Can Selective Serotonin Reuptake Inhibitors (SSRIs) cause hypogonadism, specifically low testosterone levels?

From the Guidelines

Selective Serotonin Reuptake Inhibitors (SSRIs) can potentially cause hypogonadism and lower testosterone levels in some patients. The mechanism involves serotonin's influence on the hypothalamic-pituitary-gonadal axis, where increased serotonin levels can suppress the release of gonadotropin-releasing hormone, leading to decreased luteinizing hormone and ultimately reduced testosterone production 1. Common SSRIs like fluoxetine (Prozac), sertraline (Zoloft), escitalopram (Lexapro), and paroxetine (Paxil) have been associated with hormonal changes, though not all patients experience this side effect. Patients taking SSRIs who experience symptoms like:

• decreased libido
• erectile dysfunction
• fatigue
• reduced muscle mass
• mood changes should discuss these with their healthcare provider. Laboratory testing of testosterone levels may be warranted in such cases. It's essential not to discontinue SSRI medication without medical supervision, as the benefits for treating depression or anxiety often outweigh these potential side effects. For patients concerned about testosterone levels, healthcare providers might consider alternative antidepressants with different mechanisms of action, such as bupropion (Wellbutrin), which has fewer sexual side effects and less impact on hormone levels 1. However, the current evidence does not directly link SSRIs to low testosterone levels, and more research is needed to fully understand this potential relationship. In the context of real-life clinical medicine, prioritizing the patient's overall health and well-being is crucial, and healthcare providers should weigh the benefits and risks of SSRI treatment on an individual basis.

From the FDA Drug Label

Male and Female Sexual Dysfunction with SSRIs Although changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can cause such untoward sexual experiences Table 5 Adverse EventSertraline Hydrochloride TabletsPlacebo Ejaculation Failure1(Primarily Delayed Ejaculation) 14% 1% Decreased Libido26%1%

• SSRIs and Low Testosterone: There is no direct information in the provided drug label that specifically addresses the question of whether SSRIs cause low testosterone levels.
• Related Adverse Events: The label does mention decreased libido as a potential side effect, which could be related to hormonal changes, but it does not provide a direct link to low testosterone levels.
• Clinical Decision: Given the lack of direct evidence, it is not possible to conclude that SSRIs cause low testosterone based on the information provided in the drug label 2.

From the Research

SSRIs and Testosterone Levels

• The relationship between Selective Serotonin Reuptake Inhibitors (SSRIs) and testosterone levels is complex, with some studies suggesting a potential link between SSRI use and decreased testosterone levels 3, 4.
• A study published in 2017 found that six commonly used SSRIs decreased androgens, including testosterone, and increased estrogens in the H295R cell line, a human in vitro adrenocortical cell assay 3.
• Another study published in 2021 reviewed the effects of antidepressants, including SSRIs, on testosterone and estrogen levels, and found that most antidepressants can influence these hormone levels, although the evidence is conflicting 4.

Mechanisms and Effects

• The mechanisms by which SSRIs may affect testosterone levels are not fully understood, but may involve effects on the hypothalamic-pituitary-gonadal (HPG) axis, as well as direct effects on steroid hormone synthesis 5, 3.
• SSRIs have been shown to increase prolactin levels, which can inhibit testosterone production, although this effect may not be universal and may depend on the specific SSRI used 5.
• The effects of SSRIs on testosterone levels may also be influenced by individual factors, such as dose and duration of treatment, as well as underlying medical conditions 6.

Clinical Implications

• The clinical implications of SSRI-induced changes in testosterone levels are not fully understood, but may include effects on sexual function, mood, and overall quality of life 7, 6.
• Some studies have suggested that testosterone replacement therapy may be an effective treatment for hypogonadal men with SSRI-refractory depression, although more research is needed to confirm this finding 7.
• Further studies are needed to fully understand the effects of SSRIs on testosterone levels and to determine the clinical significance of these effects 5, 4.