Hypogonadism male

Male hypogonadism is a condition where the body doesn’t produce enough testosterone, the hormone essential for male development and characteristics, or enough sperm, or both. This condition can develop before birth, during puberty, or in adulthood, affecting physical development, sexual function, and overall health.

Table of contents

• What is male hypogonadism?
• Types of male hypogonadism
• Symptoms
• Causes
• Risk factors
• Diagnosis
• Treatment
• Complications

What is male hypogonadism?

Male hypogonadism is a condition in which the body doesn’t make enough of the hormone testosterone (the male sex hormone), or enough sperm, or both^[1]. Testosterone is produced mainly in the testicles, specifically in cells called Leydig cells, and plays a key role in male growth and development during puberty^[3].

Testosterone is essential for many body functions in men. It helps maintain and develop sex organs and genitalia, muscle mass, adequate levels of red blood cells, bone density, sense of well-being, and sexual and reproductive function^[3]. The body normally controls testosterone levels carefully, with levels typically highest in the morning and declining through the day^[3].

People can be born with male hypogonadism, or it can start later in life, often from injury or infection^[1]. The cause of the condition and when it starts affect what can be done about it^[1].

Low testosterone, testosterone deficiency syndrome, testosterone deficiency, low T

Types of male hypogonadism

There are two basic types of hypogonadism, depending on where the problem originates^[6].

Primary hypogonadism, also known as primary testicular failure, originates from a problem in the testicles themselves. In this type, the testes don’t function properly to produce testosterone^[6].

Secondary hypogonadism indicates a problem in the hypothalamus or the pituitary gland, which are parts of the brain that signal the testicles to produce testosterone^[6]. The hypothalamus produces a hormone that signals the pituitary gland to make follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which then signal the testicles to produce testosterone^[6].

Your hypothalamus and pituitary gland normally control the amount of testosterone your testicles produce and release. Any issue with your testicles, hypothalamus, or pituitary gland can cause low testosterone^[3].

Symptoms

Hypogonadism can begin in the womb, before puberty, or during adulthood. Symptoms depend on when the condition starts^[1].

Symptoms during fetal development

If a baby’s body doesn’t make enough testosterone while in the womb, it can affect the outer sex organs. Depending on when hypogonadism starts and how much testosterone there is, a baby whose genes are male may be born with female genitals, genitals that are neither clearly male nor clearly female (called ambiguous genitals), or male genitals that don’t develop fully^[1].

Symptoms during puberty

Male hypogonadism that occurs in the first 10 years of life can delay puberty or cause incomplete or lack of usual development^[1]. It can get in the way of muscle mass growth, the voice getting deeper, growth of body and facial hair, and growth of the penis and testicles^[1]. It can also cause the arms and legs to grow more than the trunk of the body and growth of breast tissue, called gynecomastia^[1].

Symptoms in adulthood

In adults, hypogonadism can change certain physical traits and affect the ability to have children^[1]. Symptoms highly suggestive of hypogonadism include decreased spontaneous erections, reduced nocturnal penile tumescence (nighttime erections), low libido, and reduced testicular volume^[2].

Early symptoms in adult men might include less sex drive, less energy, and depression^[1]. Over time, men with hypogonadism can have difficulty getting and keeping an erection (called erectile dysfunction), problems having children (called infertility), and less hair growth on the face and body^[1].

Other symptoms of low testosterone in adult men include depressed mood, difficulties with concentration and memory, increased body fat, reduced muscle mass, development of breast tissue, loss of body and facial hair, shrinking testicles, and hot flashes^[3]. Low or zero sperm count, which causes male infertility, is also a symptom^[3].

• Testicles
• Pituitary gland
• Hypothalamus

Causes

Defects that interfere with interactions in the hypothalamic-pituitary-testicular axis can cause male hypogonadism, as well as primary testicular disorders. Such defects may be acquired or congenital (present from birth)^[2].

The cause of hypogonadism can be primary (problems with the testes themselves) or secondary (problems with the pituitary or hypothalamus)^[7].

Causes of primary hypogonadism

In primary hypogonadism, the testicles themselves do not function properly. Causes include certain autoimmune disorders, genetic and developmental disorders, infection, iron excess (hemochromatosis), liver and kidney disease, radiation to the gonads, surgery, and trauma^[7].

The most common genetic disorders that cause primary hypogonadism include Turner syndrome (in women) and Klinefelter syndrome (in men)^[7].

Causes of secondary hypogonadism

In secondary hypogonadism, the centers in the brain that control the gonads (hypothalamus and pituitary) do not function properly. Causes include anorexia nervosa, bleeding in the area of the pituitary, taking medicines such as glucocorticoids (steroids) and opiates, stopping anabolic steroids, genetic problems, infections, nutritional deficiencies, iron excess, radiation to the pituitary or hypothalamus, rapid significant weight loss, surgery near the pituitary, and tumors^[7].

A genetic cause of secondary hypogonadism is Kallmann syndrome. Many people with this condition also have a decreased sense of smell^[7].

Age-related changes

Testosterone levels decrease in men as they age. The range of normal testosterone in the blood is much lower in a 50 to 60 year-old man than it is in a 20 to 30 year-old man^[7]. Testosterone levels naturally decline by about 1% each year after age 30^[4].

