Definition
Hypogonadism is the condition in which the production of sex hormones and germ cells (sperm and eggs) is inadequate.
Description
Gonads are the organs of sexual differentiation: in the female, they are ovaries; in the male, the testes. Along with producing eggs and sperm, they produce sex hormones that generate all the differences between men and women. If they produce too little sex hormone, then either the growth of the sexual organs or their function is impaired.
The gonads are not independent in their function, however. They are closely controlled by the pituitary gland. The pituitary hormones are the same for males and females, but the gonadal hormones are different. Men produce mostly androgens, and women produce mostly estrogens and progesterone. Androgens regulate the development of the embryo, determining whether it is a male or a female (male in the presence of androgens and female in the absence of androgens). They also direct the adolescent maturation of sex organs into their adult form. Further, they sustain other sexual organs and their function throughout the reproductive years. Estrogen and testosterone help to maintain bone mass and strength and may protect the cardiovascular system.
Hormones can be inadequate during or after each stage of development—embryonic and adolescent. During each stage, inadequate hormone stimulation will prevent normal development. After each stage, a decrease in hormone stimulation will result in failed function and perhaps some shrinkage. The organs affected principally by sex hormones are the male and female genitals, both internal and external, and the female breasts. Body hair, fat deposition, bone and muscle growth, and some brain functions are also influenced.
Demographics
Hypogonadism may occur at any age; however, consequences differ according to the age at onset. If hypogonadism occurs prenatally (even if incomplete), sexual ambiguity may result. If hypogonadism occurs before puberty, puberty does not progress. If hypogonadism occurs after puberty, infertility and sexual dysfunction result. The demographics of hypogonadism vary depending on the cause. XYY syndrome has an incidence of one in 1,000 newborn males. However, since many males with XYY syndrome look like other males without XYY syndrome, they may never be identified.
Kallman's syndrome (KS) is the most frequent cause of hypogonadotropic hypogonadism and affects approximately one in 10,000 males and one in 50,000 females. Kallman's syndrome is found in all ethnic backgrounds. The incidence of KS in males is about five times greater than KS in females; the reason is not known. Turner's syndrome occurs in approximately one out of every 2,500 live births. However, all but 2 percent of fetuses affected by the disorder are miscarried. Of all the chromosomal abnormalities that result in spontaneous abortion or miscarriage, Turner's syndrome is the most common, accounting for about 20 percent of all miscarriages.
Causes and Symptoms
There are a number of causes of hypogonadism, including stress, elevated prolactin levels, and several genetic disorders. Sex is determined at the moment of conception by sex chromosomes. Females have two X chromosomes, while males have one X and one Y chromosome. Male sperm cells contain either an X or a Y; if the sperm with the Y chromosome fertilizes an egg, the baby will be male. Genetic defects sometimes result in changes in the chromosomes. If sex chromosomes are involved, there is a change in the development of sexual characteristics. Female is the default sex of the embryo, so most of the sex organ deficits at birth occur in boys. Some, but not all, are due to inadequate androgen stimulation. The penis may be small, the testicles undescended (cryptorchidism) or various degrees of "feminization" of the genitals may be present.
After birth, sexual development does not occur until puberty. Hypogonadism most often shows up as an abnormality in boys during puberty. Again, not every defect is due to inadequate hormones. Some are due to too much of the wrong ones. Female problems in puberty are usually not caused by too little estrogen. Turner's syndrome leads to failure of puberty in some girls due to the lack of estrogen and progesterone production. Female reproductive problems are usually related to complex cycling rhythms gone wrong. The most common problems with too little hormone happen during menopause, which is normal hypogonadism.
A number of adverse events can damage the gonads and result in decreased hormone levels. The childhood disease mumps, if acquired after puberty, can infect and destroy the testicles—a disease called viral orchitis. Ionizing radiation and chemotherapy, trauma, several drugs (spironolactone, a diuretic, and ketoconazole, an antifungal agent), alcohol, marijuana, heroin, methadone, and environmental toxins can all damage testicles and decrease their hormone production. Severe diseases in the liver or kidneys, certain infections, sickle cell anemia, and some cancers also affect gonads. To treat some male cancers, it is necessary to remove the testicles, thereby preventing the androgens from stimulating cancer growth. This procedure, called castration or orchiectomy, removes androgen stimulation from the whole body.
For several reasons, the pituitary gland can fail to produce hormones. It happens rarely after pregnancy. The pituitary used to be removed to treat advanced breast or prostate cancer. Sometimes the pituitary develops a tumor that destroys it. Failure of the pituitary is called hypopituitarism and, of course, leaves the gonads with no stimulation to produce hormones. Besides the tissue changes generated by hormone stimulation, the only other symptoms relate to sexual desire and function. Libido is enhanced by testosterone, and male sexual performance requires androgens. The role of female hormones in female sexual activity is less clear, although hormones strengthen tissues and promote healthy secretions, facilitating sexual activity.
