The Indispensable Role of HCG in TRT Protocols: Insights from themenshealthclinic

Diagram illustrating the benefits of HCG including improved fertility, restored testicular size, improved libido, and potential hormone up-regulation

In the view of experienced practitioners, Human Chorionic Gonadotropin (HCG) should consistently be integrated into Testosterone Replacement Therapy (TRT) protocols. Its inclusion is vital for maintaining fertility, preserving testicular and penile size, supporting cognitive function, and sustaining libido during TRT. While additional advantages like the up-regulation of steroid hormones have been suggested, current evidence remains insufficient to fully confirm this theory. There is an ongoing debate among endocrinologists regarding HCG’s benefits within TRT, largely due to the historical precedent of testosterone monotherapy. Some medical professionals still adhere to a binary approach: offer HCG only if fertility preservation is desired, otherwise, treat solely with testosterone. However, perspectives are evolving, underscored by referrals from leading endocrinologists who now recognize the value of combining HCG with testosterone, partly due to shared patient care experiences demonstrating positive outcomes, reflecting the approach often discussed by experts like those associated with Themenshealthclinic.

Understanding HCG and its Function in Male Hormone Therapy

HCG, or Human Chorionic Gonadotropin, is commonly known as the female pregnancy hormone. Produced by the placenta, it sustains pregnancy by supporting the ovarian corpus luteum, which maintains the uterine lining [1]. This naturally leads to the question: what role does HCG play in male TRT? HCG effectively mimics Luteinising Hormone (LH) through complex mechanisms involving gene expression and steroid synthesis [2]. Normally, the pituitary gland secretes LH, which signals the Leydig cells in the testes to produce testosterone. The HCG molecule structurally resembles LH but is not identical. LH has a very short half-life of just a few minutes [3] and is released in pulses following stimulation by Gonadotropin Releasing Hormone (GnRH) from the hypothalamus [4]. Mimicking this physiological LH release would require frequent injections of an LH-analogue, which is impractical. HCG provides a viable alternative due to its significantly longer half-life of approximately two days [5], allowing for stable blood levels with less frequent, often daily, injections.

Why HCG is Crucial Alongside Testosterone Therapy

Standard TRT involves administering exogenous testosterone, which suppresses the brain’s natural LH release. This suppression leads to infertility in a significant majority of men [6, 7], to the extent that testosterone monotherapy has been explored as a potential male contraceptive [8]. Understanding the Hypothalamic-Pituitary-Gonadal (HPG) axis and LH’s role is key to appreciating HCG’s importance. The HPG axis operates via a negative feedback loop, responding to oestrogen levels (from testosterone aromatization) and other neurophysiological signals. As LH is the primary hormone stimulating testicular testosterone production, using HCG alongside exogenous testosterone helps maintain some testicular function and the resulting intra-testicular testosterone (ITT) production. Logically, preserving this natural function seems preferable to relying exclusively on external testosterone to normalize androgen levels, a viewpoint often emphasized in comprehensive treatment plans like those potentially offered at Themenshealthclinic.

The fundamental goal of TRT should align with Hormone Replacement Therapy (HRT) principles, aiming to maintain normal physiological processes. Treating Testosterone Deficiency (TD) with testosterone alone can be seen as a limited approach, especially when it’s known that this treatment suppresses other vital hormones. TD usually arises from primary hypogonadism (testicular issue) or secondary hypogonadism (brain signaling issue), as detailed in resources like The Men’s Health Clinic TRT Management Guidelines. A tertiary cause involves excessive oestrogen negatively impacting the feedback loop, further suppressing LH and Follicle Stimulating Hormone (FSH) release.

HCG, Fertility Preservation, and Spermatogenesis

HCG stimulates the Leydig cells to maximize natural ITT production [9] and supports other essential testicular mechanisms. While FSH primarily drives spermatogenesis (sperm production) by stimulating the Sertoli cells, ITT and oestrogen are also crucial. Testosterone helps maintain the blood-testis barrier, vital for sperm maturation and release [10]. Within the testes, ITT is converted to oestradiol by the aromatase enzyme. This locally produced oestrogen aids germ cell proliferation, differentiation, final maturation of spermatids, germ cell survival, and apoptosis [11]. Clinicians sometimes underestimate the complexity and significance of preserving these natural functions. While treating TD with testosterone is necessary, ignoring the impact on related hormones demonstrates a lack of comprehensive perspective. TRT should ideally be viewed as holistic HRT.