Risk factors

Male hypogonadism is more likely to affect people who are older, have obesity, have poorly managed Type 2 diabetes, have obstructive sleep apnea, have chronic medical conditions such as kidney dysfunction or cirrhosis of the liver, or have HIV/AIDS^[3].

It is estimated that approximately 35% of men older than 45 years of age and 30-50% of men with obesity or type 2 diabetes have hypogonadism^[4]. More than 8% of men aged 50 to 79 years have low testosterone^[3].

Diagnosis

Finding male hypogonadism in childhood can help prevent problems from delayed puberty. Early diagnosis and treatment in men helps protect against osteoporosis (weak bones) and other conditions^[11].

A member of your healthcare team does a physical exam and looks at your sexual maturing to see if your pubic hair, your muscle mass, and the size of your testes are typical for your age^[11].

Blood tests can show testosterone levels. Testosterone levels are most often highest in the morning, so blood testing is usually done between 8 and 10 a.m. It might be done on more than one day^[11]. Hypogonadism is usually diagnosed when the morning serum testosterone level is less than 300 nanograms per deciliter (ng/dL) on at least 2 occasions^[2].

The normal range for early morning testosterone in a male is generally between 300 ng/dL to 1000 ng/dL, although this varies by laboratory^[2]. However, some researchers and healthcare providers feel that levels below 250 ng/dL are low^[3]. Providers also take symptoms into consideration when diagnosing low testosterone^[3].

If tests show low testosterone, further testing can help find the cause. These studies might include pituitary hormone testing, semen analysis, pituitary imaging, and gene studies^[11].

Low testosterone levels alone do not require treatment unless they are associated with symptoms of hypogonadism^[2].

Treatment

Testosterone replacement therapy can treat some types of male hypogonadism^[1]. The treatment can raise testosterone levels and help ease symptoms including less desire for sex, less energy, less facial and body hair, and loss of muscle mass and bone mass^[11].

The goals of treatment are to promote the development of and maintain secondary sexual characteristics and normal sexual function, to build and sustain normal bone and muscle mass, and to assist in the proper psychosocial adjustment of adolescents with hypogonadism^[18].

Types of testosterone replacement therapy

Testosterone taken by mouth (oral testosterone) isn’t often used for treatment of hypogonadism because it can cause serious liver problems and doesn’t keep testosterone levels even^[11]. However, the U.S. Food and Drug Administration has approved one oral testosterone replacement called testosterone undecanoate. The lymph system absorbs it, so it might not cause the liver problems seen with other oral forms^[11].

Testosterone can be given as a skin patch, skin gel, a solution applied to the armpit, a patch applied to the upper gum, or by injection^[7]. Treatment method should take into consideration patient preference, pharmacokinetics (how the drug moves through the body), potential for medication interactions, formulation-specific adverse effects, treatment burden, and cost^[13].

Monitoring during treatment

Anyone taking testosterone replacement should have a medical checkup and blood tests several times during the first year of treatment and yearly after that^[11]. This is to see how well the treatment works and to watch for side effects. Serum testosterone, hematocrit (a measure of red blood cells), and prostate-specific antigen levels should be measured at baseline and at least annually in men 40 years or older receiving testosterone replacement therapy^[13].

Alternative treatments for men wishing to preserve fertility

For men with hypogonadotropic hypogonadism who wish to preserve fertility, alternative treatment options exist. Therapy with sex steroid replacement does not confer fertility or stimulate testicular growth in men^[18]. Long-acting forms of testosterone replacement therapy lead to infertility and are inappropriate for patients wishing to conceive^[19].

Alternative options include nasal testosterone, clomiphene citrate, exogenous gonadotropins, gonadotropin releasing hormone, and aromatase inhibitors^[19]. Clomiphene citrate and exogenous gonadotropins are safe, offer good symptom control, and can successfully induce fertility in hypogonadism patients^[19].

At a time when fertility is desired, it may be induced with either pulsatile LHRH or (more commonly) with a schedule of injections of hCG (human chorionic gonadotropin) and FSH^[18].

Safety considerations

Recent high-quality evidence suggests that testosterone therapy does not increase cardiovascular risk in men with hypogonadism. A large clinical trial reported that testosterone therapy is non-inferior to placebo for incidence of major adverse cardiovascular events in men with hypogonadism and pre-existing cardiovascular disease, or at high risk for cardiovascular disease^[8].

However, the U.S. Food and Drug Administration has added information about the risk of increased blood pressure to testosterone product labels, and clinicians should regularly monitor blood pressure in patients taking testosterone therapy^[8].

Potential adverse effects of testosterone replacement include erythrocytosis (increased red blood cells), increases in prostate-specific antigen and worsening of prostate disorders including benign prostatic hyperplasia (enlarged prostate), skin effects including acne and skin irritation, and worsening of existing obstructive sleep apnea^[12].

Complications

Over time, men with untreated hypogonadism can develop erectile dysfunction, infertility, decrease in hair growth on the face and body, decrease in muscle mass, development of breast tissue, and loss of bone mass (osteoporosis)^[5].

Failure to recognize and treat men with hypogonadism may predispose them to long-term health problems, such as anemia, osteoporosis, depression, or sexual dysfunction^[23].

Hypogonadism can significantly reduce the quality of life and has resulted in the loss of livelihood and separation of couples, leading to divorce^[6].