Male hypogonadism

Urology Treatments

Male Hypogonadism

Hypogonadism in men is an endocrine disorder with many implications for sexual health and the body's metabolism. In this article, we will briefly address this problem from a medical perspective aimed at newly diagnosed patients but also at those who have been suffering from this condition for years.

Male Hypogonadism

Table of Contents

Definition

What is male hypogonadism?

Male hypogonadism is defined as a disorder characterized by decreased blood levels of testosterone (with the symptoms of this deficit), low sperm count, or both.

This generalized decrease in male sex hormones, and thus associated functions, may be due to a problem in the testicles (the place where male sex hormones are produced) in a condition known as primary hypogonadism.

However, hypogonadism may also be due to imbalances in the Hypothalamic–pituitary axis. This axis is the complex neuronal and endocrine system in charge of helping regulate several basic functions in the body, among which growth, metabolism, blood pressure and, of course, human reproduction stand out. Male hypogonadism has serious implications for men’s health. It can seriously affect everything from the ability to have children (due to low sperm count) to failure to develop external male characteristics such as metabolism, body growth, distribution of body hair, size of genitals, voice, etc.

Although the vast majority of men with hypogonadism are diagnosed during puberty or early adulthood, the hormone problem is likely congenital. That is, from birth.

This diagnosis is usually made based on laboratory blood tests to determine serum testosterone or gonadotrophin-releasing hormone levels.

The treatment to be used depends on the type of cause that is creating the androgen deficiency, generally consisting of the administration of hormone therapy (to replace the imbalance in the production of testosterone) or the hormone that favours its production.

What is the function of testosterone?

Testosterone is by far the most relevant and essential male sex hormone.

Produced at the level of the Leydig cells below the seminiferous tubules of the testicle, testosterone plays important roles in maintaining men’s health and sexual development.

It allows the development of the external sexual characteristics of men such as:

But in addition, testosterone also regulates internal functions in man, such as:

Testosterone, in turn, depends on a complex endocrine system directed from the central nervous system itself. More specifically, the hypothalamus and pituitary gland.

Low testosterone production in men

High testosterone production in men

A little bit of the physiology of the male sex hormones...

The hypothalamus is the part of the brain responsible for producing the gonadotrophin-releasing hormone (or GnRH) in a constant, pulsating way throughout life. It is estimated that it secretes this hormone every 60 to 120 minutes.

The gonadotrophin-releasing hormone travels down to the pituitary gland and stimulates the secretion of luteinizing hormone (LH) and some follicle-stimulating hormone (FSH), which travel through the bloodstream to its target tissue, the testicles.

In the testicles, Leydig cells respond to LH and produce a certain amount of testosterone (between 5 and 10 milligrams of testosterone per day).

For some unknown reason, testosterone levels in the blood are higher in the morning and lower in the afternoon. However, this fluctuation is minimal and completely physiological.

The main precursor molecule of testosterone is cholesterol. Leydig cells break down this lipid compound into a pair of intermediary metabolites: dehydroepiandrosterone (DHEA) and androstenedione, thus producing testosterone.

This testosterone is released from the testicles and travels through the bloodstream attached to plasma proteins such as albumin or sex hormone-binding globulin (called SHBG). A small proportion of testosterone can travel freely in the blood, about two per cent.

When it reaches the target organs and tissues, testosterone is converted to its most active form: dihydrotestosterone (DHT) by the 5-alpha-reductase enzyme.

Testosterone in the form of dihydrotestosterone or DHT is the most important effector in the regulation of basic processes in the male organism. For example:

One of the most important functions of testosterone is the maintenance of spermatogenesis. The Sertoli cells of the testicles, under the influence of testosterone and follicle-stimulating hormone, promote the differentiation and maturing of sperm within the seminiferous tubules. About 100 million spermatozoa are produced every day.

Testosterone (especially in the form of DHT) negatively regulates the Hypothalamic–pituitary axis. In other words, an increase in circulating testosterone inhibits the hypothalamic production of gonadotrophin-releasing hormone (GnRH) and thus, that of LH and FSH which stimulate the testicle to secrete testosterone. In this way, the levels of male hormones are under physiological parameters and therefore, the processes of the body that depend on them.

Why is this so important for men? What effects does its decrease have on the body?

Regardless of the cause, low levels of male hormones in the blood have a major impact on the tissues and organs that are sensitive to these levels and require them to carry out their functions.

A clear example of this is the production of sperm.

Without testosterone, the Sertoli cells would be insensitive to FSH levels (which may even be increased) and therefore the stimulus needed for spermatogonia to successively mature into spermatozoa would not be produced.

Without testosterone, tissue metabolism would be altered and adopt a pattern similar to that of the female sex. This is visible in men with male hypogonadism who develop less muscle mass and more fatty tissue, especially in the breasts (a condition called gynecomastia).

