Hypogonadism in Men—the Many Causes and Effects, New Treatment and Natural Therapies

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Tired, irritable and depressed, a 59-year old man struggles with the weekly crossword puzzle he’s been doing his entire adult life.[3]  

A 14-year old boy has no sense of smell and fails to develop the telltale signs of puberty like his friends and classmates.  

Could these two males be suffering from the same undiagnosed condition?[8]  

Enter “male hypogonadism”.

In the U.S., roughly 4-5 million men and boys reportedly suffer with the condition, marked by deficient male gonadal function and the under secretion of testosterone.

What is hypogonadism in men?

Hypogonadism is a medical condition that affects both sexes.  In male hypogonadism, the testicular function is impaired and the ability to produce sufficient amounts of androgen is affected.[3]

How is male hypogonadism classified?

Hypogonadism in males is classified as either primary hypogonadism or secondary hypogonadism.

Primary hypogonadism refers to testosterone deficiency that occurs as a direct result of testicular failure.

Secondary hypogonadism originates in the brain and its signaling centers that communicate with testicles to produce the correct amounts of testosterone.  Either the hypothalamus or the pituitary gland may be to blame for secondary hypogonadism.[9]  

What are the symptoms of male hypogonadism?

Testosterone provides the fundamental building blocks for many processes and functions in the body.  When testosterone levels are insufficient either from birth, or from an injury, disorder or infection, male development and function suffers.[1]

Symptoms of hypogonadism may include one or more of the following:

Pre-puberty in Boys

• Male children have arrested or slower growth overall.  Muscle and genital development is stunted.  Body hair is limited and limbs are longer in proportion to the torso of the body.  Boys with hypogonadism may have a more difficult time fitting in with peers who are maturing normally.[4]

Males (Puberty)

• Lack of facial/pubic hair
• Arrested growth of genitalia
• Voice does not deepen
• Low libido
• Low sperm production (leads to infertility)
• Lack of muscle mass
• Loss of bone may begin (osteoporosis)[1]

Post-puberty

• Males will have an underdeveloped libido, less muscle tone and may develop breast tissue.[4]

Aging Males

• Lack of libido
• Erectile dysfunction
• Cognitive impairment
• Low mood/depression
• Excess fat, especially around the middle
• Lower bone density
• Negative change in cholesterol levels
• Difficulty losing weight

What are the possible health risks for men with hypogonadism?

• In addition to the central effects of hypogonadism in males, there are other far-reaching consequences and health risks associated with the condition.

• Hypogonadism can either exacerbate existing medical conditions or create new health risks in men.

• Health risks for men with hypogonadism also include:

• Greater likelihood of developing cardiovascular disease
• Heightened risk of death due to a heart attack or stroke
• Elevated risk for metabolic syndrome, which includes elevated blood pressure, elevated levels of insulin, increase in belly fat, and high cholesterol
• Greater likelihood of diabetes
• Increased risk for prostate cancer
• Greater risk of having athersclerota of the aorta (plaque build up in an artery to the heart)
• Increased risk of more aggressive cancers[1]

What causes primary hypogonadism?

There are many causes for primary hypogonadism including genetic conditions (such as Klinefelter’s Syndrome, a chromosomal abnormality that impacts the normal development of male testicles) illness, or injury.   

Other causes of primary hypogonadism include:

• Undescended testicles—Testicles formed in the abdomen before birth fail to drop to their permanent position in the scrotum after birth.
• Mumps infection—Children or adolescents who contract mumps involving salivary glands, as well as testicles, may have permanent damage that impacts testosterone production. 
• Cancer treatment—Chemotherapy or radiation can temporarily impede sperm and testosterone production that sometimes becomes permanent.
• Hemochromatosis—Elevated levels of iron in the blood can cause pituitary gland issues that affect the production of testosterone.
• Testicular injury—Injury to testicles can inhibit testosterone production.
• Aging—The normal course of aging causes testosterone levels to steadily decline through the years.  30% of men over the age of 75 have insufficient levels of testosterone.[9]

What are the causes of secondary hypogonadism?

