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Low SHBG
Risk factors for Low SHBG:
Aromatase
Elevated Insulin Levels
Low Progesterone or Estrogen Dominance
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Recommendations for Low SHBG:
Weight Loss
Gluten-free Diet
Not recommended:
DIM (di-indolmethane)/I3C (Indole-3-Carbinol)
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Why monitor Estrone?
Estrone is the principal estrogen found in both the postmenopausal
woman and the aged male. The increase in estrone is due to the increased conversion of androstenedione and T to estrone ( E1). There is evidence
that high E1 levels may indicate increased tendency to cancer cell growth. Androstenedione (A) is a metabolic product of DHEA, and is a major source
of E2 and E1 in women; therefore patients receiving DHEA should be monitored by saliva for increases in estrone to supra-physiological levels.
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TRT in men with low SHBG
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My take home message:
Another reason to go to Quest and get
Estradiol, Bioavailable
Estradiol, Free
Actually this set would give better picture:
0 iodine
11 Zinc
27 Hemoglobin A1C
29 Lipoprotein (A) Lp(A)
56 Cortisol AM/PM
57 DHEA sulfate
58 Prolactin
49 Glucose, fasting
50 Insuline, serum
61 Progesterone
62 Pregnenolone
63 Estradiol, Bioavailable
64 Estradiol, Free
65 Estradiol, Fractionated, serum
66 Estradiol, Ultra-sensitive (is part of fractionated)
67 Estrone,serum (is part of fractionated)
68 Estrogens, Total, Serum
69 Testosterone, Free, Bio/Total (LC/MS/MS)
70 Testosterone Total (included in T panel)
71 Testosterone Free(included in T panel)
72 Testosterone Bioavailable(included in T panel)
73 SHBG(included in T panel)
74 Albumin, serum(included in T panel)
75 Dihydrotestosterone DHT
Then do balancing act to keep
A1C low
Free T & E high but not over the top
BioAvail T & E high but not over the top
Never seen FreeE and BioAvailE results, wonder how will they corelate with E2 that we talk so often about.
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SWALE
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You have to remember that elevating estrogen also tends to elevate SHBG concentration. Everyone is different, but generally you do not see high
estrogen and low SHBG.
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So; when SHBG is low;
Test all estrogens and SHBG
Apply any regulating supplements gingerly.
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MARIANCO
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TRT with Low SHBG is not simple to do because there are many other complicating factors such as:
1. SHBG is reduced further by the increase in testosterone.
2. Insulin resistance. Low SHBG is one sign of insulin resistance/diabetes. Insulin resistance can cause other hormone imbalances and impair nerve
signal transmission.
3. Hypothyroidism. Low SHBG may be a sign of inadequate thyroid hormone levels. Hypothyroidism is often present clinically though the lab tests are
normal.
4.
The duration action of testosterone is shortened by low SHBG - making one prone to a roller coaster experiences.
5. Testosterone can reduce thyroid hormone activity - resulting in anxiety or depressive symptoms depending on the severity of the reduction. There are
multiple mechanisms of action which can cause this.
6. Low SHBG may result in high free Testosterone. High Free testosterone is not necessarily good. For example, if estradiol levels and progesterone
levels are normal, the high free testosterone may result in high blood pressure. Testosterone can either lower or raise blood pressure depending on its
relationship to the other hormones.
7. etc.
Testosterone functions depend on its relationship with other hormones, neurotransmitters, and cytokines - these all are chemical messengers in the
body. Low SHBG complicates matters but is not an unsolvable problem in most people.
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Lesson from #4---Increase frequency of T shots when SHBG is low.
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MARIANCO
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Focusing on increasing SHBG is like treating a lab value rather than treating a patient.
The question I would have for a person with low SHBG is: What problems does one have?
Is it low libido, high blood pressure, heart attack risk, depression, anxiety, lack of energy, impaired concentration, urinary frequency, gynecomastia, hot
flashes, etc.?
By identifying one's problems, it will be easier to see whether or not SHBG level contributes to the problem.
SHBG has signaling properties of its own. It has its own receptors on cell membranes. When testosterone or estrogens are bound to SHBG, it can bind
to its receptors and send its message to the cell. What happens afterwards is not clear. It may be related to the formation of more hormone receptors -
but that is speculation at this point.
SHBG helps prolong the duration of action of testosterone, DHT, and estrogens. Low SHBG will increase the amount of free hormone.
Swings in hormone level may occur when low SHBG is present as destruction of the hormone is accelerated by having high free levels. This may
cause problems experienced during testosterone replacement. For example, if estrogen is more quickly destroyed/metabolized and levels drop more
quickly, one can get hot flashes or anxiety or hypertension, etc. If testosterone levels fluctuate from high to low, depression can occur as the day
progresses.
SHBG is made in the liver in response to levels of many hormones:
1. Increasing Testosterone reduces SHBG
2. Increasing DHT lowers SHBG
3. Increasing DHEA lowers SHBG
4. Increasing Growth Hormone lowers SHBG
5. Increasing Insulin lowers SHBG
6. Increasing Estrogen increases SHBG
7. Increasing Thyroid Hormone increases SHBG
The SHBG level is determine by the balance of the hormone levels.
Given one's assumed goals in TRT (high libido, good energy, etc.), it may be difficult to increase SHBG without causing problems since SHBG is
determine by a balance of hormones.
