Secondary Hypogonadism & Treatment Choices

Pharma TRT
1

35 year old male diagnose 6 months ago with secondary hypogonadism and hypothyroidism. My initial labs were:

Total Test: 186 (240-950)
Free Test: 7.0 (9-30)
LH: 2.3 (1.5-9.3)
FSH: 1.7 (1.6-8.0)
E2: 18 (<39)
SHBG: 15 (10-50)

Free T4: 1.35 (0.71-1.85)
Total T3: 115.6 (84.6-201.8)
TSH: 4.35 (0.50-4.65)

Endo decided to put me on clomid for 3 weeks to see if my pituitary would respond.
Total Test: 329 (240-950)
Free Test: 11.0 (9-30)
LH: 5.8 (1.5-9.3)
FSH: 2.9 (1.6-8.0)
E2: 22 (<39)
SHBG: 18 (10-50)

I was diagnosed with secondary hypogonadism probably as a consequence of obesity (6’2" @ 300lbs). I was given a few options for treatment including:

  1. Attempt weight reduction and reassess
  2. Continue with clomid and attempt weight reduction and reassess
  3. Start TRT and attempt weight reduction.

I didn’t like the way I felt on clomid and didn’t want that long term and for some reason felt uneasy starting TRT for secondary hypogonadism immediately so I chose option 1. Endo warned my that my current endocrine state was not conducive to weight loss and it would be an uphill battle. He started my on 100mcg Synthroid.

Fast forward 6 months later and I have been low carb dieting and exercising and lost 40 lbs. My most current labs are:

Total Test: 500 (240-950)
Free Test: 14 (9-30)
LH: 5.1 (1.5-9.3)
FSH: 5.5 (1.6-8.0)
E2: 22 (<39)
SHBG: 19 (10-50)

Free T4: 1.30 (0.71-1.85)
Total T3: 93 (84.6-201.8)
TSH: 1.87 (0.50-4.65)

Subjectively I feel good but not great. Making some better gains at the gym than in the past. Brain fogginess is lifting a bit but I’m still moody. I think I’ve made good progress with my weight reduction and pretty good increases in my T level but subjectively I’m not there yet. Furthermore, I’m rather discouraged that even with a relatively low E2 and normal SHBG a total T of 500 seems to be the maximum potential of my HPT axis. If this is the best I can do naturally I’m not satisfied.

I’ve been reading quite a bit in the past 6 months and there are a fair number of articles out there that point towards hyperglycemia/hyperinsulinemia secondary to excessive visceral fat as a primary cause of obesity-induced hypogonadism. Perhaps as important as high E2 as a potential cause. It’s interesting to note that my E2 has never been measured as elevated although I suspect early on in my obesity it was elevated before my test levels started bottoming out. Furthermore, it seems to me even if you’re secondary hypo and obese and you want to try recovery in the form of greatly reducing visceral fat stores through diet/exercise it is difficult just with the mere presence of the existing visceral fat stores and the resulting cascade of excess free fatty acids in the portal system leading to fatty liver, inflammation, insulin resistance, more hyperinsulinemia and a propensity toward fat storage in the form of visceral fat. Although I can not find a report in the literature linking c-peptide (as a measure of insulin resistance) directly to obesity-induced hypogonadism it does seem there maybe a link between insulin sensitivity and hypogonadism.

This lead me to the conclusion that I was thinking about my disease all wrong. My goal shouldn’t be to reduce weight and hope T levels respond. After all, my metabolism is setup against me achieving this goal on every level. Instead, I should be using TRT as adjunct to diet/exercise to biochemically set my body up to allow visceral fat loss. When I looked in the literature I found evidence to support this approach. Most notably is the recommendation that TRT should be used for weight loss in obesity as a primary treatment modality.

I did also consider HCG monotherapy and I think it was an option in my case assuming my Leydig cell reserve was sufficient. However there seems to be a growing consensus that test replacement is at least subjectively better at relieving low T symptoms that HCG monotherapy.

So I’ve decided to start test IM injections, wait for blood levels to stabilize and if I feel better and the numbers look good do small doses of HCG 2 and 1 day before weekly injections to keep my testicles from completely shutting down. I also hope maybe one day when I’m significantly thinner with better insulin control try a restart.

Comments are welcome. This is not saying much but my endo went along with this plan without much hesitation.

2

Normally walls of text like this make my eyes gloss over and I just close it out without reading, but I found yours fascinating for some reason. You obviously have a pretty good idea what you’re doing and you’ve done your research. Thanks for that and not expecting to be spoonfed like a dummy.

I note a few things about your bloodwork.

