In March, 2019, the FDA approved an oral testosterone capsule with the brand name Jatenzo for use in the United States.
Jatenzo is a capsule form of testosterone undecanoate that is taken twice a day with meals (ideally, the morning and evening meals.) Like many of the medications used in gender affirming care (GAC,) the clinical studies to get Jatenzo approved were not done in queer and trans populations. For Jatenzo, the clinical study population was 166 people with testes and “insufficient secretion of testosterone.” Still, we can apply those learnings to GAC.
In May, 2014, the FDA approved a nasal gel form of testosterone under the brand name Natesto. The Natesto clinical trial population was 306 people with testes and hypogonadism (low production of sex hormones.) Nasal testosterone is applied three times daily, 6 to 8 hours apart.
Neither of these forms of testosterone have been studied in people with ovaries or in adolescents. Natesto was also not tested in larger people.
Is oral or nasal T right for me?
Both are good options if needles and you aren’t friends.
Both need less care in application than gels or creams, although they should be kept away from other people and pets and stored at room temperature. If you’ve had skin reactions to other forms of testosterone, oral T may be a good choice for you.
Both may “even out” blood levels of testosterone and related mood changes due to more frequent dosing. When taken orally, blood levels of testosterone peak twice a day, about 2 hours after ingestion. When taken nasally, blood levels peak about 40 minutes after use.
Both oral and nasal T require daily administration – and nasal T is applied three times a day! This may be easier to manage for some people, and harder for others – more frequent medication doses can be a barrier to consistent use.
Risks and potential side effects of these forms of testosterone are generally the same as other forms. Testosterone can increase blood pressure in all folx, and may be stressful to the liver. There are some studies that show that nasal and topical T are potentially less stressful to the liver, but they are limited in size and the results are mixed: there’s no clear answer. Livers that have multiple stressors like other medications, alcohol intake, or conditions that affect the liver like hepatitis or “fatty” liver, may be at a higher risk of damage.
See our “All The T” resource page for an in-depth discussion of starting testosterone use and our blog “Cardiovascular Risks with HRT” for specific risk information.
What’s unique about side effects for these forms of T?
There are some side effects specific to oral and nasal T that aren’t commonly experienced when using other forms of T.
- Side effects reported by more than 2% of oral T clinical trial participants: diarrhea, upset stomach, burping, nausea, headache
- Side effects reported by more than 3% of nasal T clinical trial participants: headache, runny nose, bloody nose, nasal discomfort, colds and upper respiratory infections
- Parosmia (change in the sense of smell) was reported by about 5% of participants. If smell is one of your sensory fun places, this could be a deal-breaker.
What else is important?
Oral T should be taken with meals. The amount of fat in the meal may affect bioavailability. The prescribing information indicates better availability when the meal contains at least 30 g of fat. That’s roughly:
- Three tablespoons of butter
- Four tablespoons of peanut butter
- Three tablespoons of olive oil
- Two ounces of almonds (about 46 almonds)
- Three ounces of bacon
- Three ounces of cheddar cheese
This may be more fat than is optimal for your body, depending on your body’s needs, your other health goals, and your total cardiovascular risk.
Patients with allergic rhinitis (nasal allergy symptoms) achieved lower average blood concentrations of T during the clinical studies. It is recommended that you refrain from blowing your nose, sniffing, or laying down within one hour after using the nasal spray. If you’ve ever had a broken nose, or currently have a deviated septum, nasal T might not be a good choice for you. While it is not included in the prescribing information, conditions other than nasal allergy symptoms that cause frequent runny nose or stuffiness, like chronic sinusitis (sinus problems) may cause lower concentrations of T as well.
There is some evidence from studies in cis men that testosterone from nasal applications both reaches the brain faster and increases total testosterone levels in the brain compared to injectable testosterones. There is also evidence that higher testosterone levels in the brain (in cis men whose bodies don’t produce a lot of testosterone) positively affect mood. We don’t have good research studies in trans populations, but it may be that people who take nasal T may notice mood and “brain feel” changes faster and stronger than people who take other forms of T. We don’t have clinical experience to support this because nasal T is both relatively new and not often used.
The clinical safety trials of Natesto indicated that cis men taking nasal T had lower levels of two other androgens – DHT and DHT/T – in their blood than cis men taking other forms of testosterone. DHT is necessary for the development of secondary sexual characteristics during cis male puberty. Once again, we have no data in trans populations, but it is possible that individuals using nasal T in gender affirming care may experience slower or more subtle T-associated changes to the body.
Both formulations contain castor oil and should not be used if you are allergic or sensitive to castor oil. Jatenzo uses a gelatin capsule, and is not vegetarian. (Full ingredient information is available in the prescribing information documents available below.)
Both of these forms of T are newer and are less commonly available, so obtaining them may be more difficult than injectable T.
If you don’t have insurance, they are quite expensive. Natesto (via goodrx.com) is about $200/month. Jatenzo retails at close to $1000/month. If you do have insurance, these forms may not be included in your drug benefits, or they may require a prior authorization or evidence that you’ve tried other forms of testosterone in the past (often known as “step therapy.”) The manufacturers of both drugs have programs that may be able to help you with financial support and/or administrative support with your insurance company. Like other forms of testosterone, both oral and nasal testosterone are Schedule III drugs.
Interested in starting testosterone therapy or changing your form of testosterone? Contact us for an introductory appointment (or book now if you’re already a patient!)
Swerdloff, R.S., and Dudley, R. (2020) A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men. Therapeutic Advances in Urology, Ther Adv 2020, Vol. 12: 1–16. https://journals.sagepub.com/doi/pdf/10.1177/1756287220937232
Rogol, A.D., Tkachenko, N. and Bryson, N. (2016), Natesto™, a novel testosterone nasal gel, normalizes androgen levels in hypogonadal men. Andrology, 4: 46-54. https://doi.org/10.1111/andr.12137
Shoskes JJ, Wilson MK, Spinner ML. Pharmacology of testosterone replacement therapy preparations. Transl Androl Urol. 2016 Dec;5(6):834-843. doi: 10.21037/tau.2016.07.10. PMID: 28078214; PMCID: PMC5182226.
Claxton, Ami & Cramer, Joyce & Pierce, Courtney. (2001). A systematic review of the associations between dose regimens and medication compliance. Clinical therapeutics. 23. 1296-310. 10.1016/S0149-2918(01)80109-0.