2 - Antiandrogens and Androgen Inhibitors

Question 1

Androgens influence cutaneous structures such as hair follicles and sebaceous glands

Answer 1

True

Question 2

Free testosterone and dihydrotestosterone are biologically active androgens that affect the pilosebaceous unit

Answer 2

True

Question 3

Dihydrotestosterone is the target tissue active androgen

Answer 3

True

Question 4

Testosterone and dihydrotestosterone have a central role in the pathogenesis of androgenetic alopecia, acne vulgaris and hirsutism

Answer 4

True

Question 5

Antiandrogen refers to agents that block the androgen receptor I.e. Spironolactone, flutamide and cyproterone acetate

Answer 5

True

Question 6

Spironolactone is an antiandrogen (blocks the androgen receptor)

Answer 6

True

Question 7

Flutamide is an antiandrogen (blocks the androgen receptor)

Answer 7

True

Question 8

Androgen inhibitors block androgen synthesis

Answer 8

True

Question 9

Finasteride and Dutasteride are androgen inhibitors that specifically inhibit 5-alpha reductase

Answer 9

True (less conversion of free testosterone to dihydrotestosterone)

Question 10

Leuprolide is a gonadotropin-releasing hormone agonist that initially increases LH and FSH production by the pituitary before sustained feedback inhibition of the secretion of these 2 gonadotropins

Answer 10

True

Question 11

Progesterone and medroxyprogesterone act as both antiandrogens (block androgen receptor) and androgen inhibitors (inhibit dihydrotestosterone formation via 5-alpha reductase inhibition)

Answer 11

True

Question 12

Finasteride (type II 5-alpha reductase inhibitor) is FDA approved for men with androgenetic alopecia

Answer 12

True (in contrast, the more potent Dutasteride is FDA approved for benign prostatic hypertrophy but not for androgenetic alopecia due to blockade of both isoenzymes I and II of 5-alpha reductase)

Question 13

Testosterone can be formed in cutaneous sites, from the androgen precursor androstenedione derived from the adrenal cortex

Answer 13

True (this occurs when large amounts of androstenedione are secreted by adrenal tumours or in congenital adrenal hyperplasia)

Question 14

The ovary and adrenal cortex are the primary sources of testosterone and other androgens in women

Answer 14

True

Question 15

Androstenedione and dehydroepiandrosterone (DHEA) are produced by the ovary and adrenal gland

Answer 15

True

Question 16

Androstenedione and dehydroepiandrosterone (DHEA) produced by the ovary and adrenal gland can be converted to more potent androgens I.e. Testosterone or to Oestrogens in peripheral organs including skin

Answer 16

True

Question 17

The average daily rate of testosterone production in women is approx 0.25mg with half of this derived from metabolic conversion of androstenedione to testosterone at extra glandular sites including skin

Answer 17

True

Question 18

PCOS is caused by increased quantities of androgens secreted by the ovary resulting in alopecia, acne and hirsutism

Answer 18

True

Question 19

The 2 isoenzyme forms of 5-alpha reductase are type I and type II

Answer 19

True

Question 20

Testosterone has minimal biological activity at the pilosebaceous unit and prostate until it is converted to dihydrotestosterone by 5-alpha reductase

Answer 20

True

Question 21

Both testosterone and dihydrotestosterone bind to intracellular androgen receptor

Answer 21

True

Question 22

Both type I and type II forms of 5-alpha reductase are located in the pilosebaceous unit

Answer 22

True

Question 23

Type II isoenzyme form of 5-alpha reductase is also found in the prostate gland, epididymis and seminal vesicles (genital skin)

Answer 23

True

Question 24

Type I isoenzyme form of 5-alpha reductase is found in non-genital skin

Answer 24

True (also includes scalp and face)

Question 25

The hair follicles and sebaceous glands ducts on top of the scalp from frontal to vertex scalp host the Type II isoenzyme of 5-alpha reductase

