Pharmacological Treatment of Adult and Pediatric Hypogonadism

Pharmacological Treatment of Adult and Pediatric Hypogonadism

Testosterone Replacement Introduction Presented By: Carol Sednek FNP

Introduction Inadequate testosterone (T) production (andropause) Decline in sperm production by the testes Affects 2-4 million men Prevalence increases with age 5% receive treatment; where are the other 95%?

Clinical manifestations of andropause Sexual: ED, infertility, shrinking testes Brain/Behavioral: fatigue, poor motivation, depressed mood, irritability, sleep disturbance, poor concentration or memory Physical: gynecomastia, male body hair loss, low bone mineral density, muscle wasting, increase body fat, mild anemia Symptoms are subtle over time Modified by presence of co morbidities.

In prepubescent males the signs and symptoms may also include: Small testes, phallus and prostate Scant pubic and axillary hair Disproportionately long arms and legs Persistently high pitched voice

Citation: Meacham, Randall MD 2009

Distinguishing Primary from Secondary Hypogonadism Primary (testis dysfunction); T is low in association with high LH and FSH levels Secondary (hypothalmic or pituitary dysfunction): T is low in association with normal or low LH and FSH. Secondary may be caused by tumor or infiltrative diseases.

Causes of Secondary Hypogonadism Pathological; Kallmann syndrome, Hemochromatosis, pituitary adenoma, hypopituitarism, genetic syndromes Functional; Drugs (opioids, glucorticoids estrogens, anabolic steroids). Acute and chronic illness (liver, renal, heart, lung and Diabetes). Morbid obesity, sleep apnea. Aging.

Testosterone Replacement Therapy Testosterone esters; IM; 100mg q week, 200mg q 2 weeks; inexpensive roller coaster $100. _HDL Testosterone pelletts; SC; 2-6 75mg pelletts q 3-6 months; manufacturer $150. -HDL Buccal Testosterone 30mg BID close to physiologic range, $250. -HDL Testosterone patch; non scrotal topical, mimics circadian rhythm, $250. normal HDL Testosterone gel, 5g/day, levels in physiologic range, possible transmission to intimate contacts. $300. normal HDL Novel Testosterone therapy; phase III trail for US approval; Europe 1,000mg Q10-14 weeks.

Monitoring during therapy T, PSA, HCT, HG, LFT, Lipids. 3-6 month intervals and then yearly. Digital rectal exam; prostate cancer (+1.5; biopsy). Some recommend prostate biopsy prior to initiating therapy. Hepatic; increase with oral forms Sleep apnea; exacerbation of breathing by central mechanisms rather than changes in airway. Other Effects; breast tenderness, -testicular size, site pain, skin reactions, acne, hypertension.

Therapeutic replacement Presented by: Mary Walton FNP Hypogoandism Therapeutic replacement Presented by: Mary Walton FNP

Hypogonadism Goals of replacement therapy: 1. restore lean body mass and sexual function 2. Increase energy and wellbeing 3. Improve mood and cognition 4. Increase lean body mass 5. Reduce CVD risk 6. Stabilize physiological levels of testosterone

Hypogonadism A low testosterone level does not necessarily indicate hypogonadism

Hypogonadism Before replacement is considered a complete H&P and diagnostic tests must performed

Hypogonadism The H&P and laboratory tests will help determine if there is hypogonadism and if it is primary or secondary

Hypogonadism These Diagnostic tests should be done before considering Testosterone replacement: 1. Total Testosterone (nml range 300-900ng/dl) 2. Free Testosterone: abnormal if <5ng/dl 3. TSH 4. FSH 5. LH 6. CBC for base line (may have mild anemia) 7. PSA 8. Seminal fluid analysis (for infertility) 9. If concerned about Total testosterone level may consider a sex hormone binding globulin which can decrease the total testosterone

Hypogonadism Side effects of Testosterone Replacement: 1. Testicular atrophy, infertility 2. Acne 3. Edema, fluid retention 4. Gynecomastia 5. Erythrocytosis 6. BPH 7. Prostate cancer progression 8. Increased CVD risk (controversial) 9. Sleep apnea

