Human Chorionic Gonadotropin
Excerpt from the book
“Testosterone: A Man’s Guide” by Nelson Vergel (available on Amazon.com or in
different formats on TestosteroneWisdom.com). NelsonVergel@gmail.com
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.
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. However,
the latter is an off-label use.
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 (depending on the
compounding pharmacy, these amounts may vary). 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. Also, it is sometimes 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.
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.
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.
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Shippen’s Chorionic Gonadotrophin
Stimulation Test (for males under 75 years of age)
Even though there seems not
be an accepted and clinically proven protocol to dose HCG, Dr. Eugene Shippen
(author of the book “The Testosterone Syndrome”), has developed his own after
his own experiences. Most doctors do not follow this protocol but I am showing
it here since I get a lot of questions about it. I have never used this protocol myself since
I have been on testosterone replacement for over 15 years.
Dr. Shippen
has found that a typical
treatment course for
three weeks is best
for determining those
individuals who will
respond well to HCG
treatment. It is
administered daily by
injection 500 units
subcutaneously, Monday through Friday for three weeks. The patient
is taught to
self administer with
50 Unit insulin
syringes with 30 gauge
needles in anterior
thigh, seated with
both hands free to perform the
injection. Testosterone, total and free, plus E2 (estradiol) are measured
before starting the protocol and on the third Saturday after 3 weeks of
stimulation (he claims that salivary testing may be more accurate for adjusting
doses). Studies have shown that subcutaneous injections are equal in efficacy
to intramuscular administration.
By measuring the effect on
his HCG protocol on total testosterone, he identifies candidates that require
testosterone replacement versus those who just require having their testicles
“awaken” with HCG to produce normal testosterone. I am yet to see any data that
substantiates his approach, however.
Here is how he determines Leydig
(testicular) cell function:
1. If the HCG protocol causes less than a 20%
rise in total testosterone he suggests poor testicular reserve of Leydig cell
function (primary hypogonadism or
eugonadotrophic hypogonadism indicating combined central and peripheral
factors).
2. 20-50% increase in total testosterone
indicates adequate reserve but slightly depressed response, mostly central
inhibition but possibly decreased testicular response as well.
3. More than 50% increase in total testosterone
suggests primarily centrally mediated depression of testicular function.
He then offers these options
for treatment for patients depending on the response to HCG and patient
determined choices.
1. If there is an inadequate response ( 20%), then replacement with testosterone will be indicated.
2. The area in between 20-50% will usually
require HCG boosting for a period of time, plus natural boosting or “partial”
replacement options.
I am
yet to see
what he means
with natural boosting!
Dr. Shippen
believes that full
replacement with testosterone
is always the last
option in borderline
cases since improvement over time may frequently occur as
the testicles’ Leydig cell regeneration may actually happen. He claims that
much of this is age dependent. Up to age 60, boosting is almost always
successful. In the age range 60-75 is variable, but will usually be clear by
the results of the stimulation test. Also, disease related depression of
testosterone output might be reversible with adequate treatment of the
underlying process (depression, obesity,
alcohol, deficiency, etc.) He
claims that this positive effect will not occur if suppressive therapy is instituted
in the form of full testosterone replacement.
3. If there is an adequate response of more
than 50% rise in testosterone, there is very good Leydig cell reserve. HCG
therapy will probably be successful in restoring full testosterone output without
replacement, a better option over the long term and a more natural restoration
of biologic fluctuations for optimal response. But I am yet to see any data on
long term use of HCG used in this approach! (I invite researchers to do such
studies)
4. Chorionic HCG can be self-administered and
adjusted according to response. In younger, high output responders (T >
1100ng/dl), HCG can be given every third or fourth day. This also minimizes
estrogen conversion. In lower
level responders (600-800ng/dl), or
those with a higher estradiol output associated with full dose HCG, 300-
500 units can be given Mon-Wed-Fri. At times, sluggish responders may require a
higher dose to achieve full
testosterone response.
Dr. Shippen believes in
checking salivary levels of free testosterone on the day of the next injection,
but before the next injection to determine effecacy and
to adjust the
dose accordingly. He claims
that later as Leydig cell
restoration occurs, a
reduction in dose or
frequency of administration may
be later needed.
5. He recommends to monitor both testosterone
and estradiol levels to assess response to treatment after 2 - 3 weeks after
change in dose of HCG as well as periodic intervals during chronic administration.
He claims that salivary testing will better reflect the true free levels
of both
estrogens and testosterone.
(Pharmasan.com and others) Most insurance companies do not pay
for salivary testing. Blood testing is
the standard way to test for testosterone and estradiol.
6. Except for reports of antibodies developing
against HCG (he mentions that he has never seen this problem), the claims that
there are no adverse effects of chronic HCG administration.
Dr. Shippen’s book was
published in the late 90’s. I know of
no physician that uses his protocol. I
have no opinion on its validity. The
idea that testicular function can be improved with cycles of HCG in men with
low testosterone caused by sluggish yet functioning Leydig cells is an
interesting concept that needs to be studied. I guess that since this protocol
requires very close monitoring, many doctors have avoided using it. The off
label nature of the protocol’s use of HCG can also make it expensive for
patients who will have to pay cash for its use and monitoring.
