Human chorionic gonadotropin (HCG) is well known and widely used in fertility therapy as well as by those who have testosterone production or use issues. Human menopausal gonadotropin (HMG) is not as widely known or used as HCG but has recently received more attention as an adjunctive therapy to HCG. Mostly HCG is used by men for reasons such as testicular shrinkage while on or off testosterone (T) therapy, while on chronic T Replacement Therapy (TRT), low testosterone, low sperm counts, decreased ejaculate volume and other reasons. Even though HCG is called a gonadotropin technically speaking HCG is a placental product, which “mimics” the action of LH.
The gonadotropins (follicle stimulating hormone (FSH) and luteinizing hormone (LH) have actions on the ovaries and testes and are secreted by the anterior portion of the pituitary gland and the placenta (HCG) which acts upon the gonads of men and women to induce fertility, cause sex hormone synthesis and secretion and have many other effects.
LH and FSH are synthesized and secreted by the pituitary gland and are released as the body needs it for fertility, hormone production, physical maturation and other functions. LH is also called interstitial cell –stimulating hormone (ISCH). It stimulates intra-testicular (T) and other androgen synthesis by Lydig cells in men and thecal cells to make T and estradiol in the ovary. FSH stimulates the spermatogenic tissues of the testes and in the female the granulose cells of ovarian follicles to assist egg maturation.
The molecular make up of the alpha subunits of LH, FSH, TSH and HCG are all identical, but differ via their beta subunit. Of importance is that the beta subunit of HCG has 24 extra amino acids compared to LH. This significantly affects the half- life of HCG, which is 24 hours (50% of HCG is out of the body in 24 hours). The other gonadotropins have shorter half-lives:
Half-life of LH is 20 minutes.
FSH half-life is 3-4 hours.
HCG half-life is 24 hours
HCG STRUCTURE
HCG is composed of 244 amino acids. It heterodimeric (has two different components) having an alpha-subunit and beta-subunit. The alpha-subunit is identical to the alpha subunits of luteinizing hormone (LH), follicle stimulating hormone (FSH) and thyroid stimulating hormone (TSH). The beta-subunit is unique to HCG and contains 145 amino acids, which are twenty-four amino acids more than LH.
Human chorionic gonadotropin or HCG is a glycoprotein (sugar protein) produced during pregnancy by the developing embryo and later by the syncytiotrophoblast part of the placenta.
The beta-subunit of HCG looks like and acts-mimics LH, but has no FSH activity.
HCG is useful via its molecular mimicry of LH to stimulate LH receptors to make the Leydig cells synthesize testosterone and other androgens. In women HCG stimulates fertility and can also stimulate ovarian thecal cells to make T and other hormonal precursors that can convert to estrogen.
FSH is secreted by the anterior pituitary gland, which enhances production of androgen binding protein by the Sertoli cells in the testes to start the maturation of germ cells to become sperm. LH then turns on androgen secretion to act on these receptors.
HCG AS TUMOR MARKER
Certain cancers secrete HCG such as testicular cancer. It is a good test for male testicular cancer (HCG normal male value is 0-5 IU). In the female beta-HCG elevations can assist in diagnosis of choriocarcinomous, teratomas, hydratiform mole formation (of placenta), pregnancy and other conditions.
HCG is quite different from HMG. It is important to distinguish that HCG is made from pregnant women’s urine (the menotropins LH and FSH) are derived from purified postmenopausal women’s urine. HMG brand names include Repronex, HMG Massone 75, Humegon, Pergonal others and recombinant versions of LH and FSH.
HCG brands include: Pregnyl, Follutein, Novarel, Choragun and other brands. HCG can also be made via recombinant DNA technology.
FERTILITY AND HCG IN MEN
In men HCG is used to stimulate Leydig cells to make testosterone and other androgens. Elevated intra testicular testosterone is necessary for Sertoli cells of the testes to promote sperm production. However HCG has no direct fertility action on spermatogenesis. It acts indirectly via an androgen effect. If male infertility is the main problem then there are many HMG/HCG and other protocols to increase sperm production and function.
THE HCG DIET
The use of HCG as a dietary aid came from the British endocrinologist Albert T. W. Siemmons. He used 125 IU of HCG daily injections with a 500-calorie diet (high protein + low carbs) to treat fat boys with pituitary disease and calorie deprived pregnant women in India. Later Kevin Trudeau popularized his diet. This diet was most popular around the 1960’ s-70 and now is showing a large resurgence of popularity. The U.S. Federal Food and Drug Administration have stated that HCG use is “fraudulent and ineffective for weight loss is it given by injection or homeopathic version of HCG is illegal”.
