Hypogonadism | Disorders | Knowledge Base

Hypogonadism can occur for a number of reasons. Certain men have hypogonadism since birth while others may develop this condition later in life. Two types of hypogonadism are:

Primary hypogonadism (testicular failure) - Low serum testosterone levels and gonadotropins (FSH, LH) above the normal range.

Hypogonadotropic hypogonadism - Idiopathic gonadotropin or LHRH deficiency or pituitary - hypothalamic injury from tumors, trauma, or radiation.

Characterized by low serum testosterone levels, but with gonadotropins in the normal or low range. Men develop testicular suppression with decreased libido, impotence, decreased ejaculate volume, loss of body and facial hair, weakness, fatigue and often anemia. On testing, blood levels of testosterone are low and should be replaced. In the United States, testosterone may begiven as a bi-weekly intramuscular injection, a patch form, or a gel preparation. In other countries, oral preparations of testosterone are available.

Women develop ovarian suppression with irregular periods or absence of periods (amenorrhea), infertility, decreased libido, decreased vaginal secretions, breast atrophy, and osteoporosis. Blood levels of estradiol are low. Estrogen should be replaced and can be given orally as Premarin or Estrace, or can be given as a patch applied twice weekly. Women taking estrogen also need to take progesterone replacement (unless they have undergone a hysterectomy). Annual pap smears and mammograms are mandatory.

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Causes of secondary hypogonadism in males UpToDate

INTRODUCTION

Hypogonadism in a male refers to a decrease in either or both of the two major functions of the testes: sperm production and/or testosterone production (see "Male reproductive physiology"). 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.

Literature review current through: Aug 2015. | This topic last updated: Wed May 20 00:00:00 GMT 2015.

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Causes of secondary hypogonadism in males UpToDate

CRL for Endo Health’s Aveed

The US Food and Drug Administration (:FDA) recently issued a complete response letter (CRL) for Endo Health Solutions (ENDP) new drug application on Aveed. The company is looking to get Aveed (a long-acting testosterone undecanoate injection) approved as a treatment for male hypogonadism.

The FDA declined to approve the new drug application for Aveed in the present form, as it is apprehensive about the risks and complications which may emanate after the injection of the drug. While issuing the CRL, the US regulatory body asked Endo to develop a medication guide. Specifically, the FDA asked Endo to ensure that the Risk Evaluation and Mitigation Strategy includes the guide in addition to Elements to Assure Safe Use to address the safety issue mentioned above.

However, the US regulatory body did not ask the company to conduct additional studies on Aveed. The requirement of additional trials would have pushed up its research and development costs. Endo intends to respond to the CRL by the end of the third quarter of 2013.

We note that the Aveed setback is not the first one for Endo this year. Last month, Endo suffered a blow with the FDA turning down its request to prevent the entry of generic versions of its painkiller, Opana ER. The decision by the FDA implies that the generic formulations of the original version of Opana ER will continue to be available in the market.

Endo expects the FDA decision to impact its 2013 guidance adversely. The company expects the adverse FDA ruling to reduce 2013 total net sales of Opana ER by up to $120 million. Moreover, Endos 2013 adjusted earnings per share outlook is expected to be hurt by approximately 55 cents following the FDA verdict.

While announcing its first-quarter 2013 results, Endo stated that it expects adjusted earnings per share for 2013 in the range of $4.40$4.70 per share and revenues of $2.80$2.95 billion. The Zacks Consensus Estimate for 2013 pegs earnings at $4.31 per share on revenues of $2.8 billion. Endo intends to throw more light on its 2013 guidance in the coming months.

Moreover, another painkiller at Endo, Lidoderm is expected to face generic competition later in the year from Actavis, Inc. (ACT). This will hamper sales of the drug significantly.

Endo currently carries a Zacks Rank #3 (Hold). Jazz Pharmaceuticals (JAZZ) and Santarus, Inc. (SNTS) appear to be more attractive with a Zacks Rank #1 (Strong Buy) each.

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Male hypogonadism Symptoms – Mayo Clinic

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:

Male hypogonadism may delay puberty or cause incomplete or lack of normal development. It can cause:

In adult males, hypogonadism may alter certain masculine physical characteristics and impair normal reproductive function. Signs and symptoms may include:

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:

See a doctor if you have any symptoms of male hypogonadism. Establishing the cause of hypogonadism is an important first step to getting appropriate treatment.

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Male hypogonadism Symptoms - Mayo Clinic

Male hypogonadism Tests and diagnosis – Mayo Clinic

Your doctor will conduct a physical exam during which he or she will note whether your sexual development, such as your pubic hair, muscle mass and size of your testes, is consistent with your age. Your doctor may test your blood level of testosterone if you have any of the signs or symptoms of hypogonadism.

