Novel Testosterone Delivery & Selective Tissue Agonists
Oral (Testosterone Undecanoate/Kyzatrex), Nasal (Natesto), SARMs as Therapeutics, and Tissue-Selective Androgens
Evidence grade 3 of 5, Mixed. Read how the Atlas grades evidence.
The written rationale for this grade is still being prepared.
- FDA
- Some oral/nasal forms FDA-approved; therapeutic SARMs investigational/none approved
- WADA
- Testosterone & SARMs prohibited (S1 Anabolic Agents)
Reference only. Not medical advice.
What can go wrong
Approved oral TU (e.g., Jatenzo) carries a blood-pressure boxed warning; all testosterone therapy can suppress spermatogenesis (nasal less so), raise hematocrit, and requires monitoring. SARMs are riskier and unregulated: documented hepatotoxicity, HPG-axis suppression, lipid changes, and frequent product mislabeling/contamination; they are banned in sport (WADA S1) and not approved for any therapeutic use. Self-administration without monitoring is the dominant real-world hazard.
This is something to take to a clinician. The Atlas can tell you what is known about novel testosterone delivery & selective tissue agonists in general. It cannot tell you what is happening in your body, and the difference matters most for exactly the symptoms that bring people to this page.
Low testosterone is one driver of reduced libido and ED, so testosterone delivery innovation matters to sexual health. Genuinely approved newer options include oral testosterone undecanoate (Jatenzo 2019; Tlando, Kyzatrex) that overcame the old hepatotoxicity problem via lymphatic absorption, and nasal testosterone (Natesto), which uniquely tends to preserve gonadotropins/fertility better than injections or gels. Beyond replacement, the long-promised frontier is selective androgen receptor modulators (SARMs), tissue-selective compounds intended to give androgenic benefit (libido, muscle) with fewer prostate/cardiovascular effects. Despite decades of work, NO SARM is FDA-approved as a therapeutic; they remain investigational and are sold illegally as 'research chemicals' and gray-market supplements. The marketplace conflates approved delivery innovations with unapproved SARMs.
New ways to deliver testosterone are real and approved; 'tissue-selective' SARMs as therapeutics remain unproven.
What people take it for
These are the reasons people give for taking it. They are not effects it has been shown to have.
How it is supposed to work
Testosterone supports libido, nocturnal erections, and nitric-oxide signaling; restoring physiological levels in genuinely hypogonadal men can improve desire and erectile function (additive to PDE5 inhibitors in some). Delivery innovations solve specific problems: oral testosterone undecanoate is absorbed via intestinal lymphatics, bypassing first-pass liver toxicity that doomed older oral androgens; nasal testosterone's short pulsatile exposure tends to suppress the HPG axis less, better preserving sperm production. SARMs are non-steroidal ligands designed to activate androgen receptors selectively in muscle/bone while sparing prostate, but true tissue selectivity with proven benefit-risk has not been clinically delivered.
The catch: 'tissue-selective' SARMs never cleared the therapeutic bar
SARMs (ostarine/enobosarm, ligandrol/LGD-4033, RAD-140, and others) have been studied for muscle wasting, osteoporosis, and hypogonadism for ~20 years, yet none has achieved FDA approval as a therapeutic, efficacy/safety trade-offs (including hepatotoxicity and HPG suppression for some) and selectivity that is far less clean in humans than the marketing implies. They are explicitly NOT legal dietary supplements; the FDA has warned consumers, and products sold online are frequently mislabeled or contaminated. Conflating these with approved oral/nasal testosterone is a common marketing sleight-of-hand.
Safety in detail
Testosterone therapy involves significant physiological effects and requires evaluation and monitoring by a qualified physician. Self-administration of testosterone or SARMs without medical oversight carries documented health risks, including infertility, cardiovascular and hepatic effects, and (for SARMs) exposure to unapproved, frequently mislabeled products.
Replacement is not the same as a cycle
Physiological replacement aims to restore testosterone to a normal range and, in hypogonadal men, can improve libido/ED with monitored risks. Supraphysiological/anabolic dosing (and most SARM misuse) pushes androgen exposure above normal for physique/performance, sharply increasing risks of polycythemia, cardiovascular strain, HPG-axis shutdown, infertility, and (for some SARMs) liver injury, without added sexual-health benefit.
What it does to fertility
Exogenous testosterone suppresses LH/FSH and spermatogenesis and can cause infertility; nasal testosterone (Natesto), via short pulsatile exposure, tends to preserve gonadotropins and fertility better than gels/injections. Some SARMs also suppress the HPG axis.
What has to be monitored
The bloodwork this needs, and the reason it belongs with a clinician rather than a website.
- Total/free testosterone
- Hematocrit/hemoglobin
- PSA (age-appropriate)
- Blood pressure (esp. oral TU)
- Lipid panel
- LH/FSH and semen analysis if fertility is a concern
What people get wrong
Often saidSARMs are a safe, legal testosterone alternative
ActuallyNo SARM is FDA-approved as a therapeutic; they are not legal supplements, are frequently mislabeled/contaminated, and carry documented harms.
Often saidAll testosterone kills fertility equally
ActuallyNasal testosterone (Natesto) tends to preserve fertility better than gels/injections due to its short pulsatile profile.
Often saidOral testosterone destroys the liver
ActuallyOld C17-alkylated orals did; modern oral testosterone undecanoate is lymphatically absorbed and avoids that hepatotoxicity (though it has a BP warning).
Who profits, and who pushes back
U.S. Food and Drug Administration
SARMs are unapproved drugs, not dietary supplements; they are associated with serious safety concerns and have not been proven safe or effective.
Ranjith Ramasamy, MD
Nasal testosterone offers a fertility-sparing option that conventional TRT does not, but exogenous androgens still require careful monitoring.
What we do not know
- Will any SARM ever clear the therapeutic benefit-risk bar?
- How widely should fertility-sparing nasal T replace conventional TRT?
- Can tissue-selective androgens meaningfully reduce prostate/CV risk in humans?
At a glance
- Oral TU approved
- Jatenzo (2019), Tlando, Kyzatrex
- Nasal T
- Natesto (fertility-sparing profile)
- Approved therapeutic SARMs
- None
- SARM legal status
- Not dietary supplements; sold illegally
What this entry does not yet cover
What follows is unfinished work on our side, not a finding about Novel Testosterone Delivery & Selective Tissue Agonists. A short entry is not a safe entry.
- Cost and market. We have not documented what it sells for or who sells it.
- Supply chain. We have not mapped where it is made.
- Who uses it. We have not documented the user groups.
- What could change. No forward-looking summary yet.
- How it compares. We have not set it against the alternatives.
- Children and teenagers. We have not checked what is known about younger people.
Sources
The studies below are named and described, but not linked. You cannot open them from here and check our reading against them, which means this page is our summary of the literature rather than a document you can verify. Weigh it accordingly until the links exist.
The studies that matter
Jatenzo (oral TU) approval program2019
Lymphatically absorbed oral testosterone undecanoate approved; carries a blood-pressure boxed warning
Natesto fertility studies (Ramasamy group)2019-2021
Nasal testosterone better preserved gonadotropins/spermatogenesis than conventional TRT
Enobosarm (ostarine) trials2010s
SARM showed lean-mass gains in cancer cachexia but failed to translate into approval; selectivity/benefit-risk insufficient