Short acting: Gonadotropin-releasing hormone (GnRH)

Use: Treating infertility, induce ovulation in women with hypothalamic amenorrhea, diagnostic for hypogonadotropic hypogonadism, delayed puberty, stimulate spermatogenesis in men with hypogonadotropic hypogonadism.

Mechanism: Short acting agonist of GnRH that is pulsed IV to stimulate FSH and LH production and release; NOT IN USE ANYMORE

PHK: SC injections, pump

Side effects: less likely to cause ovarian hyperstimulation and multiple births than direct administration of LH and FSH

Contraindications: less likely o cause ovarian hyperstimulation and multiple irths than direct administration of LH and FSH

Long Acting: Gonadotropin-releasing hormone (GnRH)

Use: Prostate CA (reduce androgen production), precodious puberty, endometriosis, polycystic ovarian disease, uterine leiomyomas (fibroids), chemical castration

Mechanism: Continuous administration of these long-acting GnRH agonists causes an initial surge and then an ultimate inhibition of gonadotropin release

Adverse effects: Menopausal symptoms, Testicular atrophy, ovarian cysts, metastatic prostate cancer (problems during start of Tx; use antiandrogen)

Contraindications: Pregnancy and breast feeding

Other drugs: Goserelin (Zoladex^®)

Nafarelin (Synarel^®)

GnRH Antagonist

Use: Suppress endogenous LH and FSH for assisted reproductive technologies (ART), endometriosis and uterine fibroids; 4-5 days of therapy (short)

Mechanism: competitive GnRH receptor antagonist, suppressses LH at lower doses and FSH at higher doses

PHK: Inject SC by pt

Side effects: 

Other Drugs: Ganirelix (generic)

Folicle stimulating hormone (FSH)

Tx of infertility mechanism: stimulates development of ovarian follicles in women; stimulates spermatogenesis in men

Other Drugs: Follitropin alfa (Gonal F^®) - rFSH

Follitropin beta (Follistim^®)- rFSH

Gonadotropin mixtures (used as FSH)

Tx of infertility mechanism: hCG given to increase testosterone, then hMG (FSH) injected for several months, >50% of men become fertile after tx.; induces spermatogenesis

Use: Pituitary/hypothalamic hypogonadism with infertility, increase Testosterone for reasons other than fertility

adverse effects: ovarian enlargement, ovarian hyperstimulation syndrom, multiple births, gynocomastia

Luteinizing hormone

Tx of infertility mechanism: hCG given to increase testosterone, then hMG (FSH) injected for several months, >50% of men become fertile after tx.; induces spermatogenesis

PHK: Longer half life then LH

Effects: Required for progesterone synthesis  in luteal cells; Stimulates testosterone production in leydig cells of testes

Use: Pituitary/hypothalamic hypogonadism with infertility, increase Testosterone for reasons other than fertility

adverse effects: ovarian enlargement, ovarian hyperstimulation syndrom, multiple births, gynocomastia

Other drugs: rhCG (Chorionic gonadotropin alfa, Ovidrel^®)

Lutropin alfa (Luveris^®, Lhadi^®) - rLH

Estrogen

Physiological effect: follicle development, endometrial cell division and growth, vaginal epithelium proliferation, endocervical gland regulation, breast develpment, puberty, close epihyses of long bones, maintain bone mass/prevent bone resopriton, increases synth of clotting protines, increase platelet adhesivenes, synth of liver proteins and increase HDL

Use: Oral contraceptives (combos)

Side effects: Migraine, thromboembolism, blood clotting

Absolute contraindications: Estrogen dependent neoplasms, carcinoma of the breast, Hx of thromboembolic disorders

Relative contraindications: undiagnosed genital bleeding, unctontrolled HTN, liver disease, smoking, pregnancy

Other drugs: mestranol Estradiol (Estrace®, Estraderm®)

Conjugated estrogens (Premarin®, Cenest®) - hormone replacement therapy

Esterified estrogens (Estratab®, Menest®) - hormone replacement therapy

Nonsteroidal Estrogen

Physiological effect: decrease dysfunctional uterine bleeding

Uses: Primary hypogonadism, postmenopausal hormone replacement, oral contraceptives