Early detection in boys can help prevent problems from delayed puberty. Early diagnosis and treatment in men offer better protection against osteoporosis and other related conditions.

Doctors base a diagnosis of hypogonadism on symptoms and results of blood tests that measure testosterone levels. Because testosterone levels vary and are generally highest in the morning, blood testing is usually done early in the day, near 8 a.m.

If tests confirm you have low testosterone, further testing can determine if a testicular disorder or a pituitary abnormality is the cause. Based on specific signs and symptoms, additional studies can pinpoint the cause. These studies may include:

Testosterone testing also plays an important role in managing hypogonadism. This helps your doctor determine the right dosage of medication, both initially and over time.

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Male hypogonadism Tests and diagnosis - Mayo Clinic

Hypogonadism: Types, Causes, & Symptoms Healthline

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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Hypogonadism: Types, Causes, & Symptoms Healthline

hypogonadism | pathology | Britannica.com

hypogonadism,in men, decreased testicular function that results in testosterone deficiency and infertility.

Hypogonadism is caused by hypothalamic, pituitary, and testicular diseases. Hypothalamic and pituitary diseases that may cause decreased testicular function include tumours and cysts of the hypothalamus, nonsecreting and prolactin-secreting pituitary tumours, trauma, hemochromatosis (excess iron storage), infections, and nonendocrine disorders, such as chronic illness and malnutrition. The primary testicular disorders that result in hypogonadism in postpubertal men include Klinefelter syndrome and related chromosomal disorders, although these disorders usually manifest at the time of puberty.

Other causes of hypogonadism in men include testicular inflammation (orchitis) caused by mumps; exposure to gonadal toxins, including alcohol, marijuana, and several anticancer drugs (e.g., cyclophosphamide, procarbazine, and platinum); and radiation with X-rays. Many of the disorders that cause delayed puberty are sufficiently mild that affected men do not seek care until well into adult life. This particularly applies to those disorders that decrease spermatogenesis and therefore fertility but spare Leydig cell function.

The clinical manifestations of hypogonadism in adult men include decreased libido, erectile dysfunction (inability to have or maintain an erection or to ejaculate), slowing of facial and pubic hair growth and thinning of hair in those regions, drying and thinning of the skin, weakness and loss of muscle mass, hot flashes, breast enlargement, infertility, small testes, and osteoporosis (bone thinning). The evaluation of men suspected to have hypogonadism should include measurements of serum testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin, in addition to the analysis of semen. Men with hypogonadism who have decreased or normal serum gonadotropin concentrations are said to have hypogonadotropic hypogonadism and may need to be evaluated for hypothalamic or pituitary disease with computerized axial tomography or magnetic resonance imaging (MRI) of the head. Men with hypogonadism who have increased serum gonadotropin concentrations are said to have hypergonadotropic hypogonadism, and their evaluation should be focused on the causes of testicular disease, including chromosomal disorders.

Men with hypogonadism caused by a hypothalamic disorder, pituitary disorder, or testicular disorder are treated with testosterone. Testosterone can be given by intramuscular injection or by patches or gels applied to the skin. Testosterone treatment reverses many of the symptoms and signs of hypogonadism but will not increase sperm count. Sperm count cannot be increased in men with testicular disease, although it is sometimes possible to increase sperm count in men with hypothalamic or pituitary disease by prolonged administration of gonadotropin-releasing hormone or gonadotropins. In men with testicular disease, viable sperm can sometimes be obtained by aspiration from the testes for in vitro fertilization.

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Hypogonadotropic hypogonadism – Wikipedia, the free …

Hypogonadotropic hypogonadism (HH), also known as secondary or central hypogonadism, as well as gonadotropin-releasing hormone deficiency or gonadotropin deficiency (GD), is a condition which is characterized by hypogonadism due to an impaired secretion of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH), by the pituitary gland in the brain, and in turn decreased gonadotropin levels and a resultant lack of sex steroid production.[1]

The type of HH, based on its cause, may be classified as either primary or secondary. Primary HH, also called isolated HH, is responsible for only a small subset of cases of HH, and is characterized by an otherwise normal function and anatomy of the hypothalamus and anterior pituitary. It is caused by congenital syndromes such as Kallmann syndrome, CHARGE syndrome, and gonadotropin-releasing hormone (GnRH) insensitivity. Secondary HH, also known as acquired or syndromic HH, is far more common than primary HH, and is responsible for most cases of the condition. It has a multitude of different causes, including brain or pituitary tumors, pituitary apoplexy, head trauma, ingestion of certain drugs, and certain systemic diseases and syndromes.[1]

Primary and secondary HH can also be attributed to a genetic trait inherited from the biologic parents. For example, the male mutations of the GnRH coding gene could result in HH. Hormone replacement can be used to initiate puberty and continue if the gene mutation occurs in the gene coding for the hormone. Chromosomal mutations tend to affect the androgen production rather than the HPG axis.

