What is Hypogonadism?

Hypogonadism occurs when your sex glands produce little or no sex hormones. The sex glands, also called gonads, are the testes in men and the ovaries in women. Sex hormones help control sex characteristics, such as breast and testicle development, and pubic hair growth. Sex hormones also play a role in menstrual cycles and sperm production.

Hypogonadism may also be called gonad deficiency. In males, it may be called low serum testosterone or andropause.

Most cases of this disorder can be successfully treated.

9 Warning Signs of Low Testosterone

There are two types of hypogonadism: primary and central hypogonadism.

Primary hypogonadism means that you do not have enough sex hormones in your body due to a problem in the gonads. The gonads are still receiving the message to produce hormones from the brain, but are not able to produce them.

In central hypogonadism, the problem lies in the brain. Here the hypothalamus and pituitary glandwhich control the gonadsare not working properly.

Causes of primary hypogonadism include:

Central hypogonadism may be caused by:

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by Culley C. Carson III, MD

Hypogonadism is defined as deficient or absent male gonadal function that results in insufficient testosterone secretion. Hypogonadism may be primary due to testicular failure, or secondary due to hypothalamic-pituitary axis dysfunction, resulting in the production or release of insufficient testosterone to maintain testosterone-dependent functions and systems. Hypogonadism can also result from a combination of testicular failure and hypothalamic-pituitary axis dysfunction.

Hypogonadism affects an estimated 4 to 5 million men in the United States, and although it may occur in men at any age, low testosterone levels are especially common in older males. More than 60% of men over age 65 have free testosterone levels below the normal values of men aged 30 to 35. Studies suggest that hypogonadism in adult men is often underdiagnosed and under treated. This may be because the symptoms are easily attributed to aging or other medical causes, or ignored by patients and physicians. In fact, only about 5% of hypogonadal men receive testosterone replacement. Some experts also believe that we need to reevaluate normal testosterone the levels and lower the diagnostic cutoff for hypogonadism. By doing so, many patients who we now consider to be low- normal would probably be considered candidates for androgen replacement.

Signs and Symptoms of Hypogonadism Low testosterone, or male hypogonadism, is associated with a number of signs and symptoms, most notably loss of libido and erectile dysfunction (ED). Other signs of low testosterone include depressive symptoms, a decrease in cognitive abilities, irritability and lethargy or loss of energy. Deficient endogenous testosterone also has negative effects on bone mass and is a significant risk factor for osteoporosis in men. Progressive decrease in muscle mass and muscle strength and testicular dysfunction, often resulting in impaired sperm production, are also associated with low testosterone levels.

A younger patient may have pure hypogonadism as a primary event, whereas an older man may have an age-related decline in testosterone production that is a part of his ED profile. However, because both ED and loss of libido are hallmarks of hypogonadism, any patient who presents with ED should have a basic hormone profile to determine if he has low testosterone. Treatments to normalize testosterone can not only improve libido, energy level and the potential to have normal erections, but can also improve the response to sildenafil, if that is deemed appropriate treatment.

Screening for Hypogonadism An inexpensive and reliable screening test for hypogonadism is a morning serum total testosterone level, which measures free testosterone plus protein-bound testosterone. A morning sample is recommended, because testosterone levels demonstrate a diurnal pattern in which the highest level is reached in the early morning hours. Morning testosterone values <300 ng/dL (10.4 nmol/L) suggest hypogonadism and should be confirmed by a second assay.

If a repeat assay confirms low testosterone, luteinizing hormone (LH) should be measured to determine whether the cause is primary or secondary. LH levels <2 ng/mL suggest a hypothalamic lesion (pituitary adenoma, trauma, etc), whereas LH levels >10 ng/mL indicate primary testicular failure. Levels within the normal range suggest an age-related, decreased hypothalamic response to declining testosterone levels. In addition, serum prolactin should also be measured to rule out the presence of a pituitary tumor.

At our institution we are also currently measuring dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) levels. Some investigators believe that replacing DHEA in patients with low libidos and normal or borderline testosterone is an important component of treatment to restore sexual desire and performance. Although controlled clinical studies are needed to confirm this approach, there is growing evidence that DHEA may play an important role in the treatment of male sexual dysfunction.

ADAM Questionnaire In addition to laboratory tests and a careful physical examination, a brief screening instrument has also been developed to aid in the diagnosis of hypogonadism. Researchers at St. Louis University created the Androgen Deficiency in the Aging Male (ADAM) questionnaire, which has been shown to be a highly sensitive (88%) instrument but with low specificity (66%), largely due to questions that identify patients with depression. However, because many men with hypogonadism dont seek medical attention, instruments such as the ADAM questionnaire can be a useful way to screen for clinical symptoms of androgen deficiency. Once testosterone deficiency is confirmed, we then consider testosterone replacement therapy.

Goals of Treatment The goal of testosterone replacement therapy is to provide and maintain a normal level of testosterone, thereby restoring libido and improving erectile function; improving mood and providing a sense of well-being; decreasing fatigue; and improving lean body mass, strength and stamina. Also, because hypogonadism is the most common cause of osteoporosis in men, testosterone replacement may improve bone density to help prevent this disease and related complications.

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Male hypogonadismis defined as the underproduction of sperm or testosterone, or both, by the testes (also called testicles). Starting at puberty, the pituitary gland releases luteinizing hormone (LH), which stimulates the testicles to produce testosterone, the hormone responsible for male physical characteristics. In the testicles, follicle stimulating hormone (FSH) and LH also act together to stimulate the production of sperm.

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

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.

Male hypogonadism can beprimary(resulting from a problem with the testes) orsecondary(resulting from a problem with the pituitary gland or hypothalamus and their release of LH and FSH), or a mix.

Speaking more generally, low testosterone can be caused by:

Many older men have low testosterone levels and, in many cases, the cause isnt known.

Treatment with testosterone replacement therapy is recommended for men with consistently low testosterone levels and symptoms or signs of androgen deficiency. Men with one of the following should not be treated with testosterone replacement therapy:

The overall goal of testosterone hormone therapy is to increase testosterone levels from below the normal range to the middle of the normal range. Goals may vary from patient to patient but should include improving or maintaining the signs of masculinity (such as deep voice, beard growth, pubic hair), and improving sex drive and function,, mood and energy, muscle strength, and the amount of bone.

There are several ways to replace testosterone:

The way testosterone is given will depend on the patients preference and tolerance, and cost. The various types of testosterone therapy may have certain side effects. . Injections may be uncomfortable and linked to ups and downs in symptoms; patches may cause skin redness and rashes; gels may transfer testosterone to others who come into contact with the patients skin where the medication is applied; and buccal tablets may cause gum irritation.

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ACGT is the only public charity in the nation exclusively funding cancer cell and gene therapy research. By supporting research in discovery and translational research, we stimulate both innovation and progress.

2014 Young Investigator Award, Posted: August 27, 2014 Abstract Deadline: September 16, 2014 at 4 pm E.S.T. Invitation to Submit Application: October 10, 2014 Deadline for Completed Application: November 6, 2014at1 pm E.S.T.

View the RFA (pdf) here.

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