Human chorionic gonadotropin (HCG) (not to be confused with human growth hormone, or HGH) is a glycoprotein hormone that mimics LH (luteinizing hormone), produced in pregnancy by the developing embryo soon after conception, and later by part of the placenta. Its role is to prevent the disintegration of the corpus luteum of the ovary and to maintain the progesterone production critical for pregnancy in women. It supports the normal development of an egg in a woman’s ovary, and stimulates the release of the egg during ovulation. HCG is used to cause ovulation and to treat infertility in women.
You’re probably asking yourself why you should care about this. But in men, HCG is also used in young boys when their testicles have not dropped down into the scrotum normally. Additionally, HCG is used to increase testicular size after long-term testosterone or anabolic steroid use.
As mentioned at the beginning of the book, testosterone replacement therapy triggers the hypothalamus to shut down its production of GnRH (gonadotropin releasing hormone). Without GnRH, the pituitary gland stops releasing LH. Without LH the testes (testicles or gonads) shut down their production of testosterone. For males HCG closely resembles LH. If the testicles have shrunken after long-term testosterone use, they will likely begin to enlarge and start their testosterone production shortly after HCG therapy is instituted. HCG jump-starts your testes to produce testosterone and to increase their size.
HCG can be extracted from pregnant women’s urine or through genetic modification. The product is available by prescription under the brand names Pregnyl, Follutein, Profasi, and Novarel. Novire is another brand but it is a product of recombinant DNA. Compounding pharmacies can also make HCG by prescription in different vial sizes. Brand names of HCG in regular pharmacies cost over $100 per 10,000 IUs. The same amount of IUs cost around $50 in compounding pharmacies. Many insurance policies do not pay for HCG since they consider its use for testicular atrophy while on TRT an off label use. So, most men using it pay for it themselves and get it from compounding pharmacies that sell it a lot cheaper.
HCG is dispensed as a powder contained in vials of 3,500 IUs, 5, 000 IUs or 10, 000 IUs. You can call compounding pharmacies and have them make vials for you with different IU amounts, though. These are usually accompanied by another vial of 1 mL (or cc) of bacteriostatic water to reconstitute the powder into a liquid solution. Bacteriostatic water (water with a preservative that is provided with the prescription) is mixed in with the powder to reconstitute, or dissolve, it before injection. This type of water can preserve the solution for up to 6 weeks when refrigerated. Some patients do not use the 1 mL water vials that come with the commercially (non compounded) available product and instead get their doctors to prescribe 30 cc bottles of bacteriostatic water so that they can dilute the HCG down to a more workable concentration that is more practical for men using lower doses of HCG weekly.
HCG is given as an injection under the skin or intramuscularly (there is still debate on which method is best). The number of IUs per injection will depend on how much bacteriostatic water you add to the dry powder vial. If you add 1 mL to a 5,000 IU powder vial, then you will have 5,000 IUs per mL, so 0.1 mL would be 500 IUs. If you add 2 mL to the 5,000 IU dry powder vial, then you will have 2,500 IUs/mL; 0.1 ml (or cc) in an insulin syringe will equal 250 IUs. If you need to inject 500 IUs, then you inject 0.2 ccs of this mixture. Table 3 provides dilution volumes at different HCG powder/water proportions.
Ultra-fine needle insulin syringes are used to inject HCG under the skin, making this very easy to take even for the needle-phobic. Typical sizes are:
- 1 ml, 12.7 mm long, 30 gauge and
- 0.5 ml, 8 mm, 31 gauge syringes.
Syringes require a separate prescription. Some compounding pharmacies will automatically include them with the shipment, but do not forget to ask them. Never use the syringe that you used for injecting the bacteriostatic water into the powder for injecting yourself; the needle will be dull (I usually use a regular 23 gauge, 1 inch, 3 ml syringe to load up the water). Remember that you also need alcohol pads to clean the injection area and the tip of the vial. Typical injection sites are the abdominal area close to the navel or in the pubic fat pad. Pinch a little of fat on your abdominals and inject into that pinched area, then massage with an alcohol pad. Discard syringes into the sharps container that can be provided by your pharmacy.