However it is known that there are androgenic and estrogenic effects even at a low dose of 125 IU of daily HCG injection. Young women with good ovaries make androgens in he ovary. Estrogens have only one source and that is from androgens (male hormones) only. In women with non-functional or non-existent ovaries such as in post menopause or from surgery.
I do not see how the HCG can be of value except for the caloric deprivation. The real effect (90% +) is the likely the 500 calorie diet. Who would not lose weight with an intake of 500 calories daily? Young ovulating women treated with 125 IU HCG daily on this diet can develop tubal pregnancies, ovarian cysts, “ovarian overstimulation syndrome” and other problems.
Therapy of men with HCG can lead to increased testosterone and even estrogen levels. They may be the ones who may respond to HCG Diet protocol the best. Those trying to gain muscle will likely lose muscle on this diet. Men should avoid HCG if they have gynecomastia (male breast growth), breast or nipple soreness, lumps, cancer or increased prostate cancer risk. Those on HCG should be screened before and during use. Prolonged use of HCG can shut down a male’s endogenous natural production of LH in the pituitary gland and lead to central hypothalamic –pituitary type of hypogonadism.
THE LOW T SYNDROME
The LOW T SYNDROME can be associated with low libido, low mood-depression, low energy, erectile problems, lack of muscle gain and other problems etc. Is it caused by a problem below the belt (testicular problem)? Or is it a problem above the belt up in the brain hypothalamic –pituitary system? Most doctors do not even try to find why a patient has low testosterone. They just treat the low number and leave at that. To me that is not good medicine and I see many men being committed at relative young ages to a lifetime of Testosterone Replacement Therapy
(TRT), with consequential infertility, shrunken testicles and other problems. The below testicular diagnostic test is one important component of comprehensive testing the male of the Low T Syndrome.
hCG-TESTICULAR diagnostic stimulation test
This is a test to determine how well your testicles can respond to gonadal stimulation via a LH like substance found in HCG. If a male is making low levels of testosterone without any known medical, neurologic or other causes then in my mind the HCG-testicular stimulation test is a must do diagnostic test. This assumes that there it is a not a problem of lack of normal levels of testicular signal from the pituitary (LH) – the Low T problem is not of pituitary origin.
The test is simple just administer HCG (LH mimicker) and see what the effects are. Before testing get the following Baseline Lab Tests:
1.Ultra Sensitive estradiol – E2
2.LH
3. Total and free testosterone.
4. Prolactin
Mix into the HCG powder vial bacteriostatic water. Inject HCG subcutaneously 1000 IU every 3 days for ten times. In some cases lower doses of HCG can be used.
After the last injection do lab tests again:
1. E2- ultrasensitive. It should rise if testes are working.
2. Total and free testosterone – should rise.
3. LH test: not needed - you are injecting an LH analog.
Prolactin level not needed if normal prior to testing. If prolactin level was abnormally high the HCG–Stim Test is not indicated.
See the response scale below to determine your testes Leydig cell (T making cells, which make up only about 10% of testes volume) reserve and functional capacity to make androgens (T),
(From writings of Eugene Shippen, MD).
1.: < 20 % Increase from baseline testosterone, (total and free testosterone,) means poor Leydig cell function and or low cell numbers. These men may need a testosterone replacement protocol for a lifetime.
2.: 20-50 % Increase means adequate Leydig cell reserve-function, but somewhat depressed.
These men will need T boosting protocols on an ongoing basis.
3.: > 50% Means adequate Leydig cell function-reserve.
Means testes can function well. Baseline low T in these men may be a problem of pituitary origin (low LH levels). This will need further testing using pituitary estrogen receptor blockers called the SERMs (selective estrogen receptor blockers) to assess pituitary capacity to secrete LH and also do other hypothalamic-pituitary tests are indicated.
HCG can be used as a form of testosterone replacement therapy, augmentation and restore testicular function. If injectable testosterone or T creams and gels are causing shrinking testicular size (any shrinkage is significant) or decreased ejaculatory volume we know that HCG can be used to restore testes size and fertility in the HCG >50% response group.
The HCG-stimulation test does not answer the question whether someone has hypothalamic-pituitary disease causing low LH production. To determine this is pituitary (LH) function and reserve test for gonadotrophs –a pituitary stimulation test should be done without exogenous testosterone on “board”.
The SERMs (Clomid, Tamoxifen, Evista and others) can be used along with other methods.
HCG or HMG: WHICH IS BETTER?
