Random notes on hCG

[Daz69]

Some random notes on hCG:

hCG is a frequent adjunct to AAS cycles, and it’s use can be traced back quite a few years. It was in fact used by the East Germans during the pinnacle of their dominance in Olympic athletics. Dan Duchaine wrote about it in his Underground Steroid Handbook as did Bill Philips (back in his early years when he used to call himself W Nathaniel Philips) in his Anabolic Reference Guide.
Today’s protocols differ somewhat and I’m going to try to piece together the science to better understand what could be a good protocol.
So, what do we know about hCG from the scientific studies? Well, here goes (title of study and very brief and partial summary of results):


http://www.ncbi.nlm.nih.gov/pubmed/15162244

Int J Sports Med. 2004 May;25(4):257-63.

“Concomitant abuse of anabolic androgenic steroids and human chorionic gonadotrophin impairs spermatogenesis in power athletes” (Karila T, Hovatta O, Seppälä T.)

18 power athletes who were contemporarily using AAS and hCG were followed. At the end of the AAS the mean sperm count was 33 +/- 49 x 10 (6) /ml, with only one subject having azoospermia. The conclusions of the study were that the use of hCG maintains spermatogenesis, but they found a significant correlation between the dose of hCG and the number of morphologically abnormal spermatozoa.


http://www.ncbi.nlm.nih.gov/pubmed/6833460

J Clin Endocrinol Metab. 1983 Apr;56(4):720-8.

“Human Chorionic Gonadotropin and Testicular Function: Stimulation of Testosterone, Testosterone Precursors, and Sperm Production Despite High Estradiol Levels”(Matsumoto AM, Paulsen CA, Hopper BR, Rebar RW, Bremner WJ.)

Five normal men were given a dose of 200mg/week of Testosterone Enanthate for 3-5 months and then afterwards 5000IU of hCG was added in addition to the Testosterone Enanthate, three times per week for an additional 4-6 months. Serum E2 levels became very high (158 +/- 16 pg/ml during the treatment of both agents. The addition of the hCG increased the total T levels by an average of 5,1 ng/ml and free T levels by 0,18 ng/ml over those found by the administration of just the Test E to approximate normal testosterone values.
Serum progesterone and 17-hydroxyprogesterone fell whilst just on Test E and then increased significantly with hCG use. An increased ratio of 17-hydroxyprogesterone to T during hCG administration suggested an E2-induced block in steroid synthesis. Sperm levels increased from 1,0 +/- 1,0 x 10 (6) / ml during T-only administration to 46 +/- 16 x 10 (6) / ml during T plus hCG administration.


http://www.ncbi.nlm.nih.gov/pubmed/19575391

Mol Reprod Dev. 2009 Nov;76(11):1076-83. doi: 10.1002/mrd.21074.

“Adverse effects associated with persistent stimulation of Leydig cells with hCG in vitro” (Matsumoto AM, Paulsen CA, Hopper BR, Rebar RW, Bremner WJ.)
This study highlighted how persistent hCG stimulation induces oxidative stress and cell apoptosis in Leydig cells.


http://www.ncbi.nlm.nih.gov/pubmed/20824644

Mol Reprod Dev. 2010 Oct;77(10):900-9. doi: 10.1002/mrd.21232.

“N-acetylcysteine counteracts oxidative stress and prevents hCG-induced apoptosis in rat Leydig cells through down regulation of caspase-8 and JNK” (Aggarwal A, Misro MM, Maheshwari A, Sehgal N, Nandan D.)
This study found that NAC counteracted the oxidative stress and apoptosis in Leydig cells induced from repeated hCG stimulation.


http://www.ncbi.nlm.nih.gov/pubmed/6535446

Ann Endocrinol (Paris). 1984;45(4-5):281-90.