Answer 25

True

Question 26

The type II isoenzyme of 5-alpha reductase is absent from the occipital scalp

Answer 26

True

Question 27

Spironolactone is an aldosterone antagonist which also blocks the androgen receptor

Answer 27

True

Question 28

Spironolactone has no effect on 5-alpha reductase

Answer 28

True

Question 29

Spironolactone is a steroid molecule which resembles mineralocorticoids

Answer 29

True (aldosterone antagonist with anti-mineralocorticoid activity)

Question 30

Spironolactone may be converted to other active metabolites via progesterone 17-hydroxylase with the net result of decreased testosterone and dihydrotestosterone production

Answer 30

True

Question 31

Spironolactone is 98% protein bound

Answer 31

True

Question 32

Canrenone is the primary metabolite of Spironolactone contributing to the diuretic and antiandrogen activities of Spironolactone

Answer 32

True

Question 33

The liver rapidly metabolised Spironolactone to its primary and active aldosterone antagonist metabolite, Canrenone

Answer 33

True

Question 34

Food increases the absorption of Spironolactone

Answer 34

True

Question 35

Metabolites of Spironolactone (active metabolite canrenone, and inactive canrenoate which is converted from canrenone by hydrolysis) are excreted in urine and bile

Answer 35

True

Question 36

The unmetabolised Spironolactone does not appear in the urine

Answer 36

True (only the metabolised metabolites of spironolactone Canrenone and Canrenoate appear in the urine)

Question 37

Spironolactone has been used to treat hirsutism, acne and androgenetic alopecia

Answer 37

True

Question 38

Flutamide is more effective than Spironolactone in improving hirsutism

Answer 38

True

Question 39

Spironolactone is more effective than Finasteride in improving hirsutism

Answer 39

True

Question 40

Spironolactone may commonly cause menorrhagia and other menstrual dysfunction which usually last during the first 2-3 months of therapy

Answer 40

True

Question 41

Finasteride specifically inhibits the type II isoenzyme of 5-alpha reductase

Answer 41

True

Question 42

Dutasteride inhibits both type I and type II isoenzymes of 5-alpha reductase

Answer 42

True

Question 43

Hyperkalaemia is a potentially serious common adverse effect of Spironolactone, particularly if given to patients with severe renal insufficiency

Answer 43

True

Question 44

Spironolactone may cause gynaecomastia

Answer 44

True

Question 45

Spironolactone may cause mild GI symptoms

Answer 45

True

Question 46

Agranulocytosis is a rare adverse effect associated with Spironolactone, particularly in those with hepatic or renal impairment

Answer 46

True

Question 47

Spironolactone is contraindicated in women with a genetic predisposition to breast cancer

Answer 47

True (not be given to these women even though causal role is lacking)

Question 48

Spironolactone may cross the placental barrier

Answer 48

True (risk of feminisation of a male fetus)

Question 49

Spironolactone should not be given concurrently with other agents that increase the risk of hyperkalaemia

Answer 49

True

Question 50

Spironolactone should not be given concurrently with ACE-inhibitors (increases the risk of hyperkalaemia)

Answer 50

True

Question 51

Spironolactone should not be given concurrently with Aliskerin, a direct renin inhibitor (increases the risk of hyperkalaemia)

Answer 51

True

Question 52

Spironolactone should not be given concurrently with an Angiotensin receptor blocker (increases the risk of hyperkalaemia)

Answer 52

True

Question 53

Patients on Spironolactone should be cautioned against excessive dietary intake of potassium rich foods

Answer 53

True (risk of hyperkalaemia)

Question 54

Drosperinone is a synthetic progestin used in OCP and a Spironolactone analogue with anti-mineralocorticoid (diuretic) activity and anti-androgenic activity

Answer 54

True

Question 55

Drosperinone may cause hyperkalaemia

Answer 55

True (is a Spironolactone analogue)

Question 56

Drosperinone is contraindicated in patients with hepatic dysfunction, renal dysfunction and adrenal insufficiency

