Testosterone (Ruth, 2020) – Is low testosterone in men genetic?

photo of person lifting weights

Nebula Genomics DNA Report for Low Testosterone in Men

Is low testosterone in men genetic? We created a DNA report based on a study that attempted to answer this question. Below you can see a SAMPLE DNA report. To get your personalized DNA report, purchase our Whole Genome Sequencing!

Sample report on low testosterone in men from Nebula Genomics
Sample variants on low testosterone in men from Nebula Genomics
To learn more about how Nebula Genomics reports genetic variants in the table above, check out the Nebula Research Library Tutorial.

Introduction (Part 1 of Is low testosterone in men genetic?)

Testosterone is a sex hormone that occurs in all sexes, but differs in concentration and mode of action in men and women. 

In men, testes release testosterone largely as a reaction to LH (luteinizing hormone). This sex hormone is critical to the development of physical characteristics, like facial hair, muscle mass, formation of sex organs, sexual function, and a deeper voice, when a male child reaches puberty.

Facial hair
Testosterone is the hormone responsible for male characteristics. Pxhere.

The adrenal cortex produces small amounts of other sex hormones, but only a very small amount of testosterone. In women, the ovaries and adrenal cortex produce small amounts of testosterone, but normally not enough to trigger male characteristics. 

In the biosynthesis of the organism, cholesterol is the precursor (precursor) or progesterone is an intermediate for testosterone synthesis.

Total testosterone is composed of 98% bound testosterone, either bioactive (albumin-bound) or sex hormone binding globulin (SHBG)-bound testosterone. The remaining 1 to 2% is free testosterone.

Hypogonadism is the medical term for diminished functional activity of the gonads (testes or ovaries). Low testosterone in men is often a result of lowered activity.

Is Low Testosterone in Men Genetic?

Low testosterone is in most cases a combination of age, lifestyle factors, and genetics. Previously, multiple genetic markers have been identified that are associated with decreased blood levels. The majority of these markers are located within the globulin gene. Globulin is a protein that binds to testosterone. Increased levels of the globulin protein could reduce testosterone in the blood. 

Many of these genes can be found on the SHBG locus and on the X chromosome.

Other cases suggest that the condition is more likely driven by challenges in adolescence (such as poverty) than genetic destiny. 

On the other hand, there are some genetic conditions that result in low testosterone in men. Although these disorders affect the chromosomes, they are not hereditary. This means that they occur in the genes after conception and they are not passed through families. 

Klinefelter syndrome

Individuals with this condition have two or more X chromosomes in addition to a Y chromosome. This condition is not hereditary, but occurs after conception. The result is abnormal development of the testes and thus low levels of testosterone. Persons with this condition usually also experience enlarged breasts, reduced body hair, lower body masses, and extremely low sperm count.

Age of diagnosis of Klinefelter syndrome. a cause of low testosterone in men
Klinefelter syndrome is diagnosed at all stages of life. Wikipedia. CC-Attribution-Share Alike 3.0 Unported.

Kallmann syndrome

This condition is also linked to the X chromosome. LH and FSH hormones are impaired, decreasing the amount of testosterone that is produced. Although it can occur in both women and men, it is more common in the latter. In all cases, the individual may enter puberty late or not at all. Male testicles tend to be smaller and, as with Klinefelter syndrome, often leads to infertility.

Myotonic dystrophy

This is the most common form of adult muscular dystrophy. This genetic mutation is on the Y chromosome and is usually discovered when a person is in their 30s or 40s after testicular failure.

Epidemiology (Part 3 of Is low testosterone in men genetic?)

It is difficult to define low testosterone levels since the levels tend to vary throughout the day and may be affected by lifestyle factors such as weight, nutrition, alcohol consumption, and certain medications. 

This condition can happen to men at any age, but it is much more prevalent in older males. Some estimates suggest that the condition affects over 40% of men aged 45 and older. 

According to the Boston University School of Medicine, low testosterone in men affects an estimated 4 to 5 million men in the United States. More than 60% of men over age 65 have free testosterone levels below the normal values of men aged 30 to 35. 

Symptoms (Part 4 of Is low testosterone in men genetic?)

While the medical term for low testosterone levels is hypogonadism, the condition is also referred to as Testosterone Deficiency Syndrome (TD) or Low Testosterone (Low-T). Some common symptoms of low testosterone in men include:

  • Erectile dysfunction, or problems developing or maintaining an erection
  • Other changes in your erections, such as fewer spontaneous erections
  • Decreased libido or sex drive
  • Infertility
  • Rapid hair loss
  • Reduced muscle mass
  • Increased body fat
  • Enlarged breasts
  • Sleep disturbances
  • Persistent fatigue
  • Brain fog
  • Depression
Symptoms of low testosterone in men
Symptoms of low testosterone levels. Wikipedia. CC-Attribution-Share Alike 4.0 International.

There are controversial opinions as to the link between low testosterone and prostate cancer. While some studies seem to show that increasing testosterone through supplements improves prognosis, others suggest that suppression of the hormone may ultimately help reduce fueling cancerous prostate cells. The American Cancer Society indicates the latter approach on their website. This connection continues to be an active area of research.