“Kinetics of the steroidogenic response of the testis to stimulation by hCG. V. Blockade of 17-20 lyase induced by hCG is an age-dependent phenomenon inducible by pre-treatment with hCG” (Forest MG, Roulier R.)
hCG-induced testicular desensitisation is described as the down-regulation of LH/hCG membrane receptors, uncoupling between receptors and the adenylate cyclase, and inhibition of 17 alpha-hydroxylase-17, 20-desmolase enzymatic complex. They found that prepubertal boys and untreated hypogondaotrophic hypogonadic (HH) adult men had a similar response following a single injection of hCG (dose of 100 IU/kg bodyweight) i.e. a progressive and substantial rise in plasma T, with a peak at 96-120 hours, a modest and late rise in E2, but no significant change in delta 4-androstenedione (delta 4) or 17 alpha-hydroxprogesterone (OHP). Adult men on the other hand have a peak of plasma T and delta 4 at about 72 hours whilst OHP and E2 peak at about 24 hours. hCG was shown to inhibit 17, 20-desmolase.


http://www.ncbi.nlm.nih.gov/pubmed/3583230

Horm Metab Res. 1987 May;19(5):216-21.

“Testicular responsiveness following chronic administration of hCG (1500 IU every six days) in untreated hypogonadotropic hypogonadism” (Balducci R, Toscano V, Casilli D, Maroder M, Sciarra F, Boscherini B.)
This study puts forward the hypothesis of administering hCG more infrequently (at least in HH patients), citing the prolonged effect.


http://www.ncbi.nlm.nih.gov/pubmed/4044781

J Clin Endocrinol Metab. 1985 Nov;61(5):926-32.

“Self-priming effect of luteinizing hormone-human chorionic gonadotropin (hCG) upon the biphasic testicular response to exogenous hCG. I. Serum testosterone profile” (Ulloa-Aguirre A, Mendez JP, Diaz-Sánchez V, Altamirano A, Pérez-Palacios G.)
Subjects received an injection of 40IU/kg bodyweight of hCG on Day 1 and then 80IU/kg bodyweight after 96 hours. They found that after the first dose hCG produced a biphasic response in early and mid-pubertal boys and normal adult men, with a peak in serum T at 2-7 hours and a second peak at 48-72 hours. HH patients instead had no early peak. Following the second dose however all groups had two peaks which varied in magnitude however.


http://www.ncbi.nlm.nih.gov/pubmed/3997269

Int J Androl. 1985 Feb;8(1):28-36.

“Effects of short- and long-term administration of tamoxifen on hCG-induced testicular steroidogenesis in man: no evidence for an oestradiol-induced steroidogenic lesion” (van Bergeijk L, Gooren LJ, van der Veen EA, de Vries CP.)
This study found that the hCG induced block of the C-17, 20-lyase enzyme isn’t due to endogenous E2.


http://www.ncbi.nlm.nih.gov/pubmed/4079381

J Steroid Biochem. 1985 Nov;23(5A):651-5.

“Testicular responsiveness to hCG before and after long-term antiestrogen treatment in oligozoospermic men” (Martikainen H, Rönnberg L, Ruokonen A, Vihko R.)

After 5000IU of hCG was given to normogonadotropic oligozoospermic men levels of 17-hydroxyprogesterone (17-OHP4) and E2 were significantly elevated after 1 day and those of T after 4 days. After 3 months of 50mg/day of clomiphene citrate only the concentration of 17-OHP4 rose significantly after hCG administration. Results suggested that the E2-mediated inhibition of 17,20-lyase activity (i.e. testicular desensitisation) in the 4-ene pathway could not be totally prevented by long-term antiestrogen treatment. There was no sign of 17,20-lyase inhibition in the 5-ene pathway.


http://www.ncbi.nlm.nih.gov/pubmed/6797954

Int J Androl. 1981 Dec;4(6):628-38.

“Effect of clomiphene treatment on the human testicular response to a single dose of hCG” (Martikainen H, Leinonen P, Vihko R.)
This study found that normal adult men, after 6 days of 100mg/day of clomiphene citrate had a reduced elevation of 17-hydroxyprogesterone, dehyroepiandrosterone, androstenedione and testosterone after an injection of 5000IU hCG. Their conclusion was that hCG-induced inhibition of 17-hydroxylase, 17-20 desmolase and 3 beta-hydroxysteroid dehydrogenase-delta 4-5 isomerase is decreased during antiestrogen administration.


http://www.ncbi.nlm.nih.gov/pubmed/6693540

J Clin Endocrinol Metab. 1984 Feb;58(2):327-31.

