Side effects of androgel

Contents

Androgel

Androgel is the brand name of a testosterone treatment that’s available as a topical gel.

It’s used to treat men who have low levels of the hormone testosterone due to medical conditions such as hypogonadism.

Androgel works by restoring normal levels of the hormone testosterone in the body.

Low testosterone levels (low T) can affect muscle mass, strength, sex drive, and mood.

Androgel is used on the upper arms, shoulders, or stomach area. (Another topical testosterone medicine, Axiron, is applied to the armpit area.)

Some men with sensitive skin may tolerate Androgel better because they can rotate the area of application.

Androgel was the first testosterone gel product. It became available in the United States as a prescription medicine in 2000.

According to the manufacturer, a clinical study found that testosterone levels of 82 percent of men who used Androgel for 16 weeks returned to normal, compared with 37 percent of men who used a placebo.

The Food and Drug Administration (FDA) first approved testosterone treatment in 1953. Androgel is marketed by AbbVie Inc.

Androgel Warnings

Androgel includes a black-box warning because its ingredients can transfer to other people.

This can happen if others come in contact with the application area. Women and children, in particular, should avoid contact with Androgel.

The medicine is absorbed through the skin and can cause male physical traits in those who are exposed to it.

Call a doctor right away if a child is exposed to Androgel and experiences:

  • An enlarged penis or clitoris
  • Early development of pubic hair
  • Increased erections or sex drive
  • Aggressive behavior
  • Male pattern baldness

Call a doctor right away if a woman is exposed to Androgel and experiences:

  • Changes in body hair
  • Irregular menstrual periods
  • Acne

Follow the instructions on your product label carefully when using Androgel to avoid accidental contact with others.

Wash the application site well if you think another person will have direct skin-to-skin contact with that area.

Don’t use Androgel if you have male breast cancer or prostate cancer.

Older men who use this medicine may have a greater chance of developing an enlarged prostate or cancer. Talk to your doctor if this is a concern.

This drug shouldn’t be given to anyone younger than 18.

Androgel may increase your risk of developing a dangerous blood clot, which can lead to a heart attack or stroke. Talk to your doctor about this risk.

Keep all appointments with your healthcare provider and laboratory when using Androgel. Your doctor will want to perform regular blood tests to monitor your body’s response to the drug.

Testosterone medicines such as Androgel are considered controlled drugs.

They should be kept in a secure location away from other people. Never share this drug with another person.

Before using Androgel, tell your doctor if you have, or have ever had:

  • Cancer
  • An enlarged prostate or problems with urination
  • Diabetes
  • Heart disease or a heart attack
  • A stroke
  • Blood clots
  • Kidney or liver disease
  • Sleep apnea (a condition in which breathing stops during sleep)

Androgel may be flammable. Don’t smoke or go near an open flame until the medicine is completely dry on your body.

Pregnancy and Androgel

Androgel can cause birth defects. Pregnant women shouldn’t use this medicine and all women should avoid any contact with Androgel.

If contact does occur, wash the affected area immediately with soap and water.

Androgel can also pass into breast milk and harm a breastfeeding baby.

AndroGel

How does this medication work? What will it do for me?

Testosterone gel belongs to a group of medications known as androgens (male hormones). It is used to treat men who have testosterone deficiency.

Testosterone is a sex hormone that produces “male” physical characteristics and increases sex drive. This medication works by replacing the testosterone that would normally be produced by the body. Testosterone gel should only be used if testosterone deficiency has been confirmed by symptoms and blood tests.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are being given this medication, speak to your doctor. Do not stop using this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to using this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

Androgel is available as a gel in a pump bottle (containing a total of sixty 1.25 g doses) or unit dose packages (2.5 g or 5 g per packet). Each gram of clear, colourless, fragrance-free, hydroalcoholic gel contains testosterone 1%. Nonmedicinal ingredients: alcohol, carbomer 980, isopropyl myristate, purified water, and sodium hydroxide.

How should I use this medication?

The usual recommended dose is 5 g of gel (which contains 50 mg testosterone) applied once daily, preferably in the morning after showering or bathing. If using the pump, make sure you know how many pumps to use per application. Some people may need up to 10 g once daily.

Apply the gel to a clean, dry area of non-broken skin on the shoulders, upper arms, or abdomen. Do not apply the gel to the genitals or to any damaged skin. After applying the gel, let it dry for a few minutes, then cover it with clothing and wash your hands with soap and water to avoid getting the medication on other people’s skin. Wait at least 5 to 6 hours before, showering, or swimming. After applying the gel, allow it to dry completely before smoking or going near an open flame.

If you expect the area of skin to which you applied this medication to come into direct skin contact with another person, wash the application site with soap and water before that encounter or keep the area covered with clothing.

Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are using the medication without consulting your doctor.

It is important that you use this medication exactly as prescribed by your doctor. If you miss a dose, and it is more than 12 hours until your next dose, apply the missed dose as soon as possible and continue with your regular schedule. If it is less than 12 hours until your next dose, skip the missed dose and continue with your regular dosing schedule. Do not apply a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not use this medication if you:

  • are allergic to testosterone or any ingredients of the medication
  • are female (especially if you are pregnant or breast-feeding)
  • have, or are suspected to have, prostate or breast cancer
  • What side effects are possible with this medication?

    Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

    The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

    The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

    Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

    • acne
    • aggressive behaviour
    • changes in sexual desire or drive
    • dizziness
    • hair loss, thinning hair, or baldness
    • headache
    • mood changes
    • prostate disorders (enlarged prostate, or higher-than-normal results on the PSA test)
    • skin irritation, redness, or rash where applied
    • sleep disturbances caused by breathing problems (sleep apnea)
    • weight gain

    Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not seek medical attention.

    Check with your doctor as soon as possible if any of the following side effects occur:

    • breast soreness or enlargement
    • signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
    • high blood pressure
    • problems with urination (change in frequency or colour, dribbling, pain or straining when urinating, weak urine stream, small urine amounts)
    • signs of a blood clot in the arm or leg (tenderness, pain, swelling, warmth, or redness in the arm or leg) or lungs (difficulty breathing, sharp chest pain that is worse when breathing in, coughing, coughing up blood, sweating, or passing out)
    • symptoms of liver problems (e.g., abdominal pain, persistent vomiting, feeling unwell, fever, itching, yellowing of the skin and eyes, dark urine)

    Stop taking the medication and seek immediate medical attention if any of the following occur:

    • prolonged (more than 4 hours) or painful erections, or erections that happen too often
    • swelling of ankles and legs (for people with heart, liver, or kidney problems)
    • signs of a serious allergic reaction (e.g., swelling of face or throat, hives, or difficulty breathing)
    • signs of stroke (e.g., sudden or severe headache; sudden loss of coordination; vision changes; sudden slurring of speech; or unexplained weakness, numbness, or pain in arm or leg)
    • signs of heart attack (e.g., sudden chest pain or pain radiating to back, down arm, jaw; sensation of fullness of the chest; nausea; vomiting; sweating; anxiety)

    Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

    Are there any other precautions or warnings for this medication?

    Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

    Blood tests: Your doctor may recommend that you have regular blood tests while using this medication to check whether the medication is working and whether you are having certain side effects. Also, the use of testosterone may interfere with a number of laboratory tests. Tell all health professionals administering these tests that you are using this medication.

    Breast Cancer: Long-term use of testosterone may increase the risk of developing breast cancer. Talk to your doctor if you have concerns.

    Diabetes: This medication may affect blood sugar levels. If you have diabetes, your doctor may ask you to monitor your blood sugar carefully while using this medication.

    Heart disease: Testosterone can cause increased blood pressure and may cause fluid to build up in the body. Both conditions can increase the risk of certain types of heart disease.

    In addition, androgens have been linked to increased risk of heart disease, including congestive heart failure, increased or irregular heart rate, heart attack and stroke. If you have heart disease or risk factors for developing heart disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

    Kidney or liver disease: If you have kidney or liver disease, your doctor should monitor your condition closely while you are using this medication. Report any swelling in the feet and lower legs to a doctor immediately.

    Prostate problems: Medications such as testosterone may increase the speed at which prostate cancer or benign prostatic hypertrophy (BPH, or enlarged prostate) progresses. If you have a history of prostate cancer or BPH, or you are at risk of developing prostate cancer, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

    Sleep disorders: Treatment with testosterone may cause sleep apnea (interruption of breathing during sleep) and high blood pressure for some people, especially those with risk factors such as being overweight or having a chronic lung disease.

    Sperm counts: This medication may reduce sperm counts if high doses are used, or if it is used for a prolonged period.

    Pregnancy and breast-feeding: This medication should not be used by women, especially pregnant or breast-feeding women. It may have unwanted effects on the developing child, including masculinization of female children. Women risk exposure to the medication through skin-to-skin contact with a man wearing the gel. Men using the gel should cover the treated area with clothing after the gel has dried to avoid exposing women and children to the medication.

    Children: The safety and effectiveness of this medication have not been established for males under the age of 18. Secondary exposure in children can occur through skin-to-skin contact with a man wearing the gel. Men using the gel should cover the treated area with clothing after the gel has dried, and children should avoid contact with any unwashed clothes that were worn by of men using this gel.

    Seniors: Seniors may have an increased risk for prostate enlargement and should be evaluated for prostate cancer before starting testosterone replacement therapy.

    What other drugs could interact with this medication?

    There may be an interaction between testosterone gel and any of the following:

    • adrenocorticotropic hormone (ACTH)
    • corticosteroids (e.g., prednisone)
    • cyclosporine
    • dehydroepiandrostone (DHEA)
    • diabetes medications (e.g., chlorpropamide, glipizide, glyburide, insulin, metformin, rosiglitazone)
    • propranolol
    • warfarin

    If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

    • stop taking one of the medications,
    • change one of the medications to another,
    • change how you are taking one or both of the medications, or
    • leave everything as is.

    An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

    Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

    All material copyright MediResource Inc. 1996 – 2020. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/AndroGel

SIDE EFFECTS

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials in Hypogonadal Men

Table 2 shows the incidence of all adverse events judged by the investigator to be at least possibly related to treatment with AndroGel 1% and reported by > 1% of patients in a 180 Day, Phase 3 study.

Table 2: Adverse Events Possibly, Probably or Definitely Related to Use of AndroGel 1% in the 180-Day Controlled Clinical Trial

Other less common adverse reactions, reported in fewer than 1% of patients included: amnesia, anxiety, discolored hair, dizziness, dry skin, hirsutism, hostility, impaired urination, paresthesia, penis disorder, peripheral edema, sweating, and vasodilation.

In this 180 day clinical trial, skin reactions at the site of application were reported with AndroGel 1%, but none was severe enough to require treatment or discontinuation of drug.

Six patients (4%) in this trial had adverse events that led to discontinuation of AndroGel 1%. These events included: cerebral hemorrhage, convulsion (neither of which were considered related to AndroGel 1% administration), depression, sadness, memory loss, elevated prostate specific antigen, and hypertension. No AndroGel 1% patient discontinued due to skin reactions.

In a separate uncontrolled pharmacokinetic study of 10 patients, two had adverse events associated with AndroGel 1%; these were asthenia and depression in one patient and increased libido and hyperkinesia in the other.

In a 3 year, flexible dose, extension study, the incidence of all adverse events judged by the investigator to be at least possibly related to treatment with AndroGel 1% and reported by > 1% of patients is shown in Table 3.

Table 3: Adverse Events Possibly, Probably or Definitely Related to Use of AndroGel 1% in the 3 Year, Flexible Dose, Extension Study

Adverse Event Percent of Subjects
(N = 162)
Lab Test Abnormal+ 9.3
Skin dry 1.9
Application Site Reaction 5.6
Acne 3.1
Pruritus 1.9
Enlarged Prostate 11.7
Carcinoma of Prostate 1.2
Urinary Symptoms* 3.7
Testis Disorder** 1.9
Gynecomastia 2.5
Anemia 2.5
+Lab test abnormal occurred in 15 patients with one or more of the following events reported: elevated AST, elevated ALT, elevated testosterone, elevated hemoglobin or hematocrit, elevated cholesterol, elevated cholesterol/LDL ratio, elevated triglycerides, elevated HDL, elevated serum creatinine.
*Urinary symptoms included nocturia, urinary hesitancy, urinary incontinence, urinary retention, urinary urgency and weak urinary stream.
**Testis disorders included three patients. There were two with a non-palpable testis and one with slight right testicular tenderness.

Two patients reported serious adverse events considered possibly related to treatment: deep vein thrombosis (DVT) and prostate disorder requiring a transurethral resection of the prostate (TURP).

Discontinuation for adverse events in this study included: two patients with application site reactions, one with kidney failure, and five with prostate disorders (including increase in serum PSA in 4 patients, and increase in PSA with prostate enlargement in a fifth patient).

Increases in Serum PSA Observed in Clinical Trials of Hypogonadal Men

During the initial 6-month study, the mean change in PSA values had a statistically significant increase of 0.26 ng/mL. Serum PSA was measured every 6 months thereafter in the 162 hypogonadal men on AndroGel 1% in the 3-year extension study. There was no additional statistically significant increase observed in mean PSA from 6 months through 36 months. However, there were increases in serum PSA observed in approximately 18% of individual patients. The overall mean change from baseline in serum PSA values for the entire group from month 6 to 36 was 0.11 ng/mL.

Twenty-nine patients (18%) met the per-protocol criterion for increase in serum PSA, defined as > 2X the baseline or any single serum PSA > 6 ng/mL. Most of these (25/29) met this criterion by at least doubling of their PSA from baseline. In most cases where PSA at least doubled (22/25), the maximum serum PSA value was still < 2 ng/mL. The first occurrence of a pre-specified, post-baseline increase in serum PSA was seen at or prior to Month 12 in most of the patients who met this criterion (23 of 29; 79%).

Postmarketing Experience

The following adverse reactions have been identified during post approval use of AndroGel 1%. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (Table 4).

