Androgens And Anabolic Steroids

Front 1

The most potent androgen secreted is..

a) DHT
b) estradiol
c) testosterone

Back 1

The most potent androgen secreted is

c) testosterone

Front 2

In an adult male, 95% of testosterone comes from (blank) and the remaining 5% comes from (blank).

Back 2

In an adult male, 95% of testosterone comes from the testes (Leydig cells) and the remaining 5% comes from the adrenal cortex.

Front 3

In the periphery, testosterone is converted to DHT by what enzyme?

In the periphery, testosterone is converted to estradiol by what enzyme?

Back 3

Testosterone is converted to DHT via 5alpha-reductase.

Testosterone is converted to estradiol via aromatase.

Front 4

In males, testosterone is produced by the adrenal cortex and the testes.

What about in females?

Back 4

Sources of testosterone in females:

--synthesis is in adrenal cortex and ovaries (40-65%)
--peripheral conversion of DHEA (35-60%)

Front 5

Describe the hypothalamus / pituitary / testes feedback system in the regulation of androgen synthesis and spermatogenesis.

Back 5

Hypothalamus: GnRH release

Pituitary: LH, FSH release

Leydig cells: LH stimulates testosterone production

Sertoli cells: FSH + testosterone stimulates spermatogenesis

Spermatogenesis is maintained by testosterone once FSH is applied.

Testosterone completes negative feedback loop on GnRH and LH/FSH release.

Front 6

Without this hormone, spermatogenesis cannot take place:

a) testosterone
b) LH
c) FSH
d) DHT

Back 6

Without this hormone, spermatogenesis cannot take place:

b) LH

LH stimulates testosterone production, so without it, no testosterone would be produced and spermatogenesis could not take place.

Front 7

TRUE or FALSE

The cytosolic receptor in many tissues has a 10x higher affinity for DHT than testosterone.

Back 7

TRUE

Front 8

While DHT is the active steroid in many tissues, testosterone is the active moiety in select tissues like (blank) and (blank).

Back 8

While DHT is the active steroid in many tissues, testosterone is the active moiety in select tissues like the HYPOTHALAMUS and PITUITARY.

Front 9

Sertoli cells require these 2 things to begin spermatogenesis...

Back 9

FSH and testosterone

Front 10

Describe the effects of testosterone in the following non-reproductive tissues:

(1) liver
(2) kidney
(3) muscle
(4) skin, glands, hair
(5) hematopoietic system

Back 10

Testosterone effects in..

(1) liver: increase or decreased protein synthesis

(2) kidney: stimulation of erythropoietin

(3) muscle: dev of muscle mass/strength

(4) skin,etc: stimulation of beard, axillary, pubic hair growth; inc in temporal hair recession and balding; inc in sebum secretion

(5) hematopoietic: direct stimulation of stem cells

Front 11

Describe the effects of testosterone on..

(1) CNS
(2) bone/cartilage
(3) larynx, vocal cords
(4) mammary glands

Back 11

Testosterone effects in...

(1) CNS: facilitation of libido and sexual function; aggressive behavior

(2) bone/cartilage: promotion of epiphyseal fusion; maintains bone mass

(3) larynx: enlargement and thickening of vocal cords

(4) mammary glands: dev of gynecomastia; affected by androgen: estrogen ratio

Front 12

Describe why testosterone is a poor drug.

Back 12

(1) high first pass effect when given orally

(2) when injected, it is rapidly absorbed and metabolized

(3) has mixed anabolic and androgenic effects

Front 13

What are the chemical differences between Type A, B and C synthetic testosterone?

Which type is metabolized to testosterone proper?

Which types are orally active?

Which type produces a much lower cancer risk?

Back 13

Type A: 17beta esterification
Examples of Type A include enanthate and cypionate.

Type B: 17alpha substitution
Example is methyltestosterone.

Type C: ring alteration
Example is mesterolone.

Type A is metabolized to testosterone.

Types B and C are orally active.

Type A is associated with a lower cancer risk vs. types B and C.

Front 14

Primary testicular failure has several causes. Whether it is due to direct Leydig cell damage or Klinefelters, are testosterone elevels high or low?

What about gonadotropin levels?

What is the drug of choice in treating primary testicular failure?

Back 14

Primary testicular failure

Testosterone: low
Gonadotropin: high
Drug of choice: enanthate or cypionate (Type A)

Front 15

Testicular atrophy in secondary testicular failure may be due to a lack of (blank) or (blank).

Are testosterone levels high or low?
What about gonadotropin levels?
How do you treat secondary testicular failure?

Back 15

Testicular atrophy is due to lack of LH/FSH (hypopituitarism) or lack of GnRH (hypothalamus problem).