“Differential effect of single high dose and divided small dose administration of human chorionic gonadotropin on Leydig cell steroidogenic desensitization” (Smals AG, Pieters GF, Boers GH, Raemakers JM, Hermus AR, Benraad TJ, Kloppenborg PW.)
They found that a single high dose of hCG (1500IU) in normal men led to a peak in plasma T after 48 hours and then plasma T decreased below normal levels (roughly 70%) 7 days after the injection. 17-OHP peaked at 24 hours and then also fell. On the other hand administration of 1500IU hCG at 300IU per day over 5 days increased the values of plasma T to the same value as one single dose of 1500IU of hCG after 5 days and the levels remained elevated thereafter. The response of plasma T (area under curve) was almost double in the divided dose group. 17-OHP levels didn’t peak after 24 hours, but only gradually increased in the multiple-dose group. The increase of T exceeded the 17-OHP at almost all times, and the 17-OHP/T ratio fell to an average of 60% of baseline on Day 7. There was no initial E2 peak in the divided dose protocol and the E2/T ratio only marginally increased.


http://www.ncbi.nlm.nih.gov/pubmed/195852

Mol Cell Endocrinol. 1977 Jul;8(1):73-80.

“hCG suppression of LH receptors and responsiveness of testicular tissue to hCG” (Purvis K, Torjesen PA, Haug E, Hansson V.)
This study demonstrated how a relatively high dose (75IU of hCG in adult male rats) caused a dramatic reduction in the concentration of membrane receptors for LH in the testis. 3 days after the injection it gradually returned to normal. Reduction in the number of LH binding sites in the testis was associated with a decreased responsiveness of the testicular tissue to hCG as measured by hCG-stimulated endogenous testosterone production.


http://press.endocrine.org/doi/abs/1...51%2F6%2F1395&

The Journal of Clinical Endocrinology & Metabolism

“Resensitization of Testosterone Production in Men after Human Chorionic Gonadotropin-Induced Desensitization” (ALLAN R. GLASS, and ROBERT A. VIGERSKY)
Article states how 24 hour exposure to hCG can lead to a loss of testicular LH receptors and/or a decrease in the ability of the testis to produce testosterone in response to LH (i.e. desensitisation). They relate the desensitisation as being caused by block in the conversion of 17-hydroxyprogesterone to testosterone. In humans the desensitisation is characterised by a plateau in serum T (after an initial rise) for 4-24 hours after hCG administration despite high serum hCG and rising serum 17-hydroxyprogesterone. After 72-hour exposure to hCG, serum testosterone doubles, suggesting testis resensitisation to gonadotropin. Ten days after a single injection of hCG, serum testosterone was below baseline but serum 17-hydroxyprogesterone was still greater than baseline, thus suggesting a prolonged block in the conversion of the latter to testosterone. They suggest a shift in the pathway of endogenous testosterone production from A4 to A5.


http://www.ncbi.nlm.nih.gov/pubmed/221476

J Biol Chem. 1979 Jul 10;254(13):5613-7.

“Testicular steroidogenesis after human chorionic gonadotropin desensitization in rats” (Chasalow F, Marr H, Haour F, Saez JM.)
This study shows an initial acute rise in both lyase and 17 alpha-hydroxylase activities following a single injection of hCG. Thereafter plasma and testicular testosterone decline and do not increase after a second injection of hCG. During this period of desensitisation isolated Leydig cells were insensitive to effect of hCG. This block was correlated with a decrease in both lyase and 17 alphy-hydroxylase activities of the Leydig cells. Within 60 to 96 hours after the hCG injection there was in increase of both plasma and testicular testosterone together with a rise in activity of lyase and 17 alpha-hydroxylase.


http://www.ncbi.nlm.nih.gov/pubmed/3747510

J Steroid Biochem. 1986 Jul;25(1):109-12.

