Pharmacological Treatment of Adult and Pediatric Hypogonadism

1. Pharmacological Treatment of Adult and Pediatric Hypogonadism

2. Pharmacological Treatment of Adult and Pediatric Hypogonadism

3. Testosterone Replacement Introduction Presented By: Carol Sednek FNP

4. 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%?

5. 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.

6. 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

7. Citation: Meacham, Randall MD 2009

8. 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.

9. 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.

10. 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.

12. 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.

13. Hypogoandism Therapeutic replacement Presented by: Mary Walton FNP

15. 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

16. Hypogonadism • A low testosterone level does not necessarily indicate hypogonadism

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

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

19. 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

20. 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

21. HypogonadismRelative 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

22. 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

23. 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.

24. 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

25. 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.

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

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

28. Anabolic Steroids Presented By: Susan Pomering FNP

29. 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).

30. 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

31. 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.

32. 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

33. 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.

34. 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).

35. 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

36. 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.”

37. 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.

38. 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

39. 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

40. 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

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

42. Anabolic Steroid UseConsequences Skin • severe acne and cysts • oily scalp • jaundice • fluid retention Cardiovascular system • increases in LDL • decreases in HDL • high blood pressure • heart attacks • Left ventricular hypertrophy

43. 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

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

45. 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. 

46. Male Hypogonadism in Children

47. 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.

48. 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

49. Primary Hypogonadism • Hypogonadism can occur during fetal development, puberty or adulthood. Depending on when it develops, the signs and symptoms differ. • Fetal developmentIf 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

50. 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.