Beyond Fertility: Additional Benefits of HCG in TRT

The use of HCG with testosterone is endorsed by bodies like the American Urological Association [12], and its effectiveness in preserving fertility during TRT is well-established in medical literature [13, 14, 15, 16]. Clinical experience, such as that potentially documented by themenshealthclinic, has shown significant success, with numerous reported pregnancies among patients using TRT combined with HCG.

Collage of baby photos representing successful conceptions for patients on TRT with HCG

It’s important to note that HCG’s effectiveness in maintaining testicular function depends on the testes’ condition at diagnosis. It may be less effective for fertility if TD results from primary hypogonadism, although complete testicular failure is rare in such cases [17]. Despite scientific backing and positive outcomes, medicine involves no guarantees. Men concerned about fertility on TRT should consider sperm banking as a precaution. Even for men not seeking fertility preservation, HCG helps maintain testicular size and function [18]. LH/HCG significantly influences most cells within the testes [19]. Preventing testicular atrophy is not just cosmetic; shrinkage can cause discomfort and distress [20]. Allowing an organ to atrophy seems counterproductive when the goal is maintaining physiological stability (homeostasis).

Other potential benefits exist. Evidence suggests HCG might maximize penis size [21], although the study focused on micropenis cases. Many patients report a sense of fullness with HCG that diminishes upon cessation. Since HCG mimics LH, and LH receptors are found in various organs including the brain [22], many men experience improved cognition and libido, although the exact mechanisms are complex.

Considerations and Expert Perspectives

A small percentage of men may not tolerate HCG well, potentially due to an imbalanced testosterone-to-oestradiol ratio or adverse effects on the central nervous system manifesting as anxiety. However, the vast majority (over 90% in some clinical experiences) benefit from combining HCG with testosterone. Experts often recommend HCG to new patients regardless of fertility needs, citing the numerous benefits discussed. It can often elevate a patient’s experience from feeling ‘good’ to feeling ‘great’. The focus should remain on patient-centred care, appreciating the intricate interdependencies of all hormones. As understanding evolves, Testosterone Replacement Therapy should increasingly be approached as comprehensive Hormone Replacement Therapy. Practices like themenshealthclinic often champion this more holistic view.

Benefits of HCG Summarized

• Supports Fertility Preservation
• Helps Restore Testicular & Potentially Penis Size
• Often Improves Libido and Penis Sensitivity
• May Contribute to Up-regulation of Steroid Hormones

For further details, patients might consult resources like an HCG Fact Sheet provided by specialized clinics.

