ESTROGENS AND ANDROGENS

Estrogens Natural: Estradiol, estrone & estriol Conjugated: premarin (estrone and equillin) Steroidal synthetic: Mestranol & Ethinyl estradiol Non-steroidal synthetic: Diethylstilbesterol Rationale for synthetic: to ↑ oral-bioavailability, half-life and ↑ feedback inhibition on FSH & LH

Estradiol – Transdermal patch, IM Oral – Premarin ( Estrone + Equilin) , Estinyl estradiol , Mestranol Excretion - Renal

Estrogens: Clinical Uses Contraception: ↓ feedback release of gonadotropins Female Hypogonadism (estrogen + progestin) or ovarian failure Estrogens for hormone replacement therapy in menopausal women to ↓ bone resorption Uterine bleeding Dysmenorrhea Men with androgen dependent prostate cancer to slow the growth of the cancer cell.

Endometrial hyperplasia Increased skin pigmentation SIDE EFFECT: Nausea Breast tenderness Endometrial hyperplasia Increased skin pigmentation Increased blood coagulation at high doses Increased risk of endometrial cancer unless progestin is added Breakthrough bleeding DES clear cell adenocarcinoma of vagina in females exposed to DES in utero. Estrogen increases melanin Increase factor 2, 7, 9 & 10 as well as decrease antithrombin III

Contraindicated Patients: With estrogen-dependent neoplasm (e.g. endometrial carcinoma) At higher risk for or with breast carcinoma that are estrogen dependent Predisposed to thromboembolic disease

SELECTIVE ESTROGEN RECEPTOR MODULATOR (SERMS) Are non-steroidal compounds that bind to estrogen receptors. They can act as either agonist, partial agonists and antagonists depending on the tissue

Tamoxifene: Has various actions depending on the tissue Bone: agonist to prevent bone resorption Breast: antagonist Endometrium: a partial agonist with the risk of increasing endometrial cancer USES: estrogen dependent breast cancer SE: Hot flushes, nausea and vomiting

Raloxifene Bone: agonist Uterus and breast: antagonist USES: prophylaxis of postmenopausal osteoporosis. SE: increased risk of DVT, pulmonary embolism

Clomiphene MOA: ↓ feedback inhibition→ ↑FSH and LH USE: for infertility caused by anovulatory cycle such as those seen in patients with PCOS Side effect: multiple pregnancies, ovarian enlargement

ANTI ESTROGENS Anastrozole: MOA: is an aromatase inhibitor, resulting in decreased estrogen synthesis USE: estrogen-dependent postmenopausal breast cancer.

Progestin's Progestins can be androgenic and antiestrogenic in action Progesterone: major natural progesterone Medroxyprogesterone Norethindrone 17α-Hydroxyprogesterone Norgestrel Desogestrel: devoid of androgenic and antiestrogenic actions

Clinical Uses: Progestins Major uses: hormone contraception : ↑ feedback inhibition esp LH → no ovulation hormone replacement treatment along with estrogen to decrease endometrial cancer dysmenorrhea

Adverse Effects: Progestins reduce plasma HDL ↑LDL Breakthrough bleeding Acne, weight gain and hirsutism (androgenic effect)

ANTIPROGESTIN Mifepristone (RU-486): Used as an abortifacient, administered with misoprostol (PGE₁) Also an antiglucocorticoid SIDE EFFECT: bleeding, GI effects(nausea, vomiting) and abdominal pain

Hormonal Contraception Progestins (Mini pill) only (norethindrone or norgestrel) Estrogens and progestins (combination pills) Progestin implants Post-coital contraception uses estrogen (mestranol or etinyl estradiol) Mechanism of Action: contraception ovulation-inhibition by suppressing gonadotropins change in cervical mucus(progesterone)

Drug interaction: p450 inducers ↓ contraceptive effectiveness Can result in unwanted pregnancies

Combined oral contraceptive pill ADVANTAGE DISADVANTAGE Reliable (<1% failure) Taken daily ↓ risk of endometrial and ovarian cancer No protection against STDs ↓ pelvic infections ↑ triglycerides ↓ risk of osteoporosis Depression, weight gain, nausea, hypertension No dysmenorrhea Hypercoagulable state

SIDE EFFECTS ESTROGENS: Nausea Bloating Headache Mastalgia Increase skin pigmentation Weight gain Breakthrough bleeding Withdrawal bleeding

PROGESTIN: Weight gain Hirsutism Acne Increase LDL

Adverse Effects of combined ocps Venous Thromboembolic Disease breakthrough bleeding Withdrawal bleeding RISK FACTORS: Smoking, Increased age

ANDROGENS Testosterone - Cypionate, Enanthate,Propionate dihydrotestosterone Fluoxymesterone Danazol androstenedione Nandrolone

USES: Male hypogonadism For anabolic actions to increase muscle mass Illicit use in athletes

Replacement therapy in men Acne excessive libido & erections, increased muscle & bone mass, aggravation of pre existing prostate cancer.   Reduce plasma HDL and increase LDL

Gynecological Disorders: Androgens Danazol used in the treatment of endometriosis which is the growth of endometrial tissue outside the uterus, especially in the pelvis.

SIDE EFFECTS OF ANDROGENS SE: Excessive masculinization Premature closure of epiphysis Aggression Dependence and abuse Depression of menses and hirsutism in women

Contraindications: Androgenic Steroids Pregnant women: its teratogenic Children Androgens - Not used in children Men with prostatic carcinoma

Anti-Androgen Cyproterone acetate Flutamide Finasteride

Androgen Suppression & Antiandrogens Symptomatic Management of prostatic carcinoma Management of BPH

Antiandrogens Finasteride: Inhibits 5 alpha reductase Conversion Inhibitors Finasteride: Inhibits 5 alpha reductase decreases dihydrotestosterone levels in the prostate Uses – BPH to reduce the size of the prostate and male pattern baldness Has been replaced by α1 blockers in the symptomatic treatment of BPH DHT causes hair loss and prostate enlargement

Antiandrogens Competitive androgenic Receptor Inhibitors: Cyproterone & Cyproterone acetate Clinical use: Women - hirsutism Men - reduction of sexual drive

Antiandrogens Flutamide Competitive inhibitor of androgens Used in androgen receptor positive Prostatic Carcinoma Testosterone causes the cancer cell to grow more rapidly

Bicalutamide Effective orally for the treatment of metastatic prostatic cancer.