Chapter 10 endocrine system - general info + testosterone + estrogen/progestins

Question 1

Parathyroid hormone

Answer 1

• secreted by parathyroid glands in resposne to low serum calcium
• PTH induces bone sorption, which liberates ca++ into bloodstream
• depends on adequate serum concentration of 1,25-dihdroxy cholecalciferol (derivative of vitamin D)
  //////
• bone resorption is counterregulated by calcitonin (thyroid gland that reduces the concentration of blood calcium level when it has risen to an above normal level.)
  /////
• 2 other ways PTH inc serum Ca++
  1) synthesize more of the active form of vitamin D – 1,24-dihryoxycholecalciferol in kidney — which stimualtes production of calcium binding protein => this ca++ protein binding protein enhances calcium phosphate absoprtion from gut lumen
  2) PTH also inbhits renal ca++ excretion while promoting phosphate excretion — causing a small inc in serum ca++ levels

Question 2

Testosterone

Answer 2

• made in leydig cells in testes (smaller amounts in ovaires of females) in response to LH stimulation

actions:
* male sex organs
* sperm production
* muscle mass
* libido
* other secondary sex characteristics

indication
* androgen deficiency (growth deficits, impotence [erectile fx])
* delayed puberty in males
* palliation of breast cancer
* postpartum breat pain and engorgement

undesirable effects:
women—-
* virilism or hirsutism (excess hair most often noticeable around the mouth and chin)
* menstural irregularities
Men—-
* prostatic hyperplasia or cancer
* gynecomastia (high dose or w/ liver disease
* pattern baldness
* reduced sperm count (negative feedback)
both sexes—
* hypercalcemia
* coagulopathies
* sodium and water retention
* hyperlipidemia
* atherosclerosis
* cholestatic hepatitis (bile flow related)
* liver cancer

List of drugs
1) testosterone cypionate (IM, long acting)
2) “ enanthate
3) “ propionate (IM, short acting, palliative tx for breast cancer b/c therapy can be d/c’d rapid if hypercalcemia occurs)
4) Fluoxymesterone (short acting oral prep + more convenient, but less effect than above choices; for hypogonadism which develops in adult)
5) Methyltestosterone (similr to fluoxymesterone, buccal form available)

Question 3

Finasteride (proscar, propecia)

Answer 3

• androgen inhibitor
• stops conversion of testosterone to 5a-dihydrotestosterone (DHT)

indication
* BPH (benign prostatic hypertrophy)
* lower doses — male pattern baldness

Question 4

estrogen

Answer 4

• induce transcript of target genes via intracellular receptors

indication
* contraception
* atrophic vaginitis ((atrophic vaginitis) is thinning, drying and inflammation of the vaginal walls that may occur when your body has less estrogen. Vaginal atrophy occurs most often after menopause.)
* osteroporosis
* CV disease r/t menopause
* hemorrhagic menstrual bleeding
* failure of ovarian development
* hirsutism
* prostatic cancer

undersireable effects
* nausea (worse in morning, tolerance develops)
* breast tenderness + edema
* gynecomastia
* increased risk of endometrial cancer

contraindications
* pregnancy (teratogenic)
* estrogen dependent neoplasm
* vaginal bleed
* liver impairment
* thromboembolic disorders

list of meds
2) estradiol [estraderm] (most potent secreted by ovary // transdermal + IM + PO // — reduces osteoporosis in postmenopausal women)
3) 17-ethinyl estradiol (estinyl) — high potency + not degraded in 1st pass + used in combo w/ progestin for contraception
4) conjugated estrogens (permarin) — sulfate esters of estrogenic substances; less potent than estradoil (oral IV or vaginal effective)

Question 5

Progestins

Answer 5

• induce synthesis of specific proteins via intracellular receptors

indication
* contraception
* irregular or hemorrhagic mesntrual bleeding
* endometrial carcinoma
* hypoventilation

undesirable effects
* masculinization with long term use
* minimal toxicity

synthetic progestins not susceptible to 1st pass metabolism and be given orally

list of meds
1) progesteron (IM only, used for menstrual d/o’s)
2) medroxyprogesterone (depo-provera) (PO/IM, used for 2ndary amenorrhea (absence of menstrual periods) and hormone induced abnormal uterine bleeding; avoid in women who have potential to become pregnant in the near future)
3) megestrol (megace) — palliative chemotherapy for breast or endometrial (lining of the uterus, a hollow, muscular organ in a woman’s pelvis.) + appetite stimulant
4) norethindrone —- potent oral agent

Question 6

estrogen receptor modulator

Answer 6

• Raloxifene (evista)
• binds to estrogen receptor and induce expression of genes that maintain bone density

indication
* osteoporosis prevention

NOT AN ESTROGEN
DOES NOT MIMIC ESTROGENS IN BREAST OR UTERUS

Question 7

Oral contraceptives

Answer 7

• estrogen + progestin combinations
• higher rates of pregnanacy w/ pts taking these are d/t failing to take pill at recommended dosing intervals

dosing
* 21 days of 28 – pills containing active steroids
* 7 of the remaining days — placebos or iron pills to maintain regimen (during this week, there is withdrawal bleeding)

mech:
* suppresses ovulation by feedback inhibition @ hypothalamus and pituitary
* estrogen suppresses FSH and progestin suppresses LH
* cause cervical muscosal thickening and render endometrium inhospitable for ovum implantation

components
1) ethinyl estradiol or mestranol
2) progestin - norethidrone, ethynodiol, norethynodrel, norgestrel, or levonogestrel

dosing regimen
1) monophasic - progestin dose fixed through cycle
2) biphasic pill - low dose progestin for 10 days => high dose for 11 days
3) triphasic pill - begins low then increase every 7 days throughout 21 day cycle (closely resembles normal physiology)
* estreogen same — fixed and unchanging

side effects
1) n/v
2) breast tenderness
3) water retention
4) weight gain
5) thromboembolic episodes
6) hepatic adenomas
7) hemorrhagic stroke
8) MI
9)** endometrial cancer**

contraindications:
* hx of
1) thromboembolic disorders
2) DVT
3) cerebral vascular disease
4) liver cancer
5) estrogen dependent cancer
6) breast cancer
7) undiagnosed abnormal genitla bleeding
8) suspected pregnancy

interactions
* effects decreased when taking with AB’s (ampicillin, isoniazid, neomycin, pn V, rifampin, sulfonamides, tetracycline)
* same w/ CNS agents (barbiturates, benzo’s, phenytoin)
* contraceptives inc effects of corticosteroids and worsen side effects of tricyclic antidepressants
* oral contraceptives dec effectiveness of oral anticoagulants, anticonvulsants, and oral hypoglycemic agents

Question 8

progestin only “minipill”

Answer 8

• mechanism unclear — act by altering endometrium to prevent ovum implantation
• taken everyday! (no 7 day break in cycle)
• lack estrogen so may dec side effects

effects
1) amenorrhea
2) endometiral atrophy (thinning of uterine line)

Question 9

levonorgestrel implants (norplant)

Answer 9

• synthetic polymer capsule embedded with levonorgestrel, a progestin
• subq implant
• continually release progestin to maintain low contraceptive serum progestin levels
• failure rate similar to those of oral form
• frequent SE — prolonged, absent or irregular menstrual bleeding