Table 4: Adverse Drug Reactions from Postmarketing Experience of AndroGel 1% by MedDRA System Organ Class

Blood and the lymphatic system disorders: Elevated Hgb, Hct (polycythemia)
Cardiovascular disorders: Myocardial infarction, stroke
Endocrine disorders: Hirsutism
Gastrointestinal disorders: Nausea
General disorders and administration site reactions: Asthenia, edema, malaise
Genitourinary disorders: Impaired urination
Hepatobiliary disorders: Abnormal liver function tests (e.g. transaminases, elevated GGTP, bilirubin)
Investigations: Elevated PSA, electrolyte changes (nitrogen, calcium, potassium, phosphorus, sodium), changes in serum lipids (hyperlipidemia, elevated triglycerides, decreased HDL), impaired glucose tolerance, fluctuating testosterone concentrations, weight increase
Neoplasms benign, malignant and unspecified (cysts and polyps): Prostate cancer
Nervous system: Headache, dizziness, sleep apnea, insomnia
Psychiatric disorders: Depression, emotional lability, decreased libido, nervousness, hostility, amnesia, anxiety
Reproductive system and breast disorders: Gynecomastia, mastodynia, prostatic enlargement, testicular atrophy, oligospermia, priapism (frequent or prolonged erections)
Respiratory disorders: Dyspnea
Skin and subcutaneous tissue disorders: Acne, alopecia, application site reaction (pruritus, dry skin, erythema, rash, discolored hair, paresthesia), sweating
Vascular disorders: Hypertension, vasodilation (hot flushes), venous thromboembolism

Secondary Exposure to Testosterone in Children

Cases of secondary exposure to testosterone resulting in virilization of children have been reported in postmarket surveillance. Signs and symptoms of these reported cases have included enlargement of the clitoris (with surgical intervention) or the penis, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases with a reported outcome, these signs and symptoms were reported to have regressed with removal of the testosterone gel exposure. In a few cases, however, enlarged genitalia did not fully return to age appropriate normal size, and bone age remained modestly greater than chronological age. In some of the cases, direct contact with the sites of application on the skin of men using testosterone gel was reported. In at least one reported case, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user’s shirts and/or other fabric, such as towels and sheets .

Read the entire FDA prescribing information for AndroGel (Testosterone Gel for Topical Use)

Despite some of the controversies surrounding testosterone gels, a new study in older men finds that this treatment had positive effects from increased sexual activity and more vitality to just feeling better.

• Boosting decreasing testosterone with gel supplements is a current daily regimen of millions of men in the U.S. — turning it into a reported $2 billion industry.
• Men in the Testosterone Trials who received testosterone reported better sexual function than those in the placebo group. This included more sexual activity, improved sexual desire, and increased erectile function.
• In a 2015 Safety Announcement, the FDA said the popular treatments have not been established as safe or effective for men with common age-related issues like low libido and fatigue.
Staving off what happens to our bodies as we age is an enormous industry in the U.S. Both women and men depend on products sold over-the-counter and by prescription to relieve problems that arise as levels of women’s estrogen and men’s testosterone decrease — and bring a whole host of body changes and symptoms.

For millions of men in the U.S., boosting decreasing testosterone with gel supplements is a daily regimen—turning it into a reported $2 billion industry. But do all men experience the benefits they hope for?

In its February 16 issue, the New England Journal of Medicine published results from the Testosterone Trials in which a team of investigators aimed to determine whether there were benefits of boosting testosterone levels in men older than age 65.

The 12-month Testosterone Trials were funded in part by the National Institutes of Health as well as AbbVie, the maker of the popular testosterone product AndroGel®. AbbVie donated the testosterone and placebo gel.

“There’s a lot of hype and misperception about what testosterone does and does not do, but…in men who have low testosterone levels and have low libido there is benefit in terms of improved sexual desire and sexual activity but the magnitude of the benefit is modest.” – Shalender Bhasin, MD, Brigham and Women’s Hospital, Harvard Medical School, Boston

Researchers screened 51,085 men but were able to enroll only 790 who met all the criteria. The authors noted that, “relatively few men had a sufficiently low testosterone level to qualify.” Participants were 65 years or older and had serum testosterone levels that averaged less than 275 ng per deciliter. Three separate trials were conducted: Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. Each man participated in one or more of the three trials. One group received placebo only.

Men in the Testosterone Trials were given an initial dose of 5 g daily of AndroGel 1% in a pump bottle. Their testosterone serum levels were tested regularly and gel doses were adjusted as necessary to keep testosterone levels within the normal range for men 19 to 40 years of age.

“When men get older their testosterone levels decline and they experience a number of symptoms,” says study co-author Shalender Bhasin, MD, from Brigham and Women’s Hospital, Harvard Medical School. “Some of these symptoms are similar to those experienced by men who have testosterone deficiency. The most common complaints are sexual symptoms, but they often complain of lack of energy or lack of vitality. Older men may also experience decrease in their physical function, their mobility.”

Testosterone gel is often prescribed to offer aging men a boost from these symptoms. AndroGel shares the gel market with brands such as Axiron®, Testim®, and Aveed®. Net sales of AndroGel in 2015 equaled $692 million, according to Libby Holman, AbbVie’s senior manager of Public Affairs.

“Testosterone gel is the most commonly prescribed method in the U.S.,” says Bradley Anawalt, MD, chief of medicine at the University of Washington Medical Center, who specializes in male reproductive endocrinology. “In the rest of the world, a long-acting testosterone injection that is administered every ten to 12 weeks is the most common testosterone prescription. This injectable testosterone (testosterone undecanoate) has recently been approved for use in the U.S., but it is very expensive, nearly $4000 per year.”

Testosterone Therapy “Often Makes Them Feel Better”

There appears to be little argument to the fact that men with below normal testosterone levels experience a benefit from testosterone gel —and at times multiple benefits.

“The biggest benefit is usually in how men feel,” Anawalt says. “For hypogonadal men, testosterone therapy often makes them feel better. Many men will report improved sexual function and pleasure and some will report improved energy and vitality.”

The Testosterone Trials proved these outcomes. “The most striking and consistent improvements were in sexual function,” Bhasin says. Men who received testosterone reported better sexual function than those in the placebo group. This included more sexual activity, improved sexual desire, and increased erectile function.

In the Physical Function Trial, the men’s six-minute walking distance was measured. There was some improvement in the walking speed in all men who were included in the trial. The percent of men whose six-minute walking distance increased by at least 50 m did not differ significantly between the two groups. However, when men were asked whether their walking ability was better, they perceived that it had improved, according to Bhasin.

Results of the Vitality Trails were mixed. Men who took testosterone showed no benefit over placebo on the fatigue scale. Men on testosterone did, however, report slightly lower depression symptoms. And at the end of the trial, men in the testosterone group were more likely to report that their energy was better compared with those given placebo.

Over Prescribed Despite the Risks?

The boosts to sexual performance and mood do not come without risks. Several research studies have investigated the possible link between testosterone therapy and an increased risk of prostate cancer and heart problems. There have been mixed results with some studies reporting a benefit to testosterone — with decreased cardiovascular events and decreased mortality — and some showing an increase.

