Sensitivity of Androgen Receptors

[bigironkiller]

I have been dealing with low T for the past 4-5yrs. I have been on injections, clomid and hcg all of which raised my T to varying levels but still never felt a huge improvement. This last year or so I have vastly improved my diet and workout regime and have not taken any T products this whole year. I have no symptoms to complain about except a little fatigue on occasion. Had some blood work done and here are some highlights:

Estradiol 16pg/ml range less than 63
free t4 1.31ng/dl range .73-1.95
tsh 2.1 uiu/ml range .3-5.1
free t3 3.0pg/ml range 2.3-4.2
dhea 181ug/dl range 240-549
pregenolone 106ng/dl range 23-173
total testosterone 203ng/dl range 292-1050
calc free T 3.6ng/dl range 4.8-25
SHBG 37nmol/l range 16-94

Now like I said I feel fine I have no problem keeping/gaining strength, weight is difficult to control/keep constant( stomach fat). Im 6'3 225lb 27yrs old. My doc who ive been with for years said it looks like my androgen receptors have become very sensitive to my small amounts of testosterone( basing it off my very little improvement with T injections and testosterone levels at top of range in the past). We talked about how T has other functions besides sexual/muscle gain in the body and health benefits. We decided since I feel fine to not do any drastic changes, just minor adjustment and trial/error. He said supplementing with small dose of dhea might help, but also said small 1-2X/mth testosterone injections would just help make sure all my body cells have access to T. He was talking about maybe 100mg/month in two doses or less. Nothing set in stone but we just discussed how I feel and what my goals are. I already have kids and dont want more, im young and dont want to be saddled with medications for the rest of my life.

What are some thoughts of you guys/docs on the board.

 

[bigironkiller]

Just to clarify he said injecting the 75-100mg T per month was just to make sure all of my body was getting access to testosterone. I am feeling good so he was very clear he did not want to change how I was feeling.

 

[Michael Scally MD]

Just to clarify he said injecting the 75-100mg T per month was just to make sure all of my body was getting access to testosterone. I am feeling good so he was very clear he did not want to change how I was feeling.

Is this a joke?

 

[bigironkiller]

I think it was more of a thought/just in case, like I said he did not want to change anything if I feel good. The shot was not so much as to raise my T levels for any extended period but just to get some extra T to other cells/tissues that needed it. He said I dont need the numbers just to have the numbers. What are your thoughts Dr. on why I have so little yet feel fine? All other blood work came back excellent, cholesterol, HDL, LDL, Ha1c, etc. He gave me options nothing set in stone

 

[chemman]

Usually there is a reason [symptom] that T values are being measured. What were your symptoms 4-5 years ago? Have they resolved?

 

[Michael Scally MD]

This is a major issue. There are others. [At age 27, reading the TRT provided, I am wary you were not properly worked up for hypogonadism.]

I have a very strong suspicion that the E2 level falls well below 15 pg/ml during the month.

Estradiol 16pg/ml range less than 63

Khosla S. Update in Male Osteoporosis. Journal of Clinical Endocrinology & Metabolism 2010;95(1):3-10. Update in Male Osteoporosis

Context: Osteoporosis in men is becoming an increasingly important public health problem. One in five men over the age of 50 yr will suffer an osteoporotic fracture during their lifetime, and men who sustain fractures have an increased mortality risk.

Evidence Acquisition: Evidence was obtained by PubMed search and author’s knowledge of the field.

Evidence Synthesis: Studies using computed quantitative tomography and high-resolution peripheral computed quantitative tomography have provided new insights into the bone structural changes with aging in men, including the somewhat surprising demonstration of significant, ongoing trabecular bone loss starting in young adult life. In addition, there are now data demonstrating that serum estradiol levels are important predictors of fracture risk in men and that there is a threshold estradiol level below which not only bone loss but also fracture risk increases markedly. Criteria for diagnosing and managing osteoporosis in men are also evolving, including the application of the fracture risk assessment tool to derive 10-yr fracture risks in men. Three bisphosphonates (alendronate, risedronate, and zolendronic acid) and teriparatide are currently U.S. Food and Drug Administration approved for the treatment of osteoporosis in men, with a number of new compounds, including a monoclonal antibody against receptor activator of nuclear factor-?B ligand, selective estrogen receptor modulators, and selective androgen receptor modulators in varying stages of development.

