Sex hormones

a) Female sex hormones:

● Estrogens:
( Natural, Synthetic)
● Progestins
( Natural, Synthetic)
b) Male sex hormones:
Androgens: ( Natural, Synthetic)

Female sex hormones

Estrogens:
Natural estrogens:
◄ Esterone (E1)
◄ Estradiol (E2)
◄ Estreiol (E3)
Estradiol
● (main & more potent)
● Premenopausal period: Main source is ovaries.
● Postmenopausal & in males: is adipose tissue

Esterone and Estreiol

Produced in liver (mainly) from Estradiol, peripheral tissue ,testes and adrenal
cortex

Actions:
● growth and development of genital organs.
● proliferation of endometrium
● Estrogen induces formation of alkaline watery secretion from the cervix.
● Growth of breast with proliferation of ducts and stroma.
● Growth of pubic & axillary hair.
● Feminine body contour and behavior.
● anabolic effect similar to but weaker than testosterone.
● Βone formation
● ⬇LDL & cholesterol, and⬆ HDL & TAG
● Enhance blood coagulation
Uses:
1)Replacement therapy
● Primary ovarian failure (e.g. Turner’s syndrome).
● Secondary ovarian failure (menopause) for flushing, vaginal dryness and to
preserve bone mass.
2)Contraception.
3) Prostate cancer

Adverse effects: Contraindications:

1) major cause of postmenopausal bleeding. 1) Undiagnosed genital bleeding.
2) Breast tenderness is common. 2) Patients with breast cancer.
3) ⬆endometrial carcinoma. 3) Estrogen dependant neoplasm
4) ⬆incidence of vaginal & cervical cancer. (endometrial ca.).
5)⬆ incidence of cholestasis, gallstones 4) Liver disease.
6) Salt and water retention leading to edema 5) Thromboembolic disorders.

Antiestrogens
Tamoxifen:
● It has an anti estrogenic action on mammary tissue
● Used for palliative treatment of advanced or metastatic breast cancer.

Raloxifene
● It stimulates osteoblasts and inhibits osteoclasts.
● It is used for prevention and treatment of postmenopausal osteoporosis.

Clomiphene citrate:
It acts as a competitive inhibitor of estrogen at hypothalamic receptors ⬆GTH
✔️Ovaries enlarge and ovulation occurs.
Uses: ● Infertility in females.
● Oligospermia in males.

Anastrozole: Exemestane: Fulvestrant:

● used to treat breast cancer resistant to tamoxifen
 Progestins
Natural progestin:
● Progesterone (Pg)
Synthetic progestins:
Progesterone derivatives:
● Medroxyprogesterone acetate
● Megestrol acetate
● Hydroxyprogesterone caproate
● Norethindrone

Pharmacokinetics
● Progesterone is well absorbed from GIT.
● It has a high first pass metabolism in liver
● Metabolites excreted in urine as a glucuronide and sulfate conjugates.
● Most of synthetic progestins are metabolized slowly and more active.

Actions:
1. The main function of progesterone is to prepare uterus for implantation
of fertilized ovum and maintenance of pregnancy.
2. Cervix induces a viscid, scanty secretion.
3. Breast: progesterone causes proliferation of acini in the mammary gland.

Preparations:
• Hydroxyprogesterone caproate by IM route.
• Medroxy progesterone acetate given by oral or IM route.
• Norethindrone (Primolut N) is given orally.

Clinical uses☆☆
✔️ For contraception:
✔️ Combined with estrogen, to prevent endometrial hyperplasia and carcinoma.
✔️ For endometriosis.
✔️ Threatened abortion.
✔️ Dysmenorrhoea.
Adverse effects:
● Fluid retention, weight change.
● Irregular menstrual cycles
● Increased incidence of thromboembolism.☆

Antiprogesterone (Mifepristone):
✔️ Binds with Progesterone receptors. (partial agonist)
✔️ ⬆ sensitizes the uterus to the action of prostaglandins.
✔️ Its main use is to terminate early pregnancy in combination with a prostaglandin
✔️ Major adverse effect is prolonged bleeding.
Male Sex hormones (Androgens )

Natural androgens
●Testosterone
● Testosterone is rapidly metabolized in liver (no given orally)

Synthetic androgens
✔️ Methyl testosterone.
✔️Fluoxymesterone.
● Are less susceptible to metabolic degradation.

