Pharmacological actions of male and female sex hormones along with drug acting on uterus both relaxants and contractants

1. Estrogen and progesterone
Estrogen Progesterone
Role Induce estrus Favours pregnancy
Discovery 1923 1929
Synthetics Steroidal= Ethinyestradiol, Mestranol, Tibolone
Non steroidal= Diethylstilbesterol, Hexesterol, Dienestrol
Norethindrone, Lynestrol, Allyesterol,
Levonorgesterol, Desogestrol
Natural Estrone, Estriol, Estradiol Progesterone, 19-nortestosterone
Actions Sex organ: pubetal changes, uterus, fallopian growth,
vagina, endometrium proliferation
Uterus: Secretory changes, hyperemia,
stroma enlarge, spongy gland atrophy
↑NO Synthase and PGI2 production Weal inhibition of GnRH,
↓ reduction of malignancy

2. Estrogen Progesterone
Actions Secondary sexual characters: Breast growth, ducts and
stroma, Accumulation of fats, pubic/axillary feminine
body contour, acne
Cervix: converts watery to viscid scanty
and cellular secretions to favour sperm
motility
Metabolic effects: anabolic, ↓ Resorption, ↑calcium
absorption, ↑bone remodeling, ↑vit-D3
Metabolism: oral contraceptive impairs
glucose tolerance
↑salt and water, ↑Blood pressure, ↑ glucose, LDL ↑
HDL&TG
Vagina: pregnancy changes , leucocyte
infiltration
Breast: proliferation of acni duct
CNS: Sedative effect
Temp: 0.5C ↑ luteal phase
↑ Coagulability (II,VII, IX, X) Stimulate respiration
↑Fibrinolytic activity ↑LDL/ ↓HDL
Antagonist Tamoxifen
Clomiphene
Mifepristone

3. Estrogen Progesterone
Adverse effects Suppression of libido,
Gynceomastia and feminization,
Headache, breast engorgement, edema,
GERD, acne, mood swings
Epiphysis fusion ↑Breast cancer
Irregular bleeding ↑IM injection painful
Endometrial carcinoma Amenorrhoea
↑Breast carcinoma Blood sugar rise, diabetes precipitated
Gall stones, migrane, epilepsy, endometriosis Masculinization of female foetus and
congenital abnormalities
Uses: HRT: vascomotor disturbances (hot flushes,
chilly sensations, faintness)
Contraceptive, HRT, Dysfucntional
uterine bleeding,
Urogenital(dryness, it is) Endometriosis
Osteoporosis (calcium level) Premenstrual syndrome
Psychological (depression, mood, loss of
libido)
Abortion, carcinoma

4. Tamoxifene Mifepristone
Role Potent estrogen antagonist in breast, blood vessels,
Partial agonist: uterus, bone , liver, pituitary and per
site
Anti progestational, anti glucocorticoid,
antiandrogenic activity
Action Inhibition of breast cancer cell, and hot flushes Slowing of follicular development and
delay/failure of ovulation
Stimulation of endometrical proliferation, lowering of
Gn, prolaction levels in post menopause women
Blocks progesterone action on the endometrium
Uses Prophylactic use for breat cancer Mifespristone is partial agonist and competitive
antagonist of PR (A& B)
Adverse effect: Endometrial hyperplasia, venous
thromboembolism
Termination of pregnancy, Postcoital
contraceptive, Induction of labour
Improves lipid profile
↓LDL, Ch
Cervical ripening, Once a month contraceptive

5. Oral contraceptives
1. Used for reversible suppression of fertility
2. Earlier parts of 20th century method of contraception (condoms,
diaphragms, spermicidal creams, foam tablets)
3. Addition of small quantity of an estrogen enhanced their efficacy
4. Available forms of contraceptives
 Devices
 Hormonal contraceptives
 Injectable contraceptives
 Implants contraceptives

6. Methods Physiological role Progestin Estrogen
Combined pill Fixed dose of both estrogen and
prosgestin, while synergise to inhibit
ovulation, the progestin ensures prompt
bleeding at end of a cycle.
Norgesterol 0.3mg Ethinylestradiol 30ug
Norgesterol 0.5mg Ethinylestradiol 50ug
Levonorgesterol 0.25mg Ethinylestradiol 50ug
Desogestrel 0.15mg Ethinylestradiol 20ug
Phased pill Triphasic regimens, estrogen dose fixed,
progstrin dose increased from first phase
to third phase
Women >35yrs, with no withdrawal
bleeding
Levonorgestrel 50-75 ug Ethinylestradiol 30-40ug
Norethindrone 0.5-0.75mg Ethinylestradiol 35-35ug
Postcoital pill
(Emergency pill)
For women not taking any contraception
(but doesn’t want pregnancy)
Levonorgestrel 0.25mg Ethinylestadiol 50ug
Levonorgestrel 0.75mg
Mini pills Devised to eliminate estrogen, low dose
of progestrin is suggested, menstrual
cycle tends to become irregular and
ovulation occurs in 20-30% persons
Northindrone 0.35 mg Norgestrel 75ug

