Does Testosterone Replacement Therapy (TRT) make you infertile when taken orally?
Testosterone replacement therapy (TRT) can significantly boost your testosterone (T) levels to improve your mood, energy, sexual function, lean body mass, and overall well-being. But these benefits often come at a cost, with infertility being one of the most severe drawbacks of TRT.
Interestingly, some methods of TRT, specifically oral TRT, appear to be less detrimental to your fertility than others. The research we’ll share below will help you better understand the relationship between TRT and fertility, how oral TRT affects your sperm count and quality.
Does TRT make you infertile?
Does TRT make you sterile? While this study from 2019 refers to TRT generally as a “contraceptive,” digging deeper into the research shows that transdermal and intramuscular testosterone are the strongest contraceptive formulations. The researchers cite one Chinese study, in which azoospermia affected 93% to 98% percent of patients receiving monthly intramuscular testosterone injections over the course of six months of treatment. They also point out why the risk of side effects like infertility tend to be higher with injectable testosterone. Injections produce a variable release of the hormone into the bloodstream, which leads to peaks and troughs beyond the normal range of serum testosterone levels. This not only results in a bigger threat to one’s fertility, but also the user’s mood.
How does TRT impact fertility?
When you supplement testosterone, your body shuts down the hypothalamic-pituitary-gonadal (HPG) axis, and its natural ability to produce its own testosterone. TRT hinders the release of follicle stimulating hormone (FSH) from the pituitary gland, which impairs sperm production, and suppresses the release of luteinizing hormone (LH), which inhibits intra-testicular testosterone production. This suppression leads to low sperm count and quality.
Are the effects of TRT reversible?
There is some evidence that the effects of TRT are reversible, but only to a certain extent. Research shows that stopping TRT has led to the reversal of azoospermia in 64% to 84% of men within 110 days. For some men, it took up to two years to recover. And yet other research suggests that some TRT users might experience permanent low sperm count or no sperm at all following treatment.
Oral TRT and fertility
The most recent oral TRT formulations, which bypass the liver to boost T levels, have been shown to pose less of a risk to fertility. For instance, in a small study, only 1 of 7 volunteers given oral TRT for 10-12 weeks became azoospermic (meaning there’s no sperm in their semen), but the remaining showed either suppressed or unaffected sperm counts. The researchers concluded that this low risk to fertility was the result of testosterone levels only becoming high enough to stop certain reproductive hormones for a few hours after taking the drug.
Despite TRT injections providing an immediate and significant boost to your T levels, oral TRT has been shown to be comparatively beneficial when you take all the risks into account. In this 2022 paper, researchers compared various modalities of TRT, examining parameters like bone mineral density, muscle mass, fat mass, and libido, while simultaneously weighing the adverse side effects of each method of delivery. They concluded that oral administration was just as advantageous as other modalities in the treatment of low testosterone.
Different brands may have different effects on fertility
Just as various types of TRT yield diverse outcomes, it's important to note that not all oral TRT formulations function in a uniform manner. The most recent FDA-approved oral TRT medications include Tlando®, Jatenzo®, and Kyzatrex®.
All three medications carry the same black box warning concerning large doses of exogenous androgens; manufacturers state that spermatogenesis may be suppressed, possibly leading to adverse effects on semen parameters including sperm count. They also warn that testicular atrophy, subfertility, and infertility have been reported in men who abuse anabolic androgenic steroids and, in some cases, this impact on fertility may be irreversible. (You can see the black box warnings here for Jatenzo, Tlando, and Kyzatrex).
However, only Kyzatrex offers a reproductive toxicology study that shows the effects on fertility. The animal study found that when untreated female rats mated with males receiving two times the maximum recommended human daily dose Kyzatrex, fewer females became pregnant, fertility was lower, and preimplantation loss was higher compared to the control group. However, researchers noted there was no negative impact on fertility in males who received an equivalent dose of Kyzatrex to the maximum recommended human daily dose. This proves that when prescribed at the right dose, oral TRT like Kyzatrex poses very little threat to the user’s fertility.
Are the effects of oral TRT reversible?
In a 2022 narrative review of different TRT options, researchers pointed out that oral TRT has “easy reversibility,” meaning the effects are reversible when you stop taking it. They also highlighted other benefits of oral TRT like “ease of administration,” “adequate efficacy” and overall “patient satisfaction” similar to other forms of TRT.
In the past, oral TRT consisted of methyltestosterone, which was known to cause significant damage to the liver. Liver toxicity initially produces symptoms like nausea, fatigue, itching, and jaundice. Some studies showed that jaundice and itching can be prolonged even after stopping treatment promptly.
But newer oral TRT formulations consist of testosterone undecanoate, which bypasses the liver entirely to be absorbed by the lymphatic system. Studies show that not only does this avoid liver toxicity, but it can also improve markers of nonalcoholic fatty liver disease, which is a serious long-term condition.
Can TRT improve fertility?
While TRT is mostly known for its threat to fertility, there have been instances in which testosterone undecanoate can be helpful. In this study on men with asthenospermia, which refers to reduced sperm motility, which refers to the proper movement of sperm, testosterone undecanoate actually increased motility, leading to a higher incidence of pregnancy in couples with infertility. Compared with the placebo, testosterone undecanoate treatment resulted in pregnancy for 28.2% of couples, while the incidence of pregnancy in the group taking placebo was 11.1%.
However, not all methods of delivery for testosterone undecanoate are equal. When injected, testosterone undecanoate combined with high-dose testosterone injections (specifically testosterone cyproterone) maintains sperm suppression, representing a “promising male contraceptive regimen.”
Key takeaways:
- Testosterone replacement therapy (TRT) can significantly increase your T levels, but it may come with drawbacks, such as infertility.
- Some methods of TRT, especially oral TRT, appear to have a lower impact on fertility, with Kyzatrex posing the smallest threat to a user’s fertility.
