What is the effect of Glucagon-like peptide-1 (GLP-1) on testosterone levels?

From the Guidelines

GLP-1 receptor agonists may indirectly affect testosterone levels by promoting weight loss, which can improve testosterone levels in overweight or obese individuals, and by improving insulin resistance, although the evidence is limited and of low to very low certainty 1.

Key Points

• GLP-1 medications like liraglutide and semaglutide can lead to weight loss, which is associated with improved testosterone levels in individuals with excess body fat 1.
• The reduction in body fat can decrease the conversion of testosterone to estrogen by aromatase, an enzyme found in fat tissue 1.
• Improvement in insulin resistance with GLP-1 treatment can positively influence hormone balance, including testosterone levels 1.
• Some studies suggest that GLP-1 medications might increase sex hormone-binding globulin (SHBG), potentially reducing free testosterone levels temporarily 1.
• However, the overall metabolic benefits from weight loss typically outweigh any short-term hormonal changes 1.

Considerations

• The evidence for the effect of GLP-1 receptor agonists on testosterone levels is limited and of low to very low certainty 1.
• Monitoring testosterone levels during GLP-1 medication treatment is advisable, especially for individuals with concerns about their testosterone levels 1.
• Healthcare providers should consider the potential benefits and adverse effects of GLP-1 medications in the context of individual patient needs and health status 1.

From the Research

GLP-1's Effect on Testosterone

• The effect of GLP-1 on testosterone levels has been studied in several research papers 2, 3.
• A study published in 2019 found that liraglutide, a GLP-1 receptor agonist, increased total testosterone levels in obese men with functional hypogonadism, although the increase was less significant compared to testosterone replacement therapy (TRT) [+2.6 ± 3.5 nmol/L in LIRA vs +5.9 ± 7.2 nmol/L in TRT] 2.
• Another study published in 2015 found that adding liraglutide to lifestyle changes, metformin, and testosterone therapy improved erectile function in diabetic obese men with overt hypogonadism, and also increased testosterone levels [+T (p < 0.01)] 3.
• However, there is no direct evidence from the provided studies that GLP-1 has a significant impact on testosterone levels independent of its effects on weight loss and metabolic control.
• The studies suggest that GLP-1 receptor agonists may have a beneficial effect on testosterone levels in obese men with functional hypogonadism, but more research is needed to fully understand the relationship between GLP-1 and testosterone 2, 3.

Mechanism of Action

• GLP-1 receptor agonists have been shown to have several mechanisms of action, including augmentation of hyperglycemia-induced insulin secretion, suppression of glucagon secretion, and reduction in calorie intake and body weight 4.
• These mechanisms may contribute to the improvement in testosterone levels observed in some studies, but the exact relationship between GLP-1 and testosterone is not fully understood.

Clinical Implications

• The use of GLP-1 receptor agonists may be beneficial for obese men with functional hypogonadism, particularly those who have not responded to lifestyle changes and testosterone replacement therapy 2, 3.
• However, more research is needed to fully understand the effects of GLP-1 on testosterone levels and to determine the potential clinical implications of this relationship.