Hypogonadism

Hypogonadism
Specialty	Endocrinology

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).

Late-onset hypogonadism (LOH), Andropause or Androgen Decline in the Aging Male (ADAM), is a syndrome caused by a decline in gonadal production of testosterone in males that occurs with aging. This "male menopause" can also cause hypogonadism. However, it occurs for certain men and not for the others.

Symptoms

In men

• Effects of low testosterone in men may include: (not all are present in any single individual) and

• • Poor libido (Low sexual desire)
  • Fatigue (medical) always tired
  • Muscle loss/atrophy
  • Erectile Dysfunction
  • Increasing abdominal fat
  • Glucose intolerance (early diabetes)
  • High Cholesterol/Lipid
  • Poor sleep
  • Difficulty concentrating
  • Memory Loss-difficulty in choosing words in language
  • Depression
  • Anxiety
  • Psychological and relationship problems
  • Increase size of chest
  • Hot flushes
  • Decrease in growth of, or loss of, beard and body hair
  • Loss of bone mass (osteoporosis)
  • Irritability
  • Infertility
  • Shrinking of the testicles
  • Decrease in firmness of testicles
  • Frequent urination (polyuria) without infection/waking at night to urinate
  • Achy muscles
  • Night sweats
  • Dry Skin and/or cracking nails

In women

• Effects of low estrogen levels in women may include: (not all are present in any individual) and
  • Hot flashes
  • Irritability
  • Poor libido
  • Infertility
  • Loss of, or failure to develop, Menstruation
  • Loss of body hair
  • Loss of bone mass (osteoporosis)
  • Heart disease
  • Sleep disturbances
  • Symptoms of urinary bladder discomfort like frequency, urgency, frequent infections, lack of lubrication, discharge
  • Shrinking of breasts
  • loss of or non existent sense of smell

Diagnosis

In men

Low Testosterone can be identified through a simple blood test performed by a laboratory, ordered by a physician. This test is typically ordered in the morning hours, when levels are highest, but even in men over 60 levels can drop by as much as 13% during the day.

Normal total testosterone levels range from 300 - 1000ng/dl

Treatment is often prescribed for total testosterone levels below 350 ng/dl If the serum total testosterone level is between 230 and 350 ng/dl, repeating the measurement of total testosterone with sex hormone-binding globulin (SHBG) to calculate free testosterone or free testosterone by equilibrium dialysis may be helpful. However, there are no widely accepted diagnosis or reference ranges for Free Testosterone or Bioavailable Testosterone due to large discrepancies in the reference ranges for these tests between different testing labs.

Blood Testing

Total Serum Testosterone - Most widely accepted but does not account for SHBG or Albumin binding of total testosterone. The better test would be to get a Total and Free Testosterone, as the diagnosis and treatment with just the total testosterone only would be undesirable.

Free Testosterone by Clinical Pathology Laboratories - Most accurate test available

Free Testosterone by RIA - Least Accurate

Free Testosterone by Saliva Test - Results cannot be compared to other testing methods

Calculated Free Testosterone - An estimation of free testosterone, calculated using SHBG and Total Testosterone

Free Androgen Index - A simple ratio of Total Testosterone to SHBG, no longer widely used.

In women

Similar to men, the LH and FSH will be used, particularly in women who believe they are in menopause. These levels change during a woman's normal menstrual cycle, so the history of having ceased menstruation coupled with high levels aids the diagnosis of being menopausal. Commonly, the post-menopausal woman is not called hypogonadal if she is of typical menopausal age. Contrast with a young woman or teen, who would have hypogonadism rather than menopause. This is because hypogonadism is an abnormality, whereas menopause is a normal change in hormone levels.

Hypogonadism is often discovered during evaluation of delayed puberty, but ordinary delay, which eventually results in normal pubertal development, wherein reproductive function is termed constitutional delay. It may be discovered during an infertility evaluation in either men or women.

Treatment

Male hypogonadism is most often treated with testosterone replacement therapy (TRT). Commonly-used testosterone replacement therapies include transdermal (through the skin) using a patch or gel, injections, or pellets. Oral testosterone is no longer used in the U.S. because it is broken down in the liver and rendered inactive. Like many hormonal therapies, changes take place over time. It may take as long as 2-3 months at optimum level to reduce the symptoms, particularly the wordfinding and cognitive dysfunction. Testosterone levels in the blood should be evaluated to ensure the increase is adequate. Levels between 500-700 ng/l are considered adequate for young, healthy men from 20 to 40 years of age, but the lower edge of the normal range is poorly defined and single testosterone levels alone cannot be used to make the diagnosis. Modern treatment may start with 200mg intramuscular testosterone, repeated every 10-14 days. Getting a blood level of testosterone on the 13th day will give a "trough" level, assisting the physician in deciding whether the correct dose is being given.

Recently some have reported using Arimidex, an aromatase inhibitor used in women for breast cancer, to decrease conversion of testosterone to estrogen in men, and increase serum testosterone levels.

While historically men with prostate cancer risk were warned against testosterone therapy, that has shown to be a myth.

Other side effects can include an elevation of the hematocrit to levels that require blood to be withdrawn (phlebotomy) to prevent complications from it being "too thick". Another is that a man may have some growth in the size of the breasts (gynecomastia), though this is relatively rare. Finally, some physicians worry that Obstructive Sleep Apnea may worsen with testosterone therapy, and should be monitored.

Another feasible treatment alternative is human chorionic gonadotropin (hCG).

For both men and women, an alternative to testosterone replacement is Clomifene treatment which can stimulate the body to naturally increase hormone levels while avoiding infertility and other side effects as a consequence of direct hormone replacement therapy.