In a large 2014 UCLA study published in PLOS One, researchers analyzed health insurance claims of more than 55,000 men prescribed testosterone and reported that among men 65 and older, there was a two-fold increase in the risk of heart attack in the 90 days after filling an initial testosterone therapy prescription. In men younger than 65 with a history of heart disease, the risk was two- to three-fold in the first 90 days.

While the Testosterone Trials revealed no differences in major cardiovascular events between the testosterone and placebo groups during the 12-month study, Bhasin points out the set of trials were not powered to determine the long-term risks, particularly cardiovascular and prostate risks. “So the risk-to-benefit ratio still remains unclear and much larger and longer randomized trials are needed,” he says.

Taking note of the enormous jump in sales and proven health risks, the Food and Drug Administration issued a Safety Announcement in March 2015 against over-prescribing testosterone-boosting drugs. The FDA said the popular treatments have not been established as safe or effective for men with common age-related issues like low libido and fatigue.

The agency required drug makers to add information to the labeling about a possible increased risk of heart attacks and strokes in patients taking testosterone.

The FDA announcement further called for healthcare professionals to prescribe testosterone therapy only for men with low testosterone levels caused by certain medical conditions and confirmed by laboratory tests.

“Many men who are being prescribed T therapy are not being properly evaluated,” Anawalt says. “Some are being started on therapy without having their testosterone blood concentrations measured. Others are being diagnosed with hypogonadism based on a single blood test or tests performed on blood obtained in the afternoon.”

To be diagnosed with hypogonadism, a man must have reproducibly low blood testosterone concentrations on at least two occasions, Anawalt explains. The testosterone measurement should be performed on blood drawn between 7 and 10 a.m. when testosterone concentrations peak. The normal range is based on peak, early morning blood testosterone concentrations, he says.

“The biggest benefit is usually in how men feel. For hypogonadal men, testosterone often makes them feel better. Many men will report improved sexual function and pleasure and some will report improved energy and vitality.” – Bradley Anawalt, MD, chief of medicine, University of Washington Medical Center, Seattle

Bhasin reiterates that while many men may be using the testosterone to enhance sexual performance, the important lesson from the trial is that only men who had consistently low testosterone levels actually improved their sexual desire and function.

“So there’s a lot of hype and misperception about what testosterone does and does not do,” Bhasin says. “But…in men who have low testosterone levels and have low libido there is benefit in terms of improved sexual desire and sexual activity but the magnitude of the benefit is modest.”

—Fauntleroy is a freelance writer based in Carmel, Ind., and a regular contributor to Endocrine News. She wrote about increased research of natural products in the March issue.

Treating Low Testosterone: Axiron vs. AndroGel

Axiron and AndroGel are both medications that can help increase your testosterone levels. Both drugs contain the same active ingredient, but the forms, strengths, and application methods for these two drugs differ slightly. You also need to take precautions to avoid drug transference when using either drug.

Both products are topical drugs, meaning you apply them to your skin. Do not apply either medication to your genitals, chest, or back. If you apply your medication to any of these places, the right amount of the drug might not be absorbed. Always wash your hands thoroughly after applying either drug.

Avoid swimming, washing, or heavy sweating for up to six hours after applying AndroGel 1% strength. For AndroGel 1.62% strength and for Axiron, avoid these activities for up to two hours after applying.

Axiron

Axiron is a clear solution in a pump bottle that gives 30 milligrams (mg) per pump. It comes with an application cap that you use to apply the solution. You can pump the solution into the cap. You should apply one dose of Axiron each day to your armpit area. The skin in your armpit area is relatively thin. The medication can quickly absorb through your skin and then into your bloodstream.

When you’ve applied Axiron, rub it in using the application cap, not your fingers. Touching the solution directly as you apply it can cause too much of the medication to be absorbed into your bloodstream. It can also make it easier for you to transfer the drug to someone else. You should rinse and dry the cap after each application and also wash your hands with soap and water.

You will get the best results if you apply the Axiron at the same time each day, right after showering. If you use deodorant, apply it before you apply Axiron.

AndroGel is a clear gel. The pump dispenses a single dose of 12.5 or 20.25 mg each time you depress it. The gel packets come in one or two doses in the following strengths:

  • 20.25 mg
  • 25 mg
  • 40.5 mg
  • 50 mg

You apply one dose each day to your shoulders, upper arms, or abdomen. Apply AndroGel with the palm of your hand and massage it in.

For best results

  • Wash your hands with soap and water after applying AndroGel.
  • Allow the gel to dry before you get dressed.
  • Cover the application site with clothing.
  • Wait two hours after you use AndroGel before you apply deodorant.

Drug transference

You can accidentally transfer either drug to someone else if you touch them after applying it. If you’ll have skin-to-skin contact with someone, make sure that they don’t touch the application site until you’ve washed it with soap and water. It’s especially important to avoid transferring testosterone to women or children.

These drugs are anabolic steroids. They can cause harmful physical and psychological effects. Women who come in contact with testosterone treatments may develop acne and male characteristics, such as increased body and facial hair. Children who are routinely exposed to Axiron or AndroGel may show aggressive behavior or experience early puberty or swelling of the genitals.

How Do I Use AndroGel Bodybuilding to Get Big?

Application

    AndroGel is a testosterone gel commonly prescribed to boost testosterone levels in men. Unlike other synthetic drugs often ingested or administered intravenously, AndroGel is applied directly to the skin, soaking into the muscles and bloodstream. Using the product in gel or patch form to gain muscle mass for bodybuilding purposes is possible. However, there are a few steps involved to ensure you use the product correctly.

  1. Choose a time of day to apply AndroGel. Research has shown that it is best to apply the product in the morning. This will allow your body to absorb the gel as the day progresses. It is, therefore, important to allow the agent to properly and slowly seep its way into your bloodstream.

  2. Wash and dry your skin thoroughly before applying AndroGel. Your pores must be clean. It is, therefore, important to apply the gel or patch shortly after you bathe and your skin is free from dead skin.

  3. Apply the AndroGel as directed, only using the contents included in a single gel pouch or patch. Be sure to use the entire contents of the dose. Allow to dry for at least five minutes. After the gel dries, cover the treated areas with clothing. This will allow it to remain in contact with your skin.

Exercise and Dietary Modification

  1. Increase the intensity and frequency of power movements in your workout routine. Because your desire is to build muscle mass, exercises such as bench presses, leg presses, squats, and arm curls are important in that they involve the large muscles in your body. As AndroGel begins to work, typically during a one- to two-week period, it will gradually increase your energy levels and drive so you can handle more weights on power movements. This will push your muscle tissue to its limits. The testosterone agents in the AndroGel will work to quickly repair the tissue, allowing for rapid muscle growth.

  2. Reduce cardiovascular and aerobic exercises during periods of mass building and AndroGel cycles. It is important to utilize the effects of the gel to build muscle mass. Although aerobic workouts are important, frequent cardio exercises will eventually promote weight loss, creating a trim and cut look. Your goal is to use AndroGel to gain muscle mass. During mass-building, only perform aerobics once or twice a week in order keep your blood flowing and your heart strong. Use the majority of your energy to concentrate on mass building movements.