Without testosterone, for example, a rapid and premature weakening of the body’s bones may develop, predisposing the individual to fractures and osteoarticular problems. Libido may also be affected, along with changes in behaviour and sleep patterns.

Testosterone production in men

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symptomatology

Signs and symptoms

Low levels of androgens in the blood can produce characteristic and indicative signs and symptoms, within which there are:

The onset and intensity of symptoms depend on the age of onset of the deficiency, the length and severity of the decline in blood testosterone levels.

The latter factor (blood testosterone levels) is one of the most relevant.

The European Association of Urology (or EAU) states that normal levels of total blood testosterone should be between 280 and 1,100 ng per dL.

The onset and intensity of symptoms depend on the age of onset of the deficiency, the duration and severity of the decrease in testosterone levels in the blood.

When should I visit the doctor?

It is important to understand that these types of health problems can go unnoticed for many years or even much of a man’s life.

The signs and symptoms associated with hypogonadism (especially those related to sexual and metabolic functions) may suggest changes in testosterone production patterns.

Any unusual changes in health should be reported to your doctor. This professional will give the appropriate follow-up not only to confirm a diagnosis but also to find the cause of the alteration and therefore, the appropriate treatment.

FREQUENT CAUSES

What Causes Male Hypogonadism?

Whatever its cause, male hypogonadism involves the lowering of testosterone levels in the body. This causes alterations in all physiological processes that depend directly or indirectly on it.

Male hypogonadism is divided according to where the alteration occurs: in primary hypogonadism (also called testicular failure, due to problems in the testicle to secrete the hormone) and in secondary hypogonadism (which implies problems in the Hypothalamic–pituitary axis, the same one that regulates and stimulates testosterone secretion in the testicles).

· Types of hypogonadism ·

This type of hypogonadism is also known as testicular male hypogonadism because the decrease in testosterone is the result of problems in these glands, which are responsible for the secretion of the hormone and the production of sperm.

It is the most common type of male hypogonadism. Paradoxically, in addition to the exaggerated drop in testosterone and spermatozoa in the semen, there is a high blood concentration of gonadotrophins. Remember that these hormones are part of the endocrine circuit of the hypothalamus and pituitary gland above the testicles.

When the levels of testosterone in the blood decrease, this neuronal circuit responds by producing these hormones, without successful results given that the target tissue (the testicles) is desensitized and therefore does not react to these stimuli.

Common causes of male hypogonadism are Klinefelter syndrome or testicular tumours.

Klinefelter syndrome is a fairly rare type of genetic disease (0.2 per cent of men) that causes testicular desensitization to hormones such as FSH and LH. Tumours of the testicles, on the other hand, are the most common type of neoplasm in young men, usually caused by the influx of testicular problems during early childhood, such as maldescent of the testes into the scrotum (cryptorchidism).

Also called male hypogonadism of hypothalamic-pituitary origin, it corresponds to the second most frequent type of this male disease.

It occurs when the hypothalamus (at the base of the brain) does not produce enough gonadotrophin-releasing hormone and therefore there is no effective secretion of FSH and LH from the pituitary gland. The testicles do not receive sufficient stimuli to produce testosterone or perform spermatogenesis.

This whole set of pathologies could be congenital (from birth) or secondary to a prolactinoma.

Prolactinoma is a type of tumour that appears in the pituitary gland and that secretes high daily amounts of prolactin, the hormone in charge of maintaining the secretion of breast milk during pregnancy and lactation. Another even less frequent cause is Kallmann's syndrome, a rare genetic disease that produces, among other manifestations, anosmia (inability to perceive odours through the olfactory epithelium in the nose).

RISK FACTOR'S

Are there risk factors for male hypogonadism? What are those factors?

Health factors that significantly increase the likelihood of suffering or developing male hypogonadism include:

Complications

If hypogonadism were not treated, what complications would it bring?

The lack of male hormones could lead to major health problems depending on the stage of life of the patient.

For example, if androgen deficiency occurs in the baby inside the mother’s uterus, the child will most likely be born with little or no differentiated external genitalia.

During the years close to puberty, low levels of testosterone could delay sexual maturation, making external characteristics (beard, voice, muscles, genital growth, etc.) and internal characteristics (sperm production, etc.) take much longer to arrive. Also, the breasts may grow similarly as in women (gynecomastia).

In adult men, low testosterone results in persistent weakness, low sex drive, male sterility, erectile dysfunction, premature osteoporosis, and low skeletal muscle tissue, among others.

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Diagnosis

Diagnosis of male hypogonadism

The diagnosis of hypogonadism is made mainly based on a physical examination that allows us to know the external characteristics of the patient: height and weight, body hair, amount and distribution of body mass, enlarged breasts and underdeveloped genitals, among others. 