  1. You were definitely looking secondary hypogonadal and hypothyroid after the first lab. Good call by your doc.

  2. You had good pituitary response, but shitty testicular response, to the SERM treatment. This points in the direction of primary (adequate LH, poor Test).

  3. Your T levels seem to have improved as you lost weight. I do not know the reason for this, as your LH/FSH are similar to your previous tests. I find this interesting/odd. Were all your labs done at the same time of day (around 8 am)?

  4. Your T4 looks good, but T3 is in the shitter. This indicates poor conversion.

5 (and most importantly) Your TSH has dropped considerably, even though your T3/T4 are near identical to your previous test. This makes me wonder about Hashimoto’s. Did you have thyroid antibodies tested? I definitely would if I were you (before starting TRT treatment).

  1. Your injection protocol needs some work. Read the Protocol for Injections stickey. 2x/week injections of T, along with HCG 2-3x/week.
3

[quote]VTBalla34 wrote:
Normally walls of text like this make my eyes gloss over and I just close it out without reading, but I found yours fascinating for some reason. You obviously have a pretty good idea what you’re doing and you’ve done your research. Thanks for that and not expecting to be spoonfed like a dummy.

I note a few things about your bloodwork.

  1. You were definitely looking secondary hypogonadal and hypothyroid after the first lab. Good call by your doc.

  2. You had good pituitary response, but shitty testicular response, to the SERM treatment. This points in the direction of primary (adequate LH, poor Test).

  3. Your T levels seem to have improved as you lost weight. I do not know the reason for this, as your LH/FSH are similar to your previous tests. I find this interesting/odd. Were all your labs done at the same time of day (around 8 am)?

  4. Your T4 looks good, but T3 is in the shitter. This indicates poor conversion.

5 (and most importantly) Your TSH has dropped considerably, even though your T3/T4 are near identical to your previous test. This makes me wonder about Hashimoto’s. Did you have thyroid antibodies tested? I definitely would if I were you (before starting TRT treatment).

  1. Your injection protocol needs some work. Read the Protocol for Injections stickey. 2x/week injections of T, along with HCG 2-3x/week.[/quote]

Sorry about the wall of text. Believe it or not I was trying to pare it and some of that paring may fill in some of your questions.

Answer 1 & 2: My understanding is that obesity-induced hypogonadism looks very different early on than it does later in the progression of the disease. Early on you get the more classic hormone profile of high E2 and low-normal test. As time goes on and test continues to drop you reach a thresh hold point where there isn’t enough test to convert into E2 and eventually E2 starts to drop and can actually fall into the low-normal range. By this time the entire axis is shut down. Personally, I’ve been obese and hypogonadal for years so I wasn’t surprised that a 3 week try of clomid wasn’t the entire answer. Pituitary response was good but I can imagine after years of atrophy it takes the testicles a bit of time to recover.

The question is would this be a true primary hypogonadism or is it just a temporary consequence of really bad secondary hypogonadism? I didn’t know so I was willing to give it six months. Now at six months it seems there maybe a primary component.

Answer 3 - Labs were all done by same lab and same time of day. This increase in test has has also been interesting for me. I still think obesity-induced hypogonadism is poorly understood and everyone expects to see a high E2/low T profile. There are some recent papers in the literature looking at the acute effects of glucose intake on T and the effects of insulin sensitivity on T. I will say that I used to eat a very carb-rich diet and my c-peptide was elevated in the first labs and has dropped remarkably with the weight reduction/low carb diet - could this be a better reason/cause for my low T than high E2?

Answer 4 - I saw that too. There are some older papers that show hypocaloric diets and more specifically low carbohydrate hypocaloric diets determine T3 levels and have no effect on T4. The premise of this is T3 is the active metabolism-controlling hormone and the body will decrease T3 during times of perceived starvation to conserve energy. In other words THIS IS the slow down in metabolism people talk about on diets. What’s interesting is this happens to a lesser extent even on isocaloric low carb diets so it seems carbohydrate intake does serve a regulatory function for the thyroid. Would a boost from Cytomel be appropriate - at least during my dieting? Not sure if this will self correct but it’s just one reading.

Answer 5 - I have a strong family history of Hashimoto’s but I always come up negative.

Answer 6 - Thank you - I will read the sticky.

I also had some other issues of low D3 and B12 which I have also been correcting. D3 is just into the 40 range up from the low 20’s and I just started B12 injections.

4

If anyone is interested here is some of the literature that I spoke about and has helped me make my decision.

Curr Diabetes Rev. 2012 Mar;8(2):131-43.
Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review. Saad F, Aversa A, Isidori AM, Gooren LJ.

