Is the new Gonadorelin better than the true and trusted HCG?
HCG is the most well-known compound for directly stimulating testicular function and is used by itself as well as in conjunction with TRT (testosterone replacement therapy).
Since 2020, HCG has become very expensive and more TRT clinics and healthcare professionals don’t prescribe it anymore. Hence the resurgence of alternatives, such as Gonadorelin.
Both Gonadorelin and HCG can increase testosterone but via slightly different mechanisms. And both are useful in conjunction with a TRT program.
What is Gonadorelin?
Gonadorelin is a peptide and it’s bio-idnentical to GnRH, which is nturally released from the hypothalamus gland.
The whole steroidogenic axis starts in the hypothalamus.
Evidence accumulated in the last 15 years suggests that kisspeptin, released in the hypothalamic arcuate nucleus, triggers pulsatile GnRH (gonadotropin-releasing hormone) in mammals.
GnRH is also created in the hypothalamus, which then stimulates the anterior pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
LH and FSH then stimulate the Leydig and Sertoli cells of the testicles, respectively. This leads to an increase in sex hormones (e.g. testosterone) and sperm production.
Gonadorelin is bio-identical to gonadotropin-releasing hormone (GnRH; it’s a GnRH analog). When you inject it, it stimulates LH and FSH in the same manner.
Normally, GnRH is released in a pulsatile manner every 2 hours.
Gonadorelin only stimulates the pituitary and cannot directly stimulate the testicles to produce testosterone.
The use of gonadorelin
Gonadorelin injections are mainly used to:
- Increase your own testosterone (endogenous synthesis)
- Maintain fertility (increase sperm count) on testosterone therapy
- Prevent testicular shrinkage (size of their testicles), due to age, stress, malnutrition or when on TRT
- Restore testicular size (the testicles shrink with age as well as on hormone replacement therapy use)
- Enhance semen volume
- Increase upstream pro-hormones, such as pregnenolone and progesterone which are suppressed by TRT.
- Improve cognitive function
It can definitely make a significant difference in how you feel.
How effective is gonadorelin at increasing testosterone
100mcg of Gonadorelin was given to men and it increased their LH for over 2 hours.
As per the graph above, people who were the least responsive got about a 2-3 fold boost (8 to 30) in LH, whereas the most responsive got an almost 5-fold increase (from 20 to 100) (R).
This can help to increase testosterone.
Since GnRH is released every 2 hours, a once-daily injection won’t be as good.
The Innopump® has been created to release a certain amount of GnRH in a pulsatile manner (GnRH pulse therapy) to create a more natural rhythm. The pump releases 10ug GnRH per 90 minutes (R). According to this clinical trial, using Innopump® increased testosterone levels by around 250ng/dl after 180 days, driving it into the normal range.
Since the once-off Gonadorelin dose is 100mcg, it makes up for infrequent (once daily) dosing, compared to the smaller (10mcg), more frequent dosing of the GnRH pump.
Gonadorelin dosing
For subcutaneous injection or intramuscular injection, 100mcg is a good starting dose. Work up as needed or as advised by your doctor. Keep an eye on your estrogen levels and your testosterone-to-estradiol ratio as you increase your Gonadorelin dose.
Gonadorelin prevents testicular atrophy
Gonadorelin can help to restore normal testicular size. In this study, they gave infants with undescended testes intranasal Gonadorelin, which significantly increased their testicular volume.
In male patients, Gonadorelin is just as effective as HCG at increasing testicular volume (R).
Gonadorelin safety
Gonadorelin has been administered into a vein in doses of up to 3 mg twice daily for 28 days without any signs or symptoms of overdosage (R).
Gonadorelin is one of the safest GnRH agonists out there. Other GnRH agonists have a much longer half-life, which then over a few weeks completely shuts down testosterone production (due to desensitization). Those kinds of GnRH agonists (e.g. Leuprolide acetate) are used for androgen deprivation therapy.
Adverse effects of Gonadorelin
Rare side effects of gonadorelin can include:
- Headache
- Nausea
- Injection site pain or irritation
- Hot flashes
- Acne
- Mood changes
- Insomnia
- Increased sweating
- Painful or prolonged erection
It’s important to note that not all individuals will experience these side effects, and the severity and duration of side effects can vary.
Another “downside” of Gonadorelin is that it has to be used daily. Most TRT clinics recommend taking it at night to mimic the increase in testosterone that happens as we sleep.
The main reason why Gonadorelin’s side effects are rare is because the half-life is only 4 minutes. Something with a longer half-life, is more likely to cause side effects.
What is HCG
Human chorionic gonadotrophin (HCG) is a hormone that is produced during pregnancy. Men produce no HCG unless they have cancer or a tumor. Tumors promote HCG production (R). Thus, a man could appear to be “pregnant” due to high HCG.
HCG acts like LH, which directly stimulates the testicles to produce testosterone. Thus taking HCG will suppress LH levels.