Examples of symptoms of hypogonadism include delayed, reduced, or absent puberty, low libido, and infertility.

Treatment of HH may consist of administration of either a GnRH agonist or a gonadotropin formulation in the case of primary HH and treatment of the root cause (e.g., a tumor) of the symptoms in the case of secondary HH. Alternatively, hormone replacement therapy with androgens and estrogens in males and females, respectively, may be employed.

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Hypogonadotropic hypogonadism - Wikipedia, the free ...

Hypogonadism – Wikipedia, the free encyclopedia

Hypogonadism is a medical term which describes a diminished functional activity of the gonads the testes and ovaries in males and females, respectively that may result in diminished sex hormone biosynthesis. In layman's terms, it is sometimes called "interrupted stage 1 puberty". Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estrogen (e.g., estradiol) as hypoestrogenism, and may occur as symptoms of hypogonadism in both sexes, but are generally only diagnosed in males and females respectively. Other hormones produced by the gonads which may be decreased by hypogonadism include progesterone, DHEA, anti-Mllerian hormone, activin, and inhibin. Spermatogenesis and ovulation in males and females, respectively, may be impaired by hypogonadism, which, depending on the degree of severity, may result in partial or complete infertility.

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.

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

Women with hypogonadism will not begin menstruating and it may affect their height and breast development. Onset in women after puberty causes cessation of menstruation, lowered libido, loss of body hair and hot flashes. In boys it causes impaired muscle and beard development and reduced height. In men it can cause reduced body hair and beard, enlarged breasts, loss of muscle, and sexual difficulties. A brain tumor (central hypogonadism) may involve headaches, impaired vision, milky discharge from the breast and symptoms caused by other hormone problems.[2]

The symptoms of hypogonadotrophic hypogonadism, a subtype of hypogonadism, include late, incomplete or lack of development at puberty, and sometimes short stature or the inability to smell; in females, a lack of breasts and menstrual periods, and in males a lack of sexual development, e.g., facial hair, penis and testes enlargement, deepening voice.

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, as levels can drop by as much as 13% during the day.[3]

Normal total testosterone levels range from 3001000ng/dL (nanograms per decilitre)[4]

Treatment is often prescribed for total testosterone levels below 350ng/dL.[5] If the serum total testosterone level is between 230 and 350ng/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.

Treatment may be necessary even if the patient's total testosterone level is within the "normal" range. The standard range given is based off widely varying ages and, given that testosterone levels naturally decrease as humans age, age-group specific averages should be taken into consideration when discussing treatment between doctor and patient.[6] A twenty-seven-year-old male with a testosterone level of 380ng/dL would be in the "normal" range, but would likely have low testosterone to blame if he experiences some or many of the above symptoms. This score would put him in the bottom 5% of his age-group, but would be a more common score for a man who is 80+ years old.[6] Although, this doesn't automatically mean that a young man with 380ng/dL has the same amount of testosterone of an 80+ year old, since there is usually a big difference in SHBG levels in the bloodstream between young and elderly, resulting in a much higher free testosterone level in the young. In fact, some people with low SHBG and low-normal testosterone experience no symptoms of hypogonadism.

A downturn in the circulation of testosterone should cause the hypothalamus and pituitary gland to trigger a release of brain hormones that stimulate the testicles to ramp up production of testosterone. The specific brain hormones include gonadotropin releasing hormone (abbreviated GnRH), which is released by the hypothalamus, and luteinizing hormone (abbreviated LH), released by the pituitary. They act to control the production of testosterone in synchrony. This response system in the body is a negative feedback loop. When this loop is functioning at its best, the body gets enough testosterone to bind to receptors on the various organs that require it. In the bodies of men as they hit their thirties and forties, testosterone falls approximately 1 to 3 percent each year.[7]

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Hypogonadism - Wikipedia, the free encyclopedia

Prevalence, Diagnosis and Treatment of Hypogonadism in …

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 Hypogonadism Therapeutic Pipeline Industry Review, H2 2014 – Video


Male Hypogonadism Therapeutic Pipeline Industry Review, H2 2014
Read more at http://www.rnrmarketresearch.com/male-hypogonadism-pipeline-review-h2-2014-market-report.html This report provides comprehensive information on the therapeutic development for...

By: Richard Parker

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Male Hypogonadism Therapeutic Pipeline Industry Review, H2 2014 - Video