TRT Medications Explained: Injectables, Oral Testosterone, Enclomiphene, and More

Men diagnosed with testosterone deficiency have more treatment options today than at any previous point in the history of hormone medicine. Traditional testosterone replacement therapy is available in a range of formulations — injections, gels, patches, oral capsules, pellets, and nasal gel — each with a distinct delivery mechanism, dosing schedule, and set of practical tradeoffs. Alongside conventional TRT, a separate category of medications works by stimulating the body's own testosterone production rather than replacing it externally, with important implications for fertility and long-term hormonal function. This article explains each major medication category in plain terms, including how it works, what the evidence shows, and which considerations are most relevant for men evaluating their options with a provider.

A Note on How These Medications Differ

All testosterone replacement therapies work by introducing exogenous — externally derived — testosterone into the body to raise serum levels back into the normal physiological range. They differ in how that testosterone is delivered, how stable the resulting hormone levels are, how frequently doses must be administered, and what risks they carry.

A separate class of medications — selective estrogen receptor modulators (SERMs) such as clomiphene citrate and enclomiphene citrate — works through an entirely different mechanism. Rather than replacing testosterone, these drugs stimulate the body's own hormonal axis to produce more testosterone naturally. They are not technically TRT, but are increasingly used as an alternative, particularly in men who wish to preserve fertility. The distinction matters, and both categories are covered below.

No testosterone product is FDA-approved for the treatment of low testosterone due solely to aging. All require a clinical diagnosis of hypogonadism — confirmed low levels plus consistent symptoms — before a prescription can be written.

Injectable Testosterone

Intramuscular and subcutaneous testosterone injections are among the oldest and most widely prescribed forms of TRT. They remain a first-line option in many clinical settings due to their reliability, well-established pharmacology, and cost-effectiveness.

Testosterone Cypionate and Testosterone Enanthate

Testosterone cypionate and testosterone enanthate are the two most commonly prescribed injectable testosterone esters in the United States. Both are long-acting formulations that release testosterone gradually after injection, but are cleared from the body at slightly different rates. Testosterone cypionate has a half-life of approximately eight days; testosterone enanthate is similar at approximately four to five days, making it slightly shorter-acting.

Both are typically administered as intramuscular injections every one to two weeks, though many providers prefer smaller weekly doses to reduce the hormonal fluctuations — peaks and troughs — that can occur with less frequent, larger injections. Subcutaneous (under the skin rather than into the muscle) injection is also well tolerated and increasingly used as a more convenient self-administration option.

The primary practical considerations with injections are that they require either self-administration with a needle or clinical visits for each dose, and that testosterone levels fluctuate between injections in a way some men find affects their energy and mood. On a per-dose basis, injectable testosterone is generally the least expensive form of TRT, particularly when using generic formulations.

Testosterone Enanthate Subcutaneous Autoinjector (Xyosted)

Xyosted is an FDA-approved subcutaneous autoinjector formulation of testosterone enanthate designed for once-weekly self-administration. It delivers a fixed dose under the skin, typically in the abdomen, and is designed to simplify the injection process for men who prefer a more straightforward format than traditional syringes. It carries the same pharmacological profile as standard testosterone enanthate but in a pre-filled, fixed-dose device.

Testosterone Undecanoate Injection (Aveed)

Aveed is a long-acting injectable depot formulation of testosterone undecanoate administered as a deep intramuscular injection. It is given by a healthcare provider — not self-administered — and requires only four injections per year after an initial loading phase (a second injection at four weeks, then one every ten weeks). The extended dosing interval is a meaningful advantage for men who find weekly or biweekly injections impractical. However, Aveed carries an FDA risk evaluation and mitigation strategy (REMS) requirement due to the risk of a serious pulmonary oil microembolism or anaphylaxis immediately following injection, which is why it must be administered in a clinical setting with observation afterward.

Topical Gels and Creams

Topical testosterone products are applied daily to the skin, where the hormone is absorbed transdermally and enters the bloodstream. They are among the most widely prescribed TRT formulations in the US, favored for their ease of use and the relatively stable hormone levels they produce compared to injections.

Testosterone gels are typically applied once daily to clean, dry skin — most commonly to the upper arms, shoulders, or inner thighs depending on the specific product. They produce more consistent day-to-day testosterone levels than weekly injections, avoiding the peak-and-trough pattern some men find problematic. FDA-approved topical testosterone gels include AndroGel (1% and 1.62%), Testim, Fortesta, Vogelxo, and testosterone topical solution for axillary (underarm) application, available generically. Testosterone creams are also available by compounding pharmacy.