Hypogonadism Relative Contraindications Testosterone replacement should be avoided in men with: 1. Prostate cancer 2. Heart failure (NYH III & IV) 3. Renal insufficiency 4. Severe liver disease

Hypogonadism Injectable Testosterone: 1.Testosterone Cypionate 2. Testosterone Enanthate administered IM 50-400mg every 2-4 weeks Side effects include Fluctuating levels of Testosterone, mood swings, elevated HGB & HCT

Hypogonadism Subcutaneous implants (pellets) Administered SQ at a dose of 150-450mg (2- 6 pellets) every 3-6 months Side effects include possible expulsion of the pellets, and incision is required for implanting and removing.

Hypogonadism Topical Testosterone: 1. The patch: 5mg/day Side effects include skin irritation 2. Gel: 5g/day Side effects include skin irritation and possible transmission to intimate contacts 3. Buccal Testosterone: 30mg BID Side effects: oral irritation, alteration in taste There is now a black box warning for Androgel and Testim 1% in light of reprorts of ageressiveness or abnormally enlarged genitals

Testosterone Replacement Therapy Testosterone esters; IM; 100mg q week, 200mg q 2 weeks; inexpensive roller coaster $100. _HDL Testosterone pelletts; SC; 2-6 75mg pelletts q 3-6 months; manufacturer $150. -HDL Buccal Testosterone 30mg BID close to physiologic range, $250. -HDL Testosterone patch; non scrotal topical, mimics circadian rhythm, $250. normal HDL Testosterone gel, 5g/day, levels in physiologic range, possible transmission to intimate contacts. $300. normal HDL Novel Testosterone therapy; phase III trail for US approval; Europe 1,000mg Q10-14 weeks.

Hypogonadism Aphrodisiacs: Ginseng Raw Oysters Kelp Onion Spanish Fly Rhinoceros horn Yohimbine Tiger penis

Hypogonadism When you have a patient on Testosterone you should monitor him using the following guidelines:

Anabolic Steroids Presented By: Susan Pomering FNP

What are anabolic steroids Anabolic steroids are synthetically produced variants of the naturally occurring male hormone testosterone. Both males and females have testosterone produced in their bodies: males in the testes, and females in the ovaries and other tissues. The full name for this class of drugs is: androgenic (promoting masculine characteristics) anabolic (tissue building) steroids (the class of drugs).

History of steroids Steroids were developed in the 1940s in Germany and used experimentally on their troops during World War II, the drugs ability to stimulate tissue growth and protein synthesis lead them to believe that the drug might be beneficial to treat burn victims and other war accidents

Legal use of Steroids Steroids are used for treating anemia, because of it's ability to increase the production of red blood corpuscles. They are also used for treatment of leukemia, cancer and at times steroids are also used for general strengthening therapy. Steroids have also been tried in combination with other drugs as a means of helping AIDS patients.

Prevalence of use More than a half million 8th- and 10th- grade students are now using these dangerous drugs, and increasing numbers of high school seniors say they don't believe the drugs are risky." National Institute on Drug Abuse

Ease of Obtaining Young people have abused anabolic steroids meant for animals by getting access to veterinary steroids. These steroids are often cheaper and easier to obtain than anabolic steroids designed for peop. Steroid users are often risk-takers who use a variety of harmful substances. Twenty-five percent of steroid users share needles, which increases the risk of infectious disease. Some evidence shows that anabolic steroids can be addictive, but more research is needed. There is evidence that large doses of anabolic steroids affect the brain's chemistry and produce mental changes.

Common types of steroids Abused The illicit anabolic steroid market includes Steroids that are commercially available in the U.S. including: Fluxoymesterone (Halotestin), Methyltestosterone Nandrolone (Deca-Durabolin, Durabolin), Oxandrolone (Oxandrin), Oxymetholone (Anadrol), Testosterone, Stanozolol (Winstrol).

