HRT, also known as hormone replacement therapy, is the use of synthetic hormones to mimic traditional sex hormones. The use of testosterone HRT has been foundational and approved as the best form of treatment for transgender people for nearly a century.
Want to know more about HRT? Read about the general basics here or check out advanced information here.
What is Testosterone HRT?
Testosterone is the primary sex hormone that produces “masculine” attributes, such as facial hair, a deepened voice, and higher muscle mass. Testosterone is prescribed to individuals assigned female at birth as part of their gender transition and monitored by their healthcare team to replicate natural testosterone production levels in cisgender men.
Unlike estrogen-based feminizing hormone replacement therapy, testosterone-based HRT does NOT require suppressants since testosterone naturally overpowers estrogen when used appropriately.
Isn’t Testosterone Also Prescribed to Cisgender Men?
Yep! HRT isn’t just for transgender people and was actually created originally to support cisgender people’s needs when bodies fail to produce adequate levels of testosterone or estrogen.
Prescription testosterone is monitored closely and is not dangerous to use, unlike anabolic steroid use.
Testosterone HRT Methods
Currently, there are multiple standard ways to use testosterone for HRT. The chosen administration method depends on:
- Personal convenience
- Lifestyle
- Side effects
- Hormone stability
- Insurance concerns
| Method | Frequency | Stability | Pros | Cons |
|---|---|---|---|---|
| Injection | 1x per week, two weeks, or four weeks | Peaks and troughs | Low cost, flexible dosing | Hormone fluctuations, needles |
| Topical | 1x per day | Very stable | No needles, consistent levels | High upkeep, transfer risk |
| Pellet | 1x per three to four months | Moderate fluctuation | Very low maintenance | Hard to access |
| Nasal | 3x per day | Stable | Minimal transfer risk | High upkeep, expensive |
| Oral | 1x per day | Stable | No needles, consistent levels | Toxic to the liver |
Injectable Testosterone
Injections are the most traditional form of masculinizing hormone replacement therapy, considered the gold standard for transgender men. The most common forms include testosterone enanthate (C26H40O3), testosterone cypionate (C27H40O3), testosterone propionate (C22H32O3), and testosterone phenylpropionate (C28H36O3).
Nearly all forms of injectable testosterone are ethers suspended in sesame oil or cottonseed oil that are absorbed slowly by the body due to esterification.
Injectable testosterone comes in TWO forms.
Injectable
Also known as IM, intramuscular shots are the most common form of testosterone prescribed. IM injections use longer, thicker needles to inject testosterone into the muscle.
Intramuscular injections commonly use needles 1” to 1.5” and 21 to 23 gauge. Needle length can vary depending on individual need since the needle must be long enough to puncture the muscle, although gauge size is standard to accommodate testosterone’s viscosity.
“That’s a huge needle! Doesn’t that hurt?!”
Actually, IM injections are not nearly as painful as they look. The needle is visually terrifying, but the size does not cause any additional pain compared to subcutaneous injections.
Pain is primarily caused when the needle breaks the skin barrier and activates nerves to notify your body of injury. Once the skin is broken, the needle continues to penetrate down into the fat and muscle – but neither contains nerve endings that will cause pain.
IM injections are performed on select locations, such as the butt and thigh, since they have plenty of muscle mass. The only complicating factor that can cause additional pain during IM injections is if you hit a vein. In the event you do, pull out the needle and try the injection again with a fresh needle and spot.
Subcutaneous
Subcutaneous, or subq, shots use smaller needles to inject testosterone into the subcutaneous fat just underneath the skin. Since subcutaneous injections only penetrate those two layers, they don’t require the length associated with IM injections.
Subq injections are also compatible via self-injectors like Xyosted, a medical pen that is used with your medication to deliver the medication via its spring mechanism. While IM can be done with self-injectors, it is difficult and less common.
Both subcutaneous and intramuscular shots are meant to be self-administered, although it is possible to find a provider or family member to help if you struggle with needle phobia. Since subq injections use smaller needles, folks find them easier to manage.