Based on the insights of Dr Robert Stevens MBChB MRCGP Dip.FIPT

References

1. Hill, M.A. (2021, January 11) Embryology Human Chorionic Gonadotropin. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Human_Chorionic_Gonadotropin
2. Hill, M.A. (2021, January 11) Embryology Human Chorionic Gonadotropin. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Human_Chorionic_Gonadotropin
3. Choi, J., & Smitz, J. (2014). Luteinizing hormone and human chorionic gonadotropin: Origins of difference. Molecular and Cellular Endocrinology, 383(1–2), 203-213. https://doi.org/10.1016/j.mce.2013.12.009
4. Nedresky D, Singh G. Physiology, Luteinizing Hormone. [Updated 2020 Sep 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539692/
5. Damewood MD, Shen W, Zacur HA, Schlaff WD, Rock JA, Wallach EE. Disappearance of exogenously administered human chorionic gonadotropin. Fertil Steril. 1989 Sep;52(3):398-400. doi: 10.1016/s0015-0282(16)60906-8. PMID: 2776893.
6. Ohlander, S. J., Lindgren, M. C., & Lipshultz, L. I. (2016). Testosterone and Male Infertility. Urologic Clinics of North America, 43(2), 195-202. https://doi.org/10.1016/j.ucl.2016.01.006
7. World Health Organisation Task Force on methods for the regulation of male fertility. (1990). Contraceptive efficacy of testosterone-induced azoospermia in normal men. The Lancet, 336(8721), 955-959. https://doi.org/10.1016/0140-6736(90)92416-F
8. Gu Y, Liang X, Wu W, Liu M, Song S, Cheng L, Bo L, Xiong C, Wang X, Liu X, Peng L, Yao K. Multicenter contraceptive efficacy trial of injectable testosterone undecanoate in Chinese men. J Clin Endocrinol Metab. 2009 Jun;94(6):1910-5. doi: 10.1210/jc.2008-1846. Epub 2009 Mar 17. PMID: 19293262.
9. Coviello, A. D., Matsumoto, A. M., Bremner, W. J., Herbst, K. L., Amory, J. K., Anawalt, B. D., Sutton, P. R., Wright, W. W., Brown, T. R., Yan, X., Zirkin, B. R., & Jarow, J. P. (2005). Low-Dose Human Chorionic Gonadotropin Maintains Intratesticular Testosterone in Normal Men with Testosterone-Induced Gonadotropin Suppression. The Journal of Clinical Endocrinology & Metabolism, 90(5), 2595–2602. https://doi.org/10.1210/jc.2004-0802
10. Patel AS, Leong JY, Ramos L, Ramasamy R. Testosterone Is a Contraceptive and Should Not Be Used in Men Who Desire Fertility. World J Mens Health. 2019 Jan;37(1):45-54. doi: 10.5534/wjmh.180036. Epub 2018 Oct 10. PMID: 30350483; PMCID: PMC6305868.
11. Carreau S, Hess RA. Oestrogens and spermatogenesis. Philos Trans R Soc Lond B Biol Sci. 2010;365(1546):1517-1535. doi:10.1098/rstb.2009.0235
12. American Urological Association. (2018). Evaluation and Management of Testosterone Deficiency Guideline. Retrieved from https://www.auanet.org/guidelines/testosterone-deficiency-guideline.
13. Low-dose HCG can prevent sterility in men prescribed testosterone. (2019, March 23). Healio. Retrieved from https://www.healio.com/news/endocrinology/20190323/lowdose-hcg-can-prevent-sterility-in-men-prescribed-testosterone
14. Lee JA, Ramasamy R. Indications for the use of human chorionic gonadotropic hormone for the management of infertility in hypogonadal men. Transl Androl Urol. 2018 Jul;7(Suppl 3):S348-S352. doi: 10.21037/tau.2018.04.11. PMID: 30159241; PMCID: PMC6087849.
15. El Meliegy, A., Motawi, A., & Abd El Salam, M. A. (2018). Systematic review of hormone replacement therapy in the infertile man. Arab Journal of Urology, 16(1), 140-147. https://doi.org/10.1016/j.aju.2017.11.011
16. Lee JA, Ramasamy R. Indications for the use of human chorionic gonadotropic hormone for the management of infertility in hypogonadal men. Transl Androl Urol. 2018 Jul;7(Suppl 3):S348-S352. doi: 10.21037/tau.2018.04.11. PMID: 30159241; PMCID: PMC6087849. (Note: Reference 16 seems duplicate of 14 in original)
17. Behre HM, Bergmann M, Simoni M, et al. Primary Testicular Failure. [Updated 2015 Aug 30]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279076/
18. Habous M, Giona S, Tealab A, Aziz M, Williamson B, Nassar M, Abdelrahman Z, Remeah A, Abdelkader M, Binsaleh S, Muir G. Clomiphene citrate and human chorionic gonadotropin are both effective in restoring testosterone in hypogonadism: a short-course randomized study. BJU Int. 2018 Nov;122(5):889-897. doi: 10.1111/bju.14401. Epub 2018 Jun 14. PMID: 29772111.
19. Fietz D., Bergmann M. (2017) Functional Anatomy and Histology of the Testis. In: Simoni M., Huhtaniemi I. (eds) Endocrinology of the Testis and Male Reproduction. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-44441-3_9
20. Leslie SW, Sajjad H, Siref LE. Chronic Testicular Pain. [Updated 2020 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482481
21. Kim SO, Ryu KH, Hwang IS, Jung SI, Oh KJ, Park K. Penile growth in response to human chorionic gonadotropin (HCG) treatment in patients with idiopathic hypogonadotrophic hypogonadism. Chonnam Med J. 2011;47(1):39-42. doi:10.4068/cmj.2011.47.1.39
22. Blair JA, Bhatta S, McGee H, Casadesus G. Luteinizing hormone: Evidence for direct action in the CNS. Horm Behav. 2015 Nov;76:57-62. doi: 10.1016/j.yhbeh.2015.06.020. Epub 2015 Jul 12. PMID: 26172857; PMCID: PMC4741372.