It is also useful to evaluate the size of the testicles because male hypogonadism tends to manifest itself with poorly developed or very small gonads.

Also, the doctor may perform blood tests to check the levels of androgens and other associated hormones such as the follicle-stimulating hormone or the luteinizing hormone.

These lab tests should be done in the early morning hours, when testosterone levels are usually somewhat elevated. Semen analysis (seminogram) is also usually recommended to observe the proportion of mature spermatozoa capable of fertilizing.

In adult men with advanced pathology, it is also recommended to perform testicular biopsies to rule out neoplastic processes in the testicle such as testicular cancer.

The diagnosis in children or young people before puberty ensures that the indicated therapeutic measures have a better effect and that some processes of cellular degeneration such as osteoporosis are reverted early, preserving the fertile capacity as far as possible.

However, if hypogonadism occurs in a basic genetic pathology, the patient must seek even more specific help, such as from a specialist in medical genetics (also called medical geneticists).

The genetic abnormalities that are most likely to produce male hypogonadism are Klinefelter’s syndrome or Kallmann’s syndrome.

Techniques and treatments

Treatment of hypogonadism

Treatment in adult men

In any case, the medical management of male hypogonadism will depend on the type of hypogonadism and its intensity. The most common treatments are hormone replacement therapy and an assisted reproduction program in case the patient wishes to have children.

Hormone replacement therapy

Testosterone replacement therapy or TRT is especially useful and effective in cases of male hypogonadism of testicular origin. It may prevent and delay the complications of the disease, as well as provide the patient with a rapid replacement of testosterone and thus improve physical and mental health, including sexual desire and erections.

Testosterone hormonal pharmaceutical supplements can be found in different presentations such as:

Physical exercise, a balanced diet and supplements with calcium and vitamin D3 can maintain a man’s health and stimulate the secretion of testosterone, as well as improving his emotional state.

Unsightly and uncomfortable breast enlargement is often treated by resection surgery or liposuction.

Male hypogonadism of hypothalamic-pituitary origin requires more complex medical tests and even more specific hormonal supplements. Pituitary tumours usually require surgical resection.

Assisted Reproduction Program

Assisted reproduction programs such as in vitro fertilization and other state-of-the-art techniques in reproductive and molecular medicine have enabled many men with spermatogenesis deficits due to low testosterone levels to have children.

Treatment in children

Treatment of pediatric male hypogonadism also usually includes hormone replacement therapy, especially near the onset of puberty or during this period, to accelerate and promote its occurrence, although of course the dosage or dose is completely different.

The longer it takes for the patient to be diagnosed and treated, the more “uphill” is for us to ensure that reproductive functions are once again adequate or acceptable.

Frequent questions

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Can male hypogonadism trigger erectile dysfunction?

Yes, this is because prolonged drops in testosterone also affect negatively sex-related emotional responses. As the libido decreases, it becomes more difficult to achieve and maintain effective penile erections that allow for a full sex life.

What is female hypogonadism? How is it diagnosed and treated?

Female hypogonadism refers to a hormonal disorder of the ovaries to produce estrogens and progestogens, the quintessential female sex hormones.

In addition to altering menstrual cycles and decreasing the ability to ovulate (and therefore have children), hypogonadism also has effects on other systems. It promotes the early onset of menopause.

It is diagnosed with physical examinations and laboratory tests, to measure the blood levels of these ovarian hormones and those of the Hypothalamic–pituitary axis.

Treatment consists of hormone replacement therapy, similar to men’s but with estrogens and progestogens. It is generally performed with doses that vary according to the passage of days to stimulate or simulate the hormonal changes typical of the menstrual cycle.

Does hypergonadism exist? What is it and how does it manifest itself?

Much less frequent than hypogonadism, hypergonadism refers to the endocrine pathology in which the body of a man or woman secretes high amounts of sexual hormones per day, testosterone in men and estrogens and progestogens in women.

The most obvious clinical manifestations are alterations in body development, changes in behaviour and sleep patterns. There may also be problems with having children.

Male hypergonadism is associated with prostate cancer. <span”>Its treatment involves the administration of drugs that decrease the body’s response to testosterone. That is, they make some tissues (such as the testicles) less sensitive to testosterone.

 

Dr. Natalio Cruz

Author

Dr. Natalio Cruz


El Dr. Cruz, con 25 años de experiencia médica, ha sido hasta 2016 Jefe de la Unidad de Andrología en el Servicio de Urología del Hospital Virgen del Rocío de Sevilla, Coordinador Nacional de Andrología de la Asociación Española de Urología (AEU) y Secretario General de la ESSM, cargos que ha delgado para centrarse de lleno en el ilusionante proyecto de ofrecer una consulta médica privada de alto nivel en Sevilla.

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