hypogonadism pt 2

Question 1

Safety - Prostate

Answer 1

• T suppression is often used to treat prostate ca
  *Men with hx of prostate cancer often have low T
  and symptoms (sometimes devastating QoL)
• Small studies in this population show similar
  benefits of T compared to non-cancer patients
• Long-term data is not available
• Some experts advocating for T use if 1-year of
  apparent cure post cancer tx
  *Avoid if moderate or high risk prostate cancer, or if
  still under active surveillance

Question 2

Safety - Prostate

Answer 2

Endogenous and exogenous testosterone and the risk of prostate cancer and increased prostate‐specific antigen (PSA) level: a
meta‐analysis
Forest plots showing changes in
(a) prostate cancer
(b) prostate biopsy

Question 3

◼ Any of the following regimens, chosen on the
basis of

Answer 3

◼ the patient’s preference
◼ consideration of pharmacokinetics
◼ treatment burden
◼ cost

Question 4

T- PK

Answer 4

*Distribution
* Circulating through SHBG, small portion bound to albumin
* Approx 2% of T is free

• Metabolism
• 5-alpha reductase in skin, liver, urogenital tract
• T metabolized to DHT, estradiol
• Conjugates (sulfuric acid, glucuronic acid) excreted in urine
• Drug interactions
• Warfarin (increased INR)
• Insulin / hypoglycemics (T decreases glucose)
• Cyclosporine (increased levels, nephrotoxicity)

Question 5

T – Formulation and Serum Levels

Answer 5

slide 67

Question 6

T – Monitoring of Therapy

Answer 6

slide 68

Question 7

Non-Androgen and Non-Exogenous Therapies
Dehydroepiandrosterone (DHEA)\

The guidelines do not recommend these, but we have a few patients using a few of these things. So DHEA is something that’s not recommended, but it is broken down to testosterone. So it could slightly increase. But in general, the evidence is very poor. It’s just better to use a testosterone products. You know, how much testosterone that patient will be getting. And then you can monitor over time.

Answer 7

• Secretion and metabolism:
• secreted by the adrenal glands
• metabolized to androstenedione
• metabolized to estrone and estradiol in women; testosterone in men.
• DHEA production peaks in early adulthood and declines over time.
• Evidence
• animal studies demonstrated prevention of cancer, heart disease, diabetes, obesity, increased
  response of the immune system
• Most studies have included small samples, short duration
• Not compared to T products
• Variability
• differences between animal and human models
• doses used in studies
• effects of aging and comorbidities
• variability in DHEA serum value reference
• Safety
• Minimal AE 100 mg/d or less
• , DHEA has not been found to produce notable benefit to reverse the effect of aging
• Bottom line
• Inadequate evidence

Question 8

CAM

Answer 8

• “Popular foodstuffs (onion, garlic, and tomato),
  nutraceutical agents (pollen extract and betasitosterols), and herbal medicines (Pygeum
  africanum and Urtica dioica) are rational
  approaches.”
• Some evidence that T levels can be normalized
• Challenges:
• 12 week studies, or shorter
• Variable or non-specific outcomes

Question 9

Investigational Therapy

Finally, investigational therapies. This is an area where if someone needs something like this, they’re probably seeing an endocrinologist specializing and hypogonadism. There might be some cases where these products are used in order to preserve fertility. So it creates a different bit of a feedback loop. So you’re not suppressing the endogenous testosterone production. So you might have some spermatogenesis. We don’t have a lot of evidence with that, but this is getting a little bit into the investigational area.

Answer 9

SERM Clomiphene Competes with estrogen at receptors
at hypothalamus and pituitary
negative feedback leads to increased
FSH and LH from anterior pituitary
leads to increased T production
25 mg every other
day, titrated to 50 mg
daily (per T levels)

Gonadotropins GnRH GnRH stimulatesLH and FSH from
anterior pituitary, leading to T
production
SQ infusion pump at
5-20 mcg/h every 1- 2h
hCG Analog of LH 1500-3000 units SQ
1-3x/week

Aromatase
inhibitors
Anastrozole,
testolactone,
letrozole
inhibit peripheral conversion of T to
estradiol
lower feedback from reduced estradiol
levels on HPA in

Question 10

Controversies

Answer 10

• A combination of direct-to-consumer product advertising (DTCPA) and
  lax consensus guidelines for testosterone prescribing have, over the past
  decade, led to 10- and 40-fold increases in testosterone prescriptions in
  the United States and Canada, respectively… We join others who
  characterize the mass marketing of testosterone coupled with the
  permissive prescribing of testosterone for common, nonspecific, aging
  related symptoms as disease mongering of declines in testosterone with
  advancing age. Disease mongering is defined as “the selling of sickness
  that widens the boundaries of illness and grows the markets for those
  who sell and deliver treatments.”