The primary concern with topical formulations is the risk of unintentional testosterone transfer to others through direct skin contact. Testosterone can transfer to partners or children who touch the application site before the gel has fully dried or before the area is covered or washed. This can cause inappropriate androgenic effects in women and children who are exposed. Proper application protocols — washing hands after use, covering the application site with clothing, and washing the area before contact with others — are essential safety measures.

Transdermal Patches

Testosterone patches (brand name Androderm) are applied once daily to the skin — typically the back, abdomen, upper arm, or thigh — and deliver a controlled, continuous dose of testosterone through slow transdermal absorption throughout the day. They produce stable hormone levels and eliminate the need for injections or daily gel application.

The main drawback of patches compared to gels is a higher incidence of skin irritation at the application site, which can range from mild redness to more significant contact dermatitis requiring treatment discontinuation in some men. Rotating application sites daily reduces but does not eliminate this risk.

Oral Testosterone

For decades, oral testosterone was largely impractical due to poor bioavailability and significant hepatotoxicity associated with older formulations such as methyltestosterone. This changed with the development of testosterone undecanoate formulations that absorb via the lymphatic system rather than undergoing first-pass hepatic metabolism — largely bypassing the liver and making oral testosterone both safe and effective.

Three oral testosterone undecanoate products are currently FDA-approved in the United States:

Jatenzo

Jatenzo was the first oral testosterone undecanoate capsule approved by the FDA in the US, receiving approval in 2019. It is taken twice daily with food — specifically a meal containing fat, which meaningfully improves absorption through the lymphatic pathway. Jatenzo produces testosterone levels in the normal range in most hypogonadal men and is a viable option for those who prefer oral administration over injections or topical products.

Kyzatrex

Kyzatrex (testosterone undecanoate) received FDA approval in 2022. Like Jatenzo, it is taken orally twice daily with food and absorbs via the lymphatic pathway. It is available in multiple dose strengths to allow for individualized dosing. Clinical studies supporting its approval demonstrated that a significant proportion of men achieved testosterone levels in the normal range (300–1,000 ng/dL) with twice-daily dosing.

Tlando

Tlando is a third FDA-approved oral testosterone undecanoate formulation, also approved in 2022. It shares the same lymphatic absorption mechanism and twice-daily dosing schedule as Jatenzo and Kyzatrex. The availability of multiple oral formulations gives providers and patients meaningful choice in terms of dose strengths, capsule characteristics, and cost.

A note on blood pressure: all oral testosterone undecanoate products carry labeling warnings about the potential for increases in blood pressure. Blood pressure monitoring is a standard component of management for men using oral TRT. In February 2026, the FDA updated the labeling of all testosterone products to remove a previous boxed warning about cardiovascular risk while adding a new warning specifically about blood pressure elevation, reflecting updated data from the TRAVERSE trial.

Testosterone Pellets

Subcutaneous testosterone pellets (brand name Testopel) are small crystalline implants inserted under the skin — typically in the buttocks or hip area — by a physician during a minor in-office procedure performed under local anesthesia. The pellets dissolve slowly and release testosterone continuously over three to six months before replacement is needed.

The primary advantage of pellets is convenience: once implanted, no daily application, weekly injection, or twice-daily dosing is required. For men who struggle with adherence to daily or weekly regimens, pellets can be a meaningful practical solution.

The primary limitation is the inverse of that advantage: once implanted, the dose cannot be adjusted or removed easily if side effects arise or if the dose proves incorrect. If testosterone levels run higher than intended after implantation, the only option is to wait for the pellets to dissolve. Pellets also require a minor surgical procedure each cycle, carry a small risk of infection or extrusion at the implant site, and are generally among the more expensive TRT options. They are not routinely recommended in clinical guidelines due to limited data maintaining stable testosterone concentrations over the full dosing interval.

Nasal Testosterone Gel (Natesto)

Natesto is an FDA-approved intranasal testosterone gel delivered via a metered-dose pump into each nostril. It is applied three times daily — morning, afternoon, and evening — making it the most frequent dosing schedule of any TRT formulation. Testosterone is absorbed rapidly through the nasal mucosa, producing short-lived peaks in serum levels that decline between doses.

The high dosing frequency is a significant practical drawback for many men. However, Natesto has attracted research interest because its short half-life and rapid clearance appear to result in less suppression of LH and FSH — and therefore less impairment of sperm production — than other TRT formulations. A meaningful proportion of men on Natesto maintain LH and FSH within normal limits and preserve spermatogenesis during treatment, making it a consideration for men with secondary hypogonadism who want to treat low testosterone while minimizing fertility impact.

Common side effects include nasal irritation, runny nose, and congestion. It should not be used concurrently with other nasal products including corticosteroid nasal sprays without provider guidance.

