Sex Hormones Flashcards
Long acting GnRH agonists
Leuprolide
Goserelin
GnRH agonist drugs
- Continuous administration suppresses release of LH and FSH (after initial surge)
- used in IVF, sex steroid-dependent cancers, endometriosis, precocious puberty
GnRH antagonists (Cetrorelix and ganirelix)
- suppress LH and FSH
- Used in IVF, sex steroid-dependent CA, endometriosis, precocious puberty
Long acting GnRH agonists and antagonists differences
- Only 4-5 days of antagonist treatment vs. 3 weeks of agonist to suppress gonadotropins
- No initial surge of gonadotropins in antagonist treatment
- (agonist only) metastatic prostate CA-problems during start of treatment (use anti androgen**)
Long acting GnRH agonists and antagonists mutual side effects
- Menopausal symptoms
- Testicular atrophy
Follicle stimulating hormone (FSH) use in women
Develops ovarian follicles and supports estrogen synthesis
FSH use in men
Stimulates spermatogenesis
Human menopausal gonadotropins (hMG)
FSH & LH (aka menotropins)
-Used for FSH
Urofollitropin (uFSH, Bravelle)
Purified FSH
Luteinizing hormone (LH)
- Stimulates ovulation
- Stimulates luteinization of follicles
- Steroid production (women=progesterone synthesis; men=testosterone synthesis)
hCG (Pregnyl)
Used instead of LH, has same actions
Use of gonadotropins-general
Reversing infertility
Use for gonadotropins-men
- Inducing spermatogenesis
- LH increases testosterone (for up to a year)
- FSH then induces spermatogenesis (takes months)
Use for gonadotropins-women
- IVF (ART)
- FSH (9-12 days) stimulates ovaries and estrogen production, single dose of LH give to induce ovulation
Side effects of gonadotropins
- Uncomplicated ovarian enlargement
- Ovarian hyperstimulation syndrome**
- Multiple births (20%)**
- Gynecomastia**
(HA, depression, edema,, precocious puberty)
Gonadotropins contraindications
Sex steroid-dependent CA
Estrogens major endogenous ones
- Estradiol
- Estriol
- Estrone
Estrogens mechanism
Nuclear receptors
Estrogens Metabolism
- Conjugated by liver (excreted in bile)
- Enterohepatic circulation (reverses conjugation, increases bioavailability)
Estrogen function-ovary
prepare for ovulation
Estrogen function-uterus
endometrial growth
Estrogen function-Vaginal epithelium
Proliferation, maintenance
Estrogen function-endocervical glands
Mucous
Estrogen function-breasts
growth (pregnancy and puberty)
Estrogen function-puberty
Growth and maturation, closes epiphyses
Estrogen function-Bone
maintenance
Estrogen function-blood clotting
Synthesis of clotting proteins, increases platelet adhesiveness
Estrogen function-metabolic
- Liver (clotting factors and hormone binding proteins: SHBG, CBG, TB)
- Increases HDL and decreases LDL
- Na and H2O retention
Exogenous estrogens
- Naturally occurring estrogens are not orally active, so oral forms have been developed
- Synthetic–>oral contraceptives
- Conjugated–>HRT
- Estradiol—>creams/patches
Exogenous estrogens-uses
- Oral contraception**
- Postmenopausal hormone replacement therapy (HRT)
- Stimulating pubertal development in hypogonadic girls**
- Decrease uterine bleeding
- Suppressing ovulation in dysmenorrhea
Estrogen adverse effects
- Endometrial hyperplasia
- Nausea and breast tenderness
- Migraines**
- Gallbladder disease
- HTN
- Thromboembolism, thrombophlebitis; increased platelet aggregation; accelerated blood clotting
Estrogens contraindications
- Estrogen dependent neoplasms (ex: breast CA)**
- Undiagnosed genital bleeding
- Uncontrolled HTN
- Liver disease
- Thromboembolic disorders**
- Smoking AND over 35
- pregnancy
Antiestrogens (Tamoxifen [Novaldex])
- selective estrogen receptor modulator (SERM)
- Might decrease HDL-Toremifene (Fareston) is better for this
Tamoxifen-antagonist
- Breast: used as palliative and prophylactic treatment in breast CA (reduces risk of further breast CA)
- DOC in premenopausal women
Tamoxifen-agonist
- Bone: limits bone loss
- Uterus: May increase risk of uterine CA
- Raloxifene (Evista) is better for this –> for osteoporosis
Antiestrogens (Clomiphene [Clomid])
- SERM
- Antagonizes negative feedback of estrogen in hypothalamus**
- Stimulates LH & FSH, inducing ovulation
- Multiple pregnancies** (5-10%)
Antiestrogens (Fulvestrant [Faslodex])
Full estrogen receptor antagonist
Aromatase inhibitors (Anastrozole, Letrozole, and Exemastane)
- Exemastane is irreversible
- Do not inhibit adrenal steroid synthesis
Aromatase inhibitors Indications
- DOC-breast cancer treatment in postmenopausal women**
- Advanced breast cancer after tamoxifen failure in postmenopausal women
Aromatase inhibitors adverse effects
- GI disturbances
- Hot flashes
- Joint pain
Aromatase inhibitors contraindications
