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Male hypogonadism is a medical condition marked by insufficient production of testosterone, the hormone crucial for masculine growth and development during puberty, as well as inadequate sperm production. It can manifest at birth or later in life due to factors like injury or infection.
The effects and treatment options vary depending on the cause and timing of onset. Testosterone replacement therapy is a potential intervention for specific types of male hypogonadism.
Symptoms
Hypogonadism can manifest during fetal development, before puberty, or in adulthood, with symptoms differing based on the timing of onset.
The male reproductive system functions in generating, storing, and transporting sperm. Sperm is produced in the testicles and it combines with fluid from the seminal vesicles and prostate gland to form semen. This semen is then ejaculated from the penis during sexual intercourse.
Fetal development
Insufficient testosterone production during fetal development can lead to impaired growth of the external sex organs. Depending on the timing of hypogonadism onset and the level of testosterone present, a genetically male child may be born with:
- Ambiguous genitals that are neither distinctly male nor distinctly female
- Female genitals
- Underdeveloped male genitals
Puberty
Male hypogonadism has the potential to delay puberty or lead to incomplete or absent normal development, hindering:
- Deepening of the voice
- Development ofmuscle mass
- Growth of the penis and testicles
- Increase in facial and body hair growth
Furthermore, it can result in:
- Disproportionate enlargement of the arms and legs compared to the body’s trunk
- Development of breast tissue (gynecomastia)
Adulthood
In adult males, hypogonadism can change specific masculine physical traits and disrupt regular reproductive function. Initial signs and symptoms may involve:
- Decreased energy
- Reduced sex drive
- Feelings of depression
Over time, individuals with hypogonadism may experience:
- Infertility
- Erectile dysfunction
- Decrease in muscle mass
- Reduction in bone mass (osteoporosis)
- Reduction in facial and body hair growth
- Development of breast tissue (gynecomastia)
Severe hypogonadism can also lead to mental and emotional changes. As testosterone levels decline, some men may exhibit symptoms akin to those observed during menopause in women, such as difficulty concentrating and hot flashes.
If you manifest symptoms of male hypogonadism, it is advisable to consult your doctor. Identifying the root cause of hypogonadism is a crucial initial step in receiving appropriate treatment.
Causes
Male hypogonadism refers to a condition where the testicles inadequately produce the male sex hormone testosterone. There are two fundamental types of hypogonadism:
- Primary: Also known as primary testicular failure, this type stems from an issue in the testicles.
- Secondary: This type indicates a problem in the hypothalamus or the pituitary gland, components of the brain responsible for signaling the testicles to produce testosterone. The hypothalamus generates gonadotropin-releasing hormone, prompting the pituitary gland to produce Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH). Subsequently, luteinizing hormone signals the testes to produce testosterone.
Both the pituitary gland and the hypothalamus, governing hormone production, are situated in the brain. Hypogonadism, whether primary or secondary, can result from a congenital trait or an acquired factor later in life, such as an injury or infection. On occasions, primary and secondary hypogonadism may coexist.
Primary hypogonadism
Frequent causes of primary hypogonadism encompass:
- Undescended testicles: During fetal development, testicles typically descend from the abdomen to the scrotum. Occasionally, one or both testicles fail to descend at birth. While this condition often self-corrects in early childhood without intervention, if left unaddressed, it can result in testicular malfunction and diminished testosterone production.
- Klinefelter syndrome: Arising from a congenital abnormality of the sex chromosomes, X and Y, this condition involves the presence of two or more X chromosomes along with one Y chromosome in males. The additional X chromosome disrupts normal testicular development, leading to decreased testosterone production.
- Mumps orchitis: An infection of the testicles resulting from mumps during adolescence or adulthood can lead to damage, impacting testicular function and testosterone production.
- Hemochromatosis: Excessive iron in the blood may induce testicular failure or dysfunction of the pituitary gland, affecting testosterone production.
- Testicular Injury: Due to their external position, the testicles are susceptible to injury. Damage to both testicles can result in hypogonadism, while harm to one may not significantly impair overall testosterone production.
- Treatment for cancer: Chemotherapy or radiation therapy used in cancer treatment can interfere with both testosterone and sperm production. Although these effects are often temporary, permanent infertility is a potential outcome. Preserving sperm before initiating cancer therapy is an option for men, even though many regain fertility within a few months post-treatment.
Secondary hypogonadism
In cases of secondary hypogonadism, the testicles exhibit normal structure but function improperly due to issues with the pituitary or hypothalamus.
Various conditions can contribute to secondary hypogonadism, including:
- Aging: As men age, there is a gradual, progressive decline in testosterone production, with the rate varying widely.
- Obesity: Being significantly overweight at any age might be associated with hypogonadism.
- Medications: The use of specific drugs, including opiate pain medications and certain hormones, may influence testosterone production.
- Inflammatory diseases: Certain inflammatory conditions like sarcoidosis, histiocytosis, and tuberculosis involve the hypothalamus and pituitary gland, impacting testosterone production.
- Human Immunodeficiency Virus (HIV)/ Acquired Immunodeficiency Syndrome (AIDS): HIV/AIDS can lower testosterone levels by affecting the hypothalamus, pituitary, and testes.