Answer 56

True

Question 57

Besides the progesterone receptor, Progestins may also interact with other steroid hormone receptors I.e. Androgen receptor, estrogen receptor, mineralocorticoid receptor and glucocorticoid receptor

Answer 57

True

Question 58

Older progestins are derived from progesterone or 17-hydroxyprogesterone I.e. Medroxyprogesterone which are structurally similar to testosterone

Answer 58

True

Question 59

Due to the structural similarity of androgen and Progesterone/other progestins, these can bind to the androgen receptor and act as a substrate for 5-alpha reductase to be converted to 5-alpha-pregnane-3, 20-dione (similar to dihydrotestosterone)

Answer 59

True

Question 60

Cyproterone acetate is a progestin with antiandrogen properties

Answer 60

True

Question 61

Cyproterone acetate competes with dihydrotestosterone for the androgen receptor binding site

Answer 61

True

Question 62

Cyproterone acetate may also inhibit testosterone production

Answer 62

True

Question 63

Cimetidine, an H2 antihistamine also has antiandrogen effects through binding with the androgen receptor

Answer 63

True

Question 64

Finasteride is well absorbed

Answer 64

True

Question 65

Finasteride is metabolised in the liver and excreted in urine and faeces

Answer 65

True

Question 66

Finasteride is excreted in the urine and faeces

Answer 66

True

Question 67

After finasteride administration, serum dihydrotestosterone decreases by 65% in 24 hours

Answer 67

True

Question 68

Finasteride has no adverse consequences in female partners of men receiving finasteride who are exposed to the drug by sexual contact

Answer 68

True (no adverse effects despite minute quantities of finasteride is detectable in semen)

Question 69

Minute quantities of finasteride is detectable in semen

Answer 69

True

Question 70

The lack of scalp hair improvement in older men taking finasteride for prostatic hypertrophy is most likely due to the innate reduced response of scalp pilosebaceous units to finasteride in older men

Answer 70

True

Question 71

Finasteride is not efficacious in female pattern alopecia

Answer 71

True

Question 72

Finasteride (androgen inhibitor of 5-alpha reductase type II isoenzyme) and dutasteride (dual type I and type II 5-alpha reductase inhibitor) was associated with loss of libido, erectile and ejaculatory dysfunction in older men

Answer 72

True (though only decreased volume of ejaculate is likely to be causally related to finasteride due to dihydrotestosterone's central role in the pilosebaceous unit and prostate)

Question 73

Finasteride and dutasteride may cause gynaecomastia

Answer 73

True

Question 74

Finasteride may cause a 20-30% decrease in PSA in men 18-41 years old

Answer 74

True (finasteride reduces the size of the prostate gland and hence is also indicated in benign prostatic hypertrophy)

Question 75

Finasteride may cause a 50% decrease in PSA in men aged 50 years old

Answer 75

True (the PSA needs to be doubled in all males aged 41 and above without benign prostatic hypertrophy if the PSA is ordered while taking finasteride to reflect the true PSA level)

Question 76

Decreased libido, erectile dysfunction, or decreased volume of ejaculate have been reported in <4% of younger patients on finasteride

Answer 76

True (though only decreased volume of ejaculate is likely to be causally related to finasteride due to dihydrotestosterone's central role in the pilosebaceous unit and prostate)

Question 77

Finasteride should be used with caution in men at high risk for depression

Answer 77

True (increased rates of depression noted after 2 months)

Question 78

Finasteride is associated with a 26% risk reduction in prostate cancer, but a greater number of high grade Gleason score tumours

Answer 78

True (similar with dutasteride)

Question 79

Finasteride may result in external genitalia abnormalities in male fetuses of pregnant women who take finasteride or handle crush or broken tablets

Answer 79

True (pregnancy category X)

Question 80

The antiretroviral agent Nevirapine may reduce finasteride levels and hence efficacy

Answer 80

True

Question 81

Finasteride is extensively metabolised in the liver primarily by the CYP3A4 subfamily

