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Undetectable pregnenolone - hormones messed up

Thinktank

Senior Member
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I've been going after this hormone problem for 10 years but no doctor has ever taken me serious until recently, My LLMD ran some tests and i just received the results.

Most striking is the almost undetectable amount of pregnenolone! Then the lowish progesterone which makes sense with low pregnenolone. However DHEA sulfate is not optimal but neither low.
Then there's elevated testosteron, but i guess most of it is bound to SHBG and albumin so free and bioavailable testosteron are low-ish as well as androst.diol.
Estrone is kinda high-ish.

I have some reading to do to make some sense out of it. What do you guys think? If the pregnenolone is not a lab error then it absolutely needs to be investigated. It's a powerful neurosteroid and an absence of it can cause bad cognitive impairment.

Male, 31 y.o.

hormones.jpg
 

xks201

Senior Member
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740
That SHBG is nasty high and most likely causing a ton of fatigue. Your estrone is also high for a male. I'd be curious what your estradiol level is..
 

heapsreal

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@Thinktank
are you on testosterone replacement ?
I ask this as total T is high and if on trt not only can it shut down natural T production but also pregnenolone . Many trt gurus keep guys on pregnenolone supplements or on hcg to stimulate testicular function which can help with pregnenolone production as its made in the testicles. These interventions ate said to help mens general wellbeing while on trt.
 

Thinktank

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@xks201, estradiol level is 34. Ref. range 14 to 60.

@heapsreal, no i'm currently not on TRT or any other hormone therapy.

I have used several prohormones during my "bodybuilding" years. Actually most hormonal problems started after a cycle with M1T (methyl-1-testosterone). Since then i've developed painful gynecomastia (manboobs, but without the fat), already had surgery but it came back within a year.
 

heapsreal

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@xks201, estradiol level is 34. Ref. range 14 to 60.

@heapsreal, no i'm currently not on TRT or any other hormone therapy.

I have used several prohormones during my "bodybuilding" years. Actually most hormonal problems started after a cycle with M1T (methyl-1-testosterone). Since then i've developed painful gynecomastia (manboobs, but without the fat), already had surgery but it came back within a year.


Strange as your results don't really fit a pattern??
I have heard pregnenolone testing isn't always accurate so as A guide some go by progesterone levels, which are somewhat low but not too bad. If cortisol test is a morning test than your cortisol would be considered low as in adrenal fatigue/dysfunction??

Having cfs me or other chronic stressful issues can cause pregnenolone steel which can lower preg/cortisol levels. Could be worth trying pregnenolone supplements but start low like 5mg a day as it can initially overstimulate people when they first use preg in normal doses like 50mg.

I haven't heard of gyno without fat unless it's just breast glands that keep developing, if that's the case look into prolactin and things like bromocriptine which are sometimes used for these situations.

Have you seen an endo recently? Without scaring u, worth looking into things like benign pituatory tumours can cause funky hormone issues. Google dr Mariano who I have read treats similar things as well as the dr who runs allthingsmale forum, I can't recall his name but easy to find in a search. Might be too tricky to sort out on your own and ruling other things out first.

Keep us updated,
Cheers
 

PDXhausted

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I have used several prohormones during my "bodybuilding" years. Actually most hormonal problems started after a cycle with M1T (methyl-1-testosterone). Since then i've developed painful gynecomastia (manboobs, but without the fat), already had surgery but it came back within a year.

Did the M1T use correspond at all to the onset of your ME/CFS or Lyme symptoms?
 

Thinktank

Senior Member
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Location
Europe
@heapsreal, yup it's all very strange.
I know pregnenolone fluctuates during the day but i'm not sure by how much. Just to be sure it's not a lab-error i'm going to have it tested again together with the other hormones that fell out of range.

The blooddraw was taken around 14:00 so it's considered PM. I've had several serum cortisol AM measurements during the past 2 years and it has always turned out borderline low. I don't believe serum cortisol/DHEA is a very accurate way to measure the bioavailability so i'm going to do a salivary test soon.
I do suffer from adrenal / HPA dysfunction but the root cause probably lies with impaired hypothalamus function. Yay chronic lyme disease!