As noted with intramuscular injections, the pain associated with subq shots will be similar to IM, since pain is largely induced by breaking the skin barrier.
Never reuse needles. Make sure you’re disposing of used needles correctly and find a needle exchange program near you.
Topical Testosterone
Testosterone can be safely administered via dermal contact through gels, patches, and creams. Transdermal testosterone is applied daily in small doses and absorbed by the body throughout the day.
Hormone Stability and Pharmacokinetics
Pharmacokinetics refers to the effects of the body based on the original administration of a dose, including when it is eliminated and the time for the next dose.
Since bodies assigned female at birth cannot produce testosterone naturally, regular administration is required to maintain proper hormone levels.
One disadvantage of injectable testosterone is the pharmacokinetic cycle, causing hormonal dips and peaks. The day following testosterone injection is when testosterone levels are highest, causing side effects like mood swings and acne. Conversely, levels are lowest immediately before an injection and are associated with irritability and low energy, known as “T drop.” This cycle can be heightened or reduced based on dose frequency – some guys inject their testosterone every week, while others take it once a month.
In contrast, topical testosterone does not present noticeable dips or peaks since it is administered daily. All forms of topical testosterone produce a steady hormone dose with minimal fluctuation.
Is Topical Testosterone Less Effective Than Injections?
“I heard that topical testosterone isn’t as effective as injectable testosterone. Is that true?“
No. Empirical evidence shows that topical testosterone is just as effective as injectable testosterone. This myth is due to anecdotal accounts since many users post their results (or lack thereof) online, creating the illusion that topical testosterone is less effective. Injected testosterone may produce faster results in the first week, but this is completely negated in the following days.
The effectiveness of testosterone is NOT dependent on how it is administered.
Effectiveness is determined based on hormone levels and genetics. When undergoing hormone replacement therapy, a healthcare professional will monitor your hormone levels, and your testosterone prescription will be adjusted based on your levels.
In other words, your provider is going to make sure you obtain optimal hormone levels regardless of whether it is injectable or topical.
If you’re seeking less noticeable results from testosterone, that’s also an option – but you’ll need to find a provider that is knowledgeable in low-dose hormone replacement therapy since it’s not the norm. Again, the administration route does not matter; the lesser results are caused by a lower dose of testosterone for a set amount of time.
Genetics play a significant role in how secondary sex characteristics express themselves during hormone replacement therapy. Regardless of testosterone levels, some cisgender men struggle to ever grow facial hair or get a super deep voice. Testosterone levels influence the pace at which these results will appear, but genetics will cap off aspects like male pattern baldness, erectile tissue size, and body hair.
“Are there any downsides to topical testosterone? Why would anyone choose injectable testosterone instead?”
The application route is highly dependent on a variety of factors. Topical testosterone bypasses needle phobia (since there are no needles involved), but it has two main disadvantages.
Topical testosterone must be applied daily. Injectable testosterone is administered once every week, two weeks, or a month. Once injected, you’re free to go and forget about it until it’s time for the next dose. Thus, topical testosterone has a higher upkeep and is not recommended if you’re forgetful.
Secondly, topical testosterone must permeate the skin to be effective. This means you must make sure your hands are completely washed after applying to ensure testosterone does not transfer to other humans or animals, and avoid skin-to-skin contact on the application site even after it has dried. You also have to be wary of swimming, showering, or applying other creams (like sunscreen) on the application site since it will wash or dilute the medication.
As a minor footnote, lots of guys prefer injectable testosterone because it is cheapest. Topical testosterone can be expensive or laborious for insurance to cover.
Need help paying for prescriptions that insurance won’t cover? Try GoodRx.
Testosterone patches work the same way as gels and creams. Once applied, testosterone is absorbed through the skin via an alcohol-based gel in the patch.
Subcutaneous Testosterone Pellets
Pellets are a relatively new form that administers crystalline testosterone implanted beneath the skin.
Testosterone pellets are exceptionally small (about the size of a single grain of rice) and are inserted under local anesthesia every three to four months by a healthcare professional. Unlike other forms of HRT, pellets require visiting your provider to directly administer the medication.