As explained earlier HMG is a purified extract from the urine of postmenopausal women and contains both follicle stimulating hormone (FSH) and luteinizing hormone (LH) in equal amounts and a small amount of HCG. It is used for male and female infertility and hypogonadism. Sometime HMG and HCG are used together.
Women have more possible complications for use of these agents such as thromboembolism, ovarian hyper stimulation, multiple pregnancies and other problems. In males HMG use is generally safer to use.
SOME HMG SIDE EFFECTS (Males):
1.Local site pain
2.Fluid retention
3.Headaches
4.Fatigue
5.Allergic reactions
6.Dizziness
7.Others
HMG usually comes in 75 IU and 150 IU vials. Once reconstituted the HMG technically needs to be used right away and unused portion needs to be discarded. However some may only use one-half of the 75 IU or 150 IU vial and use the rest the next day.
Originally HMG was designed mainly for women to produce follicles and ovulation-release of eggs by the ovaries. Now the male community is beginning to use HMG sometimes alone and most often in conjunction with HCG. Since HCG is not pure FSH or LH but acts as an LH mimicker. The downside of the HMG’s is the high cost. HCG is much less expensive and one 10,000 IU vial can last for 10 to 20 injections depending on dose and frequency.
For fertility (mainly an FSH effect) HMG has greater potency and effect. My recommendation for the use of HMG is for those men who fail to get adequate effects from HCG alone to get increases of testicular size, increased sperm and other desired effects.
DOSEAGES AND USE OF HCG + HMG
1. First always use low doses and work up. Rather than the other way. Maybe your system needs less so why give too much? There are many dose choices. Some may use HCG daily even though half-life of HCG is 24 hours (50 per cent HCG gone in 24 hours).
Recent data shows you only need 500 IU of HCG every other day to keep intratesticular levels of testosterone at adequate levels.
2. Try HCG alone. There are data that too much HCG used at one time and or over time may “desensitize” Leydig cells to HCG. Many are starting to use lower HCG doses such as 250 to 500 IU every 2-3 days. Previously many used 1,000 IU or more every 3 days for 10 injections to preserve testicular Leydig cell capacity and reserve to produce testosterone and other effects.
The dose and frequency also depend on the reasons to use HCG.
3. Try HCG together with 75 IU HMG once or twice weekly = 500 IU HCG + 37.5 to 75 IU of HMG 2 days in a row. Then 500 HCG IU every 2-3 days depending on what the objectives are – elevate testosterone, increase testicle size, elevate sperm counts etc. There are no set rules on dosages and frequency of use. You will have to see what your results with HCG were first and then add HMG at 75 IU for 1 to 3 injections at once or split the HMG dose over 2 days over 3 weeks to feel and see the results. Some for fertility use HMG alone
Combined use of testosterone replacement and HCG
Some may use 500 IU HCG 2 days before their next testosterone injection and then the day of a testosterone injection with the objective to keep Leydig cells functioning, testes from shrinking, and keep ejaculate at a good volume etc. Those who are committed to long term TRT should if possible use HCG
on a weekly basis and not wait till they feel testes getting smaller.
Advantages of HCG
Cost less, insurance occasionally may pay.
Easily available.
Lot of experience of use.
Is effective when used properly.
Disadvantages of HCG
The beta subunit of HCG acts as a mimicker of LH to stimulate LH receptors and increase testosterone and other androgen production. Does not contain or act like FSH.
HCG supports sperm production via increasing intratesticular androgen production. But HCG does not have a direct effect like FSH on the Sertolli cell system
for sperm development and maturation.
Long-term use of HCG especially at high doses can produce “tolerance” or desensitization effects. When a lot and high doses of HCG are used Leydig cells may become less sensitive to HCG.
Advantages of HMG
Contains both LH and FSH.
Contains FSH, which can directly stimulate the FSH receptors of Sertoli cells and somniferous tubules to increase sperm maturation and production.
Less estrogen spiking.
Disadvantages of HMG
Cost is an issue. One vial of 75 IU vary in cost from $50 to $150 for one 75 I.U. vial. Too costly to use continuously for testosterone synthesis. But is better for fertility-for ejaculate-sperm volume and increase of testes size.
COMBINATIONS OF HCG and HMG
- If you need more testosterone than sperm production then use HCG to stimulate the Leydig cells of the testes.
--If you wish greater sperm production use HMG.
-- Can use HMG along with HCG to get both greater sperm and testosterone production and testicular enlargement faster.
--There are many ways to dose HMG depending on your goals.
--The makers of HMG encourage the use of HCG and HMG together to increase fertility.