As I mentioned before, compounded HCG is a lot cheaper than the commercially available pharmaceutical products. Sometimes it is difficult to find commercially available HCG in regular pharmacies.
A review of the literature reveals a wide range of doses of HCG used and that there is very little agreement among physicians. For male infertility, doses range from 1250 IU three times weekly to 3000 IU twice weekly (these studies did not include men on testosterone replacement).
How long does the boost in testosterone last after an injection of HCG? A study looked into that and also tried to determine if high doses would be more effective at sustaining that boost. The profiles of plasma testosterone and HCG in normal adult men were studied after the administration of 6000 IU HCG under two different protocols. In the first protocol, seven subjects received a single intramuscular injection. Plasma testosterone increased sharply (1.6 ± 0.1-fold) within 4 hours. Then testosterone decreased slightly and remained at a plateau level for at least 24 hours. A delayed peak of testosterone (2.4 ± 0.3-fold) was seen between 72–96 hours. Thereafter, testosterone declined and reached the initial levels at 144 hours. In the second protocol, six subjects received two intravenous (IV) injections of HCG (5-8 times the dose given by injection to the first group) at 24-hour intervals. The initial increment of plasma testosterone after the first injection was similar to that seen in the first protocol despite the fact that plasma HCG levels were 5–8 times higher in this case. At 24 hours, testosterone levels were again lower than those observed at 2–4 hours and a second IV injection of HCG did not induce a significant increase. The delayed peak of plasma testosterone (2.2 ± 0.2-fold of control) was seen about 24 hour later than that in the first protocol. So, this study shows that more is not better when dosing HCG. In fact, high doses may desensitize Leydig cells in the testicles. It also showed that testosterone blood levels peak not once but twice after HCG injections. I wish they had studied a lower dose than 6000 IU since very few physicians prescribe this high dose.
HCG may not only boost testosterone but also increase the number of Leydig cells in the testicles. It is well known that Leydig cell clusters in adult testes enlarge considerably under treatment with HCG. However, it has been uncertain in the past whether this expansion involves an increase in the number of Leydig cells or merely an enlargement of the individual cells. A study was performed in which adult male Sprague-Dawley rats were injected subcutaneously daily with 100 IU HCG for up to 5 weeks. The volume of Leydig cell clusters increased by a factor of 4.7 during the 5 weeks of HCG treatment. The number of Leydig cells (initially averaging 18.6 x 106/cm3 testis) increased to 3 times the control value by 5 weeks of treatment (P<0.001), while the average volume of individual Leydig cells (initially ~2200 µm3) enlarged only 1.6 times. They concluded that chronic treatment with HCG increases the number of Leydig cells in the testes of adult rats. We do not know if these results can be extrapolated to men.
Currently there are no HCG guidelines for men who need to be on testosterone replacement therapy and want to maintain normal testicular size. A study that used 200 mg per week of testosterone enanthate injections with HCG at doses of 125, 250, or 500 IU every other day in healthy younger men showed that the 250 IU dose every other day preserved normal testicular function (no testicular size measurements were taken, however). Whether this dose is effective in older men is yet to be proven. Also, there are no long-term studies using HCG for more than 2 years.
Due to its effect on testosterone, HCG use can also increase estradiol and DHT, although I have not seen data that shows if this increase is proportional to the dose used.
So, the best dose of HCG to sustain normal testicular function while keeping estradiol and DHT conversion to a minimum has not been established (I will explain why these two metabolites are important in TRT management).
Some doctors are recommending using 200–500 IUs twice a week for men who are concerned about testicular size or who want to preserve fertility while on testosterone replacement. Higher doses, such as 1,000–5,000 IUs twice a week, have been used but I believe that these higher doses could cause more estrogen and DHT-related side effects, and possibly desensitize the testicles for HCG in the long term. Some doctors check estradiol levels a month after this protocol is started to determine whether the use of the estrogen receptor modulators tamoxifen (brand name: Nolvadex) or anaztrozole (brand name: Arimidex), is needed to counteract any increases in estradiol levels. High estradiol can cause breast enlargement and water retention in men but it is important at the right blood levels to maintain bone and brain health (refer to the Gynecomastia section for more on this subject).