For example, having high Testosterone and high DHEA is not a situation where SHBG is going to be high without corresponding problems with estrogen
or thyroid.
If anything, SHBG should be most often viewed as an indicator of a problem that needs to be solved - rather than as a problem itself.
For example, SHBG is most commonly an indicator of high insulin levels - i.e. insulin resistance or diabetes. It would be then far more important to
address insulin resistance or diabetes in treatment than to focus on SHBG.
If low thyroid is a factor in low SHBG, addressing hypothyroidism is far more important.
If low estradiol is a factor in low SHBG, addressing this is more important.
If the low SHBG itself is a problem because it causes large swings in hormone levels, then working around this by achieving more stable hormone
levels is indicated.
More frequent dosing of testosterone may be required to stabilize levels. With testosterone cypionate or enanthate injections, dosing twice a week
would be better than once a week.
If frequent dosing of testosterone cannot be achieved with transdermals or injections, then a constant dose solution may be needed. This includes
testosterone patches, the buccal system, or testosterone pellet insertions. Testosterone pellet insertions may be viewed as fairly drastic since it
involves regular minor surgical procedures, but does give the most stable levels - so is a viable solution for the men with problems due to highly variable
hormone levels resulting from low SHBG.
If one suspects swings in hormone levels as a cause of problems, one can look for the swings in hormone levels by obtaining a peak and trough level of
the hormones (e.g. total testosterone, estradiol, DHT, etc.). For testosterone injections, this is a level about 24-48 hours after an injection and a level
just before the next injection. One can also obtain a midpoint level to fill out the level curve.
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Low SHBG, Total Testosterone, and Symptomatic Androgen Deficiency are Associated with Development of the Metabolic Syndrome in Non-Obese
Men
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http://anabolicminds.com/forum/male-anti-aging/52296-low-shbg-estradiol.html
Low SHBG and Estradiol by Dr. Marianco.
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The most common cause of low SHBG is excessive insulin - i.e. insulin resistance. Insulin resistance in turn leads to a cascade of events which results
other hormone imbalances such as low testosterone production, suboptimal thyroid hormone activity, adrenal fatigue, etc.
Factors which together in a balance determine SHBG are:
1. Anabolic hormones generally reduce SHBG. These include testosterone, DHEA, insulin, DHT, and growth hormone.
2. Thyroid hormone, Estrogens, and Progesterone (by increasing estrogen receptors/sensitivity), increase SHBG.
In the absence of insulin resistance, the most common other cause of low SHBG is a very high level of other anabolic hormones - most frequency high
testosterone from TRT. Those who use anabolic steroids at high doses often drive their SHBG to near zero.
When total testosterone is between 650 to 1000 ng/dl, and a person still has zero sex drive, I would look for other causes for sexual dysfunction - e.g.
other hormone, neurotransmitter, or immune system problems.
Raising SHBG does not necessarily increase the risk for Alzheimer's disease. It is important to keep in mind the factors which lead to the risk of
Alzheimer's disease.
Insulin resistance (i.e. excessive insulin levels) causes low SHBG. It also greatly increases the risk of Alzheimer's disease because it results in a higher
level of inflammatory cytokine production (Cytokines are the chemical messengers of the immune system). It is the inflammation which is one of the
underlying factors which leads to Alzheimer's disease.
SHBG level is most often a signal of the overall status of multiple hormone levels. The balance may give an indication of whether one is in an pro-
inflammatory state or anti-inflammatory state - with inflammation leading to disease such as Alzheimer's disease, heart disease, strokes, cancer, etc.
Some hormones such as some estrogens and insulin can lead to inflammation leading to illness. And other hormones such as the androgens (except
DHT), growth hormone, and thyroid hormone, can lead to an antiinflammatory state, reducing the risk for illness. The balance determines the person's
risk for illness.
What estradiol level is best for any individual often needs to be determined by trial and error. It is unique for each individual. Most do best around 30
pg/ml. But some do best at lower and higher levels. For example, I have a 65 y.o. patient with a total testosterone of 840 ng/dl and an estradiol of 47
pg/ml. He's having the time of his life - able to make love numerous times each night - after more than a decade of having no sex. The estradiol level
works for him without side effects. Some may do better with much loser levels of estradiol - the response is highly individualistic.
Even with low SHBG - which is difficult to correct since it depends on the balance of so many hormones - when the other hormones and
neurotransmitters are optimized, sex drive and the ability to have an erection can often return.
When total testosterone is supraphysiologic - i.e. over 1000 ng/dl - problems with libido and erections may occur. Testosterone increases dopamine in
the brain in order to increase sex drive, reduce depression, give pleasure to activities. The problem is that dopamine is a very fragile
neurotransmitter/hormone in its effects. Too high a dopamine level can cause tolerance to dopamine. This is similar to how one can develop tolerance
to drugs such as cocaine and amphetamines which increase dopamine levels in the brain to cause their high. This can lead to the loss of libido when
high testosterone levels are maintained for long periods of time.
Conversely, when one is deprived of testosterone (and hence dopamine) for long periods of time due to hypogonadism, one can get a high during the
first few weeks of testosterone treatment since the brain becomes supersensitive to dopamine when it has been deprived of it (e.g. making more
dopamine receptors to pick up the weaker dopamine signals). Unfortunately, as the brain then gets use to the higher dopamine levels, it will develop
some tolerance, and libido will drop off - though we often wish that hopefully a good amount remains.
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