Oral Contraceptives

Estrogen and Progestin

 What we will be
talking about today
• Hormones
• Ovulation
• History of Oral Contraceptives
• Uses of Oral Contraceptives
• Estrogen and Progestin
• Types of Oral Contraceptives
• Future of Oral Contraceptives

2
 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 cholesterol

Major steps in Steroid Hormone Binding

• http://highered.mcgraw-
hill.com/sites/0072437316/student_view0/chapter47/animations.html#

3
Interaction of Hormones with
Surface Proteins

4
 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
5
Ovulation

6
 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

7
 Uses of Oral Contraceptives

• Primary Use
– Prevent pregnancy

• Secondary Uses
– Heavy or irregular menstruation
– Endometriosis
– polycystic ovary syndrome
– dysfunctional uterine bleeding
8
 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

9
 Combined mode of action of
estrogen and progestin
• Prevents ovulation
• Thickens mucous in cervix
• Thins endometrium

10
 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

11
 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
12
Naturally occurring estrogens
Estradiol Estriol

Estrone

13
Conversion of testosterone to
estradiol

Testosterone Estradiol

14
Synthetic Estrogens

15
 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
16
 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

17
Conversion of pregnenolone
to progesterone

pregnenolone progesterone

18
 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 19
Structure of Progestins

20
Brands of Oral Contraceptives
• Alesse • Loestrin • Ortho-Novum
• Brevicon • Lo/Ovral • Ortho Tri-Cyclen
• Cyclessa • Mircette • Ovcon
• Demulen • ModiCo • Ovral
• Desogen • Necon • Tri-Levlen
• Estrostep • N.E.E. • Tri-Noriny
• Genora • Nelova • Triphasil
• Intercon • Nordette • Trivora
• Jenest • Norethin • Zovia
• Levlen • Norinyl
• Levlite • Ortho-Cept
• Levora • Ortho-Cyclen

21
 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

22
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

23
 References
• 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=prog
estin+chemical+structures&dpg=1
• http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/Hor
mones.html
• http://www.contraceptiononline.org/contrareport/article01.cfm
?art=93
• http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/G/G_
Proteins.html

24
Thank you

25