J Sex Med. 2012 Jun;9(6):1669-80. doi: 10.1111/j.1743-6109.2012.02717.x. Epub 2012 Apr 10.
Hormonal association and sexual dysfunction in patients with impaired fasting glucose: a cross-sectional and longitudinal study. Corona G, Rastrelli G, Balercia G, Lotti F, Sforza A, Monami M, Forti G, Mannucci E, Maggi M.

BMC Endocr Disord. 2011 Nov 1;11(1):18.
Effect of 12 months of testosterone replacement therapy on metabolic syndrome components in hypogonadal men: data from the Testim Registry in the US (TRiUS). Bhattacharya RK, Khera M, Blick G, Kushner H, Nguyen D, Miner MM.

Acute testosterone deprivation reduces insulin sensitivity in men.
Rubinow KB, Snyder CN, Amory JK, Hoofnagle AN, Page ST. Center for Research in Reproduction and Contraception, Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.

Circulating free testosterone in obese men after bariatric surgery increases in parallel with insulin sensitivity. Botella-Carretero JI, Balsa JA, Gómez-Martin JM, Peromingo R, Huerta L, Carrasco M, Arrieta F, Zamarron I, Martin-Hidalgo A, Vazquez C. Unit of Clinical Nutrition and Obesity, Department of Endocrinology and Nutrition, Madrid, Spain

Clin Endocrinol (Oxf). 2012 Jul 17. doi: 10.1111/j.1365-2265.2012.04486.x. [Epub ahead of print]
Abrupt Decrease in Serum Testosterone Levels After an Oral Glucose Load in Men: Implications for Screening for Hypogonadism. Caronia LM, Dwyer AA, Hayden D, Amati F, Pitteloud N, Hayes FJ. Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, 02114

5

Additionally, as is commonly seen in obesity I had elevated cortisol levels before starting my exercise/diet. Now I’m training relatively hard 4-5 days per week and cortisol is still elevated. One of the current theories about over-training is chronic moderate to high-intensity exercise results in a catabolic stress response. Essentially the body is attempting to combat an inflammatory response to muscle damage and redistribute it’s energy resources to prevent too much protein anabolism in muscles and increase glycogen stores - just in case you have run like hell - or simply to fuel the over training.

There are a number of papers that show phosphatidylserine blunts the cortisol response after exercise and in chronically stressed individuals. Like most things it’s not clear cut. Some papers say it helps, others say it doesn’t, some say it depends on the person. Additionally, this may be helpful for obese patients as too much glucocorticoid production mimics or enhances many of the metabolic problems associated with hyperglycermia/hyperinsulinemia and ultimately hypogonadism.

J Int Soc Sports Nutr. 2008 Jul 28;5:11. The effects of phosphatidylserine on endocrine response to moderate intensity exercise. Starks MA, Starks SL, Kingsley M, Purpura M, Jäger R. The University of Mississippi, 215 Turner, University, MS 38655, USA. mstarts@olemiss.edu

Sports Med. 2006;36(8):657-69. Effects of phosphatidylserine supplementation on exercising humans.
Kingsley M. Department of Sports Science, University of Wales Swansea, Singleton Park, Swansea, UK. M.I.C.Kingsley@Swansea.ac.uk

Omega-3 fatty acids administered in phosphatidylserine improved certain aspects of high chronic stress in men. Hellhammer J, Hero T, Franz N, Contreras C, Schubert M. Diagnostic Assessment and Clinical Research Organization-Daacro, Science Park Trier, Max-Planck-Str. 22, D-54296 Trier, Germany. hellhammer@daacro.de

6

Not trying to kill everyone but it’s interesting reading and if possible I’d like my post to serve as a resource for people with obesity-induced hypogonadism. Additionally, I’d like to minimize the amount of bro-science.

Here’s are some articles on D3 and hypogonadism:

Eur J Endocrinol. 2012 Jan;166(1):77-85. Epub 2011 Nov 2. Association of hypogonadism with vitamin D status: the European Male Ageing Study. Lee DM, Tajar A, Pye SR, Boonen S, Vanderschueren D, Bouillon R, O’Neill TW, Bartfai G, Casanueva FF, Finn JD, Forti G, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean ME, Pendleton N, Punab M, Wu FC; EMAS study group. Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Manchester M13 9PT, UK.

Clin Endocrinol (Oxf). 2010 Aug;73(2):243-8. Epub 2009 Dec 29. Association of vitamin D status with serum androgen levels in men.
Wehr E, Pilz S, Boehm BO, März W, Obermayer-Pietsch B. Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University Graz, Graz, Austria.

