Drug acting on endocrine system or drug

used in productive health.

BY Choudhary Sajan Gomaram

B. Pharm 5th Sem
Roll no : 87738
 Estrogen Actions
• 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.

 Estrogen
• 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 cholestaticjaundice.

• Can result in hepatic adenoma on prolonged use.

• Vasodilation by increasing the production of NO.

 Estrogen Preparations
• Natural steroidal estrogen
✓Estrone, Estradiol ( maximum),
Estriol
• Synthetic steroidalestrogen
✓ Ethinyl estradil
✓ Mestranol
✓ Tibolone
• Synthetic non steroidal
estrogens
✓ Diethylstilbesterol
✓ Dienestrol
 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 i n t e s t i n e →

enterohepatic circulation → high peripheral r a t i o →
hepatic side effects
 Therapeuticuses

• 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

 Therapeuticuses

• Estrogen Replacement Therapy ( ERT) in primary ovarian failure

• Dysmenorrhoea : painful menstrual bleeding
• Acne, hirsuitism
• Carcinoma prostrate
• DUB: dysfunctional uterine bleeding
 Adverseeffects
• 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, hepaticdysfunction
• Thromboembolic disorders
• Diabetes and fluid retention
 Contraindications

• Pregnancy

• Thromboembolic disorders

• Diabetes

• Estrogen dependent breastcarcinoma

• Endometrial carcinoma
 Progesterone Actions
• 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
Progesteronepreparations
 Pharmacokinetics

• Natural progesterone orally ineffective due to first pass

metabolism

• Synthetic progesterones are orally active

 Therapeuticuses
• 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
 Adverseeffects

• Breast engorgement
• Irregular mensturation cycle,breakthrough
bleeding

• Depression, irritability

• Weight gain, decreasedlibido

 Oral contraceptivepills
• 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
 Formulations of OCP’s

1. Monophasic (each tablet containsa 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).
 Mechanism ofaction

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.
The oestrogen in most combined preparations (second-generation
pills) is ethinylestradiol,or, or mestranol The progestogen may be
norethisterone, levonorgestrel, Orin 'third- generation' pills desogestrel
or gemstone
 ADVERSE EFFECT’s

➢ Weight gain, owing to fluid retention

➢ Glucose intolerance

➢ Mild nausea, flushing, dizziness, depression or irritability

➢ Skin changes (e.g. acne and/or an increase in pigmentation)

➢ Amenorrhoea of variable duration on cessation of taking the

pill.
➢ CVS: thromboembolism, hypertension
➢ Increase risk of Breast carcinoma. Decrease risk of ovarian and endometrial
cancer
 Non contraceptive beneficialeffects

➢ decreases menstrual symptoms such as irregular

periods and intermenstrual bleeding.

➢ Iron deficiency anemia and premenstrual tension are

reduced.

➢ Reduce benign breast disease, uterine fibroids and functional

cryst of the ovaries.
 Progesteroneonly 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.
 Mifepristone
• Anti-progestin
• Binds to progesterone receptors, blocking activity of progesterone
Uses:

• Termination of pregnancy,

• Contraceptive,

• Softening of cervix,

• Induction of labour
 SERN
• 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

 SERN

• Prevent deleterious estrogenic effects on some tissues:

endometrium, breast

• Example: clomiphene, tamoxifen,raloxifene

• Uses: breast cancer ( raloxifene), HRT ( tamoxifen),
infertility ( clomiphene)