In secondary hypogonadism, testicles develop normally, but cannot produce testosterone because of a problem with the hypothalamus or pituitary in the brain.

Causes of secondary hypogonadism include:

• Kallman Syndrome— This congenital condition involves abnormalities in the hypothalamus, which interfere with the movement of olfactory neurons (sense of smell) and the migration of neurons involved with gonadotropin-releasing hormone (GnRH) to the front of the brain during fetal development.  In Kallman syndrome, pituitary hormones are not secreted effectively.  
• Pituitary conditions—A pituitary tumor may impact the pituitary gland’s ability to release proper hormones to the testicles.
• Inflammatory diseases—Diseases such as sarcoidosis, histiocytosis, and tuberculosis alter hypothalamus and pituitary function, which may impede testosterone production.
• Stress—Excessive stress, too much exercise, and rapid, significant weight loss may trigger higher levels of cortisol, which can affect the hypothalamus and proper function.
• HIV/AIDS—The hypothalamus, pituitary, and testes may be negatively impacted by the infection or disease.
• Obesity—Excessive weight can cause hypogonadism.
• Drugs—Certain drugs that contain opiates and some hormone treatments may affect testosterone production as well.

What is the key function of testosterone?

Testosterone is necessary for proper masculine growth and the developmental changes that accompany maturation from childhood, through puberty and adulthood.  Testosterone causes secondary male sex characteristics such as facial and pubic hair growth, broadening of shoulders, increased muscle mass, and the deepening of the voice.  Sex drive and sperm production also require adequate levels of testosterone. 

How does hypogonadism occur?

As the male fetus develops, sex organs may not develop properly as a result of low testosterone.

Lower testosterone levels can arrest or inhibit puberty causing permanent changes to normal growth and development.  

Why else do men need testosterone?

Men also need testosterone to:

• Maintain muscle mass
• Properly distribute fat 
• To produce red blood cells
• Maintain proper bone mass[2] 

‍How does hypogonadism affect men?

Hypogonadism may affect a number of functions depending on the age and stage of development.

Older males may experience weakness and develop osteoporosis in older age.  Low libido, impotence, depression and irritability, and cognitive impairment may be symptomatic of testosterone insufficiency.  Men with hypogonadism also have reduced muscle mass and muscle strength.[7] 

How common is hypogonadism in men?

In U.S. and European studies of aging men, about 2.1%-12.8% of the general population suffer from hypogonadism.  As much as 60% of men over 65 have symptoms indicative of the condition.  Sadly, hypogonadism is widely under-diagnosed and less than 5% of men receive testosterone replacement treatment that could mitigate many of its negative effects.[3]

How are causes of hypogonadism different for younger men? 

Younger males may experience hypogonadism because of genetic impairments and the way the brain or the testicles form as they develop in utero.

Older men may have hypogonadism with life-altering symptoms as well, however, reduced testosterone production may be the result of age or some other medical manifestation.

Testing for Hypogonadism

Doctors screen male patients for hypogonadism with a specific blood test that evaluates morning serum total testosterone levels.  This measures free testosterone along with protein-bound testosterone as well.

If testosterone levels in the morning fall below 300 ng/dL (10.4 nmol/L), hypogonadism is likely present.

Further testing of luteinizing hormone (LH) or follicle-stimulating hormone (FSH) may be necessary to help determine whether testosterone deficiency is caused by primary or secondary issues.  Depending on those results, a blood test for serum prolactin may also be conducted.[3]

In males, LH facilitates testosterone production from Leydig cells in the testes and FSH stimulates growth of testicles and supports angrogen-binding proteins necessary for mature sperm cells.  Prolactin, the hormone necessary for milk production in pregnant women may also be significantly present in hypogonadal men.

