3. ESTROGENS
• female reproductive system:
1. Growth and development
• CNS:
1. Feedback inhibition of gonadotropin (LH/FSH) secretion.
2. stimulation of CTZ to cause nausea and vomiting.
• BLOOD:
1. Increased predisposition to deep vein thrombosis and pulmonary embolism due to increased
synthesis of factor VII, VIII, IX and X and decreased production of antithrombin III by the liver.
2. Favourable effect on lipid profile by decreasing LDL and increasing HDL.
Actions:
4. ESTROGENS
• METABOLIC
1. Glucose intolerance
2. sodium and water retention.
3. Maintain bone mass by decreasing the bone resorption.
• Increased risk of gall bladder stones and cholestatic jaundice.
• Can result in hepatic adenoma on prolonged use.
• Vasodilation by increasing the production of NO.
Actions:
6. Pharmacokinetics
Natural estrogens: orally inactive due to first pass metabolism
Synthetic estrogens: orally active
Estradiol is converted to estrone and estriol in liver/ peripheral tissue
Orally administered estrogen absorbed from intestine
enterohepatic circulation high hepatic to peripheral ratio
hepatic side effects
7. Therapeutic uses
• Oral contraceptive pills ( OCP)
• Postmenopausal Hormone Replacement Therapy ( HRT)
• No progesterone/estrogen production after menopause.
• Leading to osteoporosis, hot flushes( due to LH), vaginal atrophy, insomnia
• in HRT: Estrogen + Progesterone are given
• Estrogen Replacement Therapy ( ERT) in primary ovarian failure
• Dysmenorrhoea : painful menstrual bleeding
• Acne, hirsuitism
• Carcinoma prostrate
• DUB: dysfunctional uterine bleeding
8. Adverse effects
• In males: gynaecomastia, feminisation and decreased libido
• In females:
• breast tenderness, breast cancer risk
• withdrawal bleeding, amenorrhoea, endometrial hyperplasia
• Risk of vaginal, cervical adenocarcinoma
• Migraine, nausea
• In both genders:
• Gall stones, hepatic dysfunction
• Thromboembolic disorders
• Diabetes and fluid retention
10. PROGESTERONE
• Progesterone increases basal insulin levels.
• decrease in Na+ reabsorption.
• Progesterone increases LDL and opposes beneficial effect of estrogen
on lipid profile.
• growth of breast tissue and also participates in LH surge.
• Progestins decrease the chances of endometrial carcinoma due to
estrogen
Actions
13. Therapeutic uses
• Oral contraceptive pills, HRT : Progestins are added to decrease the
risk of endometrial and ovarian carcinoma.
• DUB: dysfunctional uterine bleeding
• Endometriosis : presence of ectopic endometrial cells outside uterus
causing bleeding
• Infertility treatment
14. Adverse effects
• Breast engorgement
• Irregular mensturation cycle, breakthrough bleeding
• Depression, irritability
• Weight gain, decreased libido
15. Oral contraceptive pills
• Oral contraceptives are medicines taken by mouth to help
prevent pregnancy.
• they are also known as birth control pills
• Types:
combined pills: estrogen+ progesterone
progesterone only pills
16. Formulations of OCPs
1. Monophasic (each tablet contains a fixed amount of
estrogen and progestin);
2. Biphasic (each tablet contains a fixed amount of estrogen,
while the amount of progestin increases in the second half
of the cycle); or
3. Triphasic (the amount of estrogen may be fixed or variable,
while the amount of progestin increases in 3 equal phases).
17.
18. Mode of action
oestrogen inhibits secretion of FSH via negative feedback on
the anterior pituitary, and thus suppresses development of the
ovarian follicle
progestogen inhibits secretion of LH and thus prevents
ovulation; it also makes the cervical mucus less suitable for
the passage of sperm
19. The oestrogen in most combined preparations (second-
generation pills) is ethinylestradiol, or mestranol
The progestogen may be norethisterone, levonorgestrel, or-
in 'third- generation' pills-desogestrel or gestodene
20.
21. Common adverse effects
weight gain, owing to fluid retention
Glucose intolerance
mild nausea, flushing, dizziness, depression or irritability
skin changes (e.g. acne and/or an increase inpigmentation)
amenorrhoea of variable duration oncessation of
taking the pill.
CVS: thromboembolism, hypertension
Increase risk of Breast carcinoma. Decrease risk of
ovarian and endometrial cancer
22. Non contraceptive beneficial effects
decreases menstrual symptoms such as irregular
periods and intermenstrual bleeding.
Iron deficiency anaemia and premenstrual tension are
reduced,
Reduce benign breast disease, uterine fibroids and functional
cysts of the ovaries.
23. Progesterone only pills / mini pills
These contain low dose of progestins (norethisterone or
levonorgestrel or ethynodiol ) without any estrogen. These
are less effective than combined OCPs.
• Minipills are preferred in women where estrogen is contra-indicated
e.g.
–– Smokers; >35 years of age; Risk factors of thromboembolism
• Progesterone only pills are given daily without any break.
24. Mifepristone
• Anti-progestin
• Binds to progesterone receptors, blocking activity of progesterone
• uses: termination of pregnancy, contraceptive, softening of cervix,
induction of labour
25. SERM
• Selective Estrogen Receptor Modulator
• Synthetic agents with tissue selective agonist and antagonist
activities on estrogen receptor ( ER)
• Beneficial estrogenic effects on some tissues: bone, brain, liver
• Prevent deleterious estrogenic effects on some tissues: endometrium,
breast
• Example: clomiphene, tamoxifen, raloxifene
• Uses: breast cancer ( raloxifene), HRT ( tamoxifen), infertility (
clomiphene)