Answer 81

True (but no important interactions result given the drug's wide therapeutic index)

Question 82

A baseline PSA is appropriate for men 50 years and older before receiving finasteride

Answer 82

True

Question 83

Blood donation is contraindicated for those taking finasteride and dutasteride for at least 6 months after the last dose of medication to prevent blood donation to a pregnant female transfusion recipient as this may cause external genitalia abnormalities in male fetuses

Answer 83

True

Question 84

It is contraindicated for dutasteride to be handled by women of childbearing potential

Answer 84

True (for the same reasons as finasteride)

Question 85

Dutasteride has a very long half life of approximately 5 weeks

Answer 85

True

Question 86

Serum concentrations of dutasteride remain detectable for up to 4-6 months after discontinuation of treatment

Answer 86

True

Question 87

Dutasteride is metabolised by CYP3A4 in the liver and care should be taken in patients on chronic CYP3A4 inhibitors

Answer 87

True (Dutasteride has long half life in contrast to Finasteride)

Question 88

HIV protease inhibitors (ritonavir, nelfinavir) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

Answer 88

True

Question 89

Hep C virus protease inhibitors (telaprevir, boceprevir) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

Answer 89

True

Question 90

Azole antifungals (ketoconazole, itraconazole) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

Answer 90

True

Question 91

SSRI antidepressants (fluvoxamine) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

Answer 91

True

Question 92

Macrolide antibiotics (erythromycin, clarithromycin) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

Answer 92

True

Question 93

Fluoroquinolones (ciprofloxacin) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

Answer 93

True

Question 94

Calcium channel blockers (verapamil, diltiazem) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

Answer 94

True

Question 95

Anti tuberculous agents (rifampicin, isoniazid) are CYP3A4 enzyme inducers that may decrease the serum levels of dutasteride

Answer 95

True

Question 96

Cimetidine (H2 antihistamine) is a CYP3A4 enzyme inhibitor that may increase the serum levels of dutasteride

Answer 96

True

Question 97

Ketoconazole may be used in the treatment of hirsutism (androgen inhibitor)

Answer 97

True

Question 98

The mini pill contains progestin only

Answer 98

True

Question 99

The combined OCP contains both an estrogen and progestin

Answer 99

True

Question 100

The estrogen in all the combined OCP is ethinyl oestradiol

Answer 100

True

Question 101

Synthetic progestin for the combined OCP are derived from 19-nortestosterone and can have androgenic, estrogenic and antiandrogenic properties

Answer 101

True

Question 102

The more androgenic progestins I.e. Norgestrel, levonorgestrel, norethindrone may induce acne, androgenetic alopecia and hirsutism

Answer 102

True

Question 103

The less androgenic progestins in the combined OCP I.e. Norgestimate, desogestrel, etonogestrel may be useful in women with acne and hirsutism

Answer 103

True (OCP is first line therapy in premenopausal women since other antiandrogens have a significant risk of teratogenecity)

Question 104

The adverse effects of oestrogen include nausea, increased breast size and tenderness, weight gain, headaches, thromboemboli, mood swings, and vaginal bleeding

Answer 104

True

Question 105

Lower dosages of oestrogen in the combined OCP result in increased rates of breakthrough bleeding

Answer 105

True

Question 106

Higher dosages of oestrogen in the combined OCP result in increased risk of thromboemboli

Answer 106

True

Question 107

Rifampin and griseofulvin alter hormone levels and are biologically plausible causes of OC failure

Answer 107

True

Question 108

Women aged 65 years and older taking oestrogen for at least 4 years have an increased risk of dementia

Answer 108

True

Question 109

Women taking Oestrogens for at least 5 years had significant increases in myocardial infarction, stroke, breast cancer, PE and VTE

Answer 109

True

Question 110

Cyproterone and Drosperinone (antiandrogen progestin) confer a 2 fold risk for VTE than levonorgestrel (progestin with androgenicity)

Answer 110

True (the risk decreases with longer duration of use and with lower doses of oestrogen)