This is Gonadal Hormones and Inhibitors(Lecture 2). It is for any medical student and teacher etc. I hope you like it.

1. Gonadal
Hormones
and
Inhibitors
(Lecture 2)
By Dr. Syeda Tahira

2. Learning Outcomes
• Effects of Progesterone on body
• Drugs related to Progesterone
• Progesterone antagonist
• Oral contraceptive

3. Progesterone
• Natural Progesterone
• Synthetic Progestins
• Sources of Progesterone(site of synthesis)
Female Male
Corpus lutum,
Placeta during Pregnancy
Adrenal Cortex
Testes
Adrenal Cortex

5. Progesterone

6. Regulation Of Progesterone Release

7. Pharmacokinetic Profile
Absorption Rapidly absorbed, high first pass metabolism in liver .
Distribution In plasma bound to CBG and albumin.
Small amount stored in body fat temporarily.
Short half life in plasma (5 min)
Metabolism In the liver, progesterone is metabolized to pregnanediol and
conjugated with glucuronic acid.
Excretion It is excreted into the urine as pregnanediol glucuronide.
Oral Micronized preparations provide adequate progestational effect.

8. MOA
 (PR) is a Progesreone activated steriod receptor.
It has 2 isoforms
PRA and PRB
Like other steriod hormones;
• It enter the cell
• Binds to nuclear and cytoplasmic receptors
• Forms a ligand –receptor complex binds to a PRE(progesterone
element).
• Activate gene transcription.

9. Physiological Effects
• It stimulates lipoprotein lipase activity.
• It promotes glycogen storage
• Progesterone also promotes ketogenesis.
• It compete with aldosterone and causing decrease in Na +
• reabsorption.
• It also increases body temperature ,respiratory responses of
Co2.
• It also have depressant and hypnotic effects on the brain.

10. Continuation
• Progesterone is responsible for breast secretory apparatus in
the breast.
• It also participates in the pre ovulatory LH surge and causes
the maturation and secretory changes in the endometrium
that are seen following ovulation.
• Suppresses uterine contractility especially during pregnancy.
• Decrease in plasma amino acid.
• increased urinary nitrogen excretion

11. Synthetic Progestins
Hydroxyprogesterone,
Medroxyprogesterone
Megestrol
Dimethisterone
Desogestrel
Norgestimate.
Gestodone
21-carbon
Progesterone analogs
19- Nortestosterone
Newer third-
generation(18-c)

14. Therapeutic Applications
• Hormonal contraception.
• Dysfunctional Uterine Bleeding
• Endometriosis
• Hormonal Replacement therapy
• Bleeding disorders when estrogens are contraindicated.
• Postpone menstural bleeding
• Diagnostic Test
Progesterone can be used as a test of estrogen secretion.

15. Adverse Effect
Headache
Depression
Weight gain
Changes in libido,
Acne and hirsutism (androgenic activity)
Reversible reduction of glucose tolerance.

16. Drug interaction
• Coadministration with potent inducers of the hepatic
microsomal metabolizing enzymes, such as rifampin, phenytoin
may increase liver catabolism of estrogens or Progestins and
diminish the efficacy of oral contraceptives.

17. Mifepristone (RU 486)
• Mifepristone is a “19-norsteroid”
 MOA: It is pharmacological antagonist at progesterone and glucocorticoid receptor.
• It has luteolytic properties.
• Long half life 20-40 hrs.
 Clinical uses
• Medical abortion
• Postcoital contraception
• Cushing syndrome(very rarely)
 Adverse effect
• Vaginal bleeding(major)
• Abdominal pain
• GIT upset
• Diarrhea
• Headache
Lilopristone(experimental
progesterone inhibitor.)
Mifepristone+Misoprostol
(PGE1) for abortion

18. Hormonal Contraception
• ORAL
• PARENTERAL, &
• IMPLANTED CONTRACEPTIVES

19. Oral contraceptive
• Oral contraceptive (Birth control) are prescription medications
that prevent pregnancy.
• Contraceptive medication contain hormones(estrogen and
progesterone, or progesterone alone)

20. Oral Contraceptives
• Combined pills
Phased pills
• Progestin only
• Emergency pills

21. Available dosage forms
• Pills
• Injections
• Topical patches
• Slow release system(vaginal rings, skin implants, IUD)

22. Combined Pills
• Combination birth control pills are a daily medication that contains 2
hormones (estrogens and progestins) to prevent pregnancy.
• Monophasic forms
• (Constant dosage of both components during the cycle )
• Biphasic
• Triphasic
• (Dosage of one or both components is changed once or twice during
the cycle)
• Most effective means of contraception except surgical sterlization.

23. What they contain?
• Estrogens
• Ethinyl Estradiol
• Mestronol
• Progestins
• Norgestimate
• Norgestrel
• Norethindrone
• Drospirenone
• Ethynodiol diacetate
• Desogestrel

24. MOA(Combination Pills)
• By blocking ovulation.
• By altering mucus in the cervix, which makes hard for sperm
to travel.
• By changing endometrium so it can not support fertilized egg
• By altering fallopin tubes so they can not effectively move eggs
towards the uterus.

26. Progestin Only
• Contain only hormone for daily use .
• May be prescribed if someone has side effect from estrogen.
Intramuscular injection of 150
mg of medroxyprogesterone
also provides contraception
for 3 months
Subdermal implant of
Norgestrel (5 yrs)
Mini pill
(low dose of
norethindrone)

27. Implanted Contraceptive

28. Emergency Contraceptive pill
• Highly effective and decrease the risk of pregnancy if
administered within 72 hrs .
Oral preparations
• Progestin only
• Estrogen only
• Combined oral contraceptive pills
• Mifepristone

29. Uses Of Contraceptive Pills
Prevent pregnancy(main)
Other uses(combination pills)
• Endometriosis
• Dysmenorrhea
• Dysfunctional uterine bleeding

30. Beneficial Effects of oral Contraceptive
Pills
Reduced risk of
• Ovarian Cyst
• Ovarian and Endometrial Carcinoma
• Benign breast disease
• Ectopic pregnancy
• Iron deficiency anemia
• Pelvic inflammatory disease
• Rheumatoid arthritis