Common Types of steroids abused Veterinary steroids that are commercially available in the U.S. include boldenone (Equipoise), mibolerone, and trenbolone (Revalor). Other steroids found on the illicit market that are not approved for use in the U.S. include ethylestrenol, methandriol, methenolone, and methandrostenolone

How are they taken Anabolic steroids dispensed for legitimate medical purposes are administered several ways including intramuscular or subcutaneous injection, by mouth, pellet implantation under the skin, and by application to the skin (e.g. gels or patches). These same routes are used for purposes of abusing steroids, with injection and oral administration being the most common. Abusers may take anywhere up to 100 times the normal therapeutic doses of anabolic steroids. This often includes taking two or more steroids concurrently, a practice called “stacking.”

How are they taken Abusers will often alternate periods (6 to 16 weeks in length) of high dose use of steroids with periods of low dose use or no drug at all. This practice is called “cycling.”   Another mode of steroid use is called “pyramiding.” With this method users slowly escalate steroid use (increasing the number of drugs used at one time and/or the dose and frequency of one or more steroids), reach a peak amount at mid-cycle and gradually taper the dose toward the end of the cycle.  

How They are Taken Doses of anabolic steroids used will depend on the particular objectives of the steroid user. Athletes (middle or high school, college, professional, and Olympic) usually take steroids for a limited period of time to achieve a particular goal. Others such as bodybuilders, law enforcement officers, fitness buffs, and body guards usually take steroids for extended periods of time. The length of time that steroids stay in the body varies from a couple of days to more than 12 months

Psychological Symptoms of Anabolic Steroid Use Psychological symptoms include: Mood swings Sleep disruption Aggressive behavior Extreme irritability Delusions Impaired judgment because of feelings that nothing can hurt you Paranoid jealousy Euphoria or an exaggerated feeling of well-being Depression after stopping steroids Lack of sexual drive after stopping steroids

Consequences of Anabolic Steroid Use Men infertility breast development shrinking of the testicles male-pattern baldness Women enlargement of the clitoris excessive growth of body hair male-pattern baldness

Consequences of Anabolic Steroid Use Liver cancer peliosis hepatitis tumors Musculoskeletal System short stature (if taken by adolescents) tendon rupture

Anabolic Steroid Use Consequences Cardiovascular system increases in LDL decreases in HDL high blood pressure heart attacks Left ventricular hypertrophy Skin severe acne and cysts oily scalp jaundice fluid retention Most of the investigations have been focused on risk factors for cardiovascular diseases, and in particular the effect of anabolic steroids on blood pressure and on plasma lipoproteins. In most cross-sectional studies serum cholesterol and triglycerides between drug-free users and non-users is not different. However, during anabolic steroid use total cholesterol tends to increase, while HDL-cholesterol demonstrates a marked decline, well below the normal range. Serum LDL-cholesterol shows a variable response: a slight increase or no change. The response of total cholesterol seems to be influenced by the type of training that is done by the athlete. When a great deal of the exercise consists of aerobic exercise, the increasing effect of AS is counterbalanced by an exercise-induced increasing effect, which may result in a net decline in total cholesterol. Aerobic training does not seem to be able to offset the steroid-induced decline in HDL-cholesterol and its subfractions HDL-2, and HDL-3.

Steroid Alternatives A variety of non-steroid drugs are commonly found within the illicit anabolic steroid market. These substances are primarily used for one or more of the following reasons: serve as an alternative to anabolic steroids alleviate short-term adverse effects related to anabolic steroid use mask anabolic steroid use

Steroid Alternatives Drugs serving as alternatives to anabolic steroids include clenbuterol, human growth hormone, insulin, insulin-like growth factor, gamma-hydroxybutyrate (GHB).

Controlling Side Effects and Concealing Use Drugs used to treat the short-term effects of anabolic steroid abuse erythropoietin, human chorionic gonadotropin tamoxifen. Diuretics and uricosuric agents may be used to mask steroid use. 

Male Hypogonadism in Children

Types of Hypogonadism There are two principal types of AHypogonadism, Primary and Secondary. Primary - This type of hypogonadism is known as primary testicular failure — originates from a problem in the testicles.

