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.

11
(No Transcript)
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

14
(No Transcript)
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 HP
  and diagnostic tests must performed

18
Hypogonadism

• The HP 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 lt5ng/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
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

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

• 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

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 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

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.

51
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.

52
Causes of Primary Hypogonadism

• Klinefelter syndrome
• Undescended testicles
• Mumps orchitis
• Hemochromatosis
• Injury to the testicles.

53
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.

54
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.

55
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.

56
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.

57
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