Transcript estrogens and androgens

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 ↑ oralbioavailability, 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
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slow the growth of the cancer cell.
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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.
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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
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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)
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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)
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• 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 state
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SIDE EFFECTS
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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
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USES:
Male hypogonadism
For anabolic actions to increase muscle mass
Illicit use in athletes
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Replacement therapy in men
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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.
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SIDE EFFECTS OF ANDROGENS
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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
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Bicalutamide
• Effective orally for the treatment of metastatic
prostatic cancer.
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