What is Male Hypogonadism?
In males, 95% of the testosterone, a key male hormone, is produced in the Leydig cells found in the testes. Problems that disrupt the interaction between the hypothalamus, pituitary gland, and testes, can lead to a condition known as male hypogonadism, which is characterized by low testosterone levels. These problems can be either acquired (developed after birth) or congenital (present at birth).
It’s useful to understand the difference between primary hypogonadism, which starts in the testes, and secondary hypogonadism, which starts in the hypothalamus or pituitary gland. Signs that a man may have low testosterone include fewer spontaneous erections, less morning erections, low sexual desire, unexplained fatigue, and smaller testicles.
The normal range for a man’s testosterone level, measured early in the morning, is typically between 300 ng/dL to 1000 ng/dL, though there’s some variation between different laboratories. If a man’s testosterone level is less than 300 ng/dL on at least two different mornings, he may be diagnosed with hypogonadism. Morning measurement is preferred as testosterone levels are usually highest then. That said, if a man continues to show symptoms of low testosterone but his levels are considered “normal,” a doctor may still diagnose him with hypogonadism.
A total testosterone level below 405.9 ng/dL is under the 5th percentile. Mature males should ideally have testosterone levels between 500 and 800 ng/dL, while younger males should have levels between 600 and 900 ng/dL. It’s worth noting that low testosterone levels on their own don’t need treatment. Only when they’re linked with the symptoms of hypogonadism, treatment might be required.
What Causes Male Hypogonadism?
Primary hypogonadism, or testicular failure, happens when there are chronically low levels of testosterone in the body alongside above-normal levels of a hormone called LH. This condition can have several causes, including Klinefelter syndrome (a genetic condition), undescended testicles, a mumps infection that impacts the testicles, hemochromatosis (too much iron in the body), certain cancer treatments, and normal aging.
Secondary hypogonadism, also known as pituitary failure, is indicated by low testosterone levels along with normal or low LH levels. This form of hypogonadism can be caused by various things, including Kallman syndrome (a genetic disorder), disorders affecting the pituitary gland (a gland at the base of the brain), HIV, obesity, surgeries, injuries, and stress.
Both types of hypogonadism can significantly affect sperm count and the quality of semen, which may impact a man’s fertility. Mild changes in the quality of semen and significant changes in sperm movement are often linked to primary hypogonadism. Hypogonadism can stem from causes that a person is born with (congenital) or develop over time (acquired).
Ambiguous genitals, a smaller than average penis, and both testicles not descending into the scrotum are all signs of low testosterone in males before puberty. In young adults, doctors should conduct tests to look for specific genetic conditions, such as Turner and Klinefelter syndromes, which can cause a deficiency in testosterone.
Risk Factors and Frequency for Male Hypogonadism
Hypogonadism, a condition associated with low testosterone levels, is often not reported accurately, diagnosed correctly or it can often be overtreated. It affects around 40% of men above the age of 45 and half the men in their 80s. Studies have shown that testosterone levels decrease by 100 ng/dL every 10 years. The occurrence of hypogonadism doesn’t seem to be influenced by race or ethnicity.
A recent study in nonobese men with diabetes found that nearly 29% had low testosterone. The most reliable indicator of testosterone deficiency in this group was the visceral adiposity index. This index is calculated using information about the waist size, body mass index, levels of serum triglycerides, and high-density lipoprotein levels.
Signs and Symptoms of Male Hypogonadism
Androgen deficiency in men is a condition where the body doesn’t produce enough male hormones. This can result in a variety of symptoms, some of which are more likely to indicate this condition than others. Key symptoms that could suggest a man has androgen deficiency include a reduced sex drive, less frequent spontaneous erections, feeling tired all the time, loss of body hair (especially under the arms and around the pubic area), changes in vision (like only seeing part of your visual field), losing your sense of smell, testicles getting smaller or starting to shrink, getting hot flashes, and having trouble having children due to having very low or no sperm count.
There are also other symptoms that are less indicative of androgen deficiency, but can still occur. These include feeling sad or easily irritated, finding it hard to concentrate, getting more body fat, a dip in physical performance, losing muscle mass, having less stamina, losing weight, feeling a lack of energy, and not feeling hungry. A man presenting these conditions should likely be tested for a low testosterone level, even if he doesn’t show any specific symptoms of this deficiency.
During a physical check-up for androgen deficiency, the doctor will check for the presence of two testicles and their size. Testicles that are less than 4 cm in size or have a volume of less than 20 cc are considered small. If the testicles have shrunk or are not present at all, this may strongly suggest hypogonadism. The doctor will also look for body hair on the face, under the arms, and around the pubic area. They will also examine the breasts for any swelling or pain.
Last but not least, changes in body hair and muscle mass reduction often take years to occur. Infertility, swelling of the breasts, and decreased size of the testicles are often seen in primary hypogonadism than in secondary hypogonadism.