Testosterone: low
Gonadotropin: low
Treatment: treat underlying cause if possible; androgens added at normal time of puberty

Front 16

Describe how testosterone both directly and indirectly stimulate RBC development.

When is such treatment useful?
When is it contraindicated?

Back 16

Testosterone stimulates erythropoiesis...

(1) indirectly by stimulating the synthesis of erythropoietin in kidneys

(2) directly by recruiting stem cells for rbc production.

This therapy is useful in the case of anemias.

However, this therapy is contraindicated in aplastic anemia.

Front 17

Even though androgens do produce a growth spurt and could be beneficial in children with delayed growth, why is this treatment questionable?

Back 17

Androgens produce a growth spurt but cause epiphyseal calcification.

Front 18

Why are androgens beneficial in treating hereditary angioneurotic edema?

What is the drug of choice?

How do men respond to this therapy compared to women?

Back 18

Hereditary angioneurotic edema is caused by a lack of an active inhibitor of the 1st component of complement, which means that the cascade is always "on" and blood vessel permeability increases.

Androgens increase the hepatic synthesis of that active inhibitor.

The drug of choice is danazol (a Type B synthetic).

Men and women respond equally.

Front 19

Consider both a normal male and a well-trained male athlete who begin to use steroids for the purpose of increasing their muscle mass.

Will one see more effects compared to the other?

What about a female? Would she see more effects or less effects compared to a male?

Back 19

Normal male: less increase in muscle mass

Well-trained athlete: greater increase in muscle mass

Female: see more of an effect compared to males because she is more sensitive to the exogenous testosterone

Front 20

What is "male menopause"?

Back 20

Androgen production in males drops off sharply after the age of 55 ("menopause").

There is a subsequent decrease in muscle mass, strength and libido.

Front 21

What are the virilizing effects of high androgen levels?

Are these related to exogenous steroids, endogenous steroids or both?

Back 21

Virilizing effects in adolescent males and females include:
--acne
--hirsuitism
--male pattern baldness
--coarsening of voice

These can occur with high levels of either endogenous or exogenous androgens.

Front 22

Why might a male athlete who has been abusing androgen steroids develop gynecomastia?

Back 22

Testosterone is converted to an estrogen by aromatase in the peripheral blood.

Front 23

Describe the effects of high androgen levels on the following:

(1) liver
(2) lipoprotein profiles
(3) behavior

Back 23

High androgen levels lead to..

(1) cholestatic hepatitis or hepatic adenocarcinoma

(2) dec HDL and inc LDL

(3) inc aggressive behavior

Front 24

Describe the effect of pulsatile GnRH signals vs. that of continuous GnRH signals on LH/FSH production.

Back 24

Pulsatile GnRH leads to increased LH/FSH production.

Continuous GnRH leads to inhibitory effects (basis of administering GnRH analogs at therapy so as to decrease LH/FSH).

Front 25

Name 2 examples of GnRH analogs.

Why are these often administered in combination with a GnRH receptor antagonist?

Back 25

(1) leuprolide acetate
(2) goserelin

These are given with a receptor antagonist to avoid an initial flare of LH/FSH production due to the GnRH signal.

Front 26

This inhibitor of androgen synthesis has been tried for prostate cancer but is not very promising.

Back 26

Ketokonazole

Front 27

What are the side effects of ketokonazole?

Back 27

(1) may cause gynecomastia and oligospermia in males

(2) inc estrogen: testosterone ratio

Front 28

What enzyme does finasteride inhibit?

What does this enzyme normally do?

For what condition is finasteride a beneficial treatment?

Back 28

Finasteride inhibits 5alpha reductase.

5alpha reductase converts testosterone to DHT in the periphery.

Finasteride is effective in treating benign prostate hyperplasia. It also blocks hirsuitism in women but is not approved for this.

Front 29

Name the 2 androgen receptor antagonists discussed.

For what conditions are these drugs a beneficial treatment?

Name the drug that these androgen receptor antagonists are often coupled with.

Back 29

Androgen receptor antagonists:
(1) cyproterone acetate
(2) flutamide

These drugs are effective for treating excess androgen production in women and for advanced prostate cancer.

These drugs are usually coupled with leuprolide acetate, a GnRH agonist.

Front 30

Describe the principle behind combined GnRH suppression and testosterone as male contraception.

Back 30

Testosterone is required for the maintenance of spermatogenesis, but is needed at an order of magnitude more than that needed for development of 2ndary sex characteristics.

So...GnRH can be suppressed in males, meaning that no testosterone is made but a male implant can be inserted (in the arm, for example) which will release sufficient hormone for the maintenance of "maleness" but not enough to promote spermatogenesis.