HCG can reduce testicular LH and reduce testicular sensitivity to LH (R). This means that after you stop HCG, your LH might be normal, but your testosterone is low.
The half-life of HCG is 36 hours, whereas that of LH is only 30 minutes (R).
The “upside” to HCG is that it’s more thoroughly studied than Gonadorelin.
The use of HCG
HCG is mainly used to:
- Prevent testicular shrinkage and restore testicular size
- Increase testosterone in hypogonadal men
- Promote fertility
- Improve libido
- Increase energy
- Help with erectile dysfunction
- Help against insomnia
HCG dosing
Everyone’s response (sensitivity) to HCG will be different which will require frequent testing to find the ideal dose for you.
A good starting dose that good TRT clinics recommend is 250IU every other day. This is usually enough to prevent testicular shrinkage, maintain fertility and prevent complete suppression of pregnenolone production while minimizing side effects.
Can HCG by itself help to increase testosterone?
Yes, HCG, by stimulating the LH receptor in the Leydig cells of the testes, promotes testosterone production. However, it’s not strong enough to get high testosterone.
According to this study, they gave hypogonadotropic hypogonadism men 1500-2000IU of HCG x3 weekly and it increased their testosterone to only 558ng/dl on average (R).
And at that dose, you risk getting very high estrogen since HCG stimulates aromatase.
Side effects of HCG
HCG can:
- Dramatically increases estradiol and unfavorably increases the testosterone-to-estradiol ratio
- Promote tumor growth
- Cause testicular insensitivity to LH
- Cause mood changes
- Cause fatigue
- Cause restlessness
- Cause headache
- Cause swelling at the injection site
- Cause mild pain or redness at the injection site
- Cause nausea
- Contribute to acne
- Worsening of prostate cancer
Difference between Gonadorelin vs HCG
Gonadorelin stimulates the pituitary to release LH and FSH. It’s great for a PCT (post-cycle therapy) to restore LH levels.
HCG acts like LH to stimulate the testes but it suppresses LH in the process and can even cause testicular insensitivity.
HCG alternatives
Since there is an ongoing national shortage that makes it nearly impossible for patients to fill prescriptions for HCG, practitioners are looking for other alternatives. Quick side note, you can still get HCG from a compounding pharmacy (but you still need to go through a healthcare provider).
Common HCG alternatives include:
- Kisspeptin
- Kisspeptin stimulates the release of GnRH in the hypothalamus.
- Gonadorelin
- Gonadorelin mimic GnRH to stimulate the pituitary to release LH and FSH.
- Clomiphene aka Clomid
- Clomiphene inhibits the estrogen receptor alpha (ERα) in the hypothalamus and pituitary, thus increasing GnRH and LH release. However, it has certain side effects such as changes in mood, blurred vision and breast/nipple tenderness. A possible reason is due to the higher estradiol-to-testosterone ratio. The usual dose is 25mg daily.
- Enclomiphene citrate
- Enclomiphene is more effective than just clomiphene but hasn’t been extensively studied yet.
- Nolvadex aka Tamoxifen
- It’s a selective estrogen receptor modulator (SERM). It blocks the ERα in the pituitary, similar to Clomid, which increases LH. Side effects include hot flushes, blurred vision and risk of stroke.
FAQ
Does gonadorelin work as good as HCG?
Yes, it increases testosterone to the same extent as HCG. The only downside is that you have to take it more frequently.
What does gonadorelin do for a man?
Gonadorelin increases testosterone, which helps eliminate low testosterone symptoms, such as low energy, poor mood, poor erections, low muscle mass, excess fat mass, etc.
How much does gonadorelin increase testosterone?
Gonadorelin is able to increase testosterone 6 fold with no difference between 5 and 40mcg (R). You can expect Gonadorelin to increase your testosterone to between 500 and 600ng/dl on average.
How does gonadorelin make you feel?
Does gonadorelin increase sperm?
Yes, Gonadorelin increases FSH, which stimulates the Sertoli cells to produce sperm.
How often should men take HCG?
Men should take HCG every 2-3 days because it has a longer half life.
Can Gonadorelin cause erectile dysfunction?
Yes, but only if it increases your estrogen-to-testosterone ratio too much. Estrogen is an independent risk factor for ED, so you want to make sure your estradiol doesn’t go over 30pg/ml.
Summary
None of what I talked about is medical advice. It’s merely a discussion on what the research shows.
Gonadorelin is just as effective as HCG at increasing testosterone, preventing testicular shrinkage and maintaining fertility, but with fewer side effects.
The only downside to Gonadorelin is that you have to inject daily, whereas HCG only had to take it every other or every third day.
If you want to increase your testosterone naturally, please check out the following article and video.
> How to maximize your testosterone naturally
10 most important fundamentals for high testosterone
>1000ng/dl Testosterone: My Step-by-Step Guide on How I Do It Naturally!
