Repro Pharma: Estrogens & Androgens, Contraceptives PDF

REPRO PHARMA Chapter 25 - Estrogens & Androgens Estrogen: Estradiol is the most potent estrogen produced by ovary & is principal estrogen in premenopausal women. Estrone is primary circulating estrogen after menopause & is generated by conversion of DHEA in adipose tissue and has 1/3rd potency than...

REPRO PHARMA Chapter 25 - Estrogens & Androgens Estrogen: Estradiol is the most potent estrogen produced by ovary & is principal estrogen in premenopausal women. Estrone is primary circulating estrogen after menopause & is generated by conversion of DHEA in adipose tissue and has 1/3rd potency than that of estradiol. 5 Estriol is produced during pregnancy synthesized by placenta. '2 MoA: RNA synthesis by interacting with nuclear chromatin. TE: Postmenopausal HT: ch Primary indication is menopausal symptoms & vaginal atrophy - Women with intact uterus - progestogen is added which reduces risk of endometrial carcinoma at - Women with only urogenital symptoms should be treated with vaginal rather than systemic estrogen. B Contraception: Combination of estrogen & progesterone used Hypogonadism: ur Development of sec: sex characteristics in young women with primary hypogonadism. Pharmacokinetics: m Ethinyl estradiol & estradiol valerate has higher potency than natural estrogens. Adverse effects: i Nausea, breast tenderness, hypertension, headache, fluid retention, inc: risk of Ta myocardial infarction, thromboembolism and breast & endometrial cancer. Selective Estrogen Receptor Modulators: Tamoxifen, Raloxifene, Bazedoxifene, Clomiphene & Ospemifene MoA: Tamoxifen - Antagonist of estrogen receptor at breast tissue & agonist at endometrium. Raloxifene - Antagonist of estrogen receptor at breast tissue, estrogen agonist at bone thereby dec: bone resorption. No action on endometrium. Bazedoxifene - estrogen antagonist on the uterus. Clomiphene - Partial estrogen agonist & interferes with negative feedback on hypothalamus thereby stimulating ovulation. TE: Tamoxifen - Treatment of metastatic breast cancer. Tamoxifen & Raloxifene - Prophylactic therapy to reduce risk of breast cancer in high-risk patients. Raloxifene - Prevention & Treatment of osteoporosis in postmenopausal women. Clomiphene - Treatment of infertility. 5 Ospemifene - Treatment of dyspareunia related to menopause. Bazedoxifene along with conjugated estrogens - Treatment of menopausal symptoms in '2 women with intact uterus. ch AE: Tamoxifen - Hot flashes, nausea, endometrial hyperplasia & malignancy. Raloxifene - Hot flashes & leg cramps, inc: risk of DVT and pulmonary embolism. - CI in patients with a history of venous thromboembolism. at Clomiphene - Headache, nausea, vasomotor flushes, visual disturbances & ovarian enlargement & inc: risk for multiple gestation. Ospemifene - Endometrial growth. B Progestogens: MoA: ur Development of secretory endometrium & maintenance after conception. Prevent ovulation by inhibiting the production of gonadotropin. TE: m Desogestrel, dienogest, drospirenone, levonorgestrel, norethindrone, norgestrel - Contraception. Medroxyprogesterone acetate - Contraception & postmenopausal HT. i Ta Progestogens are also used for control of dysfunctional uterine bleeding, treatment of dysmenorrhea & management of endometriosis and infertility. AE: Headache, depression, weight gain & changes in libido. Those derived from 19-nortestosterone (norethindrone, norethindrone acetate, norgestrel, levonorgestrel) - Acne & hirsutism. - Norgestimate & drospirenone - preferred for women with acne. Drospirenone - hyperkalemia Antiprogestin: Mifepristone (RU-486) MoA: Progesterone antagonist TE: Termination of pregnancy & is mostly combined with misoprostol (causes uterine contractions) AE: Abdominal pain, uterine bleeding & possibility of incomplete abortion. 