Human Chorionic Gonadotropin (HCG) Replacements For Men On Testosterone Therapy

Human chorionic gonadotropin, or HCG, will now be deemed a biologic product per the FDA. This means that pharmacies will no longer be able to compound HCG. Due to this industry-wide change, clinics previously using HCG in conjunction with testosterone therapy for men will be forced to use alternative treatments. HCG was used to preserve fertility and testicular size and function in men using exogenous testosterone. Some approved and clinically proven alternatives are Gonadorelin and Enclomiphene Citrate. Learn more.

What is Gonadorelin?

Gonadorelin is used primarily for men who don’t want to experience testicular shrinkage while they’re on TRT and secondarily for men who want to maintain their fertility and ability to produce their own testosterone while they’re on TRT. For men concerned about the size of their testicles, fertility and sperm count, and the amount of their ejaculate, we recommend gonadorelin not just to prevent or delay testicular shrinkage, but to specifically maintain their fertility.

Gonadorelin is bioidentical to gonadotropin releasing hormone (GnRH). In a normal and healthy young male, GnRH is released from the hypothalamus in a pulsatile manner about every two hours which then stimulates the anterior pituitary to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). The testicles respond to these pulses by producing testosterone, sperm, and other ancillary hormones. 

The comparison between Human Chorionic Gonadotropin (HCG) and Gonadorelin is highly debated. HCG works very well for most men, and gonadorelin is thought to have the same benefits when the dosage and frequency is properly administered. Human Chorionic Gonadotropin (HCG) was usually administered two to three times weekly to maintain testicular function and avoid atrophy. This frequency is unfortunately not effective with gonadorelin. Gonadorelin requires a daily (preferably nightly) subcutaneous injection.

Effect of Testosterone

Gonadorelin injections are prescribed once nightly before bed to ensure a significant amount of LH and FSH is released. The dose amount and dose frequency prescribed varies considerably from one male patient to the next. Patients must be aware that hormone therapy of any kind is a very individualized treatment. Dosage will depend on the responsiveness of their pituitary gland, the responsiveness of their testicles to their own luteinizing hormone (LH) and follicle stimulating hormone (FSH), how much the patient naturally aromatizes testosterone to estradiol, how much body fat the patient has and other lifestyle factors such as diet, exercise and sleep. 

Most younger patients who are new to testosterone therapy and who are otherwise healthy will notice that gonadorelin will maintain testicular size and function. Patients who have been on TRT with Human Chorionic Gonadotropin (HCG) and were happy with the benefits they experienced from HCG will notice a slight decrease in testicular size which will subside over the first thirty to sixty days of treatment with gonadorelin. Patients who have been on TRT without HCG will notice that it may take one or two months or longer for gonadorelin to start to obviously work. It is important to note that Human Chorionic Gonadotropin (HCG) does not work for all men, and neither does gonadorelin. Discuss the difference with our experts.

 

If you are currently using HCG as part of your Hormone Replacement Therapy, learn more about FDA-approved biological options  such as Enclomiphene Citrate or Gonadorelin.

 

What is Enclomiphene Citrate?

According to multiple published studies, enclomiphene citrate consistently increased serum total testosterone into the normal range and increased LH and FSH above the normal range. The effects on LH and total testosterone persisted for at least 1 week after stopping treatment. The usage of enclomiphene has not been found to be an adequate replacement or alternative for testosterone therapy (TRT) at this time however, is being used in conjunction with testosterone therapy to preserve testicular function in men. 

Enclomiphene is a non-steroidal estrogen receptor antagonist that has been in development for secondary hypogonadism in overweight men wishing to restore normal testicular function. Enclomiphene is the purified isomer of Clomid (Clomiphene Citrate), which has been FDA approved since 1967 for fertility in women and has been commonly used off-label in men to boost fertility and preserve fertility and testicular function in men taking exogenous testosterone. Enclomiphene stimulates the testes and increases their size to produce luteinizing hormone (LH) and follicle stimulating hormone (FSH), which is how the body naturally and endogenously produces testosterone and sperm. Initial studies demonstrated that enclomiphene maintains the androgenic benefit of clomiphene citrate without the undesirable effects attributable to zuclomiphene, which is active in the traditional clomiphene citrate. 

Men can experience adverse effects from higher-than-expected stimulation of the testicles to make testosterone and estradiol. Some men will experience a dull aching sensation from potential over stimulation of the testes. If a patient is experiencing over stimulation of their testes, a dose reduction may be needed. Adding luteinizing hormone (LH) and follicle stimulating hormone (FSH) lab tests to their blood test panels can ensure that gonadorelin or enclomiphene are effective in stimulating the pituitary gland and testes.

Request a consultation today to live life to the fullest!

Do you want to stop suffering with health issues, regain your quality of life, and live a younger vibrant life? Let us help.  Request a consultation today.

 

Disclaimer

All information is intended for your general knowledge only and is not a substitute for medical advice or treatment for specific medical conditions. The information contained is presented in summary form only and intended to provide broad understanding and knowledge. The information should not be considered complete and should not be used in place of a visit, call, consultation or advice of your physician or other healthcare provider. Only a qualified physician can determine if you qualify for and should undertake treatment. 

  1. Hill S, Arutchelvam AV, Quinton R. Enclomiphene, an estrogen receptor antagonist for the treatment of testosterone deficiency in men. IDrugs. 2009;12:109–119. 
  2. Whitten SJ, Nangia AK, Kolettis PN. Select patients with hypogonadal hypogonadism may respond to treatment with clomiphene citrate. Fertil Steril. 2006;86:1664–1668. 
  3. Kaminetsky J, Hemani ML. Clomiphene citrate and enclomiphene for treatment of hypogonadal androgen deficiency. Expert Opin Investig Drugs. 2009;18:1–9. 
  4. Gynecol Endocrinol. 1993 Jun;7(2):115-22. doi: 10.3109/09513599309152490.University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Camden.
  5. Youssef MA, Abdelmoty HI, Ahmed MA, Elmohamady M.J Adv Res. 2015 May;6(3):341-9. doi: 10.1016/j.jare.2015.01.005. Epub 2015 Jan 21.
  6. Soares AH, Horie NC, Chiang LAP, et al. Effects of clomiphene citrate on male obesity-associated hypogonadism: a randomized, double-blind, placebo-controlled study. Int J Obes (Lond). 2018;42(5):953-63.
  7. Katz DJ, Nabulsi O, Tal R, Mulhall JP. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU Int. 2012;110(4):573-8.
  8. McCullough A. Alternatives to testosterone replacement: testosterone restoration. Asian J Androl. 2015;17(2):201-5.
  9. Krzastek SC, Sharma D, Abdullah N, et al. Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism. J Urol. 2019;202(5):1029-35.
  10. Huang ES, Miller WL. Estrogenic and antiestrogenic effects of enclomiphene and zuclomiphene on gonadotropin secretion by ovine pituitary cells in culture. Endocrinology. 1983;112(2):442-8.
  11. Choi SH, Shapiro H, Robinson GE, et al. Psychological side-effects of clomiphene citrate and human menopausal gonadotrophin. J Psychosom Obstet Gynaecol. 2005;26(2):93-100.
  12. Earl JA, Kim ED. Enclomiphene citrate: A treatment that maintains fertility in men with secondary hypogonadism. Expert Rev Endocrinol Metab. 2019;14(3):157-65.
  13. Kim ED, McCullough A, Kaminetsky J. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement. BJU Int. 2016;117(4):677-85.