Treatment with Testosterone Replacement for Hypogonadism

Treatment with testosterone therapy is common in men with hypogonadism.  The objective of this type of treatment is to raise testosterone levels to normal levels in efforts to improve libido, erectile dysfunction, mood, strength, and energy.  In older men testosterone replacement helps protect or slow the progression of osteoporosis.

How is testosterone delivered?

Testosterone delivery methods vary depending on side effects, including how it affects other hormone levels, convenience, efficacy, and absorption rates.

Delivery methods include the following:

• Oral Testosterone— Testosterone undecanoate is FDA approved only for specific types of hypogonadism including Kleinfelter’s Syndrome or pituitary conditions.  It is not viable for use in men with age-related testosterone insufficiency.
• Testosterone injections—Testosterone therapy involving once-weekly self-injection at home has been recently approved for specific types of hypogonadism including primary hypogonadism and hypogonadotropic hypogonadism.
• Testosterone Patch—A transdermal patch delivers measured amounts of testosterone throughout the day and is placed on the arms, legs, back or buttocks at night.
• Testosterone Gel—Testosterone Gel 1% is applied in the morning after showering to clean dry skin on the shoulders, upper arms or abdomen and is rapidly absorbed within 2 hours. 

How does testosterone replacement treatment work?

Treatment for low levels of testosterone usually involves time-released androgen that more closely mimics the natural rhythms of the body and its distribution.  Some treatment methods may be more viable or effective than others depending on natural testosterone levels, prostate health and age and stage of male development.   

Testosterone replacement therapy does not treat infertility.[6]

What are the risks and issues associated with testosterone replacement therapy?

Risks include:

• Worsening of prostate disorders
• Increase in prostate-specific antigen (PSA)
• Skin issues such as acne
• Sleep apnea
• Excess red blood cell production and mass, which can lead to blood clots  
• Swelling in the feet or ankles
• Breast enlargement
• Higher risk of Stroke 

New Pharmacological Treatments 

Men and women are living longer than any other generation before them.  With an increased interest in midlife medicine, comes greater awareness and research into the further treatment of male hypogonadism.  Transdermal applications of testosterone and longer-lasting injectable testosterone have replaced older forms of the hormone treatment.  

Other newer pharmaceuticals have also been developed that target specific receptors, with compounds such as:

• Selective androgen receptor modulators (SARMS)
• Aromatase inhibitors
• Dihydrotestosterone 
• 7alpha-methyl-19-nortestosterone, aromatase inhibitors,
• Clomifene
• Human chorionic gonadotropin

These drugs may mitigate some of the dangerous or uncomfortable side effects of traditional testosterone therapies.[5]

Other medications to treat pituitary dysfunction (including tumors) or hypothalamus conditions may be necessary to treat hypogonadism.

Natural Treatment for Hypogonadism

Natural treatment options for men with hypogonadism may include a modified diet, targeted exercise, better sleep quality and a reduction in stress overall.[10]  Weight lifting and high-intensity exercise increase testosterone the most. Foods that support testosterone health include healthy fats, protein and carbs.  Garlic, pomegranate, eggs, and fish may be beneficial in men with low testosterone.  Vitamin D and zinc are also associated with higher levels of male androgen. 

Herbs and Plant Extracts

Tea made from the Southeast Asian evergreen tree, Eurycoma longifolia may help improve overall sexual function, testosterone production, infertility and libido in men.

Ashwagandha is an herb that may help boost testosterone levels, decrease stress and depressive symptoms, and reduce cortisol levels in the body. Ashwagandha may also improve male fertility.

Ginger, Mucuna pruriens, shilajit, and Tongkat Ali may support testosterone health as well.

If you suspect possible hypogonadism and suffer from many of the associated symptoms, it’s important to first get tested for testosterone levels either through a reputable lab or with an at-home test kit.  

The treatment you receive is dependent on specific test results, age and condition.