Does exogenous testosterone (testosterone) supplementation decrease endogenous testosterone production?

From the Guidelines

Taking testosterone supplements can indeed lead to decreased natural testosterone production in the body. When you introduce external testosterone (exogenous testosterone) through supplements or medications, your body detects the elevated testosterone levels in your bloodstream and responds by reducing its own production. This happens through a negative feedback loop involving the hypothalamus and pituitary gland, which normally regulate testosterone production by the testes. This suppression of natural testosterone production is called hypothalamic-pituitary-gonadal axis suppression.

Key Points to Consider

• The extent of suppression depends on the dose and duration of testosterone supplementation, with higher doses and longer use causing more significant suppression, as noted in studies assessing the efficacy and safety of testosterone treatment in men 1.
• Testosterone therapy often requires careful medical supervision, as stopping supplementation can lead to a period of low testosterone while the body's natural production recovers, which may take weeks to months.
• In some cases, especially after long-term use, the body's natural production may not fully recover, potentially requiring post-cycle therapy with medications like clomiphene or human chorionic gonadotropin to help restore natural testosterone production.

Clinical Implications

• The decision to start testosterone supplements should be made with caution, considering the potential for decreased natural testosterone production and the need for careful monitoring and potential post-cycle therapy.
• The American College of Physicians' evidence report on the efficacy and safety of testosterone treatment in men provides valuable insights into the benefits and risks of testosterone therapy, including the potential for hypothalamic-pituitary-gonadal axis suppression 1.
• Clinicians should weigh the benefits of testosterone supplements against the potential risks and consider alternative treatments or lifestyle modifications that may help improve testosterone levels without suppressing natural production.

From the FDA Drug Label

During exogenous administration of androgens, endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone (LH). At large doses of exogenous androgens, spermatogenesis may also be suppressed through feedback inhibition of pituitary follicle stimulating hormone (FSH)

The body produces less testosterone if you take testosterone supplements, as the endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone (LH) 2. This is also supported by another study 3.

• Key points:
  • Exogenous administration of androgens inhibits endogenous testosterone release
  • Feedback inhibition of pituitary luteinizing hormone (LH) is the mechanism
  • Large doses of exogenous androgens may also suppress spermatogenesis through feedback inhibition of pituitary follicle stimulating hormone (FSH)

From the Research

Testosterone Production and Supplements

• The body's natural production of testosterone can be affected by taking testosterone supplements, as seen in a study from 1986 4, which found that serum luteinizing hormone (LH) was significantly suppressed during intramuscular testosterone cypionate therapy.
• This suppression of LH can lead to a decrease in the body's natural production of testosterone, as LH is a hormone that stimulates the testes to produce testosterone.
• Another study from 2005 5 discusses the benefits and risks of androgen replacement therapy, including the potential for stimulating the growth of an occult prostate cancer.
• The study also mentions that the benefits of androgen therapy outweigh the risks in men with classic hypogonadism, but the balance between benefits and risks is not always clear for men with mild hypogonadism or andropause.

Effects of Testosterone Supplements on Testosterone Levels

• A study from 2009 6 discusses the goal of androgen substitution, which is to replace testosterone at levels as close to physiological concentrations as possible.
• The study also mentions that parenteral testosterone esters can produce fluctuating levels of plasma testosterone, which can be outside the physiological range for at least 50% of the time.
• Another study from 2003 7 discusses the drawbacks of currently available testosterone preparations, including large fluctuations of serum testosterone levels and frequent injections.
• The study also mentions that transdermal testosterone patches and gels can provide more stable serum testosterone levels and are effective in restoring normal hormonal values and correcting the signs and symptoms of hypogonadism.

Safety and Efficacy of Testosterone Supplements

• A study from 2020 8 evaluated the composition and advertised claims of "testosterone boosting" supplements and found that 90% of supplements claimed to "boost T", but only 24.8% had data to support these claims.
• The study also found that many supplements contained supra-therapeutic doses of vitamins and minerals, occasionally exceeding the upper tolerable intake level (UL).
• The study concludes that patients should be informed that "testosterone booster" supplements may not have ingredients to support their claims and may have negative effects on testosterone levels.