Conclusions: Despite significant advances, there remain a number of key unresolved issues regarding the pathogenesis and management of male osteoporosis, not the least of which is increasing public awareness of this important cause of morbidity and mortality in men.


Cauley JA, Ewing SK, Taylor BC, et al. Sex Steroid Hormones in Older Men: Longitudinal Associations with 4.5-Year Change in Hip Bone Mineral Density - The Osteoporotic Fractures in Men Study. Journal of Clinical Endocrinology & Metabolism;95(9):4314-23. Sex Steroid Hormones in Older Men: Longitudinal Associations with 4.5-Year Change in Hip Bone Mineral Density—The Osteoporotic Fractures in Men Study [See: Sex Steroid Hormones in Older Men: Longitudinal Associations with 4.5-Year Change in Hip Bone Mineral Density—The Osteoporotic Fractures in Men Study ]

Context: There is limited information on the association between sex hormones and bone loss in older men.

Objective: Our objective was to determine the longitudinal association between sex steroid hormones and bone mineral density (BMD).

Design and Setting: We conducted a prospective study of 5995 men aged at least 65 yr old at six U.S. clinical centers.

Participants: Sex steroid hormones were measured in a random sample of 1602 men. After exclusions, 1238 men were included in cross-sectional analyses and 969 in longitudinal analyses. Baseline sex hormones were measured using liquid chromatography-mass spectrometry. Bioavailable (Bio) estradiol (BioE2) and testosterone (BioT) were calculated from mass action equations. SHBG was measured using chemiluminescent substrate.

Main Outcome Measures: BMD of the total hip, measured at baseline and once or twice afterward over 4.6 yr of follow-up, was evaluated.

Results: The annualized percent change in hip BMD increased with decreasing BioE2 (P trend = 0.03). Men with the lowest BioE2 (<39.7 pmol/liter) compared with the highest BioE2 (?66.0 pmol/liter) experienced 38% faster rate of BMD loss (P < 0.05). There was no association between BioT and hip BMD loss. Men with lowest BioE2, lowest BioT, and highest SHBG experienced a 3-fold faster rate of BMD loss compared with men with higher levels (P = 0.02). A threshold effect of SHBG was observed; the rate of hip BMD loss increased in men with SHBG of 49–60 nM.

Conclusions: Low BioE2 and high SHBG levels were associated with lower BMD and faster hip BMD loss. The combination of low BioE2, low BioT, and high SHBG was associated with significantly faster rates of BMD loss.

 

[bigironkiller]

Usually there is a reason [symptom] that T values are being measured. What were your symptoms 4-5 years ago? Have they resolved?

Yes, at the initial doc visit 4-5yrs ago I had symptoms, although my diet and mental health was very poor back then. Initial hypogonadism Dx was made by an endocrinologist. Off the top of my head my total T was below 300 back then at age 22-23. My initial complaints were fatigue, weight gain, inability to put on muscle. I was put on T injections and noticed a little improvement but to me not worth it. I have tried numerous restart attempts with clomid/hcg but nothing ever sticks.

Currently I eat very healthy, workout 4+ times per week, have no problems gaining strength, i have morning erections 2-3 times/wk which I havent had since high school, my only complaint is that I occassionally get slight fatigue but im a dad with two kids. Like I said I feel fine and happy the way I feel.

And I do understand the importance of healthy test levels but again I feel healthy and bloodwork all points to me being in optimal health.

 

[bigironkiller]

Dr. Scally, I understand all those studies and all the other health promoting effects of testosterone. I can call up and schedual a bone density scan and call about getting e2 levels checked more often. I am going to start a low dose DHEA supplement(25mg/day) for a while before any more blood work.
Dr.
If I am on the line of other health problems of low T are they going to be gradual or am I just going to be fine until im not. As per the bone issues, etc.

 

[bigironkiller]

So Dr., after my bmd test and further blood work, if e2 is still low I could try T shots and since high end T levels didn't produce dramatic effects I could shoot for lowest T level that produced healthy e2.

 

[bigironkiller]

I apologize for the sporadic posts but a few more questions. Now I am worried about my low e2 levels as opposed to my testosterone. My thoughts are that if I feel fine with low T that is ok, but if I am not feeling the bad effects of low e2 I should focus on that.
1. im gonna give DHEA a run and do some additional blood work
and if dhea doesnt help with low e2 then,
2. Low dose clomid could help raise my e2 while not significantly raising T and giving me a healthy T/e2 ratio.