Human Chorionic Gonadotropin (hCG) is a prescriptionmedication containing chorionic gonadotropin obtained froma natural (human) origin. Chorionic gonadotropin is apolypeptide hormone normally found in the female bodyduring the early months of pregnancy. It is synthesized insyncytiotrophoblast cells of the placenta, and is responsiblefor increasing the production of progesterone, a pregnancysustaininghormone. Chorionic gonadotropin is present insignificant amounts only during pregnancy, and is used as anindicator of pregnancy by standard over-the-counterpregnancy test kits. Blood levels of chorionic gonadotropinbecome noticeable as early as seven days after ovulation,and rise evenly to a peak at approximately two to threemonths into gestation. After this point, the hormone level willdrop gradually until the point of birth.Although it possesses minor FSH-like (Follicle StimulatingHormone) activity, the physiological actions of chorionicgonadotropin mainly mimic those of the gonadotropinluteinizing hormone (LH). As a clinical drug, hCG is used asan exogenous form of LH. It is typically applied to supportovulation and pregnancy in women, most specifically thosesuffering from infertility due to low concentrations ofgonadotropins and an inability to ovulate. Due to the abilityof LH to stimulate the Leydig’s cells in the testes tomanufacture testosterone, hCG is also used with men to treathypogonadotropic hypogonadism, a disorder characterizedby low testosterone levels and insufficient LH output. Thedrug is also used in the treatment of prepubertalcryptochidism, a condition in which one or both of thetesticles have failed to descend into the scrotum. HCG isused by male athletes for its ability to increase endogenoustestosterone production, generally during, or at theconclusion of, a steroid cycle, when natural hormoneproduction has been interrupted.

History:

Chorionic gonadotropin was first discovered in 1920,767 andwas identified as a pregnancy hormone approximately 8years later.768 The first drug preparation containing chorionicgonadotropin came in the form of an animal pituitary extract,which was developed as a commercial product by Organon.Organon introduced the extract in 1931, under the trade namePregnon. A trademark dispute forced the company to changethe name Pregnyl, however, which reached market in 1932.Pregnyl is still sold by Organon to this day, although it nolonger comes in the form of a pituitary extract. Manufacturingtechniques were introduced in 1940 that allowed thehormone to be obtained by filtering and purifying the urine ofpregnant women, and by the late 1960’s were adopted by allmanufacturers formerly using animal extracts. Over the yearsthe process and manufacturing protocols have been refined,but hCG is made in essentially the same way today as it wasdecades ago. While modern preparations are of biologicalorigin, the risks of biological contaminants are said to below (although cannot be completely excluded).

Early on, the indicated uses for chorionic gonadotropinpreparations were much broader than they are presently.Product literature from the 1950’s and ’60’s recommendedthe use of these drugs for, among other things, the treatment ofuterine bleeding and amenorrhea, Froehlich’s syndrome,cryptochidism, female sterility, obesity, depression, andmale impotence. A good example of the wide uses ofchorionic gonadotropin are illustrated in the preparationGlukor, which was described in 1958 as being, “Three timesmore effective than testosterone. For tired young men in maleclimacteric. For tired old men in male senility. Beneficial inimpotence, angina and coronary heart disease,neuropsychosis, prostatitis, [and] myocarditis.“ Suchrecommendations, however, reflect an era less tightlyregulated by government agency and less reliant on provenclinical trials. Today, FDA-approved indications for hCGare limited to the treatment of hypogonadotropichypogonadism and cryptocridism in men, and anovulatoryinfertility in women.