About the gyno, yes it's just the glands that keep growing. Prolactin isn't that high in serum.

Endocrinologists have been a total waste of time so far. I do have an appointment next month to do some additional testing like ACTH stim.test, insulin resistance test and possibly an MRI to rule out any pituitary malignancy.

Another urinary hormone panel is on my todo list as well so hopefully next month i will have a lot more data.

@PDXhausted, not specifically but it has probably contributed to the development of M.E. and the destruction of my immune system.
 

Thinktank

Senior Member
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1,640
Location
Europe
These are my results from a urinary male hormones panel by Genova Diagnostics, May 2013.

malehormones1.jpg
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malehormones3.jpg
malehormones4.jpg


Estradiol (E2) is the most potent estrogen next to estrone and estriol, and is primarily formed in males from
testosterone via aromatization. Although E2 levels are significantly lower in men compared to premenopausal
women, men still require estrogen for cognitive function, as well as maintenance of bone density and various aspects
of cardiovascular function such as blood vessel health. Accordingly, low E2 levels are consistent with increased risk
of osteoporosis, endothelial dysfunction, and cognitive impairment. Low urinary E2 might result from reduced
androgens, broad-spectrum antibiotic treatment, or decreased conversion (aromatization) from androgen precursors,
including the use of aromatase inhibitors.

Conversion of 2-hydroxyestrone (2-OHE1) to 2-methoxyestrone (2-MeOE1) confers extra protection against prostate
cancer. 2-MeOE1 also possesses potent antioxidant properties. Low levels of 2-MeOE1 suggest impaired
methylation of 2-OHE1 or may simply accompany low levels of 2-OHE1. Methylation may be improved via methyl
donors such trimethylglycine, as well as cofactors such as folate, B6 and B12, and magnesium.

Low levels of 4-methoxyestrone (4-MeOE1) suggest impaired COMT-mediated methylation of 4-hydroxyestrone (4-
OHE1). Because 4-OHE1 is procarcinogenic and free radical inducing, 4-MeOE1 production is considered protective.
Methylation may be improved via methyl donors such trimethylglycine as well as cofactors such as folate, B6, B12,
and magnesium.

Like the 2-MeOE1:2-OHE1 ratio, the ratio of 4-methoxyestrone to 4-hydroxyestrone (4-MeOE1:4-OHE1) provides a
useful gauge of methylation capacity. A low ratio suggests impaired COMT-mediated methylation of 4-
OHE1. Because 4-OHE1 can convert to compounds that promote prostate cancer, a low 4-MeOE1:4-OHE1 ratio is
considered sub-optimal. Methylation may be improved via methyl donors such trimethylglycine, as well as cofactors
such as folate, B6, B12, and magnesium.

High levels of urinary DHEA are commonly due to excess supplementation, especially if urinary levels of total 17-
ketosteroids, androsterone and etiocholanolone are also elevated. High levels may also be due to a deficiency or
block of 3β-hydroxysteroid dehydrogenase enzymes.

Tetrahydrodeoxycortisol (THS) is a minor derivative of 11-deoxycortisol, which, in turn, is formed from progesterone.
11-deoxycortisol is also a precursor of cortisol via 3β-hydroxysteroid dehydrogenase (3β-HSD). High levels of THS
might thus result from excess levels of 11-deoxycortisol and/or progesterone, such as might occur with progesterone
therapy. High THS levels might also be expected from excessive adrenal stimulation, an enzymatic block in 11β-HSD
(expect low cortisol), adrenocortical carcinoma, and/or pituitary dysfunction. Confirm with other lab values.
Tetrahydrocortisone (THE) is a direct metabolite of cortisone. High levels of urinary THE are usually due to exogenous
sources. Excess cortisol and/or increased conversion of cortisol to cortisone (such as occurs in hyperthyroidism) might
also result in high THE levels. Confirm with other lab values.

