The Potential Dangers of Too Much HCG?

HCG is widely used by women as a dietary aide - it supposedly suppresses appetite - and by men for hypogonadism (clinically low testosterone) in various protocols. The usage by men is typically done

a) by itself to boost clinically low testosterone - see my page called HCG Monotherapy for more information - or

b) added 2-3 times per week (low dose) with standard testosterone replacement therapy (TRT). So the question, of course, is whether or not this type of usage of HCG is really safe.

Now, before I go on, I want to clearly say that I think that, generally speaking, HCG is safe.  Many doctors and TRT clinics are giving men HCG and I am not hearing of reported issues. And keep in mind that I am about to go on low dose HCG myself and, in my page on The Benefits of HCG for Men on TRT, make a case for HCG as a nice complementary therapy.  However, I think that some caution is in order when HCG is used in higher dosage amounts for reasons I will discuss below. (I also think you should stay away from dairy if you use HCG for reasons I will discuss below.)

My concerns started with a story that one man (Balderdasher) told on our forum:

"HCG and T together with Adex worked great (in fact, I felt better on the combination than I did on mono T). That said, I ended up getting a really rare (one in several million) benign lip tumor about a year ago (Angioleiomyoma) that continually regrew, leading to three surgeries/procedures to remove it. The Head & Neck guy I worked with was a really solid dude, and did some intensive research into what may have caused this growth. Apparently, a lot of the cases he reviewed wherein males presented with this tumor type also saw the individuals using HCG and PDE5 inhibitors, leading him to conclude that HCG + Viagra/Clomid are what did it for me. Now that you mention the clotting sides of Arimidex, however, I wouldn't be surprised if that played into it as well. All of this also coincided with a meniscus tear and some weird wrist issues that seemed to present out of nowhere (being a guy who had never broken a bone/torn anything in his life despite a lot of years of bruising and beating)."

Before I say anything else, let me just say that the above is quite rare.  That said, notice that Balderdasher was on a standard HRT clinic protocol - I was on it myself for awhile - called "The Trifecta," which includes testosterone cypionate injections, Arimidex (anastrozole) and low dose HCG.  Balderdasher's medical condition started shortly after he stopped the Trifecta as reported on  Peak Testosterone Forum:

"Shortly after coming off of TRT I was diagnosed with an extremely rare (and thankfully benign) tumor called an Angioleiomyoma in my lip, which apparently has something to do with your vasculature." [1]

Notice he mentioned that vasculature - something I will come back to in a minute - played a role.  This tumor caused quite a bit of trouble for him.  He wrote me:

"Re: the tumor - it was a nightmare. Had an ENT who performed an in-office procedure to take it out - twice. Both times it grew back swiftly. Finally, on the third go-round, he referred me to a specialist who knocked it out once and for all with surgery. It probably wouldn't have been a big deal if I'd gone this route in the first place but, unfortunately, the cumulative effects of three procedures left me with a still slightly swollen lip and a lack of sensation (not too bad, I'm really the only one who could ever tell). Could have been worse but man, definitely not something you want to deal with when you're already riding the TRT rollercoaster."

So let's go back to what his Ear, Nose and Throat specialist said, i.e. that he had been seeing quite a few cases out there with men on HCG and PDE5 inhibitors developing these kind of hypervascularized tumors.   This caught his attention because these tumors are so rare. So then the question becomes: "Is it the HCG, the Cialis / Viagra, or both?"

I suspect that HCG probably does play a role, and let me give you several reasons why I think it could contribute to a hyperstimulation of one's blood vessels and this type of tumor in some rare cases:

1.  Increasing VEGF.  VEGF stands for Vascular Endothelial Growth Factor.  VEGF is very important and stimulates angiogenesis, i.e. the development of new blood vessels.  Of course, one needs some VEGF for tissue repair and maintenance.  However, as we age, we are very vulnerable to endothelial cancers.  The endothelium is the delicate lining of our arteries, blood vessels and lymphatic system, and it is this lining that is the key to many types of cancers.  Cancers need fuel to grow rapidly and angiogenesis via the endothelium is one of the keys. 

Because of this, there are now some experts recommending an anti-angiogenic diet.  Basically, the goal of this diet is to consume foods that limit VEGF.  This has also been the source of considerable pharmaceutical research as myself. I myself actually try to generally eat this way, although I don't think an anti-angiogenic diet will usually actually reverse cancer.  However, I think it is important to make life miserable for any cancer cells and an anti-angiogenic diet can be a great weapon in your anti-cancer arsenal.

So what does that have to do with HCG?  Well, it turns out HCG stimulates VEGF:

"Our results suggest that the effects of hCG on the development and course of OHSS may be mediated by the production of VEGF/VPF by GCs [granulosa cells]." [2] 

"Luteinized granulosa cells and macrophages actively secrete vascular endothelial growth factor (VEGF) and adrenomedullin in the human ovulatory follicle. LH/human chorionic gonadotrophin (HCG) directly stimulates VEGF synthesis by granulosa cells while adrenomedullin may play a role in the process of luteinization." [3]

It should also be added that anything that stimulates nitric oxide, such as PDE5 inhibitors, will also stimulate VEGF.  Of course, many men going on PDE5 inhbitors are probably low in vascular growth factors, and so this is probably a good thing.  More study work needs to be done though - this is speculation on my part.  An example of this is that diabetics are actually low in another related growth factor called EGF, or endothelial growth factor, according to an animal study. [8] However, some men due to diet - dairy has a lot of growth factors in it for example - and genetics may have elevated growth factors and HCG or PDE5 inhibitors may throw them over the edge.  Yet another possible example of this is the fact that Viagra has been linked to skin cancer.

