Oral Contraceptives

1. Oral Contraceptives Estrogen and Progestin

2. Contents • Hormones • Ovulation • History of Oral Contraceptives • Uses of Oral Contraceptives • Estrogen and Progestin • Types of Oral Contraceptives • Future of Oral Contraceptives

3. Hormones = “chemical messenger from one cell to another” 4 classes of Hormones • Amine Derived Hormones • Peptide Hormones • Steroid Hormones • Lipid and Phospholipid Hormones Steroid Hormones -derived from cholesterol -primarily produced in adrenal cortex or gonads Types of Steroid Hormones • Anabolic steroids • Corticosteroids • Sex hormones Major steps in Steroid Hormone Binding • http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter47/animations.html# cholesterol

4. Interaction of Hormones with Surface Proteins

5. Ovulation • Follicular phase • LH and FSH concentrations increase due to GnRH • Follicular growth • Antrum fluid volume increases • Blister forms in ovary • Ovulation Phase • Follicle released from ovary  secretes estrogen • Corpus lueteum triggers release of progesterones and estrogens

6. Ovulation

7. History of Oral Contraceptives • 1937- discovery of effects of progesterone on ovulation • 1940’s- Russell Marker isolates progesterone from Mexican yams • 1951- Luis Miramontes synthesizes 1st progestin • 1960- FDA approves “the pill” • 1963- 1st oral contraceptive put on drug market • 1965- number one form of birth control • Late 1970’s- FDA mandated warning that indicated oral contraceptives carried risks of cancer and blood clots

8. Uses of Oral Contraceptives • Primary Use • Prevent pregnancy • Secondary Uses • Heavy or irregular menstruation • Endometriosis • polycystic ovary syndrome • dysfunctional uterine bleeding

9. What’s in “The Pill” • 20-40 micrograms ethinyl estradiol (synthetic form of estrogen) • Varying amounts of either levonorgestrel or norethindrone as the progestagen component • Types of Regimens • 21-day or 28-day pack

10. Combined mode of action of estrogen and progestin • Prevents ovulation • Thickens mucous in cervix • Thins endometrium

11. Gonadotropin Releasing Hormone (GnRH) • Synthesized by hypothalamus • Stimulates anterior pituitary gland to release FSH and LH • A decapetide (contains 10 amino acids) pGlu-His-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 • secretion begins at puberty • Primary Effects • secretion of estrogen and progesterone in females • secretion of testosterone in males

12. Estrogen • Primary female sex hormone • Roles of estrogen: • To develop secondary female sex characteristics • Thicken the endometrium • Regulate menstrual cycle • Regulation • Production of estrogen regulated by Follicle Stimulating hormone (FSH) and Luetinizing hormone (LH), both produced in the anterior lobe of the pituitary gland • Hypothalamus→GnRH→ Pituitary→FSH→Follicle→Estrogens

13. Naturally occurring estrogens Estradiol Estriol Estrone

14. Conversion of testosterone to estradiol Testosterone Estradiol

15. Synthetic Estrogens

16. Estrogen Receptors • Two types of Receptors • ER alpha • ER beta • Mode of Action- • 1) Estrogen passes through phospholipid bilayer • 2) Ligand binds in hydrophobic region of receptor forming cap over ligand binding pocket • 3) Estrogen and ER complex bind to estrogen response element in the nucleus to initiate transcription • 4) Translation creates proteins which target various organs and processes in the female body

17. Progesterone • Produced by • Adrenal glands • Gonads • Brain • Placenta (only during pregnancy) • Regulation- stimulated by the production of LH • Hypothalamus→GnRH→ Pituitary→LH→Corpus luteum→Progesterone • Primary Effect-prepares uterus for implantation by the proliferation of endometrium; prepares body for pregnancy • Natural progesterone- destroys digestive system when consumed orally ALL oral contraceptives contain progestin, synthetic form of progesterone

18. Conversion of pregnenolone to progesterone pregnenolone progesterone

19. Progestins • Types 1) C19- derived from testosterone 2) C21- derived from progesterone • Role • in adequate doses it inhibits ovulation • Makes your body think that it is pregnant • Reduces levels of FSH and LH • Binding • Interacts with progesterone receptors either by entering cells through phospholipid bilayer or by interacting with surface proteins

20. Structure of Progestins

21. Brands of Oral Contraceptives • Loestrin • Lo/Ovral • Mircette • ModiCo • Necon • N.E.E. • Nelova • Nordette • Norethin • Norinyl • Ortho-Cept • Ortho-Cyclen • Ortho-Novum • Ortho Tri-Cyclen • Ovcon • Ovral • Tri-Levlen • Tri-Noriny • Triphasil • Trivora • Zovia • Alesse • Brevicon • Cyclessa • Demulen • Desogen • Estrostep • Genora • Intercon • Jenest • Levlen • Levlite • Levora

22. Side Effects of Oral Contraceptives • Changes in: • Weight • Sexual desire • Vaginal discharge • Menstrual flow • Breast size • Blood pressure • complexion • Other Common side effects: • Breakthrough bleeding • Nausea headaches • Urinary tract infection • Depression • Gum inflammation

23. Future of Oral Contraceptives • Researchers continually trying to minimize adverse side effects of oral contraceptives • Pharmaceutical companies have to compete with latest forms of contraception • Contraceptive vaccines • Vaginal rings • Intrauterine Contraception • Cervical caps • Transdermal patch • Implants and injectables

24. Thank you