- Premenopausal women
- Pregnancy cat X
Progesterone
- Produced by corpus luteum
- Produced by fetal/placental unit in pregnant women
Progesterone mechanism
Nuclear receptor
Progesterone biological functions-uterus
- Converts endometrium to a secretory state*
- Maintains pregnancy*
- Suppresses contractility during pregnancy
Progesterone biological functions-endocervical glands
Regulates cervical mucus
Progesterone biological functions-breasts
Lobuloalveolar development at the end of the mammary ducts during pregnancy and puberty
Progesterone biological functions-Thermogenic action
-Increases body temperature
Progestins preparations
- Same as estrogens, progesterone is not orally active; so different formulations
- 19-nortestosterones (have both progestin and androgenic activity)
- Progesterone derivatives (have varying levels of androgen activity)
Progestins uses
- Contraception**
- Prevent endometrial hyperplasia in HRT**
- Treatment of other problems when estrogens are contraindicated
Progestins side effects
- Possible increased BP
- High doses may reduce plasma HDL levels (19-nortestosterones)
- Depression and drowsiness
Antiprogestins-Mifepristone
Progesterone/glucocorticoid receptor antagonist
Mifepristone uses
- Terminate pregnancy (w/prostaglandins)**
- Prevent implantation
Mifepristone side effects
- GI disturbances
- Pelvic pain
- Vaginal bleeding
Antiprogestins-Danazol
- Weak progestin and androgen
- Suppresses ovarian function
Danazol uses
-Used to treat endometriosis**
Danazol side effects
- Weight gain
- Edema
- Acne and oily skin
- Hirsutism
- Deepening voice
- HA
- Flush
- Libido changes
- Cramps
Contraception options
- Combination pills: estrogen and progestin
- Drospirenon/ehinyl estradiol
Combination oral contraceptives
- Inhibit ovulation** (no LH surge)
- Change cervical mucus (block sperm)
- Change endometrium (decrease implantation)
- Progestin withdrawal initiates bleeding at the end of the cycle
Combination oral contraceptives-estrogen
-Commonly ethinyl estradiol or mestranol
Combination oral contraceptives-Progestins
Commonly levonorgestrel or norethindrone
In combination oral contraceptives, what is more important?
Ratio is more important than amount
- Minimal amounts**
- Mimic normal hormonal cycle and minimize side effects**
E:P ratio in combination oral contraceptives
- Estrogen stays the same: increase progestin content at each stage
- 1 stage–>mono phasic
- 2 stages–>biphasic
- 3 stages–>triphasic
Combination oral contraceptives-Seasonale cycle
84 on, 7 off
Combination oral contraceptives-Seasonique cycle
84 on, 7 estrogen only
Combination oral contraceptives-Lybrel cycle
Always on pill
Combination oral contraceptives-adverse effects
- Increased breakthrough bleeding (especially during 1st year)
- Hard to tell if you are pregnant
Estradiol/drospirenone (mineralcorticoid antagonists; Yasmin, Yaz) advantages
- Less water retention-FDA approved fro PMDD**
- Very little androgenic properties
Natazia
- Takes advantage of estradiol vale rate to produce E2 in vivo–>bioidentical hormones**
- Uses dienogest as progestin, weird 4 cycle regimen
NuvaRing
A vaginal ring containing a 3-week supply of etonogesterel and ethinyl estradiol
Progestin only-mini pills
- 87-98% effective for birth control**
- Used for teens and breast feeding
Progestin only: Depo-Provera
3 month depot injection of medroxyprogesterone
Progestin only: Implanon
- Single silastic tube implanted in arm
- >99% effective-3 years
Progestin only: Mirena
- Intrauterine contraceptive (IUC) containing levonorgesterel
- 99.9% effective-up to 5 years
Post coital (emergency)-Plan B
- Levonorgestrel-only pill
- Taken within 72 hours after sex
- Better the sooner it is taken
- Available w/o a prescription to adults 18 years or older
Post coital (emergency)-Preven
Similar to Plan B but it also has ethyinyl estradiol as well
Post coital (emergency)-Mifepristone (RU-486, Mifeprix)
Can also be used to prevent implantation if administered within 72 hours after intercourse
Adverse effects of combination oral contraceptives
- Common is weight gain, nausea, edema, depression
- Breakthrough bleeding: progestin alone or too little estrogen
- Cardiovascular problems (clotting [women over 35, smoking], mild HTN, migraine, MI/stroke)**
- Cholestatic jaundice and gallbladder disease
- Teratogenesis**
- Fertility (can be suppressed for 3 months)
Combination oral contraceptive benefits
- Effective contraception
- Reduced risk for ovarian and endometrial cancer (50% reduction even after 2 years of treatment, protection lasts 15 years after discontinuation)
(also ovarian cysts, benign breast disease, ectopic pregnancy, iron deficiency, rheumatoid arthritis, PMS, etc.)