Side effects: Migrain Headaches, thromboembolism; blood clotting

Antiestrogen

Mechanism: Agonist in uterus and bone (prevent bone loss)/ANTAgonist in breast

Use: DOC estrogen dependent breast CA; DOES NOT relieve host flashes

Side effects: Increased risk of uterine cancer

Other drugs: Toremifene (Fareston®) - increases HDL

Antiestrogen

Mechanism: Antagonist in breast and uterus; agonist in bone and liver

Uses: Postmenopausal osteoporosis

Side effects: Hot flashes, DVT, leg cramps

Antiestrogen

Mechanism: Antagonist in hypothalamus; agonist elsewhere

Use: Infertility; used to stimulate secretion of LH and FSH

Side effects: Multiple pregnancies; hot flashes, headaches, constipation

Antiestrogen

Mechanism: Pure estrogen receptor antagonist

Uses: Pts with tamoxifen-resistant tumors

Side effects: hot flashes, GI symptoms, headache, back pain, pharyngitis

Aromatase Inhibitors

Use: DOC tx for breast CA in postmenopausal women; 2nd line tx of advanced breast CA in postmenopause women whose disease progressed during tamoxifen therapy

Adverse: menopausal symptoms

Pregnancy category X

Other Drugs: Letrozole (Femara®) Exemestane (Aromasin®)

Progestins

Physiologic effect: Uterus ->secretory state, needed to maintain pregnancy; endocervical glands->regulates cervical mucus comp.; Breasts: lobuloalveolar developmen, pregnancy, puberty; thermogenic action

Use: Oral contraceptives; prevention of endometrial hyperplasia

Side effects: increased BP, reduced HDL, depression, drowsiness

Other drugs: Medroxyprogesterone (Provera®)

Megestrol (Megace®)

Norethindrone (Aygestin®)

Norgestrel (Ovrette®)

Levonorgestrel (Plan B®)

Desogestrel (Desogen®)

Norgestimate

Anti-progestin

Mechanism: Blocks progestin binding to the progesterone receptor

Use: Pregnancy termination, also antagonizes glucocorticoid receptor

Contraindication = pregnancy or breastfeeding

Anti-progestin

Mechanism: Weak progestin, androgen and glucocorticoid that suppresses ovarian function

Use: Tx endometriosis

Combo Oral Contraceptives

Has the ability to reduce water retention, thus it is the only combo pill that is FDA approved for reducing PMDD symptoms (premenstrual dysphoric disorder)

Benefits: decreases endometrial and ovarian CA

Adverse: weight gain, depression, nausea, edema, clotting, migrain, MI, teratogeneis

Androgen

Mechanism: converted to DHT by 5a-reductase; bind androgen receptors in nuclei; DHT more potent

Physiological action: virilizing (androgenic) effects = spermatogenesis, sexual development; anabolic effects = bone density, increased AA to muscle, increased RBC mass, antagonize catabolic glucocorticoids; puberty

Uses: testicular deficiency, aging/impotence, anemia; in women = female hypopituitarism; debilitated post op pts with negative nitrogen balance

Side effects: prostate CA?; decreases test production, decreased spermatogenesis; in women = maculinization, pseudohermpahroditism; both = oily skin, acne, decreased HDL, psychological changes (agression etc.)

Other drugs: Methyltestosterone (generic)

Fluoxymesterone (Androxy®)

Oxymethalone (ANADROL-50®)

Oxandrolone (Oxandrin®)

Androgen synthesis inhibitor (antifungal)

Uses: prostate CA; hirsutism and male pattern baldness

Role in Prostate CA Tx: decreases androgen synth. to counter prostate CA

Androgen synthesis inhibitor

Uses: Prostate cancer, precocious puberty

Role in Prostate CA Tx: Reduces 17a-OH activity

Anti-androgen

Uses: Prostate CA, precocious puberty, hirsutism/male pattern baldness

Role in prostate CA Tx: androgens precipitate the CA, this counters it

Other drugs: Bicalutamide (Casodex®)

Nilutamide (Nilandron®)

Spironolactone (Aldactone®)

5α-reductase inhibitor

Use: Prostate growth and male pattern baldness (both caused by DHT?); BPH

Inhibits the enzyme that converts testosterone to DHT (most potent endogenous androgen)

Contraindications: teratogenic

Other Drugs: Dutasteride (Avodart®)