  3. Increase your protein and starchy carbohydrate intake while taking AndroGel. These calories will work with the gel in repairing increasing the size of the cells in your muscles. Increased carbohydrate calories will allow your muscles to store high levels of sugar, increasing your energy so you can gruel through heavy, mass building workouts.

The Wrap Up

It is important to utilize the effects of the gel to build muscle mass. Your goal is to use AndroGel to gain muscle mass. As AndroGel begins to work, typically during a one- to two-week period, it will gradually increase your energy levels and drive so you can handle more weights on power movements.

AndroGel & Bodybuilding

AndroGel is a pure testosterone boost in gel form. It is applied directly onto the surface of the skin. The gel is then absorbed by the body and will quickly enter the bloodstream. AndroGel introduces an androgen hormone to the body that works as a testosterone replacement. This androgen hormone replaces the testosterone that is supposed to be created naturally in the body. More testosterone = more strength in the gym.

Quick Tips for AndroGel Bodybuilding

**WARNING** Always check with your Doctor and Nutritionist before starting any new training regimen, and only take Androgel as prescribed by your Doctor.

Apply the gel early in the morning.

This causes the gel to have effects that last all through the day. Early application allows enough time for the gel to work its way through the muscles and into the bloodstream. It is important that your pores are clean before applying AndroGel. Cleans pores have an easier time absorbing the gel.

Organize an effective workout.

Intense power motions in a workout will have the best results when using the gel. Incorporate plenty of bench presses and arm curls to ensure that the added hormones in the body are put to good use. This will help to add bulk to muscles quickly and efficiently.

Eat a high protein and high carb diet.

Most muscle building experts recommend eating 1 to 2 grams of protein per pound of weight to build muscle, and this will likely help you get the most out of AndroGel too. Also eat plenty of slow digesting carbs and vegetables. Slow digesting carbs help the gel to add bulk when muscles are being repaired after a workout. Stay away from foods that are white or can be white, such as sugar, pasta, white onions, etc.

Other thoughts on using AndroGel to Build Muscle

Even men with healthy testosterone levels may wish to use AndroGel. It is proven that the added androgen hormones will help existing muscles to grow larger. This will occur at an increased speed as long as the bodybuilder understands how the product works. Most men who have used AndroGel have reported that the effects of the product seem to be the strongest when the gel is applied early in the morning. It also helps when certain workouts are avoided, such as cardiovascular workouts. Cardio workouts cause weight loss. AndroGel bodybuilders want to gain weight so that it can be transformed into muscle mass. Using AndroGel properly and designing an efficient exercise routine has proven to be extremely helpful when attempting to build muscles.

How AndroGel Effects The Muscles

AndroGel has proven itself to be one of the best ways to boost testosterone levels by adding androgen hormones to the body. Introducing new hormones to the body is the only effective way to boost testosterone in low T individuals. Other supplements may be used by body builders looking to gain muscle and energy when working out, however, AndroGel is not like any of these other synthetic products. AndroGel is unique in how it is applied to and how it affects the body.

THIS INFORMATION DOES NOT CONSTITUTE MEDICAL ADVICE AND IS NOT AFFILIATED WITH ABBVIE INC. OR ANDROGEL IN ANY WAY. ANDROGEL IS A TRADEMARK OF ABBVIE INC., WHICH DOES NOT SPONSOR, AUTHORIZE OR ENDORSE THIS WEB SITE. USE FOR INFORMATIONAL PURPOSES ONLY.

AndroGel 1.62

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

AndroGel 1.62% was evaluated in a two-phase, 364-day, controlled clinical study. The first phase was a multi-center, randomized, double-blind, parallel-group, placebo-controlled period of 182 days, in which 234 hypogonadal men were treated with AndroGel 1.62% and 40 received placebo. Patients could continue in an open-label, non-comparative, maintenance period for an additional 182 days .

The most common adverse reaction reported in the double-blind period was increased prostate specific antigen (PSA) reported in 26 AndroGel 1.62%-treated patients (11.1%). In 17 patients, increased PSA was considered an adverse event by meeting one of the two pre-specified criteria for abnormal PSA values, defined as (1) average serum PSA > 4 ng/mL based on two separate determinations, or (2) an average change from baseline in serum PSA of greater than 0.75 ng/Ml on two determinations.

During the 182-day, double-blind period of the clinical trial, the mean change in serum PSA value was 0.14 ng/mL for patients receiving AndroGel 1.62% and -0.12 ng/mL for the patients in the placebo group. During the double-blind period, seven patients had a PSA value > 4.0 ng/mL, four of these seven patients had PSA less than or equal to 4.0 ng/mL upon repeat testing. The other three patients did not undergo repeat PSA testing.

During the 182-day, open-label period of the study, the mean change in serum PSA values was 0.10 ng/mL for both patients continuing on active therapy and patients transitioning onto active from placebo. During the open-label period, three patients had a serum PSA value > 4.0 ng/mL, two of whom had a serum PSA less than or equal to 4.0 ng/mL upon repeated testing. The other patient did not undergo repeat PSA testing. Among previous placebo patients, 3 of 28 (10.7%), had increased PSA as an adverse event in the open-label period.

Table 4 shows adverse reactions reported by > 2% of patients in the 182-day, double-blind period of the AndroGel 1.62% clinical trial and more frequent in the AndroGel 1.62% treated group versus placebo.

Table 4: Adverse Reactions Reported in > 2% of Patients in the 182-Day, Double-Blind Period of AndroGel 1.62% Clinical Trial

Other adverse reactions occurring in less than or equal to 2% of AndroGel 1.62%-treated patients and more frequently than placebo included: frequent urination, and hyperlipidemia.

In the open-label period of the study (N=191), the most commonly reported adverse reaction (experienced by greater than 2% of patients) was increased PSA (n=13; 6.2%) and sinusitis. Other adverse reactions reported by less than or equal to 2% of patients included increased hemoglobin or hematocrit, hypertension, acne, libido decreased, insomnia, and benign prostatic hypertrophy.

During the 182-day, double-blind period of the clinical trial, 25 AndroGel 1.62%-treated patients (10.7%) discontinued treatment because of adverse reactions. These adverse reactions included 17 patients with PSA increased and 1 report each of: hematocrit increased, blood pressure increased, frequent urination, diarrhea, fatigue, pituitary tumor, dizziness, skin erythema and skin nodule (same patient – neither at application site), vasovagal syncope, and diabetes mellitus. During the 182-day, open-label period, 9 patients discontinued treatment because of adverse reactions. These adverse reactions included 6 reports of PSA increased, 2 of hematocrit increased, and 1 each of triglycerides increased and prostate cancer.

Application Site Reactions

In the 182-day double-blind period of the study, application site reactions were reported in two (2/234; 0.9%) patients receiving AndroGel 1.62%, both of which resolved. Neither of these patients discontinued the study due to application site adverse reactions. In the open-label period of the study, application site reactions were reported in three (3/219; 1.4%) additional patients that were treated with AndroGel 1.62%. None of these subjects were discontinued from the study due to application site reactions.

The following adverse reactions have been identified during post approval use of AndroGel 1%. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (Table 5).