“Testicular responsiveness to human chorionic gonadotrophin during transient hypogonadotrophic hypogonadism induced by androgenic/anabolic steroids in power athletes” (Martikainen H, Alén M, Rahkila P, Vihko R.)
This study essentially categorised power athletes who had used high doses of AAS for 3months as having transient HH. After an injection of hCG serum testosterone and 5 alpha-dihydrotesterone increased significantly, but there was no increase in estradiol and 17-hydroxyprogesterone. These results are consistent with those of prepubertal boys.


http://press.endocrine.org/doi/abs/1...urnalCode=jcem

The Journal of Clinical Endocrinology & Metabolism

“Low-Dose Human Chorionic Gonadotropin Maintains Intratesticular Testosterone in Normal Men with Testosterone-Induced Gonadotropin Suppression”
(Andrea D. Coviello, Alvin M. Matsumoto, William J. Bremner, Karen L. Herbst, John K. Amory, Bradley D. Anawalt, Paul R. Sutton, William W. Wright, Terry R. Brown, Xiaohua Yan, Barry R. Zirkin, and Jonathan P. Jarow)

This study found that intratesticular levels of testosterone could be maintained by low-dose hCG therapy in subjects taking 200mg/week of Testosterone Enanthate. There were three dosing regimes of hCG – 125IU, 250IU, and 500IU all every other day for three weeks. Post-treatment ITT was 25% less than baseline in the 125IU hCG group, 7% in the 250IU hCG group, and 26% higher in the 500IU hCG group.


http://www.ncbi.nlm.nih.gov/pubmed/7372789

J Clin Endocrinol Metab. 1980 Jun;50(6):1100-4.

“Prolonged biphasic response of plasma testosterone to single intramuscular injections of human chorionic gonadotropin” (Padrón RS, Wischusen J, Hudson B, Burger HG, de Kretser DM.)
Varying doses of hCG (0-6000IU) were given to normal men. There was an initial rise of testosterone after 2 hours and a second peak at 48 hours. The magnitude of the response was correlated with the dose of hCG used, and at the highest dose (6000IU) testosterone levels were still elevated 6 days later. Plasma estradiol levels showed a dose-dependent rise, with peak levels 24 hours after the injection.


http://www.ncbi.nlm.nih.gov/pubmed/6768759

J Clin Endocrinol Metab. 1980 May;50(5):879-81.

“Lack of a biphasic steroid response to single human chorionic gonadotropin administration in patients with isolated gonadotropin deficiency” (Smals AG, Pieters GF, Kloppenborg PW, Lozekoot DC, Benraad TJ.)
This study suggested that hCG temporarily depresses the conversion of 17-OHP to testosterone.


http://www.ncbi.nlm.nih.gov/pubmed/23260550

J Urol. 2013 Feb;189(2):647-50. doi: 10.1016/j.juro.2012.09.043. Epub 2012 Dec 20.

“Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy” (Hsieh TC, Pastuszak AW, Hwang K, Lipshultz LI.)
Azoospermia occurs in 40% of TRT patients. 500IU of hCG, three times per week maintains ITT values and continued spermatogenesis in TRT patients.


http://www.biolreprod.org/content/22/2/383

Biology of Reproduction March 1, 1980 vol. 22 no. 2 383-391

“Increase in Leydig Cell Number in Testes of Adult Rats Treated Chronically with an Excess of Human Chorionic Gonadotropin” (A. KENT CHRISTENSEN and KENNETH C. PEACOCK)
This very interesting study found that the number of Leydig cells increased in rats treated with 100IU hCG per day for 5 weeks.


http://www.ncbi.nlm.nih.gov/pubmed/3497025

Endocrinol Exp. 1987 Jun;21(2):143-7.