Front 31

Describe the mechanism of action of gossypol.

Is it reversible?

Back 31

Gossypol destroys elements of the seminiferous epithelium so as to impair spermatogenesis without affecting testosterone.

The effects of gossypol are reversible upon discontinuation of the drug as long as the sperm count does not fall too low.

Front 32

Why is gossypol considered a male contraceptive?

Back 32

Gossypol destroys elements of the seminiferous epithelium which impairs spermatogenesis.

It also decreases sperm motility.

Front 33

Identify the specific drug(s) described by the following...

(1) two long-acting GnRH analogs that inhibit LH/FSH production

(2) effective in treating BPH by inhibiting 5alpha reductase

(3) 2 Type A synthetic testosterones that are metabolized to testosterone proper

(4) synthetic testosterone with a ring alteration that is orally active

(5) inhibits androgen synthesis and required at high doses

(6) male contraceptive that decreases sperm motility

(7) drug of choice for hereditary angioneurotic edema

(8) Type B synthetic testosterone that is orally active and can cause liver cancer

(9) 2 androgen receptor antagonists that are effective in treating advanced prostate cancer

(10) GnRH analog that is often coupled with the drugs in #9

(11) 2 drugs of choice in treating primary testicular failure

Back 33

(1) two long-acting GnRH analogs that inhibit LH/FSH production = leuprolide acetate, goserelin

(2) effective in treating BPH by inhibiting 5alpha reductase = finasteride

(3) 2 Type A synthetic testosterones that are metabolized to testosterone proper = enanthate, cypionate

(4) synthetic testosterone with a ring alteration that is orally active = Type C, mesterolone

(5) inhibits androgen synthesis and required at high doses = ketokonazole

(6) male contraceptive that decreases sperm motility = gossypol

(7) drug of choice for hereditary angioneurotic edema = danazol

(8) Type B synthetic testosterone that is orally active and can cause liver cancer = methytestosterone

(9) 2 androgen receptor antagonists that are effective in treating advanced prostate cancer = cyproterone acetate, flutamide

(10) GnRH analog that is often coupled with the drugs in #9 leuprolide acetate

(11) 2 drugs of choice in treating primary testicular failure = enanthate, cypionate (Type A)

Front 34

Identify cause of hypogonadism (primary, seminiferous tubule disease, or Leydig cell failure) based on the following lab results:

(1) low T + high LH + normal FSH + low sperm count

(2) low T + high LH + high FSH + low sperm count

(3) normal T + normal LH + high FSH + low sperm count

Back 34

(1) low T + high LH + normal FSH + low sperm count = Leydig cell failure

(2) low T + high LH + high FSH + low sperm count = prmary hypogonadism

(3) normal T + normal LH + high FSH + low sperm count = seminiferous tubule disease

Front 35

Based on the following lab findings, is the cause of hypogonadism related to pituitary or hypothalamus dysfunction?

(1) low T + low LH + low FSH + low sperm count + low LH/FSH response to GnRH

(2) low T + low LH + low FSH + low sperm count + normal LH/FSH response to GnRH

Back 35

(1) low T + low LH + low FSH + low sperm count + low LH/FSH response to GnRH = pituitary disease

(2) low T + low LH + low FSH + low sperm count + normal LH/FSH response to GnRH = hypothalamus disease

Front 36

Why are FSH levels high when the cause of hypogonadism is seminiferous tubule disease?

Back 36

Seminiferous tubule disease is a problem related to the Sertoli cells.

Testosterone and LH levels are normal but FSH is high.

High FSH levels are due to the fact that the Sertoli cells are not producing inhibin - which usually turns "off" FSH.

And if the Sertoli cells aren't working right, spermatogenesis is not taking place, hence the low sperm count and state of hypogonadism.

Front 37

List the clinical scenarios in which you would consider prescribing anabolic/androgenic steroids.

Back 37

(1) hypogonadism
(2) 2ndary testicular failure
(3) stimulation of erythropoiesis
(4) hereditary angioneurotic edema
(5) delayed growth in kids
(6) to counter muscle wasting due to various causes
(7) aging "male menopause"

Front 38

List the clinical scenarios in which you would want to suppress androgen production.

What are the possible treatments?

Back 38

(1) male pattern baldness
(2) virilizing syndromes in women
(3) acne
(4) hyperplasia and cancer of the prostate
(5) male contraception

Possible treatments:
--orchiectomy (not preferable)
--high levels of estrogens (not preferable)
--anti-androgens (suppressors, enzyme inhibitors, receptor anatagonists)