Natesto Side Effects: What to Expect and When to Call Your Doctor

Natesto (testosterone nasal gel) is generally well-tolerated, but like all testosterone replacement therapies, it carries both common side effects and potentially serious risks. Because Natesto is administered into the nose, it also has a unique set of nasal side effects that set it apart from topical or injectable testosterone. Here is what you need to know before starting — or if you are already on it.

Common Side Effects of Natesto

The following side effects occurred in more than 3% of patients in Natesto's clinical trials:

Increased PSA (prostate-specific antigen) — Your provider will monitor PSA levels while you are on testosterone therapy.

Headache — One of the most commonly reported side effects in clinical trials.

Rhinorrhea (runny nose) — A direct result of nasal administration.

Epistaxis (nosebleed) — Usually mild; if persistent or severe, notify your provider.

Nasal discomfort or scabbing — Can occur at the application site inside the nostril.

Nasopharyngitis — Irritation of the nasal passages and throat.

Upper respiratory tract infection / bronchitis / sinusitis — Reported at low rates in clinical trials.

Most nasal side effects are mild or moderate in severity. Clinical trial data found that less than 9% of Natesto users experience significant nasal side effects. However, if nasal symptoms are persistent, you should report them to your prescriber promptly, as a temporary or permanent discontinuation of Natesto may be necessary.

Serious Side Effects: When to Call Your Doctor Immediately

The following side effects require prompt medical evaluation. Call your provider or seek emergency care if you experience:

Signs of a blood clot (DVT or pulmonary embolism): leg pain, swelling, redness, chest pain, shortness of breath, coughing up blood. Testosterone therapy increases the risk of venous thromboembolism.

Signs of a stroke or heart attack: sudden weakness on one side of the body, trouble speaking, difficulty walking, chest pain, or cold sweats. Some studies have associated testosterone replacement with increased cardiovascular risk.

Severe allergic reaction: hives, difficulty breathing, swelling of the face or throat. Stop using Natesto and seek emergency care immediately.

Signs of liver damage: yellowing of the skin or eyes (jaundice), dark urine, abdominal pain. Call your doctor right away.

Fluid retention / edema: unusual swelling in your legs or feet, especially if you have heart failure or kidney problems.

Prostate symptoms: frequent or difficult urination, weak urine stream, nighttime urination. Testosterone can worsen benign prostatic hyperplasia (BPH) or increase PSA levels.

Other Side Effects to Monitor

Polycythemia (increased red blood cells): Your provider will check hematocrit periodically. If it becomes too high, Natesto may need to be paused.

Gynecomastia: enlarged or tender breast tissue in men. Tell your provider if this occurs.

Sleep apnea: Testosterone therapy may worsen sleep apnea in men with risk factors. Report new or worsening snoring or sleep disturbance.

Decreased sperm count: All testosterone therapies can suppress sperm production. Natesto appears to suppress this less than other formulations, but discuss fertility concerns with your provider.

Changes in lipid levels: Testosterone may affect cholesterol. Periodic lipid panels are recommended during long-term therapy.

Unique Considerations for Nasal Administration

Because Natesto is applied inside the nose, it should not be used by patients with:

Chronic nasal conditions (nasal polyps, chronic sinusitis, mucosal inflammatory disorders)

A deviated anterior nasal septum (which could affect drug distribution)

Recent nasal or sinus surgery within the past 6 months

Additionally, if you have a severe rhinitis episode (such as a bad cold with significant congestion), your doctor may advise temporarily discontinuing Natesto because nasal congestion reduces absorption by 21–24%.

What Monitoring Is Required on Natesto?

Your provider should monitor the following during Natesto therapy:

Serum testosterone levels: starting at 1 month, then periodically thereafter. Target range: 300–1050 ng/dL.

Hematocrit: at 3–6 months, then annually. Discontinue if elevated.

PSA: before starting and periodically during treatment.

Blood pressure: periodically, especially in hypertensive patients.

For more detail on Natesto drug interactions and what to tell your doctor, see our guide to Natesto drug interactions.