Hypogonadism in Males
HYPOGONADISM IN MALES
HYPOGONADISM IN MALES DEFINITION
Male hypogonadism is a condition in which the body doesn’t produce enough testosterone — the hormone that plays a key role in masculine growth and development during puberty — or has an impaired ability to produce sperm or both.
You may be born with male hypogonadism, or it can develop later in life from injury or infection. The effects — and what you can do about them — depend on the cause and at what point in your life male hypogonadism occurs. Some types of male hypogonadism can be treated with testosterone replacement therapy.
HYPOGONADISM IN MALES CAUSES
Hypogonadism in a male refers to a decrease in either or both of the two major functions of the testes: sperm production and/ortestosterone production. These abnormalities can result from disease of the testes (primary hypogonadism) or disease of the pituitary or hypothalamus (secondary hypogonadism). The distinction between these disorders is made by measurement of the serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH):
- The patient has primary hypogonadism if his serum testosterone concentration and/or sperm count are low and/or his serum LH and FSH concentrations are high.
- The patient has secondary hypogonadism if his serum testosterone concentration and/or the sperm count are low and/or his serum LH and FSH concentrations are inappropriately normal or low, which would be inappropriate if gonadotroph cell function were normal.
Secondary hypogonadism differs from primary hypogonadism in two characteristics:
- Secondary hypogonadism is usually associated with similar decreases in sperm and testosterone production. This occurs because the reduction in LH secretion results in a decrease in testicular testosterone production and, therefore, in intratesticular testosterone, which is the principal hormonal stimulus to sperm production. In contrast, there is generally a greater fall in sperm production than in testosterone secretion in primary hypogonadism because the seminiferous tubules are damaged to a greater degree than the Leydig cells. Men with primary hypogonadism, therefore, might have normal serum testosterone and LH concentrations even when the number of ejaculated sperm is very low or zero and the FSH concentration is elevated.
HYPOGONADISM IN MALES PATHOPHYSIOLOGY
The gonad (ovary or testis) functions as part of the hypothalamic-pituitary-gonadal axis. A hypothalamic pulse generator resides in the arcuate nucleus, which releases luteinizing hormone (LH)-releasing hormone (LHRH), which is also termed gonadotropin-releasing hormone (GnRH), into the hypothalamic-pituitary portal system. Data suggest that a gene named KISS is important in the development of the LHRH-secreting cells.
In response to these pulses of LHRH, the anterior pituitary secretes follicle-stimulating hormone (FSH) and LH, which, in turn, stimulate gonadal activity. The increase in gonadal hormones results in lowered FSH and LH secretion at the pituitary level, completing the feedback loop. In the testes, LH stimulates Leydig cells to secrete testosterone, whereas FSH is necessary for tubular growth. In the ovaries, LH acts on theca and interstitial cells to produce progestins and androgens, and FSH acts on granulosa cells to stimulate aromatization of these precursor steroids to estrogen.
Hypogonadism may occur if the hypothalamic-pituitary-gonadal axis is interrupted at any level. Hypergonadotropichypogonadism (primary hypogonadism) results if the gonad does not produce the amount of sex steroid sufficient to suppress secretion of LH and FSH at normal levels. Hypogonadotropichypogonadism may result from failure of the hypothalamic LHRH pulse generator or from inability of the pituitary to respond with secretion of LH and FSH. Hypogonadotropichypogonadism is most commonly observed as one aspect of multiple pituitary hormone deficiencies resulting from malformations (eg, septooptic dysplasia, other midline defects) or lesions of the pituitary that are acquired postnatally. In 1944, Kallmann and colleagues first described familial isolated gonadotropin deficiency. Recently, many other genetic causes for hypogonadotropichypogonadism have been identified.
Normosmichypogonadotropichypogonadism, in which the sense of smell is not disrupted, has been associated with mutations in GNRH1, KISS1R, and GNRHRgenes. Although their exact functions are unclear, the genes TAC3 and TACR3have also been associated with normosmichypogonadotropic hypogonadism.Kallmann syndrome (anosmichypogonadotropichypogonadism) has been associated with mutations in KAL1, FGFR1, FGF8, PROK2, and PROKR2 genes. The relationship with Kallmann syndrome is thought to be because these genes are all related to the development and migration of GnRH neurons. Mutations of an additional gene, CHD7, which has been associated with CHARGE syndrome, has also been found in patients with both normosmic or anosmichypogonadotropichypogonadism.
HYPOGONADISM IN MALES SYMPTOMS
Hypogonadism can begin during fetal development, before puberty or during adulthood. Signs and symptoms depend on when the condition develops.