- Pituitary disorders: Abnormalities in the pituitary gland can hinder the release of hormones from the pituitary gland to the testicles, affecting normal testosterone production. Conditions such as a pituitary tumor or other brain tumors near the pituitary gland may result in testosterone or other hormone deficiencies. Treatment for a brain tumor, including surgery or radiation therapy, can also influence the pituitary gland, leading to hypogonadism.
- Kallmann’s Syndrome: An abnormal development of the hypothalamus, which controls pituitary hormone secretion, characterizes this syndrome. It can also impact the sense of smell (anosmia) and lead to red-green color blindness.
Risk factors
Factors that increase the risk of hypogonadism comprise:
- Advancing age
- Obesity
- Malnutrition
- HIV/AIDS
- Past chemotherapy or radiation treatment
Hypogonadism can also have a hereditary component. If any of these risk factors are present in your family medical history, it’s important to inform your doctor.
Diagnosis
Timely identification in boys can help prevent complications related to delayed puberty. Early diagnosis and intervention in men offer improved safeguarding against conditions like osteoporosis.
During a physical examination, your doctor will assess whether your sexual development, including pubic hair, muscle mass, and testes size, aligns with your age. If signs or symptoms of hypogonadism are present, your doctor may conduct a blood test to measure your testosterone levels. Since testosterone levels vary and are typically highest in the morning, blood testing is usually performed early in the day, before 10 a.m., and may be repeated on multiple days.
If tests confirm low testosterone levels, additional investigations can identify whether a testicular disorder or pituitary abnormality is the underlying cause, which may include semen analysis, hormone testing, pituitary imaging, testicular biopsy, or genetic studies.
Treatment
Treatment for boys
Treating delayed puberty in boys depends on the underlying cause. Administering testosterone supplementation via injections for three to six months can stimulate puberty and the development of secondary sexual characteristics. These include increased muscle mass, growth of facial and pubic hair, and growth of the penis.
Adult men
The primary treatment for male hypogonadism typically involves testosterone replacement therapy aimed at restoring testosterone levels to normal. This therapy effectively addresses symptoms such as reduced sexual desire, decreased energy, diminished facial and body hair, and loss of muscle mass and bone density associated with the condition.
For older men experiencing low testosterone levels and hypogonadism symptoms due to aging, the benefits of testosterone replacement therapy are not as conclusively established.
During testosterone replacement therapy, it’s recommended by the Endocrine Society that your doctor regularly assesses treatment efficacy and monitors for potential side effects. Monitoring is particularly crucial during the initial year of treatment and should continue annually thereafter.
Types of testosterone replacement therapy
In the treatment of hypogonadism, oral testosterone preparations are generally avoided due to the risk of causing severe liver issues and the challenge of maintaining consistent testosterone levels. However, an exception to this is testosterone undecanoate, an oral testosterone replacement therapy approved by the Food and Drug Administration. It’s absorbed through the lymphatic system, potentially circumventing the liver-related concerns associated with other oral testosterone forms.
Alternatively, other preparations can be considered based on factors such as convenience, cost, and insurance coverage including:
- Gel: Various gels and solutions are available for application in different ways. Depending on the brand, you can rub the testosterone onto your skin on the upper arm or shoulder or apply it to the front and inner thigh.
Your skin absorbs the testosterone, so refrain from showering or bathing for several hours after applying the gel to ensure proper absorption.|
Side effects may include skin irritation and the potential for medication transfer to another person. Refrain from skin-to-skin contact until the gel has fully dried or cover the treated area post-application. - Injection: Testosterone cypionate and testosterone enanthate are administered into a muscle or under the skin. Symptoms may fluctuate between doses depending on the injection frequency. Testosterone undecanoate is administered by deep intramuscular injection, typically every 10 weeks, at your provider’s office and may have serious side effects.
You or a family member can be trained to administer testosterone injections at home. If self-administration is uncomfortable, your doctor can perform the injections. - Patch: A testosterone patch is applied nightly to the thighs or torso. Potential side effects include severe skin reactions.
- Gum and cheek (buccal cavity): This putty-like substance, used three times a day, delivers testosterone through the natural depression above your top teeth where your gum meets your upper lip (buccal cavity). It can cause gum irritation.
- Nasal: Testosterone gel can be pumped into the nostrils, reducing the risk of medication transfer through skin contact. It must be applied twice in each nostril three times daily, which may be less convenient than other methods.
- Implantable pellets: Testosterone-containing pellets are surgically implanted under the skin every three to six months, requiring an incision.
Testosterone therapy comes with several potential risks, such as:
- Breast enlargement
- Enlargement of the prostate
- Restricted sperm production
- Elevated production of red blood cells
- Acne
- Sleep disturbances
Infertility treatment caused by hypogonadism
When a pituitary issue underlies hypogonadism, administering pituitary hormones can stimulate sperm production and restore fertility. Treatment may involve surgical removal, medication, radiation, or hormone replacement therapy for pituitary tumors.
Restoring fertility in cases of primary hypogonadism can be challenging, but assisted reproductive technology offers options. This includes various techniques designed to assist couples experiencing difficulties conceiving.