A very well known doctor in the
field of testosterone replacement, Dr. John Crisler (www.allthingsmale.com),
recommends 250 IU of HCG twice per week
for all TRT patients, taken the day of, along with the day before, the weekly
testosterone cypionate injection. After looking at countless
lab printouts, listening to subjective reports from patients, and learning more
about HCG, he reports to be shifting that regimen forward one day. In other words,
his patients who inject testosterone cypionate now take their HCG at 250 IU two
days before, as well as the day immediately previous to, their weekly
intramuscular shot. All administer their HCG subcutaneously, and dosage may be
adjusted as necessary (he reports that rarely more than 350 IU twice weekly
dose is required).
For men using testosterone
gels, the same dose every third day has anecdotally helps to preserve
testicular size (the dose of the gel has to be adjusted after a month of HCG to
compensate for the increased testosterone caused by HCG).
Some doctors believe that
stopping TRT for a few weeks in which only 1000- 2000 IU HCG weekly is used
provides a good way to stimulate testicular function without having to use HCG
continuously. I have not seen any data to support this approach. Others believe
that cycling HCG on and off while maintaining TRT may prevent any desentization
of testicular Leydig cells to HCG.
Again, no data or reports have been published on this approach.
Some men have asked me why we
cannot use HCG solely to make our own testicles produce testosterone without
the use of TRT along with it. According to Dr. Crisler,
using HCG as sole testosterone replacement option does not bring the same
subjective benefit on sexual function as pure testosterone delivery systems
do—even when similar serum androgen levels are produced from comparable
baseline values. However, supplementing the more “traditional” transdermal, or injected
options, testosterone with the correct doses of HCG stabilizes blood levels,
prevents testicular atrophy, helps rebalance expression of other hormones, and
brings reports of greatly increased sense of well-being and libido. But in excess, HCG can cause acne, water
retention, moodiness, and gynecomastia (breast enlargement in men).
Many men have complained
that their doctors do not know about HCG and how to use it (I do not blame
doctors for being confused!). Some spend a lot of time trying to find doctors
to feel comfortable prescribing it. One good way to find out what doctor in
your area may be currently prescribing it is to call your local compounding
pharmacies to ask them what doctors call them for their patients’
prescriptions.
If you decide (with the
agreement of your doctor) that you want to use HCG with your TRT regimen at 500
IU per week, then you will need 2000 IU per month. I personally do not like to
have diluted HCG sitting in my fridge for over six weeks (HCG may degrade with
time after mixed in with bacteriostatic water even when refrigerated). So, a
3000 or 35000 IU vial should suffice for 6 weeks.
Your doctor can call in the
following prescription to a compounding pharmacy (shop around for best prices.
I use APSmeds.com):
Human Chorionic
Gonadotropin, 3500 IU (or any other IU amount) vial, #1, 3 refills, as directed
Every 5 weeks, remember to
call the compounding pharmacy to get the next shipment of HCG so that you do
not run out.
After reading this section,
you probably agree with me that using HCG requires a lot of discipline since
you have to remember to inject it weekly in addition to your weekly or
bi-weekly testosterone injection. But I know of many men who have that type of
commitment since they do not want testicular size reduction. And many of us may
just be fine with our reduced testicular size as long as testosterone is
actually doing its job in improving our sex drive. And some lucky men do not
get testicular atrophy at all on testosterone (those with large testicles to
start with usually do not seem to complain about shrinkage as much as men
starting with smaller testicular size before TRT). So it is a personal decision
at the end!
As you will read in the
section “HPGA dysfunction” HCG is also used in a protocol in combination with
clomiphene and tamoxifen to attempt to bring the body’s own testosterone
production back to normal when someone needs to stop testosterone or anabolic
steroids after long-term use. This protocol only works for those who started
testosterone or anabolic steroids at normal baseline testosterone levels
(bodybuilders and athletes) and it is not intended to work in those of us who
had testosterone deficiency (hypogonadism) to start with.
As you can tell, there is no
agreement on the correct dose and frequency of HCG. I really hope that researchers in the
endocrine field compare different protocols in a controlled manner so that we
can settle this issue once and for all. I encourage pharmaceutical companies to
seek approval for using HCG for prevention of testicular atrophy in men using
TRT. This new indication can prove to be lucrative as the TRT market grows over
2 billion dollars a year in the United States as more men become aware of
hypogonadism treatment options.
PERSONAL COMMENT: I have used
HCG to reverse testicular shrinkage and it works extremely well not only for
that purpose but also for boosting sexy drive. I do have to remind myself that
as soon as I stop using it, testicular atrophy will recur. I have recently started using it in small
doses (250 IU twice a week subcutaneously) which seems to be a good maintenance
regimen for me. I get my HCG from
compounding pharmacies at $70 per 10,000 IUs since the pharmaceutical
commercial products are too expensive and rarely paid by insurance for
testicular atrophy. I remind men that HCG can increase your estradiol and DHT
blood levels, so it is important to have your doctor retest you for both of
these values after you start. Lowering testosterone dosage may be required when
using HCG along side with TRT since HCG can have an additive effect on
testosterone blood levels. But we need so much more data on HCG to stop making
assumptions and using protocols that are endorsed by anecdotal information.
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