The 11β-HSD Index is a ratio of the cortisol metabolites tetrahydrocortisol (THF) plus allo-tetrahydrocortisol (a-THF)
divided by tetrahydrocortisone (THE). It is a reflection of 11β-hydroxysteroid dehydrogenase (11β-HSD) enzyme
activity. This enzyme catalyzes the inactivation of cortisol or the activation of cortisone within the peripheral tissues
such as the adipose, liver, bone and nerve. Intracellular cortisol/cortisone equilibrium has been shown to be as
important as the circulating concentration of cortisol represented by the Urinary Free Cortisol level and may be a key
player in the modulation of cellular metabolism associated with the Metabolic Syndrome. Ratios less than 1 indicate
that cortisol is being inactivated to cortisone by 11β-HSD-2 in the peripheral tissues. This pattern has been noted in
hyperthyroidism as well as increases in growth hormone.

Androsterone is an androgenic downstream metabolite of DHEA and androstenedione via 5α-reductase, and may also
be formed directly from androstanediol, a metabolite of DHT. Elevated levels of androsterone usually occur with DHEA
administration (confirm with elevated DHEA, etiocholanolone and total 17-ketosteroids). High levels have also been
noted in hyperthyroidism, in women with polycystic ovary syndrome (especially when obese), hirsutism, and/or acne, and in men with benign prostatic hypertrophy.

Low levels of 11-keto-androsterone may be due to an androstenedione deficiency. Low DHEA and/or cortisone may
also contribute. Confirm with urinary DHEA and tetra-hydrocortisone levels.

Low urinary 11-keto-etiocholanolone levels are generally associated with androgen deficiency. This is a 5β-reduced
compound that is an end product of androgen catabolism.

Low levels of 11-hydroxy-etiocholanolone are usually due to androstenedione deficiency. However, low DHEA
(precursor of androstenedione) can also contribute to low levels. Cortisol is a minor contributor but a deficiency may
affect values. Confirm with urinary cortisol and DHEA levels.

The 5β / 5α Reductase (Etiocholanolone/Androsterone) Ratio is a sensitive indicator of the 5β-reductase vs. 5α-
reductase enzyme activities, as both androgen metabolites come from androstenedione via these two enzymatic
pathways. Etiocholanolone is produced via the 5β-reductase pathway, thus a ratio of less than 1 suggests a shift to
the 5α-reductase pathway. A lower ratio (indicating more 5α-reductase activity) has been observed in individuals with
polycystic ovary syndrome, obesity, male-pattern baldness, as well as with an intense athletic training and
consumption of a western diet. A ratio of 1 might suggest excessive tissue dihydrotestosterone (DHT), especially with
testosterone supplementation (expect higher urinary androstanediol level).

The Anabolic / Catabolic Balance is a ratio of the total 17-ketosteroids (anabolic) to the total hydroxysteroids
(catabolic). This ratio reflects the balance of growth and healing versus wear and tear in the body. A ratio greater than
1 demonstrates a net anabolic state for the patient, a beneficial finding.

High levels of urinary 17-ketosteroids occur with excess DHEA supplementation. However, elevated urinary 17-
ketosteroids may also result from high levels of testosterone (if urinary androsterone and etiocholanolone are also
high) or excessive supplementation of dihydrotestosterone, androstenedione, or growth hormone. A high protein and
high calorie diet may also elevate urinary 17-ketosteroids, as can various agents such as antibiotics. Rule out
pregnancy, tumors of the adrenals, ovary or testes, pituitary dysfunction, Cushing's disease, hirsutism (if also low to
normal 17-hydroxysteroids), PCOS, and hypertension.
 

heapsreal

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@Thinktank
it sounds like your on top of it knowledge wise. The battle sounds like it more to do with finding a good dr. I agree with you about endos. From what i have read the antiaging endos seem to be more on top of these issues ???

I see u have lyme, i think many chronic infections can bash the poor old hypothalmus that controls our hormones .

I hope u sort it out as it can complicated and messy adjusting all the individual hormones.

Cheers