drugs affecting the reproductive system

Question 1

testosterone

Answer 1

the primary male androgen

Question 2

endogenous androgens are responsible for:

Answer 2

1. Normal growth, maturation and maintenance of the male sex organs and secondary sexual characteristics
2. The skeletal growth spurt in adolescence and the termination of linear growth by fusion of the epiphyseal growth plate
3. Activation of sebaceous glands
4. Increased basal metabolic rate -> Possibly d/t the overall increase in proteins and enzymatic activity
   4.Enhanced production of erythropoietic stimulating factor, resulting in increased red blood cell production
5. Increased extracellular fluid volumes
6. Regulation of spermatogenesis and libido effects

Question 3

androgens are used for the treatment of

Answer 3

• testosterone deficiency states in men associated with primary or secondary hypogonadism
• masculinizing hormone therapy (HT) in transgender men
• treatment of endometriosis and some postmenopausal symptoms in women

Question 4

testosterone production

Answer 4

• primarily produced within the testes in interstitial or Leydig cells, located in the spaces between the seminiferous tubules
• women produce small amounts of testosterone in the menstruating ovary and the adrenals
• both sexes produce testosterone peripherally from the androstenedione, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS)

Question 5

testosterone metabolic effects

Answer 5

 carbohydrate and protein metabolism
 liver synthesis of clotting factors
 osteoclast activity
 renal production of erythropoietin
 affect lipoprotein metabolism -> results in lower HDL

Question 6

age-related low testosterone and andropause have been associated with

Answer 6

• sarcopenia: diminished muscle mass
• impaired balance
• falls
• osteoporosis
• decline in cognitive function
• higher dependency in performing activities of daily living
• functional health decline

Question 7

contraindications for use of testosterone

Answer 7

• Male breast cancer
• Prostate cancer
• Postate nodule or induration
• PSA > 4ng/mL, or > 3mg/mL in men at high risk for prostate cancer
• Hematocrit > 50%
• Severe sleep apnea
• Severe urinary s/s
• Heart failure
• Pregnancy d/t fetal harm/virilization of female fetus
• Lactation

Question 8

Prolonged used of high doses of androgens has been associated with the development of potentially life-threatening:

Answer 8

o Hepatitis
o Hepatic neoplasms
o Cholestatic hepatitis
o Jaundice
o Hepatocellular carcinoma

Question 9

peliosis hepatitis

Answer 9

Androgens may cause peliosis hepatitis
- Peliosis is the replacement of normal liver tissue with bloody cysts
- May cause a silent, fatal abdominal hemorrhage

Question 10

anabolic steroids

Answer 10

o Oxymetholone
o Stanozolol
o Oxandrolone
o nandrolone phenylpropionate
o nandrolone decanoate

Question 11

main classes of drugs associated w/ drug interactions with androgens

Answer 11

• anticoagulants
• diabetic agents
• corticosteroids

Question 12

Patients using supplemental and replacement androgen therapy will require monitoring for serum testosterone levels, as well as therapeutic effect

Answer 12

Serum testosterone level monitoring
–> Goal: normal range of serum testosterone levels  > 11.1nmol/L

o Lipid tracking
o Liver function tests
o CBC evaluation

Question 13

when should laboratory monitoring be performed for androgen therapy?

Answer 13

 At baseline
 2-3 months are initiating therapy
 Annually while on therapy

Question 14

what are antiandrogens?