If the body doesn’t produce enough testosterone during fetal development, the result may be impaired growth of the external sex organs. Depending on when hypogonadism develops and how much testosterone is present, a child who is genetically male may be born with:
- Female genitals
- Ambiguous genitals — genitals that are neither clearly male nor clearly female
- Underdeveloped male genitals
Male hypogonadism may delay puberty or cause incomplete or lack of normal development. It can cause:
- Decreased development of muscle mass
- Lack of deepening of the voice
- Impaired growth of body hair
- Impaired growth of the penis and testicles
- Excessive growth of the arms and legs in relation to the trunk of the body
- Development of breast tissue (gynecomastia)
In adult males, hypogonadism may alter certain masculine physical characteristics and impair normal reproductive function. Signs and symptoms may include:
- Erectile dysfunction
- Decrease in beard and body hair growth
- Decrease in muscle mass
- Development of breast tissue (gynecomastia)
- Loss of bone mass (osteoporosis)
Hypogonadism can also cause mental and emotional changes. As testosterone decreases, some men may experience symptoms similar to those of menopause in women. These may include:
- Decreased sex drive
- Difficulty concentrating
- Hot flashes
HYPOGONADISM IN MALES DIAGNOSIS
Hypogonadism is a medical term for decreased functional activity of the gonads. The gonads (ovaries or testes) produce hormones (testosterone, estradiol, antimullerian hormone, progesterone, inhibin B, activin) and gametes (eggs or sperm). Male hypogonadism is characterized by a deficiency in testosterone – a critical hormone for sexual, cognitive, and body function and development. Clinically low testosterone levels can lead to the absence of secondary sex characteristics, infertility, muscle wasting, and other abnormalities. Low testosterone levels may be due to testicular, hypothalamic, or pituitary abnormalities. In individuals who also present with clinical signs and symptoms, clinical guidelines recommend treatment with testosterone replacement therapy.
HYPOGONADISM IN MALES TREATMENT
Treatment for adults
Treatment for male hypogonadism depends on the cause and whether you’re concerned about fertility.
- Hormone replacement. For hypogonadism caused by testicular failure, doctors use male hormone replacement (testosterone replacement therapy, or TRT). TRT can restore sexual function and muscle strength and prevent bone loss. In addition, men receiving TRT often experience an increase in energy, sex drive and sense of well-being.
If a pituitary problem is the cause, pituitary hormones may stimulate sperm production and restore fertility. Testosterone replacement therapy can be used if fertility isn’t an issue. A pituitary tumor may require surgical removal, medication, radiation or the replacement of other hormones.
- Assisted reproduction. Although there’s often no effective treatment to restore fertility in a man with primary hypogonadism, assisted reproductive technology may be helpful. This technology covers a variety of techniques designed to help couples who have been unsuccessful in achieving conception.
Treatment for boys
In boys, testosterone replacement therapy (TRT) can stimulate puberty and the development of secondary sex characteristics, such as increased muscle mass, beard and pubic hair growth, and growth of the penis. Pituitary hormones may be used to stimulate testicle growth. An initial low dose of testosterone with gradual increases may help to avoid adverse effects and more closely mimic the slow increase in testosterone that occurs during puberty.
Types of testosterone replacement therapy
Several testosterone delivery methods exist. Choosing a specific therapy depends on your preference of a particular delivery system, the side effects and the cost. Methods include:
- Injection. Testosterone injections are safe and effective. Injections are given in a muscle. Your symptoms might fluctuate between doses depending on the frequency of injections.
You or a family member can learn to give TRT injections at home. If you’re uncomfortable giving yourself injections, a nurse or doctor can give the injections.
Testosterone undecanoate (Aveed), an injection recently approved by the Food and Drug Administration, is injected less frequently but must be administered by a health care provider and can have serious side effects.
- Patch. A patch containing testosterone (Androderm) is applied each night to your back, abdomen, upper arm or thigh. The site of the application is rotated to maintain seven-day intervals between applications to the same site, to lessen skin reactions.
- Gel. There are several gel preparations available with different ways of applying them. Depending on the brand, you either rub testosterone gel into your skin on your upper arm or shoulder (AndroGel, Testim), apply with an applicator under each armpit (Axiron) or pump on your inner thigh (Fortesta).
As the gel dries, your body absorbs testosterone through your skin. Gel application of testosterone replacement therapy appears to cause fewer skin reactions than patches do. Don’t shower or bathe for several hours after a gel application, to be sure it gets absorbed.
A potential side effect of the gel is the possibility of transferring the medication to another person. Avoid skin-to-skin contact until the gel is completely dry or cover the area after an application.
- Gum and cheek (buccal cavity). A small putty-like substance, gum and cheek testosterone replacement (Striant) delivers testosterone through the natural depression above your top teeth where your gum meets your upper lip (buccal cavity). This product quickly sticks to your gumline and allows testosterone to be absorbed into your bloodstream.
- Implantable pellets. Testosterone containing pellets (Testopel) are surgically implanted under the skin and need to be placed every three to six months.
Taking testosterone orally isn’t recommended for long-term hormone replacement because it might cause liver problems.
Keep in mind that testosterone therapy carries various risks, including contributing to sleep apnea, stimulating noncancerous growth of the prostate, enlarging breasts, limiting sperm production, stimulating growth of existing prostate cancer and blood clots forming in the veins. Recent research also suggests testosterone therapy might increase your risk of a heart attack.