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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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