Secondary Hypogonadism Indicates a problem in the hypothalamus or the pituitary gland. Parts of the brain that signal the testicles to produce testosterone. The hypothalamus produces gonadotropin- releasing hormone, which signals the pituitary gland to make follicle-stimulating hormone (FSH) and luteinizing hormone. Luteinizing hormone then signals the testes to produce testosterone

Primary Hypogonadism Hypogonadism can occur during fetal development, puberty or adulthood. Depending on when it develops, the signs and symptoms differ. Fetal development 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 it develops, and how much testosterone is present, a child who is genetically male may be born with: Female genitals Ambiguous genitals Underdeveloped male genitals

Fetal Onset Hypogonadism Causes of ambiguous genitalia in a genetic male may include: Impaired testicle development due to genetic abnormalities or unknown causes. Leydig cell aplasia, a condition that impairs testosterone production. Congenital adrenal hyperplasia. Certain forms of this genetic condition can impair production of male hormones. Androgen insensitivity syndrome, a condition in which developing genital tissues are unable to respond to normal male hormone levels.

Fetal Onset Hypogonadism 5alpha-reductase deficiency, an enzyme defect that impairs normal male hormone production. Ingestion by mother of female hormones Estrogens, or anti-androgens. This is unusual, if a woman continues taking BCP into pregnancy for several weeks. "nutritional supplements" contain plant estrogens.

Causes of Primary Hypogonadism Klinefelter syndrome Undescended testicles Mumps orchitis Hemochromatosis Injury to the testicles. This condition results from a congenital abnormality of the sex chromosomes, X and Y. A male normally has one X and one Y chromosome. In Klinefelter syndrome, two or more X chromosomes are present in addition to one Y chromosome. The Y chromosome contains the genetic material that determines the sex of a child and related development. The extra X chromosome that occurs in Klinefelter syndrome causes abnormal development of the testicles, which in turn results in underproduction of testosterone. Mumps If a mumps infection involving the testicles in addition to the salivary glands (mumps orchitis) occurs during adolescence or adulthood, long-term testicular damage may occur. This may affect normal testicular function and testosterone production. Hemochromatosis. Too much iron in the blood can cause testicular failure or pituitary gland dysfunction affecting testosterone production Injury to the testicles. Because of their location outside the abdomen, the testicles are prone to injury. Damage to normally developed testicles can cause hypogonadism. Damage to one testicle may not impair testosterone production.

Causes of Secondary Hypogonadism Kallmann syndrome. Abnormal development of the hypothalamus — the area of the brain that controls the secretion of pituitary hormones — can cause hypogonadism. This abnormality is also associated with impaired development of the ability to smell (anosmia). Inflammatory disease. Certain inflammatory diseases such as sarcoidosis, histiocytosis and tuberculosis involve the hypothalmus and pituitary gland and can affect testosterone production, causing hypogonadism.

Causes of Secondary Hypogonadism Pituitary disorders. An abnormality in the pituitary gland can impair the release of hormones from the pituitary gland to the testicles, affecting normal testosterone production. A pituitary tumor or other type of brain tumor located near the pituitary gland may cause testosterone or other hormone deficiencies. Also, the treatment for a brain tumor such as surgery or radiation therapy may impair pituitary function and cause hypogonadism.

Secondary Hypogonadism Idiopathic hypogonadotropic hypogonadism associated with anosmia (the Kallmann syndrome) or with a normal sense of smell, is a treatable form of male infertility caused by a congenital defect in the secretion or action of gonadotropinreleasing hormone (GnRH). Diagnosesd when patient has absent or incomplete sexual maturation by the age of 18.

Treatment 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.

Treatment of Hypogonadism Idiopathic hypogonadotropic hypogonadism was previously thought to require lifelong therapy. Sustained reversal of normosmic idiopathic hypogonadotropic hypogonadism and the Kallmann syndrome was noted after discontinuation of treatment in about 10% of patient with either absent or partial puberty Therefore, brief discontinuation of hormonal therapy to assess reversibility of hypogonadotropic hypogonadism is reasonable