Table 5: Adverse Reactions from Post Approval Experience of AndroGel 1% by System Organ Class

System Organ Class Adverse Reaction
Blood and lymphatic system disorders: Elevated hemoglobin or hematocrit, polycythemia, anemia
Cardiovascular disorders: Myocardial infarction, stroke
Endocrine disorders: Hirsutism
Gastrointestinal disorders: Nausea
General disorders: Asthenia, edema, malaise
Genitourinary disorders: Impaired urination*
Hepatobiliary disorders: Abnormal liver function tests
Investigations: Lab test abnormal**, elevated PSA, electrolyte changes (nitrogen, calcium, potassium , phosphorus, sodium), impaired glucose tolerance, hyperlipidemia, HDL, fluctuating testosterone levels, weight increase
Neoplasms: Prostate cancer
Nervous system disorders: Dizziness, headache, insomnia, sleep apnea
Psychiatric disorders: Amnesia, anxiety, depression, hostility, emotional lability, decreased libido, nervousness
Reproductive system and breast disorders: Gynecomastia, mastodynia, oligospermia, priapism (frequent or prolonged erections), prostate enlargement, BPH, testis disorder***
Respiratory disorders: Dyspnea
Skin and subcutaneous tissue disorders: Acne, alopecia, application site reaction (discolored hair, dry skin, erythema, paresthesia, pruritus, rash), skin dry, pruritus, sweating
Vascular disorders: Hypertension, vasodilation (hot flushes), venous thromboembolism
* Impaired urination includes nocturia, urinary hesitancy, urinary incontinence, urinary retention, urinary urgency and weak urinary stream
**Lab test abnormal includes elevated AST, elevated ALT, elevated testosterone, elevated hemoglobin or hematocrit, elevated cholesterol, elevated cholesterol/LDL ratio, elevated triglycerides, or elevated serum creatinine
***Testis disorder includes atrophy or non-palpable testis, varicocele, testis sensitivity or Tenderness

Cases of secondary exposure to testosterone resulting in virilization of children have been reported in postmarketing surveillance of testosterone gel products. Signs and symptoms of these reported cases have included enlargement of the clitoris (with surgical intervention) or the penis, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases with a reported outcome, these signs and symptoms were reported to have regressed with removal of the testosterone gel exposure. In a few cases, however, enlarged genitalia did not fully return to age appropriate normal size, and bone age remained modestly greater than chronological age. In some of the cases, direct contact with the sites of application on the skin of men using testosterone gel was reported. In at least one reported case, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user’s shirts and/or other fabric, such as towels and sheets .

Read the entire FDA prescribing information for AndroGel 1.62 (Testosterone Gel)

Testosterone for old guys

I have to take it and my wife injects it! It made me jump from 175lbs. Where I had been for 20 years to 210 in two months. At first I added a lot of water and had problems with swelling. I have always eaten VERY VERY WELL so I wondered what am I going to do.
Finally things leveled off and I have not felt this good in years. I have had a large weight room that I added onto my barn years ago, it had been collecting dust for about three years because I just didn’t have the energy.
I HAVE THE ENERGY AGAIN! Not my waist size is bigger that it ever has been but hell I’m 40 now so i deal with it. But I have kept about 25 lbs of what I’m glad to say is MOSTLY MUSCLE. My wife took a month or so to get adjusted to the new me but likes it now. It for sure helped out the bedroom life. NO MORE LETTING THE KIDS WATCH MOVIES WITH US IN OUR BED AT NIGHT TILL THEY FALL ASLEEP!
Nope that is our bedroom once again!
It has increased my energy level, made me crave food, GIVEN ME MY LIFE BACK! I will say watch you salt, I’m lucky I guess because my doctor has asked me more than once DO YOU EVER EAT SALTY FOODS, watch fatty foods, don’t overeat, get out and move that butt. Take care of yourself man this can be your chance to, like me, GET YOUR LIFE BACK.
Good luck driver I’ve loved it and the people around me have said I look 10 years younger…..and boy do I feel it.
The plus is the ladies around it will notice it, I believe they can smell it, they for sure will see it, enjoy.
I wear Polo style shirts mostly and I’ve had to buy many new shirts because the ol GUNS WILL NOT FIT. I’m only bragging a little bit here because I’ve had many many people actually grab my arms and say “#### boy what are you eating, and where do I get some”

Testosterone and the heart

Published: March, 2010

Forget clothes. In a very real sense, testosterone makes the man.

It is responsible for the deep voice, increased muscle mass, and strong bones that characterize the gender. It stimulates the production of red blood cells by the bone marrow. The hormone also has crucial, if incompletely understood, effects on male behavior: it contributes to aggressiveness, and it is essential for the libido, or sex drive, as well as for normal erections and sexual performance. Testosterone stimulates the growth of the genitals at puberty and is responsible for sperm production throughout adult life.

Although testosterone acts directly on many tissues, some of its least desirable effects don’t occur until it is converted into another male hormone, dihydrotestosterone (DHT). DHT acts on the skin, sometimes producing acne, and on the hair follicles, putting hair on the chest but often taking it off the scalp. Male-pattern baldness is one thing, but prostate disease quite another: DHT also stimulates the growth of prostate cells, producing normal growth in adolescence but contributing to benign prostatic hyperplasia (BPH) and possibly even prostate cancer in many older men.

Testosterone is the major male hormone; it belongs to the family of hormones that doctors call androgens, an appropriate name that derives from the Greek words for man-maker. But while testosterone’s effects on many organs are well established, research is challenging old assumptions about how the hormone affects a man’s heart, circulation, and metabolism.

Early worries

A direct association between testosterone and heart disease has never been established, but for many years, doctors have suspected that a link exists. The reasoning goes like this: men have much more testosterone than women, and they develop heart disease about 10 years before their female counterparts. Like other muscles, cardiac cells have receptors that bind male hormones. Animals that are given testosterone develop enlarged hearts. Athletes who abuse testosterone and other androgenic steroids have a sharply increased risk of high blood pressure, heart attack, and stroke. And in high doses, testosterone can have a negative effect on cardiac risk factors, including HDL (“good”) cholesterol levels.

Cardiovascular disease is but one of the many things that should keep athletes from abusing steroids. But the fact that large amounts of testosterone harm the heart and metabolism doesn’t necessarily mean that physiological amounts are also harmful. In fact, research is challenging these old dogmas.

Testosterone and erectile dysfunction

Erectile dysfunction (ED) becomes more common as men age. Testosterone levels decline with age. Many men with ED blame their sagging performance on sagging hormone levels. But are they correct?

To find out, the Massachusetts Male Aging Study surveyed 625 randomly selected men between the ages of 40 and 70. Forty-one percent of the men had moderate to severe erectile dysfunction, but there was no link between ED and levels of total testosterone, bioavailable testosterone, and sex hormone–binding proteins.

Doctors in Australia approached the question from the other direction, by measuring testosterone levels in 1,455 men who were referred for evaluation of ED. Fewer than 6% of the men had low testosterone levels.

ED is much, much more likely to result from cardiovascular disease, diabetes, and medication side effects than from testosterone deficiency.