Could my rise in test have been partly a function of increasing my D3 levels over the past 6 months? Perhaps. What’s clear to me is my low T is likely multifactorial and the odds are stacked against recovery with out T supplementation.

7

Cool links…I will get around to reading some of them when I have the time. I agree we need better reference material here.

I don’t know much about obesity related hypogonadism, but your theories seem to have some good structure to them so I would not discredit them by any means.

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Thought this was interesting. I’ve been doing pretty well on my diet and was down 35+ lbs when I started TRT on 8/2/12 and I’ve suddenly plateaued. Pretty strict on diet and I’m taking 1.0mg arimidex divided in 2 doses. No noticeable edema in my hands or ankles. I’ve already increased my stamina, intensity and weight at the gym. Recovery seems quicker too.

I’m not done losing weight and I don’t give blood for a few more week to see where T and E2 are but I’m going to assume some water weight and some increase in lean mass.

I’ve never had a problem with ED (even at my lowest test) but my erections seem weaker since starting TRT. Still having night-time and morning wood but not as hard. I’m also having a little more anxiety but it’s manageable.

I’d say at this point I feel really good physically but the increased anxiety and weaker erections are new. Not planning on changing anything before I see my labs.

Any thoughts?

9

Adex killed my libido and erection quality…aromasin was better in that regard. Others have noted the same.

Somethin to keep in mind.

10

Gave my first subq of HCG…is it normal that it burned like a bitch?

It was reconstituted with just sterile water in a vial as I’m waiting on bacteriostatic water. I’m just going to add benzyl alcohol to make a 1% solution tomorrow at work (in other words I didn’t add too much benzyl alcohol because I haven’t added it yet).

Think I can feel my testicles growing as I write :stuck_out_tongue:

11

Coincidentally I also just did my first shot of HCG sub-q tonight…no pain at all…I used the BAC water that came with the Novarel and all was well.

12

Hmmm weird…perhaps I just injected too quickly. Wasn’t thinking about it and obviously the viscosity is different than test cyp. I have a feeling I went fast and just did a blunt dissection of the tissue with .25mL of high pressure water.

On a similar note…and this is the worst kind of reporting…1 day subjective findings…I had great PM wood last night and this morning I woke up having to pee so badly with wood that I had to do the lean up against the wall technique. Think I was 17 the last time I did that.

Not sure if it’s placebo, increased test, the HCT or maybe a little of everything. Keep you posted VTBalla34 since we started HCT at the same time. Are going to do every other day? I was thinking of trying a set schedule to make keeping track easier.

Sun - 50mg test
Mon - 0.5mg arimidex
Tue - 250IU HCG
Wed - 50mg test
Th - 0.5mg arimidex
Fri - 250IU HCG

My thoughts although they may be misguided are: Sunday I get test but there’s not an immediate rise in test. Monday take the Arimidex to combat the rise of Sunday’s test injection and to get ready for Tuesday’s HCG. Give the HCG Tuesday and now Arimidex levels should be nice and high to conbat the E2 rise from HCG. Rinse and repeat Wed thru Fri.

Comments welcome…

13

Cool man. I don’t want to clog up your log too much with what I’m doing, but a basic rundown of my thoughts:

-500 iu 3x/week for a couple weeks to bring things back online more quickly (I have been on exogenous T without HCG for over a year)
-150 iu 2-3x/week after that. Since I only have on testicle (and he didn’t produce enough T despite LH levels 3x the normal range), my doctor and I reckon I don’t need quite as much HCG as others.
-Labs 4 weeks after I start on my normal dose (along with T=200 mg/week and Aromasin = 25 mg/week, both in divided doses) to see where things are at.

Funny you mention urination. I have been pissing frequently the last couple days. Not a lot of volume, but the “need to piss”. I imagine this is just the hcg sending signals to the prostate (?). Hopefully that goes away soon. Though I guess it could be worse.

14

I must be a big wussy because the HCG freakin’ hurts. I’ve never felt my test at all doing IM or subQ but the HCG burns like a bitch. I have a charlie-horse in my right vastus lateralis from my last injection so I tried subQ in my butt tonight and it hurts like a bitch too.

I even went as far as testing the stuff to make sure it’s legit and sure enough I’m pregnant.

Not sure I could handle into the belly…ok complaining done.

Finally have some bacteriostatic water and not just sterile water…can’t imagine it will make much of a difference but can’t hurt trying. I think next time I’m going to dilute the 5000IU into 2.5mL instead of 5mL and then I’ll only need 12.5 units (0.125mL) to get 250IU. Maybe a smaller volume will help plus I can just add bacteriostatic water to the original HCG bottle and not use a mixing bottle.