Actions
● Androgens are necessary for growth of genital organs and for appearance of
secondary sexual characteristics
● Needed for normal spermatogenesis & maturation.
● Development of skeleton & skeletal muscles (anabolic), it promotes muscle
building
● Increased erythropoiesis (↑erythropoietin).
● Increased LDL & decreased HDL.

Preparations
● Testosterone propionate, it is given by IM route.
● Methyltestosterone, by sublingual route.
● Fluoxymesterone, given by oral route (stable)
Clinical uses
● Replacement therapy in hypogonadal
● As a protein anabolic agent▪☆.
● Carcinoma of breast in premenopausal females may respond.
● For treatment of osteoporosis

Contraindications
● Carcinoma of prostate & male breast.
● Liver & kidney disease.
● During pregnancy.

Antiandrogens
1. Cyproterone acetate
2. Flutamide.
3. Finasteride.
4. Bicultamide and Nilutamide.
5. Spironolactone.
6. Ketoconazole.

Cyproterone acetate
• Has a partial agonist at Pg receptors.
• Decreases GTH Secretion.
Uses:
• Carcinoma of prostate.
• Precocious puberty.

Flutamide
• It is a potent antiandrogen.
• It causes gynaecomastia.
Uses:
• Cancer of prostate.
• Female hirsutism.

Finasteride
It inhibits 5-alpha reductase so the active form (dihydrotestosterone) not formed.
Uses:
• Cancer of prostate. (moderately effect)
• Female hirsutism.
Spironolactone
It is a competitive inhibitor of aldosterone; dihydrotestosterone
It is used in the treatment of hirsutism in females.

Bicalutamide & Nilutamide

Are potent antiandrogens, are used in the treatment of metastatic prostatic cancer.

Ketoconazole
It is an antifungal drug
It inhibits adrenal & gonadal steroid synthesis (at high doses).
It leading to gynaecomastia.

Anabolic steroids
These are synthetic androgens with high anabolic and lower androgenic activity.
Preparations:
1) Oxymetholone (given orally).
2) Stanozolol given by oral route .
3) Nandrolone phenylpropionate given by IM route.
Uses:
1) Osteoporosis
2) Catabolic state due to acute illness, trauma & major surgery.
4) Hypoplastic anemia.

Hormonal contraception
I) Female contraception types:
A) Oral.
B) Injectable.
C) Implants.
II) Male contraception

Oral female contraception

1) Combined pills:
● Contains low dose estrogen & progestin
● inhibition of ovulation.
● It is most effective (99-100% success rate). 1% failure rate ☆
● Tablets are taken daily for 21 day starting from 5th day of cycle
2) Sequential preparation:
3) Phased regimen:
4) Mini Pills:
● A low dose progestin is taken daily without gap.
● This method is used in order to eliminate S/E of estrogens..
● ☆☆Cycles are irregular, low efficiency (4% failure rate).

5) Postcoital (morning after) pill:

Mifepristone may be useful as postcoital contraceptive.

Effects of pills
1) Breast enlargement.
2) cervix hypertrophy with thick cervical secretions
3)⬇ ovarian function
4)⬆Coagulability,thromboembolism
5)increased gall stones
6)Increased skin pigmentation (chloasma )
7)⬇ rate of absorption of carbohydrate
8)Estrogen increases TG & HDL, but LDL is decreased.

Contraindications☆☆
1) Thromboembolic disorders or its history.
2) Moderate to severe hypertension.
3) Active liver disease or history of jaundice during previous pregnancy.
4) Breast or genital malignancy

Relative contraindications
1) Diabetes mellitus.
2) Obesity.
3) Smoking.
4) Mild hypertension .

Interactions
Failure of contraception may occur with simultaneous use of:
1) Enzyme inducer as phenytoin or phenobarbitone.
2) Broad spectrum antibiotics.
 Injectable contraceptives
Long acting progesterone once in several months, 2 preparations are used:
Medroxyprogesterone acetate 150-400 mg every 3-6 months.
Norethindrone enanthate 200 mg at 2-3 months.

Implant contraceptives
• Implanon.
• Norplant

Male contraception
The only way to suppress male fertility by drug is through inhibition of
spermatogenesis

Drugs tried are:

1) Antiandrogens by direct action on testis.
2) Cytotoxic drugs: cadmium, nitrofurans, and indoles suppress spermatogenesis,
but these are toxic.
3) Gossypol:.
It causes 99.9 % suppression of spermatogenesis.
Adverse effects: Hypokalaemia ,muscle weakness, Edema, Breathlessness, Neuritis

4) Estrogen & progesterones:

Act by suppressing gonadotropins.
Lead to unacceptable side effects