Natesto (Testosterone) - Nasal

What Is Natesto?

Natesto (testosterone) is a nasal gel used to replace endogenous (caused by internal factors) testosterone in people designated male at birth 18 and older with insufficient levels of endogenous testosterone as a result of certain medical conditions associated with the testes.

Natesto is classified as an androgen, or a sex hormone, and works by replacing testosterone to further develop and maintain male features. 

Natesto's testosterone replacement helps with the development and maintenance of male features, such as body hair, sex organs, vocal cords, and body fat distribution.

Currently, there is no therapeutic equivalent to Natesto, either as a generic or brand-name medication. As a result, this article will focus on Natesto, a brand-name drug that administers a prescription nasal gel through a multi-dose pump.

Drug Facts

Generic Name: Testosterone

Brand Name(s): Natesto

Drug Availability: Prescription

Therapeutic Classification: Endocrine-metabolic agent

Available Generically: Yes

Controlled Substance: Schedule III

Administration Route: Nasal

Active Ingredient: Testosterone

Dosage Form(s): Nasal gel

What Is Natesto Used For?

The Food and Drug Administration (FDA) has approved Natesto to replace testosterone in people designated male at birth with conditions that cause low or no testosterone, including:

Of note, Natesto has not been studied for use in males with low testosterone levels due to age, also known as "age-related hypogonadism".

Natesto has also not been studied in male children and adolescents under age 18 and is not approved for anyone under 18.

How to Use Natesto

If you are prescribed Natesto:

Use Natesto exactly as directed by your healthcare provider, and do not skip doses. Use Natesto in the nose only. Do not use it on the mouth or skin. Natesto can be used with certain nasal sprays that contain decongestants, such as oxymetazoline.

Natesto should not be used with other nasal sprays because safety and efficacy have not been studied. Before using Natesto for the first time, prime your pump, following the directions in your medication guide. Before using Natesto, blow your nose gently.

Use one pump in each nostril three times daily or as directed. Apply it at about the same times each day. Space the doses about six to eight hours apart.

Do not blow your nose or sniff for an hour after using Natesto. Wash your hands with soap and water if any gel gets on your hands.

Storage

Store Natesto at room temperature, away from direct light, heat, and moisture.

Do not store it in the bathroom. Discard used dispensers in household trash in a way that prevents children or pets from accessing them. Because Natesto contains testosterone, it is classified as a controlled substance (Schedule III), which can cause abuse and dependence.

Testosterone can be a target for people who abuse medications. Keep Natesto in a safe place where others cannot get to it. Keep Natesto out of reach and out of sight of children and pets.

Do not share your medication with anyone else, even if they have similar symptoms or medical conditions. It is against the law to sell or give away this medication.

Off-Label Uses

Sometimes Natesto is used off-label for indications that are not FDA-approved.

Healthcare providers may prescribe a testosterone replacement, such as Natesto, to transgender males (a female transitioning to male) to help develop male features and suppress female features.

Testosterone therapy is sometimes prescribed off-label for males with low testosterone levels and experiencing symptoms to help replace testosterone and maintain secondary sex characteristics (such as body hair and muscle mass).

Although Natesto is not approved for age-related low testosterone, older adult males with symptoms may sometimes be prescribed testosterone replacement off-label if the benefits outweigh the risks.

How Long Does Natesto Take to Work?

After a single dose of Natesto, the highest levels of testosterone are reached in about 40 minutes. However, it may take several weeks to start to see an improvement in symptoms.

What Are the Side Effects of Natesto?

This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your pharmacist or healthcare provider. You may report side effects to the FDA at fda.gov/medwatch or 800-FDA-1088.

Common Side Effects

The most common side effects of Natesto are:

Severe Side Effects

Call your healthcare provider right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency.

Serious side effects and their symptoms can include the following:

  • Anaphylaxis (serious allergic reaction): Get emergency medical help if you have urticaria (hives), difficulty breathing, or swelling of the face, lips, tongue, or throat
  • Prostate cancer: Symptoms may include difficulty urinating, frequent urination, pain while urinating, blood in the urine
  • Benign prostatic hyperplasia (BPH) worsening: Symptoms may include difficulty urinating, frequent urination, feeling of urgency to urinate
  • Blood clot in the lung: Be alert to chest pain, cough, wheezing, fast breathing, and coughing up blood
  • Blood clot in the leg: Be aware of pain, swelling, warmth, and redness in one or both legs
  • Possible increased risk of stroke and heart attack
  • High red blood cell (RBC) levels
  • Abuse and dependence
  • Development of male sex characteristics in females or children from secondary exposure
  • Liver problems or liver cancer (from long-term, high-dose use): Be alert to nausea, stomach pain, itching, appetite loss, dark urine, clay-colored stools, or jaundice (yellowing of the skin or whites of the eyes)

Long-Term Side Effects

There is little information on the long-term use of Natesto.