7. Mechanism
of
action
Inhibition of GnRH
Progestrin reduces LH
frequency
Estrogen reduces FSH
frequency
Dislodge a just a
implanted blastocyst or
may interfere with
fertilization/
implantation
Blastocyst may fail to
implant because of
endometrium
(Hyperproliferative or
hypersecretory or
atrophic)
Uterine and tubal
contractions modified
to disfavor fertilization
Thick cervical mucus
secretion hostile to
sperm penetration is
evoked by progestin
action
1
2
3
4
5

8. a) Discontinuation of OC results in full return of fertility (?)
b) If women on combined pill misses to take a tablet (?)
c) If pregnancy occurred during use of hormonal contraceptive (?)
d) Obese women (Dose of ethinylestradiol) (?)
e) If break through bleeding occurs (?)
f) In women with contraindication for estrogen (?)

9. Adverse effects Contraindication
Non serious side effects: Nausea, vomiting, Headache (Migrane),
Bleeding and spotting, Breast discomfort
Thromboembolic, coronary and
cerebrovascular
Side effects that appear
later
Weight gain, acne and increase body
hair, Chloasma (Pigmentation of cheeks,
nose and forehead), pruritus vulvae,
diabetes precipitation, mood swings,
abdominal distention are occasional
Hypertension, hyperlipidaemia,
active liver disease,
suspected/over, avoid excess risk
of postoperative
Serious complications Leg vein thrombosis and pulmonary
embolism
Diabetes, obesity
Coronary and cerebral thrombosis Smoking
Rise in BP Undiagnosed vaginal bleeding
Estrogen raise plasma HDL/LDL Mentally ill
Genital carcinoma Age above 35 years
Benign hepatoma Mild hypertension
Gallstone Migraine, gall bladder disease

10. Mechanism of action
(Male contraceptives)
Complete suppression
of Spermatogenesis
Gonadotropin
suppression
(Inhibits testosterone
secretion)
1 2
3
4

11. Drug action on uterus can primarily affect
Endometrium: Estrogen
Progestrin
Myometrium:
Sympathetic
Parasympathetic
innervations

12. Drugs acting on uterus

13. Uterine stimulants
Increase uterine motility, especially at term
1) Posterior pituitary hormone: Oxytocin, Desamino oxytocin
2) Ergot alkaloids: Ergometrine (Ergonovine)
3) Prostaglandins: PGE2/PGF2alpha/ I5-Methyl PGF2∞/
Misoprostol
4) Miscellaneous: Ethacridine, Quinine

14. Oxytocin
What? Nonapeptide secreted along with vasopression
Secretion Posterior pituitary
Release or stimulation Coitus, Parturition, suckling
Actions Uterus: Increase the force and frequency of contractions (only with high
doses)
Estrogen sensitizes uterus to oxytocin
At term (restricted to fundus and body only)
Breast: Oxytocin contracts the myoepithelium of mammary alveoli and
forces milk into bigger milk sinusoids
CVS: higher dose causes Vasodilation – reflex tachycardia
Kidney: High dose exerts ADH like action –urine output (?)
Physiological role: Labour
Milk ejection reflex
Neurotransmission

15. Oxytocin
Uses Induction of labour (post maturity , prematurely, diabetic mother, erythroblastosis,
ruptured membranes or placental insufficiency)
Uterine inertia
Postpartum haemorrhage (contract the smooth muscle along with blood vessels)
Breast engorgement
Oxytocin challenge test: to check uteroplacental adequency (inject low doses of
oxytocin)
Adverse effects Too strong uterine contraction, foetal soft tissue injury, uterus rupture, foetal asphyxia
and death
Water intoxication: due to ADH like action
Uterine relaxants
(Tocolytics)
Adrenergic agonists (Ritodrine Beta 2 selective agonist)
Calcium channels blockers (Nifedipine)
Oxytocin antagonist (Atosiban)
Magnesium sulfate
General anesthetics, indomethacin and halothane