Hormone Replacement Therapy, Androgen Replacement, and Phosphodiesterase Type 5 Inhibitors

Question 1

What is the primary indication for systemic estrogen therapy and estrogen/progestin therapy?

Answer 1

Treatment of moderate to severe menopausal s/s

Question 2

What type of hormonal therapy should women with an intact uterus receive and why?

Answer 2

Combination progesterone with estrogen to reduce the risk of endometrial cancer (endometrial hyperplasia and cancer possible with just 6mos of unopposed estrogen therapy)

Question 3

What should be the duration of treatment of hormonal therapy?

Answer 3

The shortest time possible

**not for prevention of coronary artery disease

Question 4

Common Estrogen preparations include:

Answer 4

Oral
Transdermal patch 
Intravaginal creams and tablets 
Vaginal rings 
Topical gels, lotions, sprays
Phytoestrogens

Question 5

Why is transdermal application preferred over oral estrogen in HRT?

Answer 5

Oral estrogen is significantly affected by first-pass metabolism causing significantly higher hepatic concentrations increasing hepatic production of thyroxine-binding globulin, TGs, HDL, clotting factors and adversely affected saturation of bile with cholesterol

Question 6

Transdermal application of estrogen also has a decreased risk of:

Answer 6

VTE, stroke, and effects on serum lipids (d/t hepatocyte effects)

Question 7

Low dose estrogen (w/o uterus) or progestin/estrogen (intact uterus) patches are available for _________ but may not be able to treat ____________ .

Answer 7

Osteoporosis

Hot flashes

Question 8

Oral estrogen conversions and serum concentrations include:

Answer 8

Conjugated equine estrogen and estradiol which are both converted to estrone and then estrone sulfate in the liver

Question 9

How does the body store estrone sulfate and how does this allow serum estradiol levels to remain level?

Answer 9

Collects in a large pool that the body is able to pull from to maintain level concentrations even though estrogen is dosed once daily.

Question 10

The most potent oral estrogen is:

Answer 10

Ethinyl estradiol

Use in low doses in HRT

Question 11

Vaginal estrogen is used in low doses for _____ ______ .

Answer 11

vaginal atrophy

high concentrations can be achieved in the vaginal tissue with minimal systemic effects

Question 12

What is CI after administration of vaginal estrogen?

Answer 12

Intercourse

Question 13

Vaginal estrogen is used in high doses for ________

Answer 13

Vasomotor symptions

Vaginal rink(Femring) releases 0.05-0.1mg of estradiol

Question 14

Topical estradiol, available as lotion, gel, or topical spray (Evamist), is used to treat:

Answer 14

Vasomotor symptoms

Question 15

What risk accompanies topical estradiol administration?

Answer 15

Risk to children and pets

Application from elbow to wrist poses largest risk of unintended exposure

Question 16

Which HRT occurs naturally in plants, fruits, and vegetables?

Answer 16

Phytoestrogens (may contain estrogenic and antiestrogenic properties

Question 17

3 major types of phyoestrogens include:

Answer 17

Isoflavones: Soybeans, chickpeas, lentils
Coumestans
Lignans: Flaxseeds, lentils, grains, fruits, vegetables

Question 18

What product used by many menopausal women is not proven safe or effective?

Answer 18

Dietary soy products

Question 19

What is male androgen replacement used for?

Answer 19

Hypogonadism as evidenced by decreased serum testosterone concentrations and symptoms

Question 20

Why can’t native testosterone be used to treat hypogonadism?

Answer 20

While it is well absorbed it is rapidly hepatically metabolized and cannot maintain therapeutic concentrations

Question 21

Testosterone enanthate and testosterone cypionate (Depo-testosterone): administration, conc, AE

Answer 21

IM
Gradually released from oil-based vehicle
Prolonged serum concentration but with peaks and troughs
Fluctuations in mood, energy, and libido

Question 22

Testosterone patches (Androderm) and topical gels (Androgel): Conc, AE

Answer 22

Stable serum testosterone concentrations= more stable mood, energy, and libido
AE: skin irritation

Question 23

AE of male androgen replacement:

Answer 23

Erythrocytosis (esp. injectables)

Infertility, gynecomastia, and hyperlipidemia d/t suppression of HPA axis suppressing testicular function

Question 24

Topical formulation may pose risk to:

Answer 24

Children and pets (premature dev, aggression, etc.)

Question 25

When is male androgen replacement used in females?

Answer 25

Perimenopause d/t dec. libido

Transgender patients

Question 26

Uses of phosphodiesterase type 5 inhibitors include:

Answer 26

Erectile dysfunction and pulmonary HTN

Sildenafil (Viagra, Revatio), Vardenafil (Levitra, Staxyn), Tadafil (Cialis, Adcirca)

Question 27

MOA of phosphodiesterase type 5 inhibitors in erection:

Answer 27

Release of NO in corpus cavernosum during sexual stimulation (without stim, no effect). NO increased cGMP levels causing smooth muscle relaxation in corpus cavernosum allowing inflow of blood (erection)
PDE5 inhibitors, inhibits PDE5-the enzyme that degrades cGMP.

Question 28

MOA of phosphodiesterase type 5 inhibitors in PAH:

Answer 28

Inhibits PDE5, the enzyme that degrades cGMP in smooth muscle of pulmonary vasculature

Question 29

AE of PDE5 Inhibitors include:

Answer 29

HA
Flushing
MI, sudden death

(d/t vasodilation in systemic vascular sm. muscle-rare because PDE5 only in small amounts in vascular sm. muscle)

Question 30

With what are PDE5 inhibitors CI?

Answer 30

Nitrates

May result in severe hypotension (too much NO and too much cGMP)