HCG has no significant thyroid-stimulating activity. This isspecifically pointed out because hCG was once widely usedfor the treatment of obesity. The trend seemed to havebecome popular in 1954, after a paper was published by Dr.A.T.W. Simeons claiming that chorionic gonadotropin wasan effective adjunct to dieting. According to the study,patients were able to effectively stave off hunger withseverely low-calorie diets provided they took the hormoneinjections. Dubbed the Simeons diet, people all across thecountry were soon subjecting themselves to severe calorierestriction (500 calories per day) and taking hCG injections.Soon after, the hormone itself became the main focus for fatloss. In fact, by 1957 it was said that hCG was the mostcommonly prescribed medication for weight loss. Morerecent and comprehensive investigations, however, refutethat there is any anorexic or metabolic advantage to the useof hCG.769 In 1962, the Journal of the American MedicalAssociation had already been warning consumers about thehCG-inclusive Simeons diet, stating the more basic fact thatsevere calorie restriction, which causes the body to sacrificemuscle and organ tissue to obtain necessary protein, wasmore hazardous than obesity itself. By 1974, the FDA hadhad enough of the hCG fat loss claims, and mandated thefollowing statement to be included with all prescribingliterature. “HCG HAS NOT BEEN DEMONSTRATED TOBE EFFECTIVE ADJUNCTIVE THERAPY IN THETREATMENT OF OBESITY. THERE IS NOSUBSTANTIAL EVIDENCE THAT IT INCREASESWEIGHT LOSS BEYOND THAT RESULTING FROMCALORIC RESTRICTION, THAT IT CAUSES A MOREATTRACTIVE OR ’NORMAL’ DISTRIBUTION OF FAT,OR THAT IT DECREASES THE HUNGER ANDDISCOMFORT ASSOCIATED WITHCALORIERESTRICTED DIETS.” This warning persists onall product sold in the U.S. today. In spite of this warning andevidence to the contrary, some clinics still promote the use ofhCG for dieting purposes.

Human Chorionic Gonadotropin is a widely popular drugpreparation today, owing to the fact that it remains anindispensable part of ovulation therapy for many cases offemale infertility. Popular preparations in the U.S. presentlyinclude Pregnyl (Organon), Profasi (Serono), and Novarel(Ferring), although many other trade names have beenpopular for chorionic gonadotropin preparations over theyears. This drug is also sold widely outside of the UnitedStates, and can be found under many additional trade names,too numerous to list here. Owing to the fact that this drug isnot controlled on a federal level, U.S. athletes andbodybuilders unable to find a local physician willing toprescribe the drug to treat steroid-induced hypogonadismoften order the product from international pharmacy sources.Given that this drug is cheap and rarely counterfeited, mostinternational sources are trusted. Although recombinantforms of chorionic gonadotropin have been introduced tomarket in recent years, the vast supply and low cost ofbiological hCG continues to make it a staple product for bothlabeled and off-label uses.

Structural Characteristics:

Chorionic gonadotropin is an oligosaccharide glycoproteincomposed of 244 amino acids. It has an alpha subunit that is92 amino acids long and identical to that of luteinizinghormone (LH), follicle-stimulating hormone (FSH), andthyroid-stimulating hormone (TSH). It has a beta subunit thatis unique to hCG.

How Supplied:

Human Chorionic Gonadotropin is widely available invarious human and veterinary drug markets. Composition anddosage may vary by country and manufacturer, but typicallycontain 1,000, 1,500, 2,500, 5,000, or 10,000 internationalunits (IU) per dose. All forms are supplied as a lyophilizedpowder, requiring reconstitution with sterile diluent (water)before use.

Administration (General):

Human Chorionic Gonadotropin is generally given byintramuscular (IM) injection. The subcutaneous route is alsoused, and has been deemed to be roughly equivalenttherapeutically to IM injections.770 Peak concentrations ofchorionic gonadotropin occur approximately 6 hours afterintramuscular injection, and 16 to 20 hours aftersubcutaneous injection.

