Short answer: In the 90-day Natesto study of 78 men using it three times daily, the most common reactions were PSA increased (5.1%), then headache, runny nose, nosebleed, nasal discomfort, nasopharyngitis, bronchitis, upper respiratory infection, sinusitis and nasal scab (3.8% each). The study had no placebo group. Across 306 men, nasal reactions were mostly mild or moderate. Natesto has no boxed warning.
What Natesto is approved for: Natesto is approved as replacement therapy in adult males with low or absent natural testosterone due to primary hypogonadism (testicular failure) or hypogonadotropic hypogonadism (a pituitary or hypothalamus cause). The label says safety and efficacy have not been established in men with "age-related hypogonadism" or in males under 18 (section 1).
Source
NATESTO (testosterone) nasal gel, CIII, prescribing information and Patient Information. Acerus Pharmaceuticals. DailyMed, version published July 29, 2026. DailyMed setid dea6bed1-eaca-11e3-ac10-0800200c9a66
No. The current Natesto label has no boxed warning.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Natesto.
| Adverse reaction | Natesto (11 mg of Testosterone) Three Times Daily (N=78) n (%) |
|---|---|
| PSA increased | 4 (5.1) |
| Headache | 3 (3.8) |
| Rhinorrhea | 3 (3.8) |
| Epistaxis | 3 (3.8) |
| Nasal discomfort | 3 (3.8) |
| Nasopharyngitis | 3 (3.8) |
| Bronchitis | 3 (3.8) |
| Upper respiratory tract infection | 3 (3.8) |
| Sinusitis | 3 (3.8) |
| Nasal scab | 3 (3.8) |
Open-label 90-day study; 78 of 306 men with morning testosterone of 300 ng/dL or less used 11 mg three times daily. There was no placebo group. PSA increased meant a rise of more than 1.4 ug/L from baseline or a PSA above 4.0 ug/L. Reactions at more than 2% but under 3% were blood pressure increased, taste change, nasal dryness, nasal congestion and cough.
| Adverse reaction | Natesto 11 mg TID (N=69) n (%) |
|---|---|
| Nasopharyngitis | 6 (8.7) |
| Rhinorrhea | 5 (7.2) |
| PSA increased | 4 (5.8) |
| Parosmia | 4 (5.8) |
| Nasal discomfort | 4 (5.8) |
| Nasal Scab | 4 (5.8) |
| Upper respiratory tract infection | 3 (4.3) |
| Bronchitis | 3 (4.3) |
| Procedural pain | 3 (4.3) |
| Pain in extremity | 3 (4.3) |
| Headache | 3 (4.3) |
| Epistaxis | 3 (4.3) |
69 men who used Natesto three times daily in the 90-day study and the first 90-day extension.
Nasal reactions across all 306 men at any dose over up to a year: nasopharyngitis 8.2%, runny nose 7.8%, nosebleed 6.5%, nasal discomfort 5.9%, altered sense of smell (parosmia) 5.2%, nasal scab 5.2%, upper respiratory infection 4.2%, nasal dryness 4.2% and nasal congestion 3.9%.
Stopping for side effects: 6 of 306 men, one each for nasal discomfort, headache, taste change, PSA increase, an allergic reaction (hives, swollen lips and tongue), and muscle and joint aches with fever, chills and small skin bleeds.
Hematocrit went above 55% in 4 of 306 men; it never exceeded 58%. Mean PSA rose by 0.2 ng/mL after 90 days, 0.1 ng/mL after 180 days and 0.2 ng/mL after 360 days.
In TRAVERSE, a heart-outcomes study of a testosterone gel on the skin (not Natesto), major heart events were 7.0% vs 7.3% on placebo; arrhythmias needing treatment (5.2% vs 3.3%), atrial fibrillation (3.5% vs 2.4%), acute kidney injury (2.3% vs 1.5%) and fractures (3.5% vs 2.5%) were higher on the gel.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Nasal side effects. Runny nose, nosebleeds, nasal discomfort and scabbing were reported, almost all mild or moderate, but long-term nasal safety data are limited. Nasal symptoms are reported to the prescriber, who may refer to an ear, nose and throat specialist or stop Natesto.
Chronic nasal conditions. Natesto is not recommended for people with a history of nasal disorders, nasal or sinus surgery, a nasal fracture in the last 6 months or one that caused a deviated septum, mucosal inflammatory disorders such as Sjogren's syndrome, or sinus disease.
Polycythemia (high red blood cells). Hematocrit is checked before starting, again 3 to 6 months later, then yearly. If it is high, Natesto is stopped until it comes down.
Blood clots. Deep vein thrombosis and pulmonary embolism have been reported with testosterone products. In TRAVERSE, clots occurred in 1.7% on a testosterone gel vs 1.2% on placebo. If a clot is suspected, Natesto is stopped.
Enlarged prostate and prostate cancer. BPH symptoms may worsen, and androgens may raise prostate cancer risk. Prostate cancer is checked for before starting, 3 to 6 months later, and then by usual screening.
Blood pressure increases. Testosterone can raise blood pressure, which can raise heart risk over time. Blood pressure is checked periodically, and Natesto is not recommended with uncontrolled high blood pressure.
Abuse. Testosterone has been abused at high doses, often with other anabolic steroids, which can cause serious heart and mental health problems.
Not for use in women. Natesto is not indicated for women and must not be used by women who are or may become pregnant or are breastfeeding (section 4).
Sperm production. Large doses of testosterone may suppress sperm production and lower sperm count.
Liver effects. Serious liver problems have been linked to high-dose oral 17-alpha-alkyl androgens. Natesto is not known to cause them, but if signs like jaundice appear, it is stopped while the cause is checked.
Edema. Androgens can cause salt and water retention, which can be serious in people with heart, kidney or liver disease.
Gynecomastia. Breast enlargement may develop and may persist.
Sleep apnea. Testosterone may worsen sleep apnea, especially with obesity or chronic lung disease.
Lipid changes. Blood fats can change; lipids are checked periodically, particularly after starting.
High calcium. In cancer patients at risk of high calcium, calcium is checked regularly.
Thyroid lab values. Androgens can lower thyroxine-binding globulin and total T4 on tests, without a change in free thyroid hormone or signs of thyroid disease.
From the Patient Information that comes with Natesto:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.