However, there is more information about the long-term use of testosterone in general:

Clinical guidelines from the American College of Physicians, published in the Annals of Internal Medicine in 2020, noted that in 20 studies (with a follow-up ranging from less than one year to over 10 years), there was no increased risk of death, heart events (like stroke or heart attacks), prostate cancer, or blood clots in the lungs or legs.

However, the study also noted a lack of evidence of long-term safety and that most studies did not include men with heart disease.

Subsequently, the best course of action would be to consult your healthcare provider, who can consider your individual factors like age, medical conditions, and symptoms, and weigh the risks versus benefits of testosterone treatment.

Report Side Effects

Natesto may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication. If you experience a serious side effect, you or your healthcare provider may send a report to the FDA's MedWatch Adverse Event Reporting Program or by phone (800-332-1088).

Dosage: How Much Natesto Should I Take?

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The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For nasal dosage form (gel):
    • For hormone replacement:
      • Adults—11 milligrams (mg), or 1 pump actuation in each nostril, 3 times a day (once in the morning, once in the afternoon, and once in the evening, about 6 to 8 hours apart).
      • Children—Use and dose must be determined by your doctor.

Modifications

Potential users should be aware of the following before starting treatment with Natesto:

Older adults: Males 65 and older should consult their healthcare provider before using Natesto. According to the prescribing information, there is not enough data from clinical studies in this population to determine if there is a greater risk of heart disease, prostate cancer, and worsening of BPH.

Use in females/pregnant and breastfeeding females: Natesto is not approved for use in females of any age (and if used in pregnant/breastfeeding women, Natesto could cause serious harm to the unborn fetus).

Children: Natesto is not approved for any person under the age of 18.

Kidney/liver issues: Natesto has not been studied in people with kidney or liver problems, therefore people with any type of kidney or liver impairment should consult their healthcare provider before starting treatment.

Missed Dose

If you miss a dose of Natesto, use it as soon as you remember. However, if it is almost time for the next dose, skip the missed dose. Do not use extra medicine to try to make up for a missed dose.

Overdose: What Happens If I Take Too Much Natesto?

There is no information available on the potential for overdose with Natesto. The prescribing information reads, "No cases of overdose with Natesto have been reported in clinical trials."

What Happens If I Overdose on Natesto?

If you think you or someone else may have overdosed on Natesto, call a healthcare provider or the Poison Control Center (800-222-1222). If someone collapses or isn't breathing after taking Natesto, call 911 immediately.

Precautions

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It is very important that your doctor check your progress while you are using this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to use it. Blood and urine tests may be needed to check for unwanted effects.

Do not use Natesto® together with other medicines given into your nose (eg, oxymetazoline), unless your doctor says it is okay.

This medicine should not be used by women. Testosterone may cause birth defects if a pregnant woman comes in contact with the medicine. Make sure your doctor knows if your sexual partner is pregnant. If a pregnancy occurs while you are using this medicine, tell your doctor right away.

This medicine may cause nasal problems. Check with your doctor right away if you have a runny nose, congestion, sneezing, nosebleeds, nasal discomfort, nasal scabbing, or nasal dryness while using this medicine.

This medicine may cause blood clotting problems. Check with your doctor right away if you have a chest pain, trouble breathing, coughing up blood, numbness or weakness in your arm or leg, or on one side of your body, or pain in your lower leg (calf) while using this medicine.

This medicine may increase your risk of having a heart attack or stroke. Tell your doctor right away if you have chest pain that may spread to your arms, jaw, back, or neck, faintness, headache, nausea, vomiting, trouble breathing, trouble seeing or speaking, or unusual sweating.

This medicine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.

Tell your doctor if your female partner or child starts to have male-like body changes while you are using this medicine. Such changes may include hair growth on the face, a deeper voice, or a significant increase in acne. The changes may also include an enlarged penis or clitoris, early development of pubic hair, increased erections or sexual desire, aggressive behavior, and bone problems.

In some cases, this medicine may decrease the amount of sperm men make and affect their ability to have children. If you plan to have children, talk with your doctor before using this medicine.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

This medicine may cause fluid retention (edema) in some patients. Tell your doctor right away if you have bloating or swelling of the face, arms, hands, lower legs, or feet, tingling of the hands or feet, or unusual weight gain or loss.

