Estrogens |
Ethinyl estradiol | Activation of estrogen receptors leads to changes in the rates of transcription of estrogen-regulated genes | See Table 40–1 | Oral, parenteral, or transdermal administration • metabolism relies on cytochrome P450 systems • enterohepatic recirculation occurs | Moderate toxicity: Breakthrough bleeding, nausea, breast tenderness Serious toxicity: Thromboembolism, gallbladder disease, hypertriglyceridemia, migraine headache, hypertension, depression In postmenopausal women: breast cancer, endometrial hyperplasia (unopposed estrogen) Combination with cytochrome P450 inducer can lead to breakthrough bleeding and reduced contraceptiveefficacy |
Mestranol: a prodrug that is converted to ethinyl estradiol, contained in some contraceptives Estrogen esters (eg, estradiol cypionate): long-acting estrogens administered IM and used for hypogonadism in young females |
Progestins |
Norgestrel | Activation of progesterone receptors leads to changes in the rates of transcription of progesterone-regulated genes | See Table 40–1 | Oral, parenteral, or transdermal administration • metabolism relies on cytochrome P450 systems • enterohepatic recirculation occurs | Weight gain, reversible decrease in bone mineral density (high doses) |
Progesterone derivatives: medroxyprogesterone acetate, megestrol acetate Older 19-nortestosterone derivatives: norethindrone, ethynodiol Newer 19-nortestosterone derivatives: desogestrel, norelgestromin, norgestimate, etonogestrel Spironolactone derivative: drospirenone |
Antiestrogens |
SERMS |
Tamoxifen | Estrogen antagonist actions in breast tissue and CNS • estrogen agonist effects in liver and bone | Prevention and adjuvant treatment of hormone-responsive breast cancer | Oral administration | Hot flushes, thromboembolism, endometrial hyperplasia |
Toremifene: similar to tamoxifen Raloxifene: approved for osteoporosis and prevention of breast cancer in selected patients; antagonist effects in breast, CNS, and endometrium and agonist effects in the liver Clomiphene: used for ovulation induction; antagonist effect in pituitary increases gonadotropin secretion |
Receptor antagonist |
Fulvestrant | Estrogen receptor antagonist in all tissues | Adjuvant treatment of hormone-responsive breast cancer that is resistant to first-line antiestrogen therapy | Intramuscular administration | Hot flushes, headache, injection site reactions |
Aromatase inhibitors |
Anastrozole | Reduces estrogen synthesis by inhibiting aromatase enzyme | Adjuvant treatment of hormone-responsive breast cancer | Oral administration | Hot flushes, musculoskeletal disorders, reduced bone mineral density Joint symptoms (arthralgia, arthrosis, arthritis, cervical spondylosis, osteoarthritis, and disk herniation) |
Letrozole: similar to anastrozole Exemestane: irreversible aromatase inhibitor |
GnRH agonist |
Leuprolide | See Chapter 37 | | | |
GnRH receptor antagonist |
Ganirelix, cetrorelix | See Chapter 37 | | | |
Other |
Danazol | Weak cytochrome P450 inhibitor and partial agonist of progestin and androgen receptors | Endometriosis, fibrocystic breast disease | Oral administration • drug interactions due to cytochrome P450 inhibition | Acne, hirsutism, weight gain, menstrual disturbances, hepatic dysfunction |
Antiprogestin |
Mifepristone | Progestin and glucocorticoid receptor antagonist | Used in combination with a prostaglandin (eg, misoprostol) for medical abortion | Oral administration | Gastrointestinal disturbances (mostly due to coadministration of misoprostol) • vaginal bleeding, atypical infection |
Androgens |
Testosterone | Androgen receptor agonist | Male hypogonadism • weight gain in patients with wasting syndromes | Transdermal, buccal, subcutaneous implant | In females, virilization In men, high doses can cause gynecomastia, testicular shrinkage, infertility |
Fluoxymesterone, methyltestosterone: oral androgens |
Testosterone esters (eg, testosterone cypionate): long-acting androgens for parenteral administration |
Anabolic steroids (eg, oxandrolone, nandrolone decanoate): increased ratio of anabolic-to-androgenic activity in laboratory animals, cholestatic jaundice, liver toxicity |
Antiandrogens |
5α-reductase inhibitors |
Finasteride | Inhibition of 5α-reductaseenzyme that converts testosterone to dihydrotestosterone | Benign prostatic hyperplasia (BPH), male-pattern hair loss | Oral administration | Rarely, impotence, gynecomastia |
Dutasteride: Similar to finasteride |
Receptor antagonists |
Flutamide | Competitive inhibition of androgen receptor | Advanced prostate cancer | Oral administration | Gynecomastia, hot flushes, impotence, hepatoxicity |
Bicalutamide, nilutamide: similar to flutamide but lower risk of hepatotoxicity Spironolactone: mineralocorticoid receptor antagonist used mainly as a potassium-sparing diuretic (see Chapter 15); also has androgen-receptor antagonist activity, used for the treatment of hirsutism |
GnRH agonist |
Leuprolide | See Chapter 37 | | | |
GnRH receptor antagonist |
Abarelix, degarelix | See Chapter 37 | | | |
Synthesis inhibitor |
Ketoconazole (see Chapter 48) | Inhibition of cytochrome P450 enzymes involved in androgen synthesis | Advanced prostate cancer that is resistant to first-line antiandrogen drugs | Oral administration | Interferes with synthesis of other steroids • many drug interactions due to cytochrome P450 inhibition |