Administration (Men):

When used to treat hypogonadotropin hypogonadism, currentFDA-approved protocols recommend either a short 6-weekprogram, or a long-term program lasting up to 1 year,depending on the individual needs of the patient. Prescribingguidelines for short-term use recommend that 500 to 1,000units to be given 3 times a week for 3 weeks, followed by thesame dose twice a week for 3 weeks. The long-termrecommendations call for 4,000 units to be administered 3times weekly for 6 to 9 months, after which point the dosageis reduced to 2,000 units 3 times weekly for an additional 3months. Bodybuilders and athletes use hCG either on cycle,in an effort to maintain testicular integrity during steroidadministration, or after a cycle, to help restore hormonalhomeostasis more quickly. Both types of use are deemedeffective when properly applied.

Post-Cycle:

Human Chorionic gonadotropin is often used with othermedications as part of an in-depth Post Cycle Therapy (PCT)program focused on restoring endogenous testosteroneproduction more rapidly at the end of a steroid cycle.Restoring endogenous testosterone production is a specialconcern at the conclusion of each cycle, a time whensubnormal androgen levels (due to steroid inducedsuppression) could be very costly to the physique.The mainconcern is the action of cortisol, which in many ways isbalanced out by the effect of androgens. Cortisol sends theopposite message to the muscles than testosterone, or tobreakdown protein in the cell. Left unchecked by a low levelof testosterone, cortisol can quickly strip much of your newmuscle mass away. Protocols for the post-cycle use of hCGgenerally call for the administration of 2000-3000 Unitsevery 2nd or 3rd day, taken for no longer than 2 or 3 weeks.If used for too long or at too high a dose, the drug mayactually function to desensitize the Leydig’s cells toluteinizing hormone, further hindering a return tohomeostasis. For a more comprehensive view of hCG’s rolein a proper hormonal- recovery program, please refer to thePost Cycle Therapy section of this book.

On-Cycle:

Bodybuilders and athletes may also administer HumanChorionic Gonadotropin throughout a steroid cycle, in aneffort to avoid testicular atrophy and the resulting reducedability to respond to LH stimulus. In effect, this practice isused to avoid the problem of testicular atrophy, instead oftrying to correct it later on when the cycle is over. It isimportant to remember that the dosage needs to be carefullymonitored with this type of use, as high levels of hCG maycause increased testicular aromatase expression (raisingestrogen levels),771 and also desensitize the testes to LH.772As such, the drug may actually induce primary hypogonadismwhen misused, greatly prolonging, not improving, therecovery window. Current protocols for the use of hCG inthis manner involve administering 250 IU subcutaneouslyevery 3rd or 4th day throughout the length of the steroidcycle. Higher doses may be necessary for some individuals,but st no point should exceed 500 IU per injection.

These on-cycle HCG protocols were developed by Dr. JohnCrisler, a well-known figure in the anti-aging and hormonereplacementfield, for use with his testosterone replacementtherapy (TRT) patients. Although TRT is often administeredon a long-term basis, testicular atrophy is a commoncosmetic complaint of patients irrespective of themaintenance of normal androgen levels. Dr. Crisler’s hCGprogram is designed to alleviate this concern in a manner thatis acceptable for longer-term use. For those interested inprecisely timing their hCG shots in relation to a prescribedtestosterone replacement program, Dr. Crisler recommendsthe following in his paper,“An Update to the Crisler hCGProtocol,” “…my test cyp TRT patients now take their hCGat 250IU two days before, as well as the day immediatelyprevious to, their IM shot. All administer their hCGsubcutaneously,and dosage may be adjusted as necessary (Ihave yet to see more than 350IU per dose required)… ThoseTRT patients who prefer a transdermal testosterone, or eventestosterone pellets (although I am not in favor of same), taketheir hCG every third day.

Administration (Women):

When used to induce ovulation and pregnancy in anovulatoryinfertile woman, a dose of 5,000 to 10,000 units isadministered one day following the last dose ofmenotropins.The timing is specific so that the hormone isgiven precisely at the right moment in the ovulation cycle.Human Chorionic Gonadotropin is not used by women forphysique- or performance-enhancing purposes.