- Reduced sexual desire
- Decreased spontaneous erections
- Fatigue and lethargy
- Loss of body hair
- Changes in vision
- Loss of smell
- Decreased testicle size
- Hot flashes
- Infertility with low or no sperm count
- Feeling down or irritable
- Poor focus
- Increase in body fat
- Decreased physical performance
- Reduced muscle mass
- Reduced stamina
- Weight loss
- Decreased appetite
Testing for Male Hypogonadism
It’s believed that up to a quarter of men receiving testosterone treatment haven’t had their testosterone levels examined before beginning, and about half haven’t even after starting the treatment. What’s more alarming is that up to a third of men receiving testosterone replacement therapy for a condition called hypogonadism, which involves low testosterone levels, don’t actually meet the criteria for having the condition.
Routine screening for everyone is not advised, but people with certain conditions like HIV, kidney failure, type 2 diabetes, infertility, severe lung conditions, unexplained anemia, and weak or brittle bones should think about getting screened. Other risk factors include testicle shrinkage after chemotherapy, radiation therapy to the testicles, chronic opioid use or abuse, infertility, pituitary gland problems, and chronic steroid use.
There’s a test called the Androgen Deficiency in Aging Males (ADAM) which can help in initially spotting male hypogonadism. It’s a questionnaire with 10 questions aimed to identify men who show signs of low testosterone levels. However, it’s worth noting that some guidelines, like the ones from the American Urological Association, don’t advise using these questionnaires. This is because they can’t replace a thorough evaluation with the patient, including appropriate lab tests. The questionnaires, even validated ones, don’t always accurately indicate a diagnosis and are not a substitute for lab testing.
Initial lab testing should include measuring your testosterone levels through blood samples taken in the early morning. Two results showing testosterone levels under 300 ng/dL are often enough to diagnose biochemical (or non-symptomatic) male hypogonadism. But remember, this diagnostic criteria may change depending on the lab. To clinically diagnose male hypogonadism, you need to have associated symptoms. Only if you are experiencing symptoms should you be treated for low testosterone.
Since two blood samples are required for a diagnosis, other hormones like follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin can be tested from the second blood sample. If both of your testosterone levels come back lowered, additional tests, like thyroid and vitamin hormone tests, a blood count, iron levels, and others are recommended. A prostate-specific antigen (PSA) test should also be done on all hypogonadal patients over 40 before starting therapy. If you have symptoms related to high estrogen levels, like breast enlargement, pain, tenderness, nipple sensitivity, or discharge, your estrogen levels should be checked. If they’re high, you’ll likely be referred to an endocrine specialist. Testosterone therapy is not advised if your hematocrit, or the proportion of red blood cells in your blood, is higher than normal. If that’s the case, your testosterone supplementation should be reduced, or you may need to stop it altogether.
Testosterone injections have been tied to the highest chance of getting polycythemia (too many blood cells) from treatment for hypogonadism. If your prolactin hormone levels are high (usually considered to be 2 to 3 times the normal upper limit), and if you have extremely low testosterone levels alongside normal or low LH levels, you may have a condition called prolactinoma, and should get an MRI of your pituitary gland done. If you’re interested in having children, full reproductive testing should be undertaken. Those with hypogonadotropic hypogonadism who want to have children should consider genetic testing.
Usually, free testosterone levels do not need to be measured, unless it’s suspected that there’s a problem with the protein that testosterone binds to in the body. The binding of testosterone to this protein can change as you age, with obesity, and can be corrected with weight loss. It can also be impacted by type 2 diabetes, hypothyroidism, and liver disease. Excessive obesity has been associated with a form of hypogonadism related to the hypothalamus part of the brain. The most reliable way to test free testosterone is through a lab analysis method called equilibrium dialysis, as other methods are generally deemed unreliable.
Treatment Options for Male Hypogonadism
If a patient is dealing with hypogonadism (a condition in which the body doesn’t produce enough sex hormones) but doesn’t have any symptoms, there’s typically no need for treatment. Only if there are symptoms possibly linked to low testosterone levels should treatment be considered. Managing these symptoms might involve lifestyle changes like losing weight or exercising more.
Oral testosterone supplements, such as methyltestosterone, are generally not recommended because they can cause liver problems. Research has shown that testosterone therapy in men with proven hypogonadism can provide noticeable improvement in various areas, such as sex drive, mood, body mass, and more. However, there’s not enough conclusive evidence to show that it impacts other symptoms like fatigue or mental function.
There are some promising findings that testosterone supplementation could be a positive tool in the treatment of depression in men with hypogonadism, but we need more research in this area. Testosterone therapy might raise the risk of some cardiovascular issues or blood clots, so it’s important to monitor health closely when using it. If a patient has recently had a major cardiovascular event, they should wait at least 3 to 6 months before starting testosterone therapy.
If a patient is actively trying to conceive, they should avoid testosterone therapy since it can significantly reduce sperm count and impair fertility. Clomiphene citrate is a different treatment option that could help men with hypogonadism without affecting sperm count or fertility. However, it may not be effective if the patient’s levels of certain hormones are already high.
Testosterone replacement therapy might involve different methods like oral, nasal, or injectable forms of testosterone, but the goal is always to increase testosterone levels without causing dangerous complications. It’s important for patients to access treatment options that work best for them and communicate with their healthcare provider about any potential risks or unwanted side effects.
Potential complications of testosterone therapy can include prostate or breast cancer, sleep apnea, or high protein levels in the blood, among other things. It’s crucial to monitor these risks throughout treatment. Testosterone therapy doesn’t appear to cause prostate cancer, but if a patient already has this cancer, using testosterone could potentially raise some concerns.
Finally, monitoring of the patient is critical during treatment for hypogonadism. Regular check-ups, including labs and physical assessments, can ensure that the treatment is effective and safe.
What else can Male Hypogonadism be?
When a man experiences low levels of sex hormones, it’s a condition called male hypogonadism. Doctors have a list of conditions that can cause similar symptoms, and they need to rule these out to confirm a diagnosis of hypogonadism:
- 5-alpha-reductase deficiency
- Androgen insensitivity syndrome
- Anorexia nervosa
- Congenital adrenal hyperplasia
- Depression
- Past use of androgens
- Hyperparathyroidism
- Hyperprolactinemia (excessive levels of a hormone called prolactin)
- Infertility not related to hypogonadism
- Kallman syndrome (they’ll specifically look for this if a man has reduced or absent sense of smell)
- Klinefelter syndrome
- Malnutrition
- Cancer
- Micropenis
- Osteoporosis
- Pituitary gland masses (doctors will especially consider this if a patient reports vision disturbances)
- Shrinkage of the testicles
- Turner syndrome
What to expect with Male Hypogonadism
The outlook is very good for men who have symptoms of male hypogonadism and receive treatment in accordance with medical guidelines and proper follow-up. Male hypogonadism is a condition where the body doesn’t produce enough testosterone, which is the hormone that plays a key role in male growth and development. This condition is typically not curable, but it can effectively be managed with treatments such as clomiphene or testosterone replacement therapy.
Best results can be achieved when there is proper follow-up after the treatment, and the treatment is adjusted as needed to use the lowest possible dosage that still relieves symptoms and avoids side effects.
Possible Complications When Diagnosed with Male Hypogonadism
Male hypogonadism and its treatment can lead to several complications including acne, heart condition exacerbation, breast disorders, and lower sperm count that result in infertility. These conditions can also lead to polycythemia, a condition where your body makes too many red blood cells, potentially causing blood clots. Other complications include increased risk of cardiovascular events, prostate cancer growth, and irritation on areas where treatment patches or gels are applied. Other possible side effects might be sleep apnea, emotional disturbances due to steroid, or shrinkage of testicles.
Conflicting information is present about the cardiovascular risks associated with testosterone, with studies like the TOM and TEAAM trials providing differing results.
The TOM trial studied 209 men and found that using testosterone gel daily after 6 months was linked to increased cardiovascular events. This trial didn’t monitor serum testosterone levels.
On the other hand, the TEAAM trial of 2015 that monitored 308 men over 3 years found no difference in cardiovascular risk when testosterone was administered. Also, another study discovered that, after 12 weeks of treatment, testosterone undecanoate reduced fasting glucose and waist circumference while also improving the thickness of the wall of the carotid arteries and high sensitivity C-reactive protein, which is associated with inflammation.
Common Side Effects:
- Acne and similar skin problems
- Exacerbation of heart failure
- Breast disorders
- Low sperm count (Infertility)
- Polycythemia
- Potentially increased risk of blood clots
- Potential increased risk of cardiovascular events
- Prostate cancer acceleration
- Stimulation of prostate growth (benign)
- Skin reaction to patches or gels
- Sleep apnea
- Steroid induced emotional disorders
- Shrinkage of testicles (Testicular atrophy)
Preventing Male Hypogonadism
Spreading awareness and knowledge about male hypogonadism (a medical condition where the body doesn’t produce enough male hormone, testosterone) is an important part of public health projects aimed at preventing this condition and reducing its impact. The first step is raising awareness about the things that increase a person’s risk of getting the condition. Health initiatives highlight the importance of living a healthy lifestyle and going for routine health check-ups to spot potential problems early.
Education is also really important because it ensures that both healthcare professionals and regular people have the most recent and accurate knowledge about the causes, symptoms, and treatments available for male hypogonadism. When healthcare providers understand this condition well, it becomes easier for them to detect the condition early and manage it properly, which can improve patient health and overall public health. By sharing knowledge about this condition, what causes it, and the benefits of detecting and treating it early, people can make better choices about their health.
Patients need to know what must be true for them to be considered for testosterone therapy – a common treatment for male hypogonadism. This includes having low testosterone levels on at least 2 different occasions and a specific symptom related to hormones that could get better with extra testosterone.
It’s essential for patients to be warned that using too much testosterone can have harmful effects and can permanently change fertility. People who want to have children should consider other treatments instead of adding extra testosterone, like taking the medicines clomiphene or hCG.
Using testosterone when it’s not necessary is strongly discouraged, and people receiving this treatment need regular checks of their testosterone levels, PSA (a protein made by cells in the prostate gland), Hgb (a protein in red blood cells that carries oxygen), and Hct (the percentage of blood volume that is made up of red blood cells). If the treatment doesn’t relieve symptoms or make a big difference after 6 months, the patient may need to stop taking the testosterone.