For women, estradiol and progesterone are replaced. Some types of fertility defects can be treated, others cannot. Some physicians will also give testosterone to women, mainly to increase libido.

Classification

Deficiency of sex hormones can result in defective primary or secondary sexual development, or withdrawal effects (e.g., premature menopause) in adults. Defective egg or sperm development results in infertility. The term hypogonadism is usually applied to permanent rather than transient or reversible defects, and usually implies deficiency of reproductive hormones, with or without fertility defects. The term is less commonly used for infertility without hormone deficiency. There are many possible types of hypogonadism and several ways to categorize them. Hypogonadism is also categorized by endocrinologists by the level of the reproductive system that is defective.Physicians measure gonadotropins (LH and FSH) to distinguish primary from secondary hypogonadism. In primary hypogonadism the LH and/or FSH are usually elevated, meaning the problem is in the testicles, whereas in secondary hypogonadism, both are normal or low, suggesting the problem is in the brain.

Affected system

• Hypogonadism resulting from defects of the gonads is traditionally referred to as primary hypogonadism. Examples include Klinefelter syndrome and Turner syndrome. Mumps is known to cause testicular failure, and in recent years has been immunized against in the US. A varicocele can reduce hormonal production as well.

• Hypogonadism resulting from hypothalamic or pituitary defects are termed secondary hypogonadism or central hypogonadism (referring to the central nervous system).
  • Examples of Hypothalamic defects include Kallmann syndrome.
  • Examples of Pituitary defects include hypopituitarism.

• An example of a hypogonadism resulting from the lack of hormone response is androgen insensitivity syndrome, where there are inadequate receptors to bind the testosterone, resulting in a female appearance despite XY chromosomes.

Primary or secondary

• Primary - defect is inherent within the gonad: eg. Noonan syndrome, Turner syndrome (45X,0), Klinefelter syndrome (47XXY), XX males with SRY gene
• Secondary - defect lies outside of the gonad: eg. Kallmann syndrome and Polycystic ovary syndrome, also called hypogonadotropic hypogonadism.. Hemochromatosis and diabetes mellitus can be causes of this as well.

Congenital vs. acquired

• An example of congenital hypogonadism (present at birth) in females is Turner syndrome, and in males is Klinefelter syndrome.
• An example of acquired hypogonadism is the Anabolic Steroids Induced Hypogonadism (ASIH), and childhood mumps. Additionally, there is some evidence men whose mothers ingested the endocrine disruptor diethylstilbestrol for potential miscarriage may have hypogonadism.

Hormones vs. fertility

Hypogonadism can involve just hormone production or just fertility, but most commonly involves both.

• Examples of hypogonadism that affect hormone production more than fertility are hypopituitarism and Kallmann syndrome; in both cases, fertility is reduced until hormones are replaced but can be achieved solely with hormone replacement.
• Examples of hypogonadism that affect fertility more than hormone production are Klinefelter syndrome and Kartagener syndrome.

Testosterone

Testosterone is a key steroid hormone produced in the body, which plays an important role in many fundamental physical processes. Hormones are essentially chemical signaling molecules, that activate certain processes in the body, through a receptor mechanism. A signaling molecule like testosterone, binds with the various chemical receptors in the body, to trigger various bodily processes. A steroid is a particular chemical type of hormone called terpenoid lipid.

It is the hormone that initiates most of the sexual developmental processes in a male and also contributes to other vital processes. Hence it is also called the male sex hormone as it manifests all the typical male qualities and physical processes. The testosterone secretion timing and amount is regulated by the hypothalamus and the pituitary gland in the brain through a complex signaling mechanism. It is also produced in the female body but in comparatively very lesser amounts. The female equivalent of testosterone is estrogen, the female sex hormone.

Testosterone is synthesized from cholesterol by mostly the Leydig cells in the male testicles. In females, it is synthesized in the ovaries by Thecal cells in very small quantities. In males, testosterone plays the very important role of initiating sperm production in the sertoli cells of the male testes. Drop in the levels of testosterone causes problems in cognitive processes, depression, sleep disorders, fatigue, decrease in libido and erectile dysfunction. It is also known to cause excessive fat accumulation. Hypogonadism may be induced after the chronic use of anabolic/androgenic steroids (AAS). The negative-feedback system of the hypothalamic-pituitary-gonadal axis (HPTA) shuts down pituitary production of gonadotropins after extended exposure to AAS.

Coping

Hypogonadism can have many psychological effects, especially in younger patients due to infertility and appearance. A supportive family that understands the condition is paramount, as well as psychological treatment. Possible treatments include the use of regular injections or the application of gels or ointments.

Testosterone and longevity

A longitudinal (18 year) study published by The Endocrine Society and funded by the National Institute on Aging and the American Heart Association stated: Men over 50 may not live as long if they have low testosterone. The study looked at death from any cause in nearly 800 men ages 50 to 91 years who were living in a southern California community and who participated in the Rancho Bernardo Study in the 1980s. At the beginning of the study, almost one-third of these men had suboptimal blood testosterone levels for men their age. The men with low testosterone levels had a 33 percent greater risk of death during the next 18 years than the men with higher testosterone. This difference was not explained by smoking, alcohol intake and level of physical activity or by pre-existing diseases such as diabetes or heart disease.

The new study is the second report linking the deficiency of this sex hormone with increased death from all causes over time, said study author Gail Laughlin, PhD.

Hypogonadism and baldness

Bald men have lower testesterone levels than non-bald men, this testosterone dificiency can lead to diabetes mellitus and metabolic syndrome

External links

• GeneReview/NIH/UW entry on Hypogonadotropic Hypogonadism Overview
• NIH
• eMedicine
• Low testosterone information

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