Male Hypogonadism

1 What is Male Hypogonadism?

Male hypogonadism is a condition in which the body does not produce enough of the testosterone hormone; the hormone that plays a key role in masculine growth and development during puberty.

Hypogonadism can significantly reduce the quality of life and has resulted in the loss of livelihood and separation of couples, leading to divorce. It is also important for doctors to recognize that testosterone is not just a sex hormone.

There are researches being published to demonstrate that testosterone may have key actions on

  • metabolism,
  • on the vasculature,
  • and on brain function,

in addition to its well-known effects on bone and body composition. There are two basic types of hypogonadism that exist:


This type of hypogonadism – also known as primary testicular failure – originates from a problem in the testicles.


This type of hypogonadism indicates a problem in the hypothalamus or the pituitary gland – parts of the brain that signal the testicles to produce testosterone.

The hypothalamus produces the gonadotropin releasing hormone, which signals the pituitary gland to make the follicle-stimulating hormone (FSH) and luteinizing hormone. The luteinizing hormone then signals the testes to produce testosterone.

Either type of hypogonadism may be caused by an inherited (congenital) trait or something that happens later in life (acquired), such as an injury or an infection.

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2 Symptoms

Symptoms of male hypogonadism entirely depend and reflect upon age.

Age at onset of testosterone deficiency dictates the clinical presentation:

  • congenital,
  • childhood-onset,
  • or adult-onset hypogonadism.

Congenital hypogonadism may be of 1st-, 2nd-, or 3rd-trimester onset.

Congenital hypogonadism of 1st-trimester onset results in inadequate male sexual differentiation. Complete absence of testosterone effects results in normal-appearing female external genitals. Partial testosterone deficiency results in abnormalities ranging from ambiguous external genitals to hypospadias.

Second- or 3rd-trimester onset of testosterone deficiency results in microphallus and undescended testes.

Childhood-onset testosterone deficiency has few consequences and usually is unrecognized until puberty is delayed. Untreated hypogonadism impairs development of secondary sexual characteristics.

As adults, affected patients have poor muscle development, a high-pitched voice, a small scrotum, decreased phallic and testicular growth, sparse pubic and axillary hair, and an absence of body hair.

They may develop gynecomastia and eunuchoidal body proportions (span > height by 5 cm and pubic to floor length >crown to pubic length by > 5 cm) because of delayed fusion of the epiphyses and continued long bone growth.

Adult-onset testosterone deficiency has varied manifestations depending on the degree and duration of the deficiency. Decreased libido;

  • erectile dysfunction;
  • decline in cognitive skills,
  • such as visual-spatial interpretation;
  • sleep disturbances;
  • vasomotor instability (in acute, severe male hypogonadism);
  • and mood changes, such as depression and anger, are common.

Decreased lean body mass, increased visceral fat, testicular atrophy, osteopenia, gynecomastia, and sparse body hair typically take months to years to develop.

Testosterone deficiency may increase the risk of coronary artery disease.

3 Causes

Causes of male hypogonadism vary depending on its type.

Primary Hypogonadism

Common causes of primary hypogonadism include:

  • Klinefelter's Syndrome: This condition results from a congenital abnormality of the sex chromosomes, X and Y. A male normally has one X and one Y chromosome. In Klinefelter's syndrome, two or more X chromosomes are present in addition to one Y chromosome. The Y chromosome contains the genetic material that determines the sex of a child and the related development. The extra X chromosome that occurs in Klinefelter's syndrome causes abnormal development of the testicles, which in turn results in the underproduction of testosterone.
  • Undescended testicles: Before birth, the testicles develop inside the abdomen and normally move down into their permanent place in the scrotum. Sometimes, one or both of the testicles may not descend at birth. This condition often corrects itself within the first few years of life without treatment. If not corrected in early childhood, it may lead to malfunction of the testicles and reduced production of testosterone.
  • Mumps orchitis: If a mumps infection involving the testicles in addition to the salivary glands (mumps orchitis) occurs during adolescence or adulthood, long-term testicular damage may occur. This may affect normal testicular function and testosterone production.
  • Hemochromatosis: Too much iron in the blood can cause testicular failure or pituitary gland dysfunction, affecting testosterone production.
  • Injury to the Testicles: Because of their location outside the abdomen, the testicles are prone to injury. Damage to normally developed testicles can cause hypogonadism. Damage to one testicle may not impair testosterone production.
  • Cancer treatment: Chemotherapy or radiation therapy for the treatment of cancer can interfere with testosterone and sperm production. The effects of both treatments are often temporary, but permanent infertility may occur. Although many men regain their fertility within a few months after the treatment ends, preserving sperm before starting cancer therapy is an option that many men consider. 
  • Normal aging:Older men generally have lower testosterone levels than younger men do. As men age, there's a slow and continuous decrease in testosterone production.

