M4 L2 Gonadosteroids Flashcards
what are the female sex hormones?
- estrogens: development of female sex characteristics
- progestins: control ovarian cycle + maintenance of pregnancy
what are the male sex hormones?
androgens: development of male sex characteristics
sex hormones are controlled by
hypothalamus and pituitary gland
through -‘ve feedback mechanism
how r sex hormones released
hypothalamus releases GnRH, and pituitary then releases LH and FSH which stim testosterone in testes, and estrogen/progesterone in ovaries
3 types of estrogen
- natural (endogenous)
ex: estradiol, secreted by the ovaries - semisynthetic
ex: ethinylestradiol (inactive prodrug), estradiol valerate - synthetic
ex: mestranol, stilboestrol
how is estrogen absorbed through
- GIT
- Skin
- Mucous membrane
how is estrogen transported
by binding too…
albumin, and sex steroid-binding globulin
estrogen half life
+/- 13 hrs
what is the metabolism and degradation of estrogen
- liver
- synthetic estrogens are less prone to degradation than natural
how is estrogen excreted
thru kidneys in urine
therapeutic indications of estrogen
- contraception in females
- replacement therapy due to estrogen deficiency
(menopausal sympt, female hypogonadism) - transgender hormonal therapy
- menstrual disorders
- acne
- prostatic cancer
what causes female hypogonadism
due to impaired ovarian function
types of female hypogonadism
- pre-pubertal (delayed puberty)
- post-pubertal (2ndary amenorrhea and infertility)
treatment of primary hypogonadism
- begins at 11-13 yrs of age
- aim to stim development of 2ndary sex characters and menstruation and stim optimal growth
- small doses of estrogen on days 1-21 of each month (to mimic normal cycle
what is hyperestrogenemia
- increased estrogen levels
- in males this can cause feminization, and infertility
in females this can cause endometrial carcinoma, and breast cancer
what are 4 antiestrogens
- tamoxifen
- clomiphene
- letrozole
what is tamoxifen
- estrogen receptor blocker
- used to treat hormonally responsive breast cancer*
what is clomiphene
- selective estrogen receptor modulator (SERM) -> this inhibits estrogen-mediated -‘ve feedback on hypothalamus and increases GnRH, FSH and LH levels
- ovulation induction: used in treatment of infertility*
what is letrozole
- aromatase enzyme inhibitor -> decrease estrogen synthesis
indications:
- hormonally responsive breast cancer (post-menopausal women)
- ovulation induction - treatment of infertility
- gynecomastia in men
Types of progestins
- natural
- synthetic (1st, 2nd, 3rd gen compounds
ex of natural progestins
progesterone
secreted by corpus luteum and placenta
ex of synthetic 1st generation compounds
medroxyprogesterone, norethindrone, norgestrel
ex of synthetic 2nd generation compounds
levonorgestrel
ex of synthetic 3rd generation compounds
- desogestrel, gestodene, norgestimate
- least androgenic effect
therapeutic indications of progestins
- contraception in females
- hormone replacement therapy
- menstrual disorders
- dysmenorrhea (painful menstruation)
- endometriosis
- endometrial carcinoma
what is mifepristone
- progesterone receptor blocker (antiprogestin)
- indication: therapeutic abortion
hormonal contraception options
- oral contraceptives
- injections and implants
- transdermal patch
what are combined oral contraceptives
- combo of estrogen and progestin
- most popular
- 2 types: monophasic (fixed dose), bi- or triphasic (variable dose)
what is progestin mini pill oral contraceptives
low dose progestin
monophasic OCC
estrogen: ethinyl estradiol 2 ug (days 1-21)
progestin: desogestrel 150 ug (days 1-21)
triphasic OCC
estrogen: 20ug (like monophasic)
progestin: desogestrel increases by 25 each 7 days for 21 days from 100-150 ug
minipill OCC
norgestril 75 ug (everyday
what do estrogen-progestin combos do?
- suppress ovulation, thicken cervical secretions, inhibit implantation
what does low-dose progestin do
- thicken cervical secretions
- inhibit implantation
- variable suppression of ovulation by effect on FSH/LH
adverse effects of the combined OCC
- salt and water retention (causes edema)
- hypertension
- vascular disorders (increases risk of clot formation)
- migraine/headache
- depression
- post pill amenorrhea
absolute contraindications of combined OCC
- pregnancy
- breast feeding
- thromboembolic disease
- breast/cervical/endometrial cancer
- undiagnosed vaginal bleeding
relative contraindications of combined OCC
- hypertension
- impaired liver function
- migraine
contraceptive injections
long acting progestins
- IM injections every 3 months
- ex: medroxyprogesterone (provera)
contraceptive implants
long acting progestins
- SC insertion of small capsules
- effective for 3-5 yrs
- ex: levonorgestrel (norplant)
what is hormone replacement therapy
- estrogen replacement in postmenopausal women (low dose compared to contraceptives)
- progestin can be added to reduce risk of endometrial carcinoma
benefits of hormone replacement therapy
- prevention of changes associated with menopause: osteoporosis, flushing, headaches, insomnia, genital tract atrophy, cardiovascular disease
ex of natural androgens
- testosterone
- dihydrotestosterone (DHT)
- dehydroepiandrosterone (DHEA)
- androstenedione
ex of synthetic androgens
- methyltestosterone
- ethylestrenol
- stanozolol
mech of action of androgens
regulate gene expression by activating a nuclear receptor
effects of androgens
- development of primary and secondary male sex characters
- maturation of sperm
- anabolic effect: some synthetic androgens have more anabolic than androgenic activity (ex: stanozolol)
therapeutic indications of androgens
- hormone replacement: male hypogonadism, hypopituitarism
- anemia: androgens stim erythropoiesis
- breast cancer: androgens may downgrade receptor expression
- anabolic agents: compensate for protein loss, often abused by body builders and athletes
male hypogonadism types
primary: testicular failure
secondary: hypothalamic-pituitary disease
male hypogonadism treatment
aim:
- stim development of male secondary sex characters
- maintain muscle and bone mass
regimen:
- oral: TDS
- transdermal patch: every 24 hrs
- IM injection: every 2-3 weeks
- subdermal implants every 4-6 months
hyperandrogenemia in females
- virilization sympt: hirsutism, acne, amenorrhea, clitoral enlargement and deepening of voice
- during preg: masculinization of external genitalia of infants
hyperandrogenemia in prepubertal male children
precocious puberty
what is an example of an androgen suppressor
leuprolide acetate
what is the mech of action for androgen suppressors
there is an interruption of GnRH receptors which causes a decrease in FSH and LH, which leads to decrease in testosterone or estrogen to +/- 10% of basal levels
what are androgen suppressors used to treat
- prostatic carcinoma
- endometriosis
- breast cancer
what is the administration of androgen suppressors
IM or SC injection every 1, 3, 4, or 6 months
what is an example of androgen receptor inhibitors
cyproterone acetate
mech of action for androgen receptor inhibitors
- androgen receptor competitive antagonist
- progestin action
what are androgen receptor inhibitors used to treat
- prostatic carcinoma
- precocious puberty in boys
- acne
- hirsutism and virilization in women
adverse effects of androgen receptor inhibitors
hepatotoxic
administration of androgen receptor inhibitors
oral
male oral contraceptive: gossypol
- from seeds in cotton plant
- inhibits sperm production
- efficacy comparable to female OCC
- adverse effects: irreversibility, hypokalemia