Similar to the dips and peaks mentioned for injectable testosterone, pellets will suffer the same issue. They provide immense convenience since you only have to worry about the application every few months, but you’ll have starker dips during T drop.
“Pellets sound cool! Why haven’t I heard more about them??”
Likely because they’re hard to access. Injectable IM and subq testosterone are the standard methods, so you have to go out of your way to request pellets.
Just because a provider prescribes HRT doesn’t mean they’re knowledgeable or comfortable with pellets – so you’ll have to find a provider that specializes in it.
Nasal Testosterone Gel
Natesto is a form of hormone replacement therapy that utilizes a nasal gel to administer testosterone every six to eight hours.
It works similarly to topical testosterone, but it significantly reduces the risk of accidental transfer. On the other hand, nasal testosterone requires more upkeep since it is administered multiple times each day.
Due to how new nasal testosterone is, it’s rare to come across. As of the time of this article, there are no generic versions available and are considered too cost-prohibitive for most folks.
Oral, Sublingual, and Buccal Testosterone
Testosterone is also administrable orally through a pill, BUT it is not recommended for hormone replacement therapy due to how testosterone is compounded and dissolved by the body over time.
The chemical composition of testosterone is frequently modified to improve its functionality and allow the body to better absorb the medication. When modified synthetic testosterone enters the bloodstream, the excess ether compounds are cleaved off during hydrolization and force the testosterone to return to its bioidentical form, similar to naturally occurring hormones, ready to perform its associated tasks. Without the modification, testosterone would not be effective in slowly releasing hormones into the body.
When oral medications are administered, they are first absorbed through the gastrointestinal tract and passed into the liver. Without synthetic modifications, pure bioidentical testosterone is overwhelmingly metabolized through the liver, rendered ineffective. However, synthetic modifications to oral testosterone (such as methyltestosterone) are extremely hard on the liver and considered too toxic for long-term HRT when other safer methods are readily available.
Testosterone undecanoate, another form of oral testosterone, is considered safer but is also not recommended since it is eliminated from the body within a few hours and requires excessively frequent dosages that are expensive on the body and wallet.
Sublingual and buccal testosterone administer medication via dissolving it under the tongue or against the surface of one’s gums. Since it isn’t swallowed, sublingual and buccal testosterone avoids extreme liver toxicity that other forms of oral testosterone cause. Both are virtually impossible to find in the United States.
Want to learn more nerdy stuff about how synthetic testosterone works? Hudson’s Guide is detailed and explains the chemistry.
Frequently Asked Questions (FAQ)
Is testosterone safe to use long-term?
Yes. Long-term use of testosterone is generally considered safe, but only under the supervision of a healthcare professional to ensure your hormone levels are optimal.
There are a great deal of scary articles out there that claim testosterone is dangerous. Studies currently show that testosterone-based hormone replacement therapy is safe – although there is a lack of long-term high-quality data to study limitations in previous studies, since long-term studies require… time.
Testosterone does impact your health, but not in any particularly scary way. Cardiovascular issues, sleep apnea, and metabolic changes increase, BUT these changes place transgender men at the exact same risk as cisgender men with naturally occurring testosterone. HRT does not put you at an adverse risk, and monitoring prevents potential issues like polycythemia from happening.
Does brand name matter, or will using generic medication cause inferior results?
No. Pharmaceutical companies will say otherwise, but brand name doesn’t impact HRT effectiveness. The only thing that matters is the active ingredients and dosage.
Does injectable testosterone cause faster results than topical versions?
No. As explained in the topical testosterone section, accounts of injectable testosterone being more effective are anecdotal and not aligned with empirical evidence. Effectiveness of testosterone is determined by dose and HRT level, not administration route.
When will I see the effects of HRT?
That depends on dosage and genetics. Some changes, such as clitorial enlargement and acne, will occur quickly, while things like body hair and hairline changes can happen a decade into HRT. Look at the men in your family and consider how puberty impacted them to predict how HRT will manifest changes.
Read my basic guide to HRT for information on effects and timelines.