TRT and Pregnancy: Essential Considerations for Partners

Men with total testosterone levels below 300 ng/dL have a 1.5-fold increased risk of developing cardiovascular disease within a decade, irrespective of traditional risk factors (Xu et al., Journal of the American Heart Association, 2023) [1]. While testosterone replacement therapy (TRT) effectively addresses symptoms of hypogonadism and improves overall health markers, a common and often surprising consequence for men on exogenous testosterone is its impact on fertility. The reality is counterintuitive: more external testosterone does not equal more sperm.

Last Updated: OCTOBER 2024

The TRT Fertility Paradox: Understanding the Mechanism

Exogenous testosterone, whether administered via injection, gel, or pellet, signals to your brain that the body has sufficient testosterone. This signal, in turn, suppresses the hypothalamic-pituitary-gonadal (HPG) axis. Specifically, the hypothalamus reduces its production of gonadotropin-releasing hormone (GnRH), which then leads to a decrease in the pituitary gland’s secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

LH and FSH are crucial for natural testosterone production and, more critically, for spermatogenesis within the testes. LH stimulates the Leydig cells in the testes to produce endogenous testosterone, while FSH directly promotes sperm maturation. When these signals are suppressed, the testes reduce their own testosterone synthesis and, consequently, their sperm production. This often leads to oligospermia (low sperm count) or even azoospermia (absence of sperm).

“Although TRT may improve symptoms of hypogonadism, it can suppress endogenous testosterone production and spermatogenesis by inhibiting the hypothalamic-pituitary-gonadal (HPG) axis,” state the American Urological Association (AUA) guidelines on Testosterone Deficiency [2]. This suppression is the root cause of TRT-induced infertility. Testicular atrophy, a reduction in testicle size, is also a common side effect due to the decreased activity of these organs.

The Problem with Outdated Testosterone Thresholds

It is essential to understand the context of what defines “low testosterone.” The widely cited lower bound of 300 ng/dL for total testosterone was established decades ago, based on a population that included older men and those with various chronic illnesses from the 1970s. This threshold often leads to underdiagnosis and undertreatment, with many men experiencing significant symptoms of hypogonadism at levels above this arbitrary cutoff. Access to TRT should be based on clinical symptoms correlated with lab values, not solely on an outdated numerical threshold. A healthy young man’s typical total testosterone range is often much higher, frequently above 600 ng/dL.

Strategies for Fertility Preservation and Restoration on TRT

For men considering or currently on TRT who wish to conceive, several strategies exist to mitigate or reverse the impact on spermatogenesis.

1. Sperm Banking Before Starting TRT

The most definitive method for fertility preservation is to cryopreserve sperm before initiating TRT. This ensures a viable sample is available, regardless of future TRT use or recovery of natural fertility. This is often recommended for men who are certain about future parenthood but need to start TRT immediately for symptomatic relief.

2. Co-administration of Human Chorionic Gonadotropin (HCG)

HCG is a gonadotropin that mimics the action of LH. When administered alongside exogenous testosterone, HCG stimulates the Leydig cells in the testes to continue producing intratesticular testosterone. This endogenous testosterone is crucial for local spermatogenesis, preventing or reducing the HPG axis suppression’s impact on sperm production.

• Mechanism: HCG directly activates LH receptors on Leydig cells, bypassing the suppressed pituitary LH signal.
• Dosage: Common protocols involve 500–1000 IU of HCG administered 2–3 times per week, alongside a standard TRT regimen of 100–200mg testosterone cypionate or enanthate per week.
• Benefits: Helps maintain testicular size and function, preserving sperm production while benefiting from exogenous testosterone.
• Evidence: A study by Liu et al. (2013) published in Andrology demonstrated that “Exogenous human chorionic gonadotropin maintains spermatogenesis in men on testosterone replacement therapy” [3]. Their research showed that HCG co-administration could preserve testicular volume and spermatogenesis in men receiving testosterone.

3. Selective Estrogen Receptor Modulators (SERMs): Enclomiphene

Enclomiphene citrate is a non-steroidal selective estrogen receptor modulator. It works by blocking estrogen receptors in the hypothalamus, which prevents estrogen from inhibiting GnRH release. This disinhibition leads to increased GnRH, subsequently boosting LH and FSH production from the pituitary. Higher LH and FSH levels then stimulate the testes to produce more endogenous testosterone and sperm.

• Mechanism: Acts centrally to increase LH and FSH, thereby stimulating natural testosterone and sperm production.
• Dosage: Typically prescribed at 12.5–25mg daily.
• Use Case: Often used as a standalone treatment for secondary hypogonadism where fertility is a primary concern, as it raises endogenous testosterone while preserving or enhancing fertility. It can also be used to help restore fertility after cessation of TRT.
• Distinction from TRT: Unlike TRT, which replaces testosterone exogenously, enclomiphene encourages the body to produce its own testosterone.
• Side Effects: Potential for visual disturbances, mood changes, or estrogen-related effects, though generally well-tolerated.

4. Managing Estrogen with Anastrozole

While sometimes used on TRT to control high estradiol (E2) levels resulting from testosterone aromatization, anastrozole (an aromatase inhibitor) must be used cautiously when fertility is a concern. While high E2 can negatively impact fertility, low E2 is also detrimental to spermatogenesis and overall health. The ideal E2 range for fertility and optimal health on TRT is generally between 20–40 pg/mL. Excessively lowering E2 can impair sperm quality and motility.

• Dosage: If necessary, very low doses such as 0.25–0.5mg once or twice a week, titrated based on E2 levels.
• Recommendation: Prioritize HCG or enclomiphene for fertility, and only use anastrozole if E2 is pathologically high (e.g., above 60 pg/mL) and causing symptoms, ensuring not to crash E2.

5. Ceasing TRT for Fertility Restoration

For men who have been on TRT and wish to restore natural fertility, discontinuing exogenous testosterone is necessary. The HPG axis recovery period varies significantly among individuals, ranging from several months to over a year, and complete recovery to pre-TRT levels is not guaranteed. During this period, strategies like HCG, enclomiphene, or a combination may be used to help “kickstart” the HPG axis and stimulate spermatogenesis. Regular semen analyses are crucial to monitor progress.

Lab Monitoring for Fertility Protocols

Close monitoring of hormone levels and sperm parameters is essential when pursuing fertility while on TRT or attempting to restore it.