Steroids female oral contracepti

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Steroids female oral contracepti Powered By Docstoc
					By: Judy Garza
 Steroid Hormones
 Oral Contraceptives
 Abortifacient
 Ovulation
 Mechanism of Action: Oral
 Mechanism of Action: Abortifacients
 Male Hormonal Contraceptives
 Side Effects
 Future
   Steroids that act as hormones.
   Grouped into five groups by the receptor to which they
     • Glucorticoids, mineralcorticoids, androgens,
       estrogens, and progestagens.
   Synthesized from cholesterol in the gonads and adrenal
   Carried in the blood going to specific carrier proteins
    (ex. Sex hormone binding globulin or corticosteroid
    binding globulin).
   In cytoplasm they can
    undergo an enzyme-mediated
    alteration like reduction,
    hydroxylation, or
   The steroid binds to the
    specific receptor.
   The steroid receptor
   The steroid-receptor ligand
    complex binds to specific
    DNA sequences and induces
    transcription of its target
   Medications taken by mouth for the purpose of birth
   They are a class of synthetic steroid hormones that
    suppress the release of follicle-stimulating hormone
    (FSH) and luteinizing hormone (LH) from the anterior
    lobe of the pituitary gland.
   FSH and LH are called gonadotropic hormones and
    they stimulate the release of progesterone and
    estrogen from the ovaries which are responsible for
    modulating the menstrual cycle.
   1500 years ago – papyrus
   Early 1900’s- Ludwig
    Haberlandt coined the term
    “hormonal sterilisation.”
   Nov. 1921- Haberlandt
    presented his work.
   1927- Haberlandt published
   1929- Adolf Butenandt
    isolated the first female sex
    hormone, estrone.
   1934- Butenandt isolated
    progesterone from pig
   1948- Russel Marker
    synthesized progesterone
    using wild yam (Dioscorea).
   1951- Gregory Pincus,
    Margaret Sanger, et al. began
   1960- 1st pill introduced
    (Envoid 10mg)
   1970: Introduction low dose or
    second generation of OCS
   1980: biphasic or triphasic
   1990: 3rd generation OCS
    (O + P has less androgenic
   A substance that induces
   Controversy over the use of
   Types:
     • Herbal (ex. Brewer’s yeast,
       vitamin C, wild carrot,
       black cohosh, slippery elm,
       pennyroyal, nutmeg,
       mugwort, papaya, vervain,
     • Pharmaceutical
       (Mifepristone and
 Ancient Greece – the
  colony of Cyrene had
  an economy based on
 All throughout history,
  herbs have been used
  as a means of
 Modern days surgical
  methods and
  medications are used.
   Process in the menstrual
    cycle where a mature ovarian
    follicle ruptures and
    discharges an egg (ovum).
   Ovulation is triggered by a
    spike in the amount of Follicle-
    Stimulation Hormone
    (FSH)and Luteinizing
    Hormone (LH) released from
    the pituitary gland.
   Gonadoptopin releasing
    hormone (GnRH) stimulates
    the expression of LH and FSH.

 Progesterone   is the only naturally occurring
 All have antiestrogenic and
  antigonadotropic properties.
 Differ in their affinity for progesterone
  receptors and side-effects.
 Only synthetic progestagens are used in
  oral contraceptives.
                                                     Progesterone (aka

     Norethisterone              Norethynodrel

                      Synthetic Progesterones

Levonorgestrel                                   Chlormandinone acetate

   There are two progesterone receptors: PR-A and PR-B.
   Both have AF-1 and AF-2 transactivation domains.
   Since the ligand-binding domains are identical, there is no
    difference in ligand binding.
   Upon binding to progesterone, the receptors are
    phosphorylated and form dimers that bind with high selectivity
    to progesterone response elements (PREs) located on target
   Transcriptional activation occurs after recruitment of co-
    activators like SRC-1 in order to have histone acetylase activity.
   This increases the accessibility of general transcriptional
    proteins to the target promoter.
                        Progestin-Only Contraceptive
              •In the stomach, ovulation is inhibited by
              suppressing function of the
              hypothalamic-pituitary-ovarian axis.
              •It then modifies the midcycle surges of
              luteinizing hormone (LH) and follicle-
              stimulation hormone (FSH).
LH, FSH       •In the ovaries, hormone production is
              •There are modifications made to the
              ovaries that are unfavorable to
              implantation and the cervical mucus is
              •Also, it inhibits sperm action.

•In oral contraceptives, the
estrogens mainly used are
mestranol and ethinyl
•It is produced in the ovaries
by FSH and LH.
•Too much estrogen can
cause side effects such as
stroke, deep vein
thrombosis, invasive breast
cancer, heart attack, etc.

   Composed of 4 rings.
   The phenolic A ring is the principle structure that is responsible for
    selective, high-affinity binding to both receptors.
   Sterodial estrogens arise from androstendione or testosterone by
    aromatization of the A ring.
   Reaction is catalyzed by a cytochrome P450 monooxygenase enzyme
    complex that uses NADPH and oxygen as co-substrates.

 Act primarily on the pituitary to control the
  amplitude of gonadtropic pulses and
  contribute to the amplitude of GnRH pulses
  secreted by the hypothalamus.
 They also inhibit gonadotropin (LH and
  FSH) release during the menstrual cycle,
  but then they have a mid-cycle stimulatory
  action that increases the amount released
  causing LH to surge.

 The  hormone enters the cell and binds to an
  estrogen receptor (ESR 1, ESR 2).
 Binding causes a conformational change and
  causes receptor to dimerize which increases the
  affinity and rate of receptor binding to DNA.
 ER dimer binds to estrogen response elements
  located in the promoter region of target genes
  where it then can regulate many of the same
  target genes.
                                              Estrogen + Progestins
                                             (aka Combination Oral

   Progestins bind to albumin and sex hormone binding
    globulin in plasma then diffuse into cell cytoplasm
   Estrogen is lipid soluble and thus diffuses.
   Once in the cell, they regulate the transcription of specific
    genes in the uterus.
   Actions of hormones are mediated by their hormone
    receptors which are nuclear transpcription factors whose
    transcriptional regulartory activity is mediated by the
    binding of the specific steroid to these molecules.
   Once the receptors bind hormone, they bind to cis-acting
    sequences in the promoter region of responsive genes
    and regulate transcription of these genes.
                                         Estrogen + Progestin (aka
                                                Combination Oral

   The progestin negative feedback decreases the frequency
    of GnRH released.
   This decreases the release of FSH and LH which inhibit
    follicle development.
   Estradial levels do not increase (no positive feedback).
   In addition it decreases the amount of and viscosity of the
    cervical mucus, inhibiting sperm penetration.
   Estrogen also contributes to decreasing the amount of FSH
    produced by negative feedback on the anterior pituitary.
   No ovulation occurs as a result
       Estrogen + Progestin (aka
              Combination Oral
     •Same amount of estrogen and
     progestin in each active