Xyy Syndrome
XYY syndrome is a chromosome disorder that affects males. Males with this disorder have an extra Y chromosome. The error that causes the extra Y chromosome can occur in the fertilizing sperm or in the developing embryo. There are no physical abnormalities in most males with XYY syndrome. However, some males can have one or more of the following characteristics. Males who have XYY syndrome are usually normal in length at birth but have rapid growth in childhood, typically averaging in the seventy-fifth percentile (taller than 75 percent of males their same age). Many males with XYY syndrome are not overly muscular, particularly in the chest and shoulders. Individuals with XYY syndrome often have difficulties with their coordination. As a result, they can appear to be awkward or clumsy. During their teenage years, males with XYY syndrome may develop severe acne that may need to be treated by a dermatologist.
Men with XYY syndrome have normal, heterosexual function, and most are fertile. However, numerous cases of men with XYY syndrome presenting with infertility have been reported. Most males with XYY syndrome have normal hormones involved in their sperm production. However, a minority of males with XYY syndrome may have increased amounts of some hormones involved in sperm production. This may result in infertility due to inadequate sperm production. The actual incidence of infertility in males with XYY syndrome is unknown.
Kallman's Syndrome
Kallman's syndrome is a disorder of hypogonadotropic hypogonadism, delayed puberty, and anosmia (the inability to smell). Kallman's syndrome is a birth defect in the brain that prevents release of hormones and appears as failure of male puberty. Some boys have adequate amounts of androgen in their system but fail to respond to them, a condition known as androgen resistance. Hypogonadotropic hypogonadism (HH) occurs when the body does not produce enough of two important hormones, luteinizing hormone (LH) and follicle stimulating hormone (FSH). This results in underdeveloped gonads and often infertility. Anosmia, the inability to smell, was first described with hypogonadotropic hypogonadism in 1856, but it was not until 1944 that an instance of Kallman's reported the inheritance of the two symptoms together in three separate families. Hence, the syndrome of hypogonadotropic hypogonadism and anosmia was named Kallman's syndrome (KS). Affected people usually are detected in adolescence when they do not undergo puberty. The most common features are HH and anosmia, though a wide range of features can present in an affected person. Other features of KS may include a small penis or undescended testicles in males, kidney abnormalities, cleft lip and/or palate, clubfoot, hearing problems, and central nervous system problems such as synkinesia (the performance of an unintended movement when making a voluntary one), eye movement abnormalities, and visual and hearing defects.
Diabetes Mellitus
Type 1 diabetes (diabetes mellitus) occasionally has been associated with hypogonadism. Most cases seem to be due to the hypogonadism of malnutrition and respond to improved control. Some specific conditions associated with diabetes mellitus, such as hemachromatosis, and the Laurence-Moon Biedl, Alstrom, and Cushing syndromes, also typically produce hypogonadism. Normal gonadal function is required for normal male development of the genital tract and for maintenance of some elements of male sexual behavior. The most clearly androgen-dependent aspects include libido, sexual activity, and spontaneous erections. In normal, young males with hypogonadism, sexual acts, fantasies, and desire are significantly diminished. Spontaneous erections also decrease by approximately 40 percent. Replacement with testosterone prevents these changes, suggesting that an intact male gonadal system is required to maintain sexual function. However, visual and possibly tactile stimulus-bound erections are not impaired in males with hypogonadism after infancy. This implies that androgen action is not required to maintain the capacity for erection.
Turner's Syndrome
Turner's syndrome is a genetic disorder caused by a missing X chromosome that occurs only in females. Women with Turner's syndrome are characterized by short stature, absence of secondary sexual characteristics, infertility, and a number of other physical abnormalities. Women with Turner's syndrome are born with underdeveloped ovaries that are eventually replaced by connective tissue. Because of the resulting lack of sex hormones, these individuals do not have menstrual periods and their breasts remain undeveloped, although they may develop underarm and pubic hair. Turner's syndrome does not affect intelligence, although persons with the condition have poor spatial perception and mathematical aptitude, often accompanied by learning disabilities.