This medicine may affect the results of the prostate specific antigen (PSA) test, which may be used to detect prostate cancer. Make sure you tell all of your doctors that you are using this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

What Are Reasons I Shouldn't Take Natesto?

Natesto is not appropriate for everyone. Before taking Natesto, tell your healthcare provider about your medical conditions, medical history, and family history.

You should not take this medication if you are allergic to testosterone or any of the inactive ingredients in Natesto. 

Other people who should not take Natesto include:

Natesto may be prescribed with caution in some people, only if the healthcare provider determines it is safe. This includes:

  • Males who are at risk for prostate cancer
  • Males with BPH
  • Older adults
  • Males with kidney or liver problems
  • Males with cancer who are at risk for hypercalcemia (high calcium)
  • Males with heart disease or heart failure
  • Males with high cholesterol
  • Males with diabetes
  • Males with chronic lung disease or sleep apnea
  • Males with obesity
  • Males with polycythemia (a type of blood cancer)
  • Males with a history of nasal disorders, sinus or nasal surgery, or sinus disease
  • Males who have had a nasal fracture in the past six months
  • Males with a deviated septum (a condition where the wall between nasal passages is displaced to one side, making one nasal air passage bigger than the other)
  • Males with a mucosal inflammatory disorder such as chronic obstructive pulmonary disease (COPD) or inflammatory bowel disease
  • Males with Sjogren's syndrome (an immune system disorder that causes dry eyes and dry mouth)

What Other Medications May Interact With Natesto?

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter (OTC) medicines, and vitamins or supplements.

While taking Natesto, do not start any new medications without initial approval from your healthcare provider.

Some potential drug interactions associated with the simultaneous use of Natesto include:

These drug interactions do not necessarily mean that they can not be taken with Natesto; however, a dosage adjustment and additional monitoring may be required. Always consult your healthcare provider regarding drug interactions and how they may affect you.

This is not a full list of drug interactions. Other drug interactions may occur with Natesto. Consult your healthcare provider for a complete list of drug interactions.

What Medications Are Similar?

There are other various formulations of testosterone - including injections, oral capsules, and patches or gels, that can be used to replace testosterone in males, such as:

  • Depo-Testosterone (testosterone cypionate) injection
  • Xyosted (testosterone enanthate) injection
  • Jatenzo (testosterone undecanoate) oral capsules
  • Kyzatrex (testosterone undecanoate) oral capsules
  • Tlando (testosterone undecanoate) oral capsules
  • Androderm (testosterone) transdermal patch
  • AndroGel (testosterone) transdermal gel
  • Fortesta (testosterone) transdermal gel
  • Testim (testosterone) transdermal gel
  • Vogelxo (testosterone) transdermal gel

This list is a list of drugs also prescribed to replace testosterone. It is not a list of drugs recommended to take with Natesto. Ask your healthcare provider if you have any questions.

Frequently Asked Questions

  • What is Natesto used for?

    Natesto is a prescription nasal gel that contains testosterone. It is used for adult males with certain medical conditions who either do not make enough or do not make any testosterone.

  • What are the side effects of Natesto?

    Common side effects may include a runny nose, common cold symptoms, increased PSA levels, altered sense of smell/taste, nasal discomfort or scabbing, bronchitis, headache, bloody nose, sleep apnea, swollen male breast tissue, and the potential for a sinus infection.

    Other, serious side effects can occur too, such as prostate cancer and/or the potential for abuse and dependence. Before taking Natesto, discuss the side effects with your healthcare provider.

  • How does Natesto work?

    Natesto works by replacing the testosterone that the body is not making on its own.

How Can I Stay Healthy While Taking Natesto?

To stay healthy while taking Natesto, follow your healthcare provider's recommendations.

For example, you will need regular bloodwork to check your PSA levels, hematocrit levels (the proportion of red blood cells in your blood), calcium levels, and cholesterol. If you have BPH, you will be monitored for worsening symptoms.

If you take a blood thinner, such as warfarin, you will need more frequent monitoring. Your healthcare provider may also recommend monitoring your blood pressure regularly at home.

Keeping up with your healthcare provider's appointments and monitoring will help you feel your best while using Natesto.

Medical Disclaimer

Verywell Health's drug information is meant for educational purposes only and is not intended as a replacement for medical advice, diagnosis, or treatment from a healthcare provider. Consult your healthcare provider before taking any new medication(s). IBM Watson Micromedex provides some of the drug content, as indicated on the page.

11 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Karen Berger, PharmD
Karen Berger, PharmD, is a community pharmacist and medical writer/reviewer.