Combination oral contraceptive absolute contraindications
- Thrombophlebitis
- Thromboembolic phenomena**
- Cerebrovascular disorder
- Estrogen-dependent neoplasms**
- Pregnancy
Combination oral contraceptive relative contraindications
- Liver disease**
- teens prior to epiphyseal closure
- Asthma; eczema
- Migraine; HTN
- Diabetes
- Optic neuritis (retrobulbar neuritis)
- Seizure disorders
- Smoking and over 35 yo
Combination oral contraceptive drug interactions
- P450 inducers reduce effectiveness (phenytoin, rifampin, carbamazepine, etc.)
- Antibiotics can reduce effectiveness (stops enterohepatic circulation)
(oral contraceptives decrease effectiveness of anticoagulants, anticonvulsants, tricyclic antidepressants, guanethidine, oral hypoglycemics)
HRT-options/considerations
- Younger patients w/HRT appear to not have as many side effects (within 10 years)
- Hysterectomies-estrogen only**
- Used in girls w/no ovarian development
- Raloxifene does NOT affect CHD, but does prevent osteoporosis and breast CA , but no effect on hot flashes
HRT-routes of administration
- Creams for urogenital tract
- Transdermal good for osteoporosis w/less CHD effects
HRT adverse effects
- Endometrial CA-progestins produce
- Breast CA-small risk**
- Gallbladder disease
- Cardiovascular**
HRT advantages
- Menopausal symptoms
- Osteoporosis
- Heart disease
HRT concerns
- Breast CA?
- Strokes
Androgens virilizing (androgenic) effects
- Spermatogenesis
- Sexual development
Androgens anabolic effects
- Increased bone density
- Increased amino acid incorporation into muscle
- Increased Red blood cell mass
- Antagonize catabolic effects of glucocorticoids
Androgens puberty effects
-Development of secondary sexual characteristics in males
Androgen uses (testosterone and methyl testosterone) men
Testicular deficiency
Androgen uses women
-Female hypopituitarism (estrogens and androgens)
Androgen uses both sexes
- Hypoproteinemia of nephrosis
- Negative nitrogen balance patients
Androgen side effects-men
- Decreased spermatogenesis
- May exacerbate prostate CA
Androgen side effects-women
- Masculinization
- Pseudohermaphroditism of fetus in pregnant women
Androgen side effects-both sexes
- Baldness
- Fluid retention, edema
- Oily skin, acne**
- Decreased HDL*, increased LDL
- Psychological changes
Androgen receptor antagonists-Flutamide (Eulexin), others
- Used in prostate CA w/long-acting GnRH agonist
- Hepatotoxic-reversible
Androgen receptor antagonists-Spironolactone (Aldactone)
- Mineralcorticoid antagonist
- High doses antiandrogen
- Uses: Hirsutism* and PMS in women, Precocious puberty*
5 alpha-reductase inhibitors (Finasteride & Dutasteride)
- Inhibits 5 alpha-reductase (no DHT)**
- Suppresses male sex accessory organs w/o affecting libido
- Uses: benign prostatic hyperplasia, male pattern baldness**
- Teratogenic