Answer 14

Antiandrogens act as androgen antagonists by blocking the androgen receptor or by suppressing the androgen production

Question 15

antiandrogen medication classes

Answer 15

• 5a-reductase inhibitors
• Gonadotropin-releasing inhibitors
• Hormonal oncological agents with androgen deprivation effects

Question 16

5a-reductase inhibitors - key medications

Answer 16

 finasteride (Propecia, Proscar)
 dutasteride (Avodart)

Question 17

spironolactone (Aldactone) as an antiandrogen

Answer 17

an aldosterone antagonist and an inhibitor of 5a-reductase

• indicated for use as K-sparing diuretic
• d/t antiandrogenic properties, used in the treatment of:
   female hirsutism
   acne
   PCOS
   Premenstrual syndrome/premenstrual dysphoric disorder (PMS/PMDD)

Question 18

clinical use of 5a-reductase inhibitors

Answer 18

an option for BPH management when an enlarged prostate is present or for PSA > 1.5 ng/mL

Question 19

Finasteride

Answer 19

5mg PO daily
- Maximum reduction in prostate size or symptom improvement may not be evident for 12 months
- Noticeable improvement should occur after 6 months
- Treatment should continue as long as patient is responsive to therapy -> reported up to 6 years

Question 20

adverse effects of 5a-reductase inhibitors

Answer 20

o Erectile dysfunction
o Ejaculatory dysfunction
o Decreased libido
o Gynecomastia

Because of these side effects, 5a-reductase inhibitors are regarded as second-line agents for sexually active men

Question 21

5a-reductase inhibitors for BPH

Answer 21

not typically 1st line therapy
- good first choice for the symptomatic patient w/ a significantly enlarged prostate (> 30-40 g by ultrasound)

Combination therapy is often used for significantly enlarged prostate and elevated PSA of greater than or equal to 1.4 ng/mL

Question 22

5a-reductase inhibitor outcomes

Answer 22

Noticeable changes from baseline in prostate size and s/s are typically evident in 6 months
- Results in a mean PSA reduction of 50% by 6-12 months of continuous treatment
- If this PSA reduction is not seen -> patient should be evaluated for prostate cancer

Question 23

contraindications for the use of estrogen-only products

Answer 23

contraindicated in women with an intact uterus

d/t risk of endometrial hyperplasia and endometrial cancer

Question 24

effects of estrogen on the reproductive system

Answer 24

• Maturation of the female reproductive organs
• Development of female secondary sexual characteristics
• Regulation of the menstrual cycle
• Endometrial regeneration post menstruation

Question 25

physiological effects of estrogen on other body systems

Answer 25

1. Closure of long bones after pubertal growth spurt 2. Maintenance of bone density by decreasing the rate of bone resorption through antagonizing the effects of parathyroid hormone 3. Maintenance of the normal structure of skin and blood vessels through its actions on the endothelial cels in the arterial walls, including the induction of nitric oxide to facilitate vasodilation and oxygen uptake by cells 4. Reduction of motility of the bowel 5. Alteration of select protein production and activity 6. Increased fat deposition in the SC tissues, breasts, buttocks, and thighs 7. Enhancing blood coagulability by increasing the production of fibrinogen 8.Facilitating the shift of intravascular fluid into extracellular space through action on the RAAS system (retention of Na and water by the kidney), resulting in increased extracellular fluid volume --> Particularly during pregnancy 9. Maintaining the stability of the thermoregulatory center in the brain

Question 26

considerations for extended use of hormone therapy

Answer 26

 Persistent vasomotor s/s  QoL issues  Prevention of osteoporosis in women w/ elevated risk of fracture

Question 27

FDA-approved indications for HT

Answer 27

- Bothersome vasomotor s/s - Prevention of bone loss - Hypoestrogenism caused by hypogonadism - GU s/s

Question 28

HT carries an increased risk for

Answer 28

o MI o Stroke o Dementia

Question 29

estrogen uses in primary care

Answer 29

- HRT after oophorectomy - In natural menopause for treatment of hot flashes, vaginal atrophy, and irregular menstrual bleeding - As a component of hormonal contraception - used in gender-affirming treatment for male-to-female transgender persons

Question 30

absolute contraindications for estrogen therapy

Answer 30

- Current or prior history of an estrogen-dependent cancer - Current pregnancy - Undiagnosed dysfunctional uterine bleeding - DVT - Arterial thromboemboli within the prior year - Clotting disorders - Severe hepatic disease