5 Contraceptives: Oral: '2 Combination of estrogen & progestin is the most common type of oral contraceptive. - Most common estrogen used is ethinyl estradiol. ch - Most common progestins used - norethindrone, norethindrone acetate, levonorgestrel, desogestrel, norgestimate & drospirenone. - 21-24 days with 4-7 days placebo (total regimen 28 days) Transdermal patch: Ethinyl estradiol & norelgestromin at - Applied each week for 3 weeks with no patch on the 4th week. B - Less effective in women with weight greater than 90 kg. Vaginal ring: ur Ethinyl estradiol & etonogestrel - Left in vagina for 3 weeks & taken out on 4th. Progestin-only pills (Mini-pill): m Norethindrone - Used in patients who are breast-feeding or with contraindications to estrogen-containing products. i Ta Injectable progestin: Medroxyprogesterone acetate - Injected IM or SC every 3 months AE - Weight gain, amenorrhea & bone loss. - Shouldn't be continued for more than 2 years. Progestin implants (along with IUDs- Long acting reversible contraceptives [LARC]) Etonogestrel - Offers contraception for 3 years. AE- Irregular menstrual bleeding. Progestin IUD: Levonorgestrel - Offers contraception for 3-5 years - suitable method for women who desire long-term contraception. - CI in patients with PID or history of ectopic pregnancy. AE: Heavy menstrual bleeding. 5 - Copper IUD provides contraception for 10 years. '2 Postcoital contraception: HD of levonorgestrel - preferred within 72hrs. ch Ulipristal (progesterone agonist/antagonist) - indicated for emergency contraception within 5 days of unprotected intercourse. at MoA: Negative feedback which blunts release of FSH & inhibits LH secretion. Also thicken cervical mucus. B AE: Estrogens - Breast fullness, fluid retention, headache, nausea, hypertension. Progestins - Depression, acne, hirsutism, changes in libido, inc: risk of thromboembolism, thrombophlebitis, myocardial infarction & stroke. ur - Most commonly in women who are above 35 & smoke so progestin only pills are preferred in them. - Cervical cancer incidence increases in hormonal contraceptives. m - Oral CC are CI in presence of cerebrovascular & thromboembolic disease, estrogen-dependent neoplasms, liver disease & pregnancy. i Androgens: Ta MoA: Bind to specific nuclear receptor in target cell. TE: Used for treatment of primary hypogonadism or secondary hypogonadism. Treatment of chronic wasting associated with HIV or cancer. Unapproved use to inc: lean body mass, muscle strength & endurance in athletes & bodybuilders. These agents are classified as controlled substances especially DHEA is touted as anti aging hormone (performance enhancer). - Testosterone/methyltestosterone used along with estrogen for treatment of menopausal symptoms in women unresponsive to estrogen alone. Danazol - Treatment of endometriosis & fibrocystic breast disease. AE- Weight gain, acne, decreased breast size, deepening voice, inc: libido & inc: hair growth. RoA: Esters (testosterone cypionate/enanthate) - IM 5 Methyltestosterone & fluoxymesterone - Oral Oxandrolone & oxymetholone (17a-alkylated derivatives of DHT) - Oral '2 AE: Inc: serum LDL & lower serum HDL, fluid retention & peripheral edema, inc: risk of MI & ch stroke. Hepatic side effects with 17a-androgens & skin irritation with topical formulations. at Females - Masculinization, acne, growth of facial hair, deepening of voice, male pattern baldness & excessive muscle development. Menstrual irregularities do occur. - CI in pregnancy B Males- Priapism, impotence, dec: spermatogenesis, gynecomastia, cosmetic changes like females & prostatic hyperplasia. Children - abnormal sexual maturation & growth disturbances resulting from premature closure of epiphyseal plates. ur Athletes- Premature closing of epiphysis of long bones stunting growth. Reduction of testicular size, hepatic abnormalities, inc: aggression (roid rage) & major mood disorders. m Antiandrogens: Flutamide, bicalutamide, enzalutamide & nilutamide - competitive inhibitors i Used in treatment of prostate cancer. Ta Finasteride & dutasteride inhibit 5a-reductase & used for treatment of benign prostatic hyperplasia.