Oral Oral ContraceptivesContraceptivesEstrogen and Progestin

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What we will be What we will be talking about todaytalking about today

• Hormones

• Ovulation

• History of Oral Contraceptives

• Uses of Oral Contraceptives

• Estrogen and Progestin

• Types of Oral Contraceptives

• Future of Oral Contraceptives

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Hormones 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

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Interaction of Hormones Interaction of Hormones with Surface Proteinswith Surface Proteins

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OvulationOvulation• 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

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OvulationOvulation

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History of Oral History of Oral ContraceptivesContraceptives

• 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

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Uses of Oral Uses of Oral ContraceptivesContraceptives

• Primary Use– Prevent pregnancy

• Secondary Uses– Heavy or irregular menstruation– Endometriosis– polycystic ovary syndrome – dysfunctional uterine bleeding

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What’s in “The Pill”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

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Combined mode of Combined mode of action of estrogen and action of estrogen and

progestinprogestin• Prevents ovulation• Thickens mucous in cervix• Thins endometrium

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Gonadotropin Gonadotropin Releasing Hormone Releasing Hormone

(GnRH)(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

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EstrogenEstrogen• 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

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Naturally occurring Naturally occurring estrogensestrogens

Estradiol

Estrone

Estriol

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Conversion of Conversion of testosterone to testosterone to

estradiolestradiol

Testosterone Estradiol

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Synthetic EstrogensSynthetic Estrogens

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Estrogen ReceptorsEstrogen ReceptorsTwo types of Receptors• ER alpha• ER beta

Mode of Action-1) Estrogen passes through

phospholipid bilayer2) 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

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ProgesteroneProgesterone• 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

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Conversion of Conversion of pregnenolone to pregnenolone to

progesteroneprogesterone

pregnenolone progesterone

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ProgestinsProgestins

• Types1) 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

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Structure of Structure of ProgestinsProgestins

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Brands of Oral Brands of Oral ContraceptivesContraceptives

• Alesse• Brevicon• Cyclessa• Demulen • Desogen • Estrostep • Genora• Intercon• Jenest • Levlen • Levlite• Levora

• 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

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Side Effects of Oral Side Effects of Oral ContraceptivesContraceptives

• 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

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Future of Oral Future of Oral ContraceptivesContraceptives

• 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

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ReferencesReferences• http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601

050.html• http://en.wikipedia.org/wiki/Estrogen• http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Sex

Hormones.html• http://www.emc.maricopa.edu/faculty/farabee/biobk/BioBookR

EPROD.html• http://en.wikipedia.org/wiki/Gonadotropin_releasing_hormone• http://www.contraceptiononline.org/slides/slide01.cfm?

q=progestin+chemical+structures&dpg=1• http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/

Hormones.html• http://www.contraceptiononline.org/contrareport/

article01.cfm?art=93• http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/G/

G_Proteins.html

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Thank youThank you