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ESTROGENS AND ANDROGENS
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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
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• Estradiol – Transdermal patch, IM
• Oral – Premarin ( Estrone + Equilin) , Estinyl estradiol , Mestranol
• Excretion - Renal
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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.
• 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. 5
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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
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• 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
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Raloxifene
• Bone: agonist• Uterus and breast: antagonist• USES: prophylaxis of postmenopausal
osteoporosis.• SE: increased risk of DVT, pulmonary embolism
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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
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ANTI ESTROGENS
• Anastrozole:• MOA: is an aromatase inhibitor, resulting in
decreased estrogen synthesis• USE: estrogen-dependent postmenopausal
breast cancer.
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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
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Clinical Uses: Progestins Major uses:
• hormone contraception : ↑ feedback inhibition esp LH → no ovulation
• hormone replacement treatment along with estrogen to decrease endometrial cancer
• dysmenorrhea
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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
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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
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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 state18
SIDE EFFECTS• ESTROGENS:• Nausea• Bloating• Headache• Mastalgia• Increase skin pigmentation• Weight gain• Breakthrough bleeding• Withdrawal bleeding
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• PROGESTIN:• Weight gain• Hirsutism• Acne• Increase LDL
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Adverse Effects of combined ocps • Venous Thromboembolic Disease
• breakthrough bleeding• Withdrawal bleeding
• RISK FACTORS: Smoking, Increased age
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ANDROGENS
• Testosterone - Cypionate, Enanthate,Propionate
• dihydrotestosterone• Fluoxymesterone • Danazol • androstenedione • Nandrolone
• USES:• Male hypogonadism• For anabolic actions to increase muscle mass• Illicit use in athletes
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Replacement therapy in men • Acne• excessive libido & erections, • increased muscle & bone mass, • aggravation of pre existing prostate cancer.• Reduce plasma HDL and increase LDL
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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
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Contraindications: Androgenic Steroids• Pregnant women: its teratogenic
• Children Androgens - Not used in children
• Men with prostatic carcinoma
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Anti-Androgen
• Cyproterone acetate • Flutamide • Finasteride
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Androgen Suppression & Antiandrogens
Androgen Suppression:
• Symptomatic Management of prostatic carcinoma
• Management of BPH
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Antiandrogens 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
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Antiandrogens
Competitive androgenic Receptor Inhibitors: • Cyproterone & Cyproterone acetate
Clinical use: • Women - hirsutism• Men - reduction of sexual drive
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Antiandrogens
Flutamide
• Competitive inhibitor of androgens• Used in androgen receptor positive Prostatic
Carcinoma
Bicalutamide
• Effective orally for the treatment of metastatic prostatic cancer.
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