Secondary Hypogonadism

In secondary hypogonadism, the testicles are normal, but function improperly due to a problem with the pituitary or hypothalamus. A number of conditions can cause secondary hypogonadism, including:

  • Kallmann syndrome: Abnormal development of the hypothalamus – the area of the brain that controls the secretion of pituitary hormones – can cause hypogonadism. This abnormality is also associated with the impaired development of the ability to smell (anosmia).
  • Pituitary disorders: An abnormality in the pituitary gland can impair the release of hormones from the pituitary gland to the testicles, affecting normal testosterone production. A pituitary tumor or other type of brain tumor located near the pituitary gland may cause testosterone or other hormone deficiencies. Also, the treatment for a brain tumor such as surgery or radiation therapy may impair pituitary function and cause hypogonadism.
  • Inflammatory disease: Certain inflammatory diseases such as sarcoidosis, Histiocytosis, and tuberculosis involve the hypothalmus and pituitary gland and can affect testosterone production, causing hypogonadism.
  • HIV/AIDS: This virus can cause low levels of testosterone by affecting the hypothalamus, the pituitary, and the testes.
  • Medications: The use of certain drugs, such as, opiate pain medications and some hormones, can affect testosterone production.
  • Obesity: Being significantly overweight at any age may be linked to hypogonadism.
  • Stress-induced Hypogonadism: Stress, excessive physical activity, and weight loss have all been associated with hypogonadism. Some have attributed this to stress-induced hypercortisolism, which would suppress hypothalamic function.

4 Making a Diagnosis

Diagnosis of male hypogonadism begins with a medical history and physical examination. Many possible symptoms and signs may suggest low testosterone, or androgen deficiency, in adult men:

  • Incomplete sexual development
  • Reduced sexual desire (libido) and activity
  • Decreased spontaneous (night-time and morning) erections
  • Breast discomfort or enlargement
  • Loss of body hair, reduced shaving
  • Very small or shrinking testes
  • Inability to father children; low or zero sperm counts
  • Height loss, low bone mineral density, easily broken bones
  • Reduced muscle bulk and strength
  • Hot flushes, sweats
  • Decreased vitality (low energy, excessive fatigue)
  • Mild depression

Blood tests determine whether testosterone levels are in the normal range. This is generally 300 to 1,000 ng/dL (10.4 to 34.7 nmol/L), but the normal range may differ depending on the laboratory that conducts the test.

To diagnose low testosterone, a man generally needs to have more than one early-morning blood test. If his blood testosterone is repeatedly low, then tests of pituitary gland function, such measuring LH and FSH levels, must also be done.

5 Treatment

Testosterone replacement therapy is the primary treatment option for male hypogonadism. Ideally, the therapy should provide physiological testosterone levels, typically in the range of 300 to 800 ng/dL.

The goals of therapy are to:

  • Restore sexual function, libido, well-being, and behavior
  • Produce and maintain virilization
  • Optimize bone density and prevent osteoporosis
  • In elderly men, possibly normalize growth hormone levels
  • Potentially affect the risk of cardiovascular disease
  • In cases of hypogonadotropic hypogonadism, restore fertility

To achieve these goals, several testosterone delivery systems are currently available in the market. Clinical guidelines recommend reserving treatment for those patients with clinical symptoms, rather than for those with just low testosterone levels.

Transdermal Patch

Transdermal patches deliver continuous levels of testosterone over a 24-hour period. Application site reactions account for the majority of adverse effects associated with transdermal patches, with elderly men proving particularly prone to skin irritation. Local reactions include

  • pruritus,
  • blistering under the patch,
  • erythema,
  • vesicle formation,
  • indurations,
  • and allergic contact dermatitis.

A small percentage of patients may also experience headache, depression, and gastrointestinal (GI) bleeding. Some patients report that the patch easily falls off and is difficult to remove from the package without good dexterity. Transdermal patches are more expensive than injections, but the convenience of use and maintenance of normal diurnal testosterone levels are advantageous.

Topical Gel

Application in the morning allows for testosterone concentrations that follow the normal circadian pattern. Topical testosterone gels also provide longer-lasting elevations in serum testosterone, compared to transdermal patches. Similar to patches, testosterone delivered via gels does not undergo first-pass metabolism.

Adverse effects associated with therapy include

  • headache,
  • hot flushes,
  • insomnia,
  • increased blood pressure,
  • acne,
  • emotional labiality,
  • and nervousness.

