Progestins and Anti Progestins

Progestins

Chemistry

21 carbon compounds to which non-phenolic ring and different groups are attached.

Source & Biosynthesis

Natural and synthetic

Classification

Natural

•             Progestrone

Synthetic

1. Progestrone derivatives

•       Hydroxyprogestrone caproate
•       Medroxyprogestrone acetate

2. 17-Ethinyl testosterone derivatives

•       Dimethisterone

3. 19-Nortestosterone derivatives

•       Norethindrone
•       Desogestrel
•       Norgestimate

Pharmacokinetics

Routes of administration –oral, i/M, implants, transdermal, form of depo preparations

Hydroxylation & conjugation occurs in the body, excreted in urine

Mechanism of action

Two isoforms of progesterone receptors are present – A & B –these are intracellular receptors, mechanism is same as estrogen.

Physiological & Pharmacological Effects

Neuroendocrine effects

Because of feedback on releasing hormones regulate release of different gonadotropins and gonadal hormones

Reproductive system

Development of uterus and endometrial lining responsible for glandular growth. In secretory phase, responsible for start of menstrual bleeding.

Mammary glands

Glandular/acinar growth

Metabolic effects

• Increased basal levels
• Produced in response to carbohydrate diet.
• Lipid metabolism increase in lipoprotein lipase activity, increase in LDL and cholesterol. Effect is opposite to estrogens.
• Decreased amino acids in plasma leading to decreased nitrogen excretion.

CNS effects

• Depressant effect hypnotic –given bedtime
• Body temperature increased during mid cycle time increased if used as predictor of ovulation, exact mechanism is not known.

Effect on respiration

• Increased ventilator response to carbon dioxide
• Decreased blood carbon dioxide during luteal phase
• Maintains pregnancy, changes responsible for placenta formation
• Suppress uterine contractions

Adverse effects

a.      Hypertension
b.      Decreased HDL increased atherosclerosis
c.       Increased chances of breast cancer

Therapeutic Uses

1. Contraception
2. Hormone replacement therapy
3. Abnormal / Dysfunctional Uterine Bleeding
4. Dysmenorrhea / Endometriosis
5. Diagnostic Uses

See whether estrogen, if on stoppage of progesterone withdrawal bleeding, if no estrogen no withdrawal bleeding

6. Endometrial carcinoma –decreased chances when given with estrogen
7. Luteal phase support –rise in temperature
8. Premature labor
9. Habitual abortions –controversial use

Anti-progestins

Mifepristone

Acts on progestrone & glucocorticoid receptors 

Uses

• Contraceptive 600 mg single dose post coital as emergency contraceptive
• Abortifacient – PGE₁

In early pregnancy during 1^st two months along with PGE1 pessaries used (4-6 mg given for 4 days or 800 mg for 2 days along with 1 mg PGE1 pessary as abortifacient

• Endometriosis
• Cushing’s syndrome
• Breast cancer
• Meningiomas