From the Guidelines
For men who want to maintain fertility while addressing low testosterone symptoms, human chorionic gonadotropin (hCG) therapy is the primary alternative to traditional testosterone replacement therapy (TRT). According to the most recent guideline updates, exogenous testosterone therapy should be avoided in males pursuing or planning to pursue family building in the near future, as it provides negative feedback to the hypothalamus and pituitary gland, inhibiting gonadotropin secretion and potentially decreasing or ceasing spermatogenesis 1.
Alternative Therapies
Instead, hCG therapy can stimulate the testes to produce natural testosterone while preserving sperm production. A typical regimen involves subcutaneous injections of 500-2500 IU of hCG 2-3 times weekly, followed by FSH injections when indicated, after testosterone levels are normalized on hCG 1. This approach maintains intratesticular testosterone levels necessary for spermatogenesis while raising serum testosterone.
Combination Therapies
Another option is combining hCG with selective estrogen receptor modulators (SERMs) like clomiphene citrate or tamoxifen, which work by blocking estrogen's negative feedback on the hypothalamus, thereby increasing natural testosterone production 1. These medications can be effective for 3-6 months while trying to conceive. Regular semen analysis and hormone level monitoring are essential during treatment.
Key Considerations
It is crucial to note that recovery of sperm to the ejaculate occurs in most azoospermic males after cessation of testosterone therapy, but the time course of recovery may be prolonged and can be months or rarely years 1. Therefore, exogenous testosterone therapy should be avoided in males pursuing or planning to pursue family building in the near future. In those that may want to pursue paternity in the more distant future, testosterone therapy may be offered, but the patient should be counseled about testosterone’s inhibitory effects on spermatogenesis and the time course required for resumption of spermatogenesis after cessation.
From the FDA Drug Label
INDICATIONS AND USAGE ... Selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a pituitary deficiency) in males. The alternative for testosterone replacement therapy if you want to have kids pretty soon is hCG (IM), as it can be used to treat hypogonadotropic hypogonadism in males, which may help preserve fertility.
- hCG can stimulate testicular function, which is necessary for sperm production.
- This option may be considered for individuals who want to have children soon, as testosterone replacement therapy can suppress natural testosterone production and sperm development. 2
From the Research
Alternatives to Testosterone Replacement Therapy for Fertility
If you want to have kids pretty soon, there are alternative options to testosterone replacement therapy (TRT) that can help improve fertility. These alternatives include:
- Human chorionic gonadotropin (hCG) 3, 4
- Selective estrogen receptor modulator (SERM) 3, 4, 5, 6
- Estrogen antagonist 3
- Aromatase inhibitors (AIs) such as letrozole or anastrozole 3, 7, 5
- Gonadotropins 4
- Clomiphene citrate and tamoxifen, although their use is off-label and data supporting their efficacy is insufficient 4
How These Alternatives Work
These alternatives work by stimulating endogenous testosterone production, increasing sperm concentration and motility, and improving fertility. For example:
- AIs such as letrozole or anastrozole can increase sperm concentration, total sperm count, and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels 7
- SERMs can increase serum testosterone levels, although their effect on sexual symptoms and semen parameters is unclear 5
- hCG and gonadotropins can stimulate sperm production and improve fertility 3, 4
Considerations and Precautions
When considering these alternatives, it's essential to consult with a physician to determine the best course of treatment. Some of these alternatives may have potential side effects or interactions, and their long-term safety profile is not fully understood 5. Additionally, some alternatives may not be suitable for all individuals, such as those with certain medical conditions or taking certain medications.