In girls, hypogonadism during childhood will result in lack of menstruation and breast development and short height. If hypogonadism occurs after puberty, symptoms include loss of menstruation, low libido, hot flashes, and loss of body hair. In boys, hypogonadism in childhood results in lack of muscle and beard development and growth problems. In males the usual complaints are sexual dysfunction, decreased beard and body hair, breast enlargement, and muscle loss. If a brain tumor is present (central hypogonadism) there may be headaches or visual loss or symptoms of other hormonal deficiencies (such as hypothyroidism). In the case of the most common pituitary tumor, prolactinoma, there may be a milky breast discharge. People with anorexia nervosa (excessive dieting to the point of starvation) also may have central hypogonadism.
When to Call the Doctor
Parents should consult a family physician or pediatrician if their child has any signs or symptoms of hypogonadism. Establishing the cause of hypogonadism is an important first step to getting appropriate treatment. Children may require a consultation with an endocrinologist, a physician who specializes in the hormone-producing (endocrine) glands. If the primary care physician suspects the condition is present, he or she may refer the child to an endocrinologist. Parents may also consider taking the child directly to an endocrinologist without a referral.
Diagnosis
As of the early 2000s, there are accurate blood tests for most of the hormones in the body, including those from the pituitary and even some from the hypothalamus. Chromosomes can be analyzed, and gonads can be, but rarely are, biopsied. Tests may be done that check estrogen levels (women) and testosterone levels (men) as well as FSH levels and LH levels, the pituitary hormones that stimulate the gonads. Other tests may include a thyroid level; sperm count; prolactin level (milk hormone); blood tests for anemia, chemistries, and iron; and genetic analysis. Sometimes imaging is necessary, such as a sonogram of the ovaries. If pituitary disease is suspected, a magnetic resonance imaging (MRI) or computerized tomography (CT) scan of the brain may be done.
Treatment
Replacement of missing body chemicals is much easier than suppressing excesses. Estrogen is recommended only to control hot flashes and sweats after menopause but is used in young women who do not produce hormones on their own. Estrogen can be taken by mouth, injection, or skin patch. It is strongly recommended that the other female hormone, progesterone, be taken by women who have an intact uterus as well, because doing so prevents overgrowth of uterine lining and uterine cancer. Testosterone replacement is available for males who are deficient. Testosterone comes in the form of an injection, patch, or gel.
Alternative Treatment
Ethinyl estradiol, an estrogen derivative, is sometimes used for the treatment of hypogonadism.
Prognosis
Many forms of hypogonadism are potentially treatable and have a good prognosis.
Prevention
People should maintain normal body weight and have healthy eating habits to prevent anorexia nervosa. Other causes may not be preventable.
Parental Concerns
Adolescents with hypogonadism may have problems fitting in socially due to delayed sexual development. Testosterone replacement therapy can induce puberty, and at a slow pace in order to allow time for adjustment to body changes and new feelings. In girls with hypogonadism, complications include the social implication of failing to go through puberty with peers (if hypogonadism occurs before puberty). A supportive family that understands the diagnosis of hypogonadism is important. Adolescents may need psychological or family counseling. Support groups can help people with hypogonadism and related conditions cope with similar situations and challenges.
See also Intersex states; Turner syndrome.
Resources
Books
Turner's Syndrome: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, CA: Icon Health Publications, 2004.
Winters, Stephen J. Male Hypogonadism: Basic, Clinical, and Therapeutic Principles. Totowa, NJ: Humana Press, 2004.
Periodicals
Carlson, Robert H. "Panel: Here are Twenty-Five Recommendations on Hypogonadism." Urology Times 31 (November 2003): 22.
Godek, Brent W., and Neil S. Skolnik. "Hypogonadism in Men." Family Practice News 34 (May 15, 2004): 28.
Sadovsky, Richard. "Androgen Deficiency in Women: Review of the Subject." American Family Physician (December 15, 2001): 2000.
——. "Effect of Male Hypogonadism on Bone Architecture: Tips." American Family Physician (December 15, 2003): 2297.
Sullivan, Michele G. "Guidelines Take New Look at Management of Hypogonadism in Men (Testosterone Replacement Options)." Internal Medicine News 36 (February 1, 2003): 6.
Organizations
American Association of Clinical Endocrinologists. 1000 Riverside Avenue, Suite 205, Jacksonville, FL 32204. Web site: www.aace.com.
National Institute on Child Health and Human Development. PO Box 3006, Rockville, MD 20847. Web site: www.nichd.nih.gov.
Web Sites
"Hypogonadism." Medline Plus, November 14, 2002. Available online at www.nlm.nih.gov/medlineplus/ency/article/001195.htm (accessed November 10, 2004).
"Male Hypergonadism." Ohio Health, 2004. Available online at www.ohiohealth.com/healthreference/reference/E97FDCB5-E617-4C36-859B911C1A0E9257.htm (accessed November 1o, 2004).
[Article by: J. Ricker Polsdorfer Ken R. Wells]
