Professional Documents
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Reproductive
Reproductive
Reproductive
REPRODUCTIVE—PHARMACOLOGY
Degarelix -
Goserelin –/+
Leuprolide
Anterior
pituitary
LH
FSH
LH LH
Ovary FSH Testis
Oral contraceptives
Danazol -
Ketoconazole
Danazol - P-450c17 - Ketoconazole
Spironolactone
Tamoxifen
Raloxifene
–/+ Androgen-receptor Flutamide
complex
- Cyproterone
Spironolactone
Goserelin, leuprolide
MECHANISM GnRH analogs. When used in pulsatile Leuprolide can be used in lieu of GnRH.
fashion act as GnRH agonists. When used
in continuous fashion first transiently act as
GnRH agonists (tumor flare), but subsequently
act as GnRH antagonists (downregulate
GnRH receptor in pituitary FSH and
LH).
CLINICAL USE Uterine fibroids, endometriosis, precocious
puberty, prostate cancer, infertility.
ADVERSE EFFECTS Hypogonadism, libido, erectile dysfunction,
nausea, vomiting.
Degarelix
MECHANISM GnRH antagonist. No start-up flare.
CLINICAL USE Prostate cancer.
ADVERSE EFFECTS Hot flashes, liver toxicity.
Hormone replacement Used for relief or prevention of menopausal symptoms (eg, hot flashes, vaginal atrophy),
therapy osteoporosis ( estrogen, osteoclast activity).
Unopposed estrogen replacement therapy risk of endometrial cancer, progesterone/progestin is
added. Possible increased cardiovascular risk.
Combined Progestins and ethinyl estradiol; forms include pill, patch, vaginal ring.
contraception Estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge. No estrogen surge no
LH surge no ovulation.
Progestins cause thickening of cervical mucus, thereby limiting access of sperm to uterus.
Progestins also inhibit endometrial proliferation endometrium is less suitable to the
implantation of an embryo.
Adverse effects: breakthrough menstrual bleeding, breast tenderness, VTE, hepatic adenomas.
Contraindications: smokers > 35 years old ( risk of cardiovascular events), patients with risk of
cardiovascular disease (including history of venous thromboembolism, coronary artery disease,
stroke), migraine (especially with aura), breast cancer, liver disease.
Tocolytics Medications that relax the uterus; include terbutaline (β2-agonist action), nifedipine (Ca2+ channel
blocker), indomethacin (NSAID). Used to contraction frequency in preterm labor and allow
time for administration of steroids (to promote fetal lung maturity) or transfer to appropriate
medical center with obstetrical care.
Danazol
MECHANISM Synthetic androgen that acts as partial agonist at androgen receptors.
CLINICAL USE Endometriosis, hereditary angioedema.
ADVERSE EFFECTS Weight gain, edema, acne, hirsutism, masculinization, HDL levels, hepatotoxicity, idiopathic
intracranial hypertension.
Testosterone, methyltestosterone
MECHANISM Agonists at androgen receptors.
CLINICAL USE Treat hypogonadism and promote development of 2° sex characteristics; stimulate anabolism to
promote recovery after burn or injury.
ADVERSE EFFECTS Masculinization in females; intratesticular testosterone in males by inhibiting release of LH (via
negative feedback) gonadal atrophy. Premature closure of epiphyseal plates. LDL, HDL.
Antiandrogens
Finasteride 5α-reductase inhibitor ( conversion of Testosterone 5α-reductase
DHT (more potent).
testosterone to DHT). Used for BPH and
male-pattern baldness. Adverse effects:
gynecomastia and sexual dysfunction.
Flutamide, Nonsteroidal competitive inhibitors at androgen
bicalutamide, receptors. Used for prostate carcinoma.
apalutamide,
enzalutamide
Ketoconazole Inhibits steroid synthesis (inhibits 17,20
desmolase/17α-hydroxylase). Used in PCOS to reduce androgenic symptoms.
Spironolactone Inhibits steroid binding, 17,20 desmolase/17α- Both can cause gynecomastia and amenorrhea.
hydroxylase.
Tamsulosin α1-antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for α1A/D
receptors (found on prostate) vs vascular α1B receptors.
Minoxidil
MECHANISM Direct arteriolar vasodilator.
CLINICAL USE Androgenetic alopecia (pattern baldness), severe refractory hypertension.