG?

 

[Jon]

Why do such incredibly high carbohydrate diet cultures (West Africans/Papuan Tribes etc) show such little signs of having low SHBG or attributes/symptoms associated with decreased SHBG?

Probably because the balance of their endocrine system is ideal

 

[Elephanto]

Copy-pasting from a response about SHBG I gave :

One method to compensate by raising SHBG is Olive Oil (1-2tsps daily), but also fixing Insulin Resistance. High sugar intake (Fructose) can cause a fatty liver, and the induced lipogenesis shuts down SHBG. See this Too Much Sugar Turns Off Gene That Controls Effects Of Sex Steroids. Niacinamide, by inhibiting lipogenesis, can help with that. Reducing total fat intake will also help. Fiber intake has been positively correlated with SHBG. Fiber is one thing that works in a bell curve (negative effects when completely avoided and in excess), especially when you combine vegetal fiber with antiseptics like olive/coconut oil, vinegar, salt, parsley, cilantro, dried ginger etc (like Peat's Raw Carrot Salad). It latches to decaying stuff, endotoxins in your gut and moves mostly undigested all the way to your colon for evacuation. Helps reduce estrogen this way and reduces inflammation that leads to Insulin Resistance. Zinc, Coconut Oil/MCTs and Ginger increase SHBG by promoting HNF-4Alpha. Reducing inflammation, especially the cytokine TNF-Alpha which reduces SHBG/HNF4-Alpha, will help. I think selfhacked has a page on ways to reduce tnf-alpha if you check on google. I also made this thread a while ago : Importance Of HNF4-alpha In Liver Health (and Possibly Androgenic Alopecia). Reducing Iron will lead to higher SHBG in many ways, like reducing the oxidation of organs involved in glucose metabolism so preventing Insulin resistance.