“Plasma testosterone response to repeated human chorionic gonadotropin administration is increased in trained athletes” (Jezová D, Komadel L, Mikulaj L.)
Despite similar basal testosterone levels between trained and untrained subjects, the former group had a significantly greater response to repeated hCG stimulation (3000IU on three consecutive days).


http://www.ncbi.nlm.nih.gov/pubmed/447810

J Clin Endocrinol Metab. 1979 Jul;49(1):12-4.

“Leydig cell responsiveness to single and repeated human chorionic gonadotropin administration” (Smals AG, Pieters GF, Drayer JI, Benraad TJ, Kloppenborg PW.
A single injection of 1500IU of hCG significantly increased plasma testosterone levels for at least 96-120 hours in normal men. There was no additional Leydig cell stimulation from repeated hCG injections given within 48 hours after a single dose.


My thoughts and take-home conclusions from the studies:
 

• hCG is biphasic in normal men (i.e. un-suppressed by AAS) with an initial peak between 2 and 7hours, and a second peak at between 48 and 72 hours.
• The magnitude of the testicular response is correlated with the dose of hCG.
• hCG can maintain spermatogenesis during AAS use.
• After a single injection of 1500IU of hCG, plasma testosterone levels are significantly increased for at least 96-120 hours but fall to about 70% of baseline after a week, whilst after a shot of 6000IU hCG the levels are still elevated after a week. This for me is an important result, since a common protocol on “bro” forums is a single weekly shot of 1000IU of hCG. Now if after 1500IU of hCG in normal adult men not using AAS plasma T falls to 70% of baseline then it stands to reason that a lower dose of hCG (i.e. 1000IU) in AAS-users will mean that plasma T will be even lower after a week. Since hCG has been demonstrated to cause oxidative damage to Leydig cells, I’m not sure that higher doses (especially for longer periods) can be a good thing. Furthermore increasing doses of hCG induce morphologically abnormal spermatozoa.
• There is no Leydig cell stimulation if hCG is administered whilst testes are desensitised. When 1500IU of hCG was administered there was no further Leydig cell stimulation if hCG was administered again within 48 hours.
• 250IU of hCG, administered every other day, is clinically proven to closely maintain ITT levels with baseline in subjects on a weekly dosage of 200mg of testosterone enanthate. Furthermore these lower doses reduce testicular desensitisation (as shown by lower rises of 17-OHP on such doses). Now my conjecture is that since 300mg of testosterone enanthate causes the same amount of (near-total) gonadotropin and sperm suppression as a low dose of only 100mg per week (see “Effects of Chronic Testosterone Administration in Normal Men: Safety and Efficacy of High Dosage Testosterone and Parallel Dose-Dependent Suppression of Luteinizing Hormone, Follicle-Stimulating Hormone, and Sperm Production”), the same dosage of hCG should be equally effective on a dosage of 500mg of testosterone enanthate, i.e. a common and effective dose for bodysculpting purposes.
• All things equal, trained individuals respond better to hCG.
• The use of an anti-estrogen at least partially prevents desensitisation to hCG. This is probably a moot point however if using lower doses, but it suggests that an anti-estrogen could be useful if using higher doses of hCG for any reason.
• NAC appears to prevent desensitisation to hCG, but dose isn’t known in humans.
• Based on what I've read it seems to me that a good protocol could be 250-500IU of hCG every other day whilst using AAS.

[yeelang]

Been running HCG for over a year straight, just had bloodwork done as I'm about to start taking HMG and wanted a baseline. No changes over the last year.

 

imo 500/1000IU doesn't matter, it just needs to stay the same and keep your leydigs in a good homestatis. I'm on 500IU every 4th day, which isn't required but I get it cheap and it keep me Peter North'd.

 

 

 

 

 

[al-ex]

I'm Curious. ... define "cheap" hcg for me?

[yeelang]

any AAS that's less than a cup of coffee per serving I consider cheap

[al-ex]

Yeelang....nice one, that is real cheap!

[al-ex]

hMG is something id like to try. What is a good price to expect to pay, anyone?

[yeelang]

That's a lot of cups of coffee at the moment

[al-ex]

Haha luvit! Like Ovidrel at $180/ml or more?