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Control of Female Hormones: Overview
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Control of Male Hormones: Overview
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Leuprolide
- Mechanism:
- -GnRH analog
- -agonist properties when used in a pulsatile fashion
- -antagonist properties when used in continuous fashion (↓FSH, LH)
- Clinical Use:
- -infertility (pulsatile)
- -prostate cancer (continuous - use with flutamide)
- -uterine fibroids (continuous)
- -precocious puberty (continuous)
- Toxicity:
- -antiandrogen
- -nausea
- -vomiting
"Leuprolide can be used in lieu of GnRH"
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Testosterone, Methyltestosterone
- Mechanism:
- -agonist at androgen receptors
- Clinical Use:
- -hypogonadism
- -promotes development of secondary sex characteristics
- -stimulate anabolism to promote recovery after burn or injury
- Toxicity:
- -causes masculinization in females
- -reduces intratesticular testosterone in males by inhibiting release of LH → gonadal atrophy
- -premature closure of epiphyseal plates
- -↑ LDL
- -↓ HDL
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Antiandrogens
- Finasteride
- Flutamide
- Ketoconazole
- Spironolactone
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Finasteride
- Mechanism:
- -a 5α-reductase inhibitor (decreased conversion of testosterone to DHT)
- Clinical Use:
- -BPH
- -Male Pattern Baldness
To prevent male-pattern hair loss, give a drug that will encourage female breast growth
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Flutamide
- Mechanism:
- -nonsteroidal competitive inhibitor of androgens at the testosterone receptor
- Clinical Use:
- -prostate carcinoma
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Ketoconazole
- Mechanism:
- -inhibits steroids synthesis (inhibits 17,20 desmolase)
- Clinical Use:
- -PCOS (prevent hirsutism)
- Toxicity:
- -gynecomastia
- -amenorrhea
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Spironolactone
- Mechanism:
- -inhibits steroids binding (MC R antagonist that also affects androgen receptor)
- Clinical Use:
- -PCOS (prevent hirsutism)
- Toxicity:
- -gynecomastia
- -amenorrhea
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Estrogens (ethinyl estradiol, DES, mestranol)
- Mechanism:
- -bind estrogen receptors
- Clinical Use:
- -hypogonadism
- -ovarian failure
- -menstrual abnormalities
- -HRT in postmenopausal women
- -in men with androgen-dependent prostate cancer
- Toxicity:
- -increased risk of endometrial cancer
- -bleeding in postmenopausal women
- -vaginal clear cell adenocarcinoma in women exposed to DES in utero
- -increased risk of thrombi
- Contraindications:
- -ER positive breast cancer
- -history DVTs
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Selective Estrogen Receptor Modulators (SERMs)
- Clomiphene
- Tamoxifen
- Raloxifene
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Clomiphene
- Mechanism:
- -partial agonist at estrogen receptors in hypothalamus
- -prevents normal feedback inhibition and increased release of LH and FSH from pituitary, which stimulates ovulation
- Clinical Use:
- -infertility
- -PCOS
- Toxicity:
- -hot flashes
- -ovarian enlargement
- -multiple simultaneous pregnancies
- -visual disturbances
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Tamoxifen
- Mechanism:
- -estrogen receptor antagonist on breast tissue
- Clinical Uses:
- -treat and prevent recurrence of ER-positive breast cancer
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Raloxifene
- Mechanism:
- -estrogen agonist on bone
- -reduces reabsorption of bone
- Clinical Uses:
- -osteoporosis
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Hormone Replacement Therapy
- Clinical Uses:
- -relief or prevention of menopausal symptoms (hot flashes, vaginal atrophy)
- -osteoporosis (increased estrogen decreases osteoclast activity)
- Toxicity:
- -unopposed ERT increases the risk of endometrial cancer (add progesterone)
- -possible increased cardiovascular risk
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Anastrozole/Exemestane
- Mechanism:
- -aromatase inhibitors
- Clinical Uses:
- -used in postmenopausal women with breast cancer
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Progestins
- Mechanism:
- -bind progesterone receptors
- -reduce growth and increase vascularization of endometrium
- Clinical Use:
- -used in OCPs
- -used in the treatment of endometrial cancer and abnormal uterine bleeding
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Mifepristone (RU-486)
- Mechanism:
- -competitive inhibitor of progestins and progesterone receptor
- Clinical Use:
- -termination of pregnancy
- -administered with misoprostol (PGE1)
- Toxicity:
- -heavy bleeding
- -GI effects (N/V, anorexia)
- -abdominal pain
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Oral Contraception (synthetic progestins, estrogen)
- Mechanism:
- -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 (limits access of sperm to uterus)
- -progestins also inhibits endometrial proliferation (makes it less suitable for implantation)
- Clinical Use:
- -contraception
- Contraindications:
- -smokers > 35 years (increased risk of CV events)
- -hx of thromboembolism and stroke
- -hx of estrogen dependent tumor
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Terbutaline
- Mechanism:
- -β2 agonist
- -relaxes uterus
- Clinical Use:
- -reduce premature uterine contractions
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Tamsulosin
- Mechanism:
- -α1-antagonist
- -inhibits smooth muscle contraction
- -selective for α1AD receptors on prostate (not vascular receptors)
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Sildenafil, Vardenafil
- Mechanism:
- -inhibit PDE5
- -causes increased cGMP → smooth muscle relaxation in corpus cavernosum
- -increases blood flow and penil erection
- Clinical Use:
- -erectile dysfunction
- Toxicity:
- -HA
- -flushing
- -dyspepsia
- -impaired blue-green color vision
- -risk of life-threatening hypotension in patients taking nitrates
"Sildenafil and vardenafil fill the penis"
"Hot and sweaty" but then Headache, Heartburn and Hypotension"
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Danazol
- Mechanism:
- -synthetic androgen that acts as partial agonist at androgen receptors
- Clinical Use:
- -endometriosis
- -hereditary angioedema
- Toxicity:
- -weight gain
- -edema
- -acne
- -hirsutism
- -masculinization
- -decreased HDL levels
- -hepatotoxicity
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