Testosterone replacement therapy (TRT) suppresses the natural production of testosterone by the testes. It also reduces sperm production. In most men, it reduces sperm production to levels below what is necessary for fertility. As a result, most men on testosterone therapy are infertile.
While this side effect may not concern certain men, men looking to conceive a child or remain fertile must be aware of this potential side effect of TRT. While infertility is usually reversible, the testosterone dosage must either be decreased or TRT must be stopped all together.1
Fortunately, maintaining fertility may be accomplished by also taking human chorionic gonadotropin (HCG) during testosterone therapy. Adding HCG to TRT may sustain continued sperm production necessary for conception in patients on testosterone therapy.2,3
Why Does Testosterone Therapy Suppress Sperm Production?
The body controls the amount of testosterone produced through a feedback mechanism. When levels are low, chemicals signals released by the hypothalamus and pituitary gland stimulate the testes to produce testosterone. The hypothalamus releases gonadotropin releasing hormone (GnRH). Then, GnRH stimulates the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH). The FSH and LH then stimulate the testes to produce testosterone.4
When levels are normal/high, testosterone, itself, acts on the hypothalamus and pituitary gland by preventing these same chemicals signals to tell the body no more testosterone is needed.
Exogenous testosterone taken during testosterone therapy tells the testes not produce more testosterone. It inhibits the release of GnRH, FSH, and LH. Consequently, it inhibits testosterone production by the testes.5
Since sperm production requires high levels of testosterone within the testes and testosterone therapy suppresses testosterone production by the testes, testosterone therapy reduces sperm production. During testosterone therapy, the amount of testosterone in the body is normal, but the amount of testosterone within the testes is below normal.6
Human Chorionic Gonadotropin and Fertility
Men looking to maintain fertility during testosterone therapy may discuss adding human chorionic gonadotropin to their TRT regimen with their physician. In men, HCG stimulates the testes to produce testosterone. This testosterone promotes sperm production because intratesticular testosterone (testosterone within the testes) is necessary for sperm production. In addition to helping to maintain fertility, HCG may also restore testicular size.
HCG Therapy for Sperm Production
The following guidelines come from the American Association of Clinical Endocrinologists (AACE) for men with insufficient sperm production. As a note, these guidelines are not specifically for men on testosterone therapy.
According to the AACE Clinical Guidelines, to restore sperm production, HCG should be the initial therapy of choice for at least 6 to 12 months. Therapy with HCG is generally begun at 1,000 to 2,000 IU injected intramuscularly two to three times a week. Both testosterone levels and sperm counts should be monitored monthly.7
Two studies with men specifically on testosterone replacement therapy show that 500 IUs every other day also maintains normal sperm production.
HCG alone can often restore sperm production.8,9 As such, treatment is usually initiated with it alone without follicle stimulating hormone (FSH) or human menopausal gonadotropin (HMG) because HCG is a fraction of the cost of FSH or HMG.
If sperm production has not been initiated within 6 to 12 months of therapy with HCG, the AACE recommends that administration of an FSH-containing preparation is initiated in a dosage of 75 IU injected intramuscularly three times a week along with the HCG regimen. After 6 months, if sperm are not present or are present in very low numbers (<100,000/mL), the human menopausal gonadotropin (or FSH) dosage can be increased to 150 IU intramuscularly three times a week for another 6 months.10
As a note, it is imperative that the female partner undergoes assessment for optimal fertility before or concurrently with consideration of therapy in the man.
HCG Storage and Administration
Unlike testosterone, which is a single molecule, human chorionic gonadotropin is a peptide. More specifically, it is a long string of 237 molecules known as amino acids. Due to its complexity, HCG must be stored properly to prevent decomposition over time.
Typically HCG comes in the form of a powder in a sterile ampule to prolong its shelf life. In order to use, it must be reconstituted/remixed with bacteriostatic water (sterile water containing an anti-bacterial agent).
When stored at room temperature, unmixed peptides can be kept for approximately 60 days, but reconstituted peptides must be used within 48 hours. When stored in a refrigerator between 35 and 45 degrees Fahrenheit, unmixed peptides can be stored for 18 months, whereas mixed peptides must be used within two months.
Ideally, it should be stored in the refrigerator between 35 and 45 degrees Fahrenheit and kept separate from food and beverages to avoid any cross contamination risk. Unmixed HCG may be frozen one time. Mixed peptides should not be frozen. When frozen, unmixed peptides can be kept for approximately 24 months.
Once reconstituted with bacteriostatic water, HCG is given as an injection intramuscularly or subcutaneously (under the skin in the fat layer). Intramuscular injections are typically given in either the glutes, quadriceps, or deltoids. Subcutaneously injections are typically given under the skin in the abdomen.
1. Miner MM. Low Testosterone Medscape CME Expert Column Series. Issue 3: Delivering Safe and Effective Testosterone Replacement Therapy. Medscape Education. 2011.
2. Coviello AD, Matsumoto AM, Bremner WJ, Herbst KL, AmoryJK, Anawalt BD, Sutton PR, Wright WW, Brown TR, Yan X, Zirkin BR, Jarow JP. Low-Dose Human Chorionic Gonadotropin Maintains Intratesticular Testosterone in Normal Men with Testosterone-Induced Gonadotropin Suppression. J Clin Endrocrinol and Metab. 2005. 90 (5): 2595–2602.
3. Hsieh TC, Pastuszak AW, Hwang K, Lipshultz LI. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy. J Urol. 2013. 189 (2): 647-50.
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5. Matsumoto AM. Effects of chronic testosterone administration in normal men: safety and efficacy of high dosage testosterone and parallel dose-dependent suppression of luteinizing hormone, follicle-stimulating hormone, and sperm production. J Clin Endocrinol Metab. 1990. 70:282–287.
6. Dickerson LM, Shrader SP, Diaz VA (2008). “Chapter 8: Contraception”. In Wells BG, DiPiro JT, Talbert RL, Yee GC, Matzke GR. Pharmacotherapy: a pathophysiologic approach. McGraw-Hill Medical. pp. 1313–28. ISBN 0-07-147899-X.
7. AACE Hypogonadism Task Force. American association of clinical endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients—2002 update. Endocrine Practice. 2002; 8 (6): 439-456.
8. Finkel DM, Phillips JL, Synder PJ. Stimulation of spermatogenesis by gonadotropins in men with hypogonadotropic hypogonadism. N Engl J Med. 1985; 17 (5): 497-501.
9. Mulhall JP, Hsiao W. Men’s Sexual Health and Fertility: A Clinician’s Guide. Springer Science + Business Media. New York, NY. 2014.
10. Matsumoto AM, Paulson CA, Bremner WJ. Stimulation of sperm production by human luteinizing hormone in gonadotropin-suppressed normal men. J Clin Endocrinol Metab. 184; 59 (5): 882.