Alternatives to TRT: Selective Estrogen Receptor Modulators (SERMs)

The medications described above all introduce exogenous testosterone into the body — they replace what the body is not making. SERMs work differently: rather than substituting for testosterone, they trick the brain into stimulating the body's own hormonal axis to produce more testosterone naturally.

SERMs block estrogen receptors in the hypothalamus — the brain region that regulates the reproductive hormone axis. Estrogen normally provides negative feedback to the hypothalamus, signaling it to reduce production of gonadotropin-releasing hormone (GnRH). When a SERM blocks that feedback, the hypothalamus senses a relative estrogen deficiency and increases GnRH output, which in turn drives the pituitary to release more luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH signals the testes to produce more testosterone; FSH supports sperm production. The result is increased endogenous testosterone — produced by the man's own testes — alongside preserved or improved spermatogenesis.

Because SERMs stimulate rather than suppress the HPG axis, they do not cause the testicular atrophy, sperm suppression, or fertility impairment associated with conventional TRT. This makes them particularly relevant for younger men and men who wish to father children.

Clomiphene Citrate (Off-Label Use in Men)

Clomiphene citrate is FDA-approved for the induction of ovulation in women. It has been used off-label in men to treat secondary hypogonadism for several decades. Clomiphene is a mixture of two isomers: enclomiphene (the trans isomer), which acts as an estrogen receptor antagonist, and zuclomiphene (the cis isomer), which has some estrogen receptor agonist activity. The agonist activity of zuclomiphene can contribute to side effects including elevated estradiol levels, gynecomastia, and mood changes in some men.

Clinical evidence supports clomiphene's ability to raise testosterone and LH in men with secondary hypogonadism, and it has a long track record of use in urology and endocrinology practices. In a systematic review and meta-analysis of ten randomized controlled trials involving 819 patients, SERM therapy (clomiphene and enclomiphene combined) produced a mean testosterone increase of 273.76 ng/dL compared to placebo, with significant improvements in LH and FSH. Men treated with clomiphene citrate achieve testosterone levels comparable to those on conventional TRT, with the added benefit of preserved fertility.

Enclomiphene Citrate (Off-Label Use in Men)

Enclomiphene citrate is the purified trans isomer of clomiphene. Unlike clomiphene, it does not contain the zuclomiphene component that acts as an estrogen agonist. This distinction has clinical significance: enclomiphene raises testosterone and LH without substantially increasing estradiol, which reduces the risk of estrogenic side effects.

Enclomiphene is not FDA-approved for any indication in men and is not FDA-approved for any purpose at this time. It is available through compounding pharmacies and prescribed off-label by providers who work in men's hormonal health. Its use in men is considered investigational, and long-term safety data are more limited than for conventional TRT or clomiphene.

Enclomiphene citrate raises testosterone levels comparable to topical testosterone gel in men with secondary hypogonadism, while simultaneously preserving sperm counts — an outcome not observed with testosterone gel. Enclomiphene produces a median testosterone increase of 166 ng/dL with a lower rate of adverse effects — including decreased libido, reduced energy, and mood changes — compared to clomiphene.

Because enclomiphene is not FDA-approved, men should be aware that it is used outside of approved labeling, that its long-term safety profile is not as well characterized as that of FDA-approved treatments, and that it is only appropriate for men with secondary hypogonadism — not primary hypogonadism — since it requires a functioning pituitary-gonadal axis to work.

How to Choose Between These Options

No single medication is universally optimal. The right choice depends on several individual factors:

The type of hypogonadism matters. Men with primary hypogonadism — where the testes themselves cannot produce adequate testosterone regardless of stimulation — are not candidates for SERMs like enclomiphene or clomiphene, since those drugs rely on intact testicular function. For these men, conventional TRT is the only pharmacological option.

Fertility intentions are critical. All conventional TRT formulations suppress the HPG axis and reduce or eliminate sperm production during treatment. Men who wish to preserve fertility — now or in the future — should discuss SERMs, Natesto, or human chorionic gonadotropin (hCG) as alternatives or adjuncts with their provider before starting conventional TRT.

Lifestyle and adherence preferences influence formulation choice meaningfully. A man who travels frequently may find pellets more practical. A man who is needle-averse will prefer oral or topical options. A man who wants to avoid the daily routine of a gel may prefer injections. These practical considerations directly affect long-term adherence, which is essential for any hormonal treatment.

Monitoring requirements are similar across formulations but vary slightly in what is being tracked. All TRT requires regular blood tests for testosterone levels, hematocrit, and PSA; oral formulations require additional attention to blood pressure; nasal gel requires awareness of nasal side effects.

A licensed healthcare provider — whether a urologist, endocrinologist, or primary care physician with experience in men's hormonal health — can evaluate the type and degree of hypogonadism, assess relevant comorbidities, and recommend the formulation most appropriate for each individual's clinical profile and goals.