Question 31

relative contraindications for estrogen therapy

Answer 31

o CV disease o Uncontrolled HTN o DM o Gallbladder disease o Obesity o Endometriosis o Seizure disorder o Migraine

Question 32

contraindications for ethinyl estradiol

Answer 32

patients who smoke and are older than 35v y/o

Question 33

common drug interactions for estrogen therapy

Answer 33

o Anticoagulants o Tricyclic antidepressants o Barbiturates o Anti-TB meds o Corticosteroids o Seizure control meds o Drugs for spasticity

Question 34

conjugated equine estrogen (Premarin) for relief of peri/postmenopausal s/s

Answer 34

Available in doses from 0.3-1.25 mg - Suppression of hot flashes has been shown to be best at 0.625mg, followed by 0.45mg and 0.3mg/day Vasomotor s/s begin to decrease by the 2nd week of therapy - Reach maximum effect by the 8th week of therapy

Question 35

micronized estradiol (Estrace) for relief of peri/postmenopausal s/s

Answer 35

The only bioidentical estrogen-alone product available in pill form - Available in 0.5-2mg doses - Vasomotor suppression at 1-2mg doses - 0.5mg doses have been used for osteoporosis prevention

Question 36

synthetic conjugated estrogen-A (Cenestin) for relief of peri/postmenopausal s/s

Answer 36

o Available in 0.3-1.25mg doses o Total daily dose of 1.25 mg to relieve vasomotor s/s

Question 37

synthetic conjugated estrogen-B (Enjuvia) for relief of peri/postmenopausal s/s

Answer 37

o Available in 0.3-1.25 mg doses o 0.3mg produces vasomotor s/s relief

Question 38

estropipate (Ogen, Ortho-EST) for relief of peri/postmenopausal s/s

Answer 38

Available in 0.75-6mg doses

Question 39

two formulations of estrogen available in combination contraceptive preparations

Answer 39

Ethinyl estradiol (EE) - Used in the vast majority of hormonal contraceptive formulations - Most preparations containing between 20-35 mcg of EE Mestranol - Weaker

Question 40

estrogen component of hormonal contraception

Answer 40

- Suppresses FSH release and therefore prevents the development of a dominant follicle - Adds to cycle control - Decreasing irregular bleeding patterns commonly found w/ progestin-only methods

Question 41

the progesterones include

Answer 41

- progesterone (Prometrium, Progesterone in Oil, Crinone, Prochieve) - medroxyprogesterone acetate (Provera) - norethindrone (Aygestin) - megestrol acetate (Megace)

Question 42

there are several androgen-derived progestins available in oral contraceptive preparations

Answer 42

o Norethindrone o norethindrone acetate o ethynodiol diacetate o norgestrel o desogestrel o levonorgestrel o norgestimate

Question 43

effects of progestin on the reproductive organs

Answer 43

- thickening of the endometrium and increasing its complexity in preparation for pregnancy - thickening of cervical mucus - thinning of vaginal mucosa - relaxation of smooth muscles of the uterus and fallopian tube

Question 44

progestin's actions outside of the reproductive system

Answer 44

- stimulates lipoprotein activity and seems to favor fat deposition - increases basal insulin levels and insulin response to glucose - promotes glycogen storage in the liver - promotes ketogenesis - competes with aldosterone in the renal tubule to decrease sodium resorption - increases body temp

Question 45

drug interactions with progestins

Answer 45

Two drugs known to have specific interactions w/ progestins - aminoglutethimide -rifampin Results in a decrease in effectiveness of progestin therapy

Question 46

major uses for progesterone therapy

Answer 46

- perimenopausal and postmenopausal hormone therapy - as contraception alone and in combination w/ estrogen

Question 47

medroxyprogesterone acetate (Depo-Provera)

Answer 47

progestin only IM injection  150mg dose every 3 months  Inhibits secretion of gonadotropins -> prevents follicular maturation -> results in endometrial thinning