Complex relationships

It’s hard for scientists to study heart disease. One reason is that there are so many cardiac risk factors, including family history, age, gender, blood pressure, cholesterol, blood sugar, obesity, smoking, exercise, and personality.

It’s also hard for scientists to study testosterone. There is an exceptionally wide range of normal values. Healthy men can have testosterone levels between 270 and 1,070 nanograms per deciliter (ng/dL). Levels vary during the day, with peak values in the early morning. The hormone travels in the blood in three ways: on its own as free testosterone, while tightly bound to the protein sex hormone–binding globulin, or while weakly bound to the protein albumin. Testosterone levels change during life; total testosterone falls by about 1% a year starting around age 40, while free and weakly bound testosterone (which are collectively known as bioavailable testosterone) fall by almost 2% a year. Testosterone levels are temporarily boosted by exercise, but levels are decreased by excessive body fat, particularly abdominal fat. Finally, some of a man’s testosterone is converted to estradiol, an estrogen that affects blood vessel function and metabolism in both men and women.

Heart disease and testosterone are mighty complex on their own, and studies that evaluate the two together are more complex still. Scientists who undertake these daunting investigations must account for all the things that influence heart disease and all the variables that affect testosterone. They must also decide whether to study men with normal testosterone levels or men who have low levels (called hypogonadism), either because of natural factors or because of androgen-deprivation therapy for prostate cancer. And doctors who investigate the effects of testosterone therapy can do so either in healthy men or in patients with cardiovascular disease. Finally, even if results suggest that testosterone might help the heart, the effects of hormone therapy on the rest of the body would also have to be considered.

With all these pitfalls, it’s not surprising that more research is needed to fill in all the blanks. Still, even if current information can’t tell us if testosterone can protect a man’s heart, it can dispel fear that physiologic levels of the hormone are toxic.

Raging hormones?

Testosterone gets the credit — and blame — for everything from road rage and a 90-mile-an-hour fastball to prostate cancer. But can it also explain wild swings in the stock market?

To find out, researchers in England measured testosterone and cortisol (a stress hormone) in saliva samples from 17 male stock traders twice a day for eight days. They found that a high testosterone level in the morning was linked to a successful, money-making trading day. In contrast, high cortisol levels were recorded during volatile, up-and-down trading sessions.

It’s just one small, preliminary study. But if testosterone is linked to male aggression, it could explain risk-taking investment practices. Be aware, though, that aggressive trading can trigger losses as well as gains.

Testosterone and cardiac risk factors

In high doses, androgens tend to raise LDL (“bad”) cholesterol levels and lower HDL cholesterol levels. That’s one of the things that gave testosterone its bad reputation. But in other circumstances, the situation is very different. Men who receive androgen-deprivation therapy for prostate cancer drop their testosterone levels nearly to zero, and when that happens, their cholesterol levels rise. Even within the normal range, men with the lowest testosterone levels tend to have the highest cholesterol levels. And when doctors from the Mayo Clinic reviewed 30 trials of testosterone-replacement therapy, they did not find any overall effect of hormone treatment on cholesterol levels, for good or ill.

Diabetes is another important cardiac risk factor. Androgen-deprivation therapy produces insulin resistance and increases the risk of diabetes. Obesity increases the risk of both diabetes and heart disease. Men with low testosterone have more body fat and more of the abdominal fat that’s most harmful than men with higher hormone levels, but since obesity itself reduces testosterone, it’s not clear which is the cause and which the effect.

Peripheral artery disease (PAD) is an important form of atherosclerosis in its own right, and it also signals an increased risk for heart disease. A Swedish study of over 3,000 men with an average age of 75 linked low testosterone and high estradiol levels to an increased risk of PAD.

There is less information about the relationship between testosterone and other cardiac risk factors. At present, the hormone does not appear linked to hypertension or inflammatory markers.

Symptoms of testosterone deficiency

Red flags

  • Low libido (sex drive)

  • Osteoporosis or low-trauma fractures

  • Hot flashes and night sweats

  • Infertility

Less specific symptoms

  • Decreased spontaneous erections

  • Loss of height

  • Loss of muscle bulk

  • Fatigue or lethargy

  • Depression

  • Anemia

  • Breast enlargement

  • Reduced facial or body hair

  • Shrinking or very small testicles

  • Diminished physical function

Testosterone therapy and cardiovascular function

Low testosterone levels have been linked to various cardiac risk factors, but that doesn’t prove that low levels actually cause heart disease. Still, if testosterone therapy could help men with heart disease, it would bolster the argument that testosterone may be safe for the heart. Only a few small, short-term studies have been published to date, and the results offer mixed support for this theory.

Blood vessels and heart muscle cells have receptors that latch on to testosterone. Men who undergo androgen-deprivation therapy develop abnormally stiff arteries. In men with atherosclerosis and normal testosterone levels, short-term treatment with testosterone improves vascular reactivity and blood flow.

If testosterone helps blood vessels widen, it might be able to improve angina in men with coronary artery disease. A 2000 trial evaluated 46 men with stable angina and low-normal blood testosterone levels who were randomly assigned to 12 weeks of treatment with a testosterone patch or a placebo. Each man underwent a standard exercise stress test before and after treatment. Compared with the placebo-treated subjects, men on testosterone displayed improved exercise tolerance at the end of the trial — but the difference was slight, amounting to an average gain of just 26 seconds.

A similar 2004 study compared testosterone injections with placebo in 10 men with angina and low testosterone levels. One month of treatment produced a 74-second gain in exercise tolerance without changing HDL or LDL cholesterol levels. In another 2004 trial, 20 men with heart failure were given testosterone injections or placebo. After 12 weeks, testosterone produced a 33% increase in the distance the men were able to walk on a treadmill as well as a decrease in symptoms.

A 2008 study administered an oral testosterone preparation or a placebo to 22 men with coronary artery disease and low testosterone levels. Hormone therapy produced a modest increase in blood flow to the heart muscle by widening healthy, but not partially blocked, coronary arteries. Testosterone also boosted heart muscle contractions. However, treatment had no effect on the pain of angina, and it did reduce HDL cholesterol levels.

Testicular transplants

Testicular transplantation has intrigued doctors for centuries — mostly, one suspects, older male doctors.

Dr. John Hunter performed the first successful animal experiments in the mid-18th century, transplanting the testicles from a rooster to a hen. In the 19th century, doctors began to experiment with animal-to-human transplantation, but their attempts to rejuvenate aging men were uniformly unsuccessful. That didn’t stop thousands of men from submitting to the operation in the 1920s; it was a fad that rejuvenated only its promoters. Fortunately, the “goat-gland operation” was exposed as quackery, bringing similar ventures to a well-deserved halt.

In 1935, doctors discovered the male hormone testosterone. Testosterone therapy quickly became the standard treatment for men with low levels of the hormone, or hypogonadism, though its role for aging men with normal testicular function remains highly debatable.