UPDATE:  I contacted Balderdasher, the man in the story above, and asked him if he was consuming any dairy at the time.  It turns out that he was having yogurt in both the morning and evening when he developed the tumor.  According to my understanding, this could also have contributed, because dairy is quite high in growth factors, especially EGF.  EGF, epidermal growth factor, is not just involved in skin cancer but has been associated with several other cancers, including anal and lung.  One EGF compound, betacellulin, is particularly potent and plentiful in milk.

2. Increasing Angiogenesis.  So, if HCG stimulates VEGF, does it actually encourage angiogensis?  The answer is 'yes!'  There are many studies and reviews that have looked at this:

"Vascular endothelial growth factor (VEGF)-dependent angiogenesis plays a crucial role in the corpus leteum formation and their functional maintenances in mammalian ovaries. We recently reported that the activation of hypoxia-inducible factor (HIF)-1a signaling contributes to the regulation of VEGF expression in the luteal cells (LCs) in response to hypoxia and human chorionic gonadotropin (HCG)." [4]

"In this manuscript, we demonstrate an angiogenic effect of hCG in several in vivo (chick chorioallanto c membrane, matrigel plug assay, aortic ring assay) and in vitro experimental models." [5]

"Prior exposure to hCG amplified MCP1 secretion by ESCs in response to IL1B and triggered the release of angiogenic activity in vitro in which MCP1 appeared to play a significant role." [6]

Of course, the significance of this is that HCG stimulates both VEGF and angiogenesis, and so it would seem reasonable that it could contribute to the growths that the above physician is seeing.  Remember that PDE5 inhibitors, such as Cialis and Viagra.  I also think that dairy consumption could play a role as well.

3. Placental Hormone - That Should Tell You Something.  One thing that most men on HCG do not know until later is that HCG is NOT LH.  They may also be surprised to know that HCG is actually a placental hormone.  The placenta is the organ in a woman that nourishes and takes care of the fetus.  HCG actually fulfills a very unique purpose for a newborn:  fueling the rapid growth of the unborn child.  Basically, the fetus is put on "turbo growth" mode by HCG. 

In other words, more is not always better. 

Turbo growth mode is great for the little ones, but not so for us as we age, because it could leave us vulnerable to cancer and other growths.  Another great example of this is IGF-1, interleukin growth factor-1.  You want abundant IGF-1 when you are young to maximize size and development.  However, elevated IGF-1 levels in older adults are associated with rapid aging, diabetes and cancer.  Again, once your body has accumulated decades of DNA damage and toxins along with decreased antioxidant and enzyme levels, extreme caution is warranted in increasing growth factor levels.  "Going back to the womb" is not always a good idea.

4. Epidermal Growth Factor.  LH and HCG stimulate another growth factor called Epidermal Growth Factor.  As you may have guessed from the name, overly high levels have been linked to melanoma. [7]

5.  Long Half Life. Most men starting on HCG do not realize that it has a much longer half life than LH - 24 hours versus 20 minutes. They are usually told that HCG is LH and, therefore, is very natural.  Again, this is simply not the case.  HCG is a similar molecule and does trigger the same receptors.  But it is not chemically identical with LH.  Furthmore, one could argue that HCG clearly has a longer half life in order to constantly trigger fetal growth, whereas LH occurs in nice short bursts that are much more safe for an adult.

MY CONCLUSION:  Again, I am not trying to be alarmist here.  I believe that HCG will be found to be safe for most men, especially younger, when they do finally study it in long term.  Furthermore, literally hundreds of thousands of men have used it with few reported side effects.  However, I personally will shy away from HCG at my age (55) to play it safe until more study work is done.  Of course, you have to do your own research and talk to your own physician if you are interested in HCG.

Also, remember that I have more concern than most because I had a high PSA value a couple of years ago.    You can read about my story here:  High PSA But No Cancer. While it's true that I now have my PSA almost down to the levels when I first started cypionate, I have to play it safe due to my age (55) and one time PSA value of 6.3.  (Current PSA:  1.75.)

NOTE:  You may be wondering why I left PDE5 inhibitors such as Viagra and Cialis off the hook.  I guess I should also mention that PDE5 inhibitors also stimulate VEGF and angiogenesis according to several studies.  So could it be the PDE5 inhibitor more than HCG?  Sure.  Again, until we know more, I am going to wait on HCG since the two may synergistically raise VEGF. 



2) J Clin Endocrinol Metab. 1995 Jun;80(6):1967-71, "Human chorionic gonadotropin-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulosa cells: importance in ovarian hyperstimulation syndrome.

3) Reproductive Biomedicine, 2009, 18(6):743 749, "LH/HCG stimulation of VEGF and adrenomedullin production by follicular fluid macrophages and luteinized granulosa cells"

4) African Journal of Biotechnology, 2011, 10(42), "Overexpression of hypoxia-inducible factor prolylhydoxylase attenuated by HCG-induced vascular endothelial growth factor expression in luteal cells"

5) FASEB J, 2006 Dec, 20(14):2630-2, "Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium"

6) Biology of Reproduction, Published online before print July 18, 2012, "Human Chorionic Gonadotropin Triggers Angiogenesis via the Modulation of Endometrial Stromal Cell Responsiveness to Interleukin 1: A New Possible Mechanism Underlying Embryo Implantation"

7) J Invest Dermatol, 2013 Jan,133(1):230-8, "Epidermal growth factor facilitates melanoma lymph node metastasis by influencing tumor lymphangiogenesis.

8) The Egyptian Journal of Histology, Jun 2011, 34(2):403-414, "Effect of sildenafil (Viagra) on epidermal growth factor expression in submandibular gland of diabetic male rats: histological and immunohistochemical study"