As far as the HCG goes…my boys are big and hanging low…my mood has been very good lately too.

15

Just pinch your belly fat a few inches away from your belly button and inject there…that is by far the easiest method of Sub-Q…I can’t even imagine trying to do subq into my ass lol

The BAC water should help

16

Well just did an entire mL of B12 in my thigh and didn’t feel a thing so it’s definitely the HCG solution. Wonder if the sterile water to too hypotonic…I’m not going to waste a vial of HCG mixed with sterile water but I can’t wait to move onto my second vial reconstituted with bacteriostatic water.

17

Maybe you could add the BAC to your existing solution to dilute it.

18

Could be all in my head but since starting HCG I’m in a really really good mood, erections are great and since starting TRT/HCG I’m making huge gains at the gym. Still doing 50mg test twice weekly and 250IU HCG three times weekly.

My exercise tolerance is MUCH better than it’s every been and it seems like every time I go I can go up in weight from the previous time. In the past 3 weeks I’ve gone from 35 lbs dumbbells to 50 lbs dumbbells for curls (maintaining good form of course) and have been putting muscle on in my shoulders and chest (two areas I’ve always struggled with) really fast. When you’ve been walking around for however many years with a test of 150…even normal feels really good. I’ve made more progress on TRT in the past month as far as changing my body composition than I made in the past year working my ass off at the gym and dieting.

Going for tests in a few weeks.

19

New labs. Feeling good but not great. Making good physical gains at the gym and mood is good but not great. Libido is slowly decreasing and erections are little less hard. Still lifting 3 or 4 times per week and cardio 3-4 times per week. Interestingly weight loss has completely stopped since starting TRT - lean mass is going up and I’m still eating a relatively low carb calorie restricted diet.

Currently Regiment:
Test Cyp: 50mg 2X per week
HCG: 333UI 3X per week
0.5mg adex 2X per week
100mcg Synthroid per day

10,000UI D3 daily
Gave myself a few 1000mg injections of B12 and now will be giving them monthly.

Old —> new labs taken 3 days after last Test/HCG/Adex (note - old labs were from Quest and new are from Labcorp)

Total Test: 500 (240-950) —> 500 (348-1197)
Free Test: 14 (9-30) —> 18.1 (8.7-25.1)
LH: 5.1 (1.5-9.3) —> 0.1 (1.7-8.6)
FSH: 5.5 (1.6-8.0) —> <0.2 (1.5-12.4)
E2: 22 (<39) —>12.8 (7.6-42.6)
SHBG: 19 (10-50) —> 14.9 LOW (16.5-55.9)

Newly tested:
DHEA-S: 171.6 (160-449)
Prolactin: 7.9 (4.0-15.2)

Free T4: 1.30 (0.71-1.85) —> Not tested
Total T3: 93 (84.6-201.8) —> Not tested
TSH: 1.87 (0.50-4.65) —> 1.960 (0.450-4.50)

Newly tested:
Total T4: 6.7 (4.5-12.0)
T3 Uptake: 38 (24-39)
Free Thyroxine Index: 2.5 (1.2-4.9)

Hematocrit: 46.6 (38.5-50.0) —> 46.0 (37.5-51.0)

Vit B12: 522 (200-1100) —> 1100 (211-946)
Vit D3: 31 (30-100) —> 53.1 (30-100)

Total Cholesterol: 194 (125-200) —> 175 (100-199)
Triglycerides: 119 (<150) —> 92 (0-149)
HDL: 47 (>40) —> 55 (>39)
LDL: 123 (<130) —> 102 HIGH (0-99) - There’s a note that as of 09/10/2012 the reference range was lowered for my age bracket. Still pretty damn good.

My translation:

tT is the same but this is really my trough being 3 days out right?
fT is high because my SHBG dropped down.
E2 is low on 1.0mg Adex per week. Since my SHBG is low is this really a problem? In other words it’s low but there’s more bio available.

Not sure what to make of DHEA-S as this is the first time testing for it. Seems low to me.

Prolactin looks fine.

T3 uptake is high meaning my thyroxine-binding globulin is low which can be seen in TRT and hypothyroidism. My last total T3 was on the low side at 93 (76-181). Maybe need a T3 med?

D3 is getting up there but want it to be higher. B12 shots really DO WORK!

My lipid profile is getting better.

Thoughts are welcome!

20

Very much improved everywhere. If you are still having erection/mood problems maybe try to knock your Adex dose back a bit. Add an extra day or two in between doses, or take smaller doses if possible.

Do not be discouraged about the gym progress. You can’t keep your newbie progression/gains forever!