Although application site reactions occur, skin irritation is approximately 10 times less frequent with gels than with transdermal patches. Advantages associated with topical gel include maintenance of normal diurnal testosterone levels and documented increases in bone density. Potential problems associated with the gel are the potential for transfer of the gel from person to person and the cost.

Buccal Tablets

Buccal testosterone tablets release testosterone in a pulsatile manner, similar to endogenous secretion. With this route, the peak testosterone levels are rapidly achieved and a steady state is reached by the second dose following twice-daily dosing.

Similar to gel and transdermal products, buccal administration avoids first-pass metabolism. Food and beverage do not alter drug absorption. Although well-tolerated, transient gum irritation and a bitter taste is the chief adverse effects associated with this route.

Gum irritation tends to resolve within the first week. Other adverse effects include dry mouth, toothache, and stomatitis. Some patients find the buccal tablet uncomfortable and report concern about the tablet shifting in the mouth while talking.

Implantable Pellet

The surgically implanted pellet slowly releases testosterone via zero-order kinetics over many months (up to six months), although peak testosterone levels are achieved within 30 minutes. The chief complaints associated with this formulation are pellet extrusion, minor bleeding, and fibrosis at the site.

Intramuscular Injections

The testosterone is suspended in oil to prolong absorption. Peak levels occur within 72 hours of administration, but intramuscular administration is associated with the most variable pharmacokinetics of all the formulations. In the first few days after administration, supraphysiological testosterone levels are achieved, followed by subphysiological levels near the end of the dosing interval.

Such fluctuations, are often associated with wide variations in mood, energy, and sexual function, and prove distressing to many patients. To reduce fluctuations, lower doses and shorter dosing intervals (two weeks) are often used.

Injection site reactions are also common, but are rarely the reason for discontinuation of therapy. Despite the fluctuations in testosterone levels, intramuscular injections provide a cost-effective option and the convenience of two- to four-week dosing intervals.

Disadvantages associated with injections include visits to the doctor's office, visits for dose administration, and lack of physiological testosterone patterns.

Oral Tablets

Although relatively inexpensive, oral products undergo extensive first-pass metabolism and therefore require multiple daily doses. Oral products are associated with elevated liver enzymes, GI intolerance, acne, and gynecomastia.

Regardless of the treatment option, patients should be aware of the risks associated with testosterone therapy, including:

Patients should be educated on the signs and symptoms of these adverse effects and instructed to notify their doctor if any of these occur.

6 Alternative and Homeopathic Remedies

The best remedy for any disease such as hypogonadism is to maintain a healthy lifestyle and trips with your doctor.

A true cure in treating any condition is to do a diet, adequate exercise and control emotions, as these cause reactions that damage our body.

Always follow a basic diet which can help the body to be well nourished and normal functions are performed satisfactorily.

You should avoid all refined product:

  • snacks,
  • products with many colors or sugar diet,
  • sugar,
  • white bread,
  • white flour,
  • refined and fried foods and sausages that only fill the body with toxins.

Furthermore, it should include supplements such as L-Arginine, which help increase sexual libido.

Testosterone can be increased through the consumption of certain foods such as:

  • walnuts,
  • almonds,
  • dried apples,
  • pecans,
  • plums,
  • peanuts,
  • raisins, etc.

7 Lifestyle and Coping

Lifestyle modifications are necessary in order to cope with male hypogonadism.

To deal with this disease, you should understand how emotions influence our body, its functions. It is important to know that excessive stress causes severe imbalances in the body.

Stress can be caused, in this case, by some factors such as feelings of not being able to express, concern for not being sufficiently "good", lack of self-esteem, creativity frustration, guilt, self-punishment, etc.

These feelings occur because we were taught to think we should feel in certain way. Then, the body begins to slow down or block certain functions due to the influence of resistance states, stress, etc.

Stop criticizing yourself. Accept yourself as you are to activate a new creativity in your lives will make you feel comfortable, inspired and well structured.

It is advisable to read about how to understand your emotions and keep out anger or rage, because this is a poison that attacks us from inside.

Some alternative therapies that can help you are:

  • bio-energy,
  • reflexology,
  • acupressure,
  • and chi-nei-tsan.

Practicing yoga and tai chi can help create harmony inside you and you’ll feel a harmonious energy.

8 Risks and Complications

There are several risks and complications associated with male hypogonadism.

In men, hypogonadism results in loss of sex drive and may cause:

Men normally have lower testosterone as they age.

However, the decline in hormone levels is not as dramatic as it is in women.

9 Related Clinical Trials