Oral Contraceptives

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Oral Contraceptives

• Estrogen and Progestin

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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

cholesterol
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The Sex Steroids

• Female Sex Steroids Include
• Estrogens and Progestins
• The most potent estrogen is estradiol.
• Male Sex Steroids Include
• Androgens
• The androgen found in blood is testosterone.

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Female or Male?

• All three classes of endogenous steroids are
  present in both males and females.
• But, the production and circulating plasma levels
  of estrogens and progestins are higher in females
  and that of androgens are higher in males.

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Female Sex Drive

• However, sexual desire in women is probably more
  dependent upon androgens, secreted by the adrenal
  glands and ovaries, than estrogen.
• Sex drive is maintained beyond menopause, a time
  when estrogen levels become very low.

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Interaction of Hormones with Surface Proteins
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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

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Ovulation
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During Pregnancy

• The levels of estrogen and progesterone increase
  during pregnancy
• A good source of estrogens is the urine of
  pregnant women.

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History of Oral Contraceptives

• 1937- discovery of effects of progesterone on
  ovulation
• 1940s- Russell Marker isolates progesterone from
  Mexican yams
• 1951- Luis Miramontes synthesizes 1st progestin
• 1950s Studies show that the combination of an
  estrogen and a progestin prevents contraception.
• 1960- FDA approves the pill
• 1963- 1st oral contraceptive put on drug market
• 1965- number one form of birth control
• Late 1970s- FDA mandated warning that indicated
  oral contraceptives carried risks of cancer and
  blood clots

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Uses of Oral Contraceptives

• Primary Use
• Prevent pregnancy
• Secondary Uses
• Heavy or irregular menstruation
• Endometriosis
• polycystic ovary syndrome
• dysfunctional uterine bleeding

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Whats 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 action of estrogen and progestin

• Prevents ovulation
• Thickens mucous in cervix
• Thins endometrium

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How does it work?

• Estrogen and progesterone can inhibit pituitary
  gonadotropin release, thereby preventing
  ovulation.
• In practice, oral contraceptives, particularly
  the minipill (contains only progesterone-like
  substances), do not always prevent ovulation, but
  they are still effective because they have other
  contraceptive effects.

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How does it work?

• Progestogens affect the composition of the
  cervical mucus, reducing the ability of the sperm
  to pass through the cervix.
• They also inhibit the estrogen-induced
  proliferation of the endometrium, making it
  inhospitable for implantation.

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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

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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?Estrogen
  s

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Naturally occurring estrogens
Estradiol
Estriol
Estrone
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Metabolism of Estradiol

• Estradiol itself is not orally bioavailable, due
  to its rapid oxidation in the liver

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Biosynthesis of estradiol
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Synthetic Estrogens
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Synthetic Estrogens

• Note that the synthetic estrogens contain a
  tertiary alcohol, instead of a secondary alcohol.
• This tertiary acetylenic alcohol cannot be
  oxidized to the corresponding ketone, thus is
  metabolically stable, and orally bioavailable.

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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

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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

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Conversion of pregnenolone to progesterone
pregnenolone progesterone
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Metabolism of Progesterone

• Progesterone itself is not orally bioavailable,
  partially due to its metabolism

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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

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Structure of Progestins
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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

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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

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Abortifacients

• An antagonist of progesterone can interfere with
  the early stages of pregnancy

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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

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References

• http//www.nlm.nih.gov/medlineplus/druginfo/medmas
  ter/a601050.html
• http//en.wikipedia.org/wiki/Estrogen
• http//users.rcn.com/jkimball.ma.ultranet/BiologyP
  ages/S/SexHormones.html
• http//www.emc.maricopa.edu/faculty/farabee/biobk/
  BioBookREPROD.html
• http//en.wikipedia.org/wiki/Gonadotropin_releasin
  g_hormone
• http//www.contraceptiononline.org/slides/slide01.
  cfm?qprogestinchemicalstructuresdpg1
• http//users.rcn.com/jkimball.ma.ultranet/BiologyP
  ages/H/Hormones.html
• http//www.contraceptiononline.org/contrareport/ar
  ticle01.cfm?art93
• http//users.rcn.com/jkimball.ma.ultranet/BiologyP
  ages/G/G_Proteins.html