Causes (Part 5 of Is low testosterone in men genetic?)

The most significant cause of low testosterone in men is age. It is believed that testosterone levels peak in adolescence and early adulthood and begin to decline by about 1% per year starting around age 30.

Younger men may also experience low testosterone. In these cases, increased risk of the condition is more likely to be comorbid with a different underlying condition or the result of a separate illness or injury.

According to Healthline, some contributing factors include:

  • High cholesterol levels
  • High blood pressure
  • Being overweight or obese
  • Drinking excessive amounts of alcohol
  • Using illegal drugs
  • Using anabolic steroids
  • Taking certain prescription medications such as steroids and opiates, especially in excess

Other medical conditions that may accompany or cause low levels:

  • Hypothalamic or pituitary disease or tumors
  • Injuries, tumors, or other conditions affecting your testicles including inflammation related to childhood mumps
  • Inherited diseases, such as Kallman’s syndrome, Prader-Willi syndrome, Klinefelter syndrome, or Down syndrome
  • Type 2 diabetes, heart disease, liver disease, or AIDS
  • Cancer treatments such as radiation and chemotherapy

Diagnosis (Part 6 of Is low testosterone in men genetic?)

The condition can be diagnosed around puberty, which is ideal so that treatment can begin early. However, many men are unaware of their low testosterone levels until later in adulthood. Many males are diagnosed when they realize they have fertility problems. 

It’s important to seek medical advice if you think you have this condition so that you can obtain prescribed medication. Your health care provider may conduct a physical exam and ask questions regarding the development of characteristics such as pubic hair, muscle mass, and size of testes.

Testosterone levels are measured via a standard blood test that looks for one or more types of testosterone in the blood. Because levels tend to fluctuate throughout the day and may be affected by lifestyle choices, such as alcohol consumption, it is difficult to get the full picture with just one test. In most cases, your doctor will order a few blood tests on different dates to help diagnose low testosterone in males. The highest levels tend to be around early morning, which is why many of these tests are done before 10 am. 

If low testosterone in men is observed through the blood test, you may be given additional tests that can rule out or confirm a testicular disorder of pituitary gland abnormality. These tests include:

  • Hormone testing
  • Semen analysis
  • Pituitary imaging
  • Genetic studies
  • Testicular biopsy

Did you know you can test for low testosterone in men at home at a fraction of the cost? Learn more in our article about at home testosterone tests.

Treatment (Part 7 of Is low testosterone in men genetic?)

According to Mayo Clinic, low testosterone treatment in men depends on the age of diagnosis and the cause of the low levels. For most adults, the condition is treated with testosterone replacement therapy. This type of hormone replacement therapy is generally provided to young men who wish to increase the characteristics the condition takes away, such as sexual drive, facial hair, and muscle mass.

Adults

There are many different testosterone products that vary in how they are administered. Most need to be taken long term. Some are more convenient than others, which may influence you and your doctor’s decision. 

Oral: Oral testosterone replacement therapies are generally not prescribed mainly due to side effects that damage the liver. A new oral treatment, testosterone undecanoate (Jatenzo), was approved by the FDA in 2019. This preparation is absorbed by the lymph nodes, allowing it to bypass the liver. 

Gel: Depending on the brand, gels are applied either to the upper arm/shoulder or front/inner thigh. The medicine is absorbed through the skin so it is important not to wash the gel off for several hours. Skin irritation may occur. It is also important to avoid inadvertently transferring the medication to another person through skin to skin contact. 

A gel used to treat low testosterone in men
Testogel is a medication used to treat low testosterone levels in men.  www.doctor-4-u.co.uk/. Flickr.

Injections: Testosterone cypionate (Depo-Testosterone) and testosterone enanthate are injections given in a muscle or under the skin. They can normally be given at home by either yourself or a family member. An alternative is testosterone undecanoate (Aveed). This is a deep intramuscular injection that is typically given every 10 weeks. It must be given at your doctor’s office and can have serious side effects.

Patch: There is a testosterone-containing patch (Androderm) available that is applied on either the thigh or torso. Mild side effects, such as skin irritation, may occur.

Gum and cheek (buccal cavity): This is a small putty-like substance applied to the gumline three times a day. The testosterone replacement is absorbed into your bloodstream where your gum meets your upper lip. Gum irritation may occur.

Nasal: This testosterone gel (Natesto) can be applied in the nostrils. It is pumped into each nostril twice, three times a day. It tends to be more inconvenient than other options.

Implantable pellets: Testosterone-containing pellets (Testopel) can be surgically implanted under the skin every three to six months.

Infertility

Depending on the cause of low testosterone, there may be treatment to restore fertility. If a pituitary problem is the cause, pituitary hormones can be given that stimulate sperm production and fertility. Pituitary tumors can be either surgically removed or treated with chemotherapy or radiation.

In most other cases where fertility cannot be restored, there are technological options that can help couples conceive.  

Children

If a boy is experiencing delayed puberty, it may be possible to induce it with hormonal supplements. Three to six months of testosterone supplementation given as an injection is usually recommended. After this time, the child normally develops the traditional male characteristics such as facial hair and muscle mass. 

If you liked this article, you should check out our other posts in the Nebula Research Library!