Testosterone therapy makes it unnecessary to consider testicular transplantation to boost virility, but it doesn’t resolve the question of transplants for infertility. American surgeons achieved success in this area in 1977, when they transplanted a testicle from a healthy man to his identical twin who was born without testicles. More recently, surgeons in Russia and China have experimented with transplants between unrelated men. They have reported some success, but only in recipients who were treated with powerful immunosuppressive medications.

Testicular transplantation is technically possible, but the operation should not be considered except in extremely rare circumstances.

There must be an easier way to treat testosterone deficiency. And there is.

Cardiac events and mortality

Four small, brief trials of testosterone’s effect on treadmill performance in men with heart disease hint that the hormone may be helpful. Clearly, though, it’s much more important to see if testosterone therapy can change the risk of actual clinical cardiovascular events. The Mayo Clinic scientists who reviewed 30 placebo-controlled trials of testosterone therapy identified only six that reported clinical events. Together, these studies evaluated 147 men who received placebo and 161 who received testosterone for up to three years; testosterone did not appear to change the incidence or severity of cardiovascular events, though there was a trend toward more heart problems in the men who got the hormone.

The most important cardiovascular event is death from heart disease. The Massachusetts Male Aging Study linked high free testosterone levels with a modest increase in risk of death from coronary artery disease, but other studies report the opposite, finding that low testosterone levels are associated with an increased risk of cardiac death. None of these observational studies establish causality, and none can tell us if testosterone therapy is heart-healthy or -harmful; more research is needed.

Are we the men we were?

Testosterone levels decline slowly as men age. But a 2007 study suggests that since 1987, the hormone’s levels have fallen in American men independent of age. Researchers measured testosterone levels in 1,532 randomly selected men during three time periods, 1987–89, 1995–97, and 2002–04. There was a slow but steady decline in average testosterone levels over the study period. In all, an average, healthy 65-year-old in 2002 had about 15% less testosterone than a similar 65-year-old in 1987. Since smoking boosts testosterone levels, and obesity has the opposite effect, the scientists checked to see if the change could be explained by a decline in smoking or an increase in obesity, but neither possibility held up. More research is needed to find out why testosterone levels have declined.

Testosterone-replacement controversy

Heart disease is the number one killer of American men, but most men who receive testosterone therapy are taking the drug to treat other organs. Testosterone therapy may be safe for the heart, but how about the rest of the body?

Testosterone deficiency affects about 6% of American men; most are in the older age groups. Although the problem is relatively common, it is underdiagnosed. According to one survey, only 12% of men with androgen deficiency were receiving treatment.

Experts do not recommend routine testing for testosterone deficiency. But you should request a test if you have symptoms such as those listed above.

If you have your testosterone levels measured, try to have the blood drawn between 7 a.m. and 10 a.m. But since normal levels vary so widely, how do you know if your results are really low? As a rule of thumb, if your total testosterone is above 300 ng/dL, your free testosterone is above 5 ng/dL, or your bioavailable testosterone is above 150 ng/dL, true deficiency is unlikely.

But even if your levels are low, you may benefit from a period of observation and repeat testing before starting treatment. That’s because a report from the Massachusetts Male Aging Study found that over half the men with symptomatic testosterone deficiency improved without any treatment at all.

Causes of testosterone deficiency include testicular failure due to genetic errors, mumps, severe trauma, alcoholism, and cancer chemotherapy and radiation. In other cases, the problem originates in the pituitary gland of the brain; causes include tumors (almost all benign), head trauma, brain surgery, various medications, some hereditary disorders, severe malnutrition, and chronic illnesses.

Men with hypogonadism should receive testosterone-replacement therapy. Exceptions include patients who have had prostate or breast cancer, unexplained high PSA levels, prostate nodules or severe BPH, elevated high red blood cell counts or abnormally viscous (“thick”) blood, untreated obstructive sleep apnea (respiratory pauses during sleep that may increase the risk of high blood pressure, heart attack, and stroke), or severe heart failure.

Until recently, men who needed testosterone required injections of the hormone every one to three weeks. Now, most men use skin patches (Testoderm, Androderm), gels (AndroGel, Testim), or tablets that are placed on the surface of the gums (Striant). All these products require a doctor’s prescription and, except for injections, all are expensive. A safe testosterone pill has not yet been approved in the U.S.

Women and children beware

The FDA has received reports of premature puberty and behavioral changes in children who have inadvertently come into contact with a man’s testosterone gel. The FDA advises women and children to avoid contact with application sites on the skin of men who use these gels. Men should wash their hands with soap and water after each application. They should also cover the application site with clothing after the gel dries, and then wash the area with soap and water before any skin-to-skin contact with another person.

Testosterone tinkering

If the FDA’s estimates are correct, about 250,000 American men are receiving testosterone for hypogonadism, the only condition for which the hormone is approved. But some 1.75 million prescriptions for testosterone products were written by American doctors in 2002, at a cost of $400 million — and the numbers have continued to soar. Why are all these men taking testosterone? And should they?

Heart disease is not the only thing that is related to age. As the years pile on, men lose muscle mass and bone density; the red blood cell counts sag; sexual ardor declines; mood, energy, and memory drift down; and body fat increases. In theory, at least, testosterone therapy might blunt or reverse each of these woes.

That makes testosterone sound pretty good, and it’s why so many men are turning to the drug. But the theoretical benefits should be balanced against the theoretical risks.

The most serious long-term complications of testosterone therapy include an increased risk of prostate diseases, both BPH and possibly prostate cancer. Other potential side effects include polycythemia (an excessive number of red blood cells), sleep apnea, gynecomastia (benign breast enlargement), acne, and liver disease. Cholesterol abnormalities and heart disease were once on that list, but they now appear unlikely.

Do the potential gains of testosterone treatment outweigh the possible pains? Nobody knows. To date, only small, short-term studies have been completed. They report few side effects, but benefits are decidedly mixed. For example, a study of 237 healthy 60- to 80-year-old men with low-normal testosterone levels found that six months of treatment produced an increase in muscle mass but did not reduce abdominal fat or improve bone density, mental function, or physical performance. The study did not evaluate heart disease, but it did find that testosterone reduced HDL cholesterol levels. A smaller study of 81 testosterone-deficient men with an average age of 57 reported that 36 months of testosterone replacement produced subjective improvement in symptoms and reduced the average cholesterol level from 204 mg/dL to 167 mg/dL — but 5% of the men were diagnosed with prostate cancer after an average of 33 months of therapy.

More research is needed to learn how testosterone affects the heart and the rest of a man’s body and mind. That’s where women stood before the Women’s Health Initiative turned medical “wisdom” on its ear when researchers reported that hormone therapy does more harm (breast cancer, heart attacks, and strokes) than good, particularly for older women. But because federal funding agencies are worried about the possible risks of long-term testosterone therapy, a “Men’s Health Initiative” is not in the works.

Without good data, what’s a guy to do? The best advice is to protect your heart and your body by taking care of known risk factors, such as cholesterol, blood pressure, diabetes, obesity, and tobacco exposure. And don’t forget that diet and exercise remain the keys to reducing the risk of heart disease: shedding body fat and building up muscles and bones; improving memory, mood, and vigor; and slowing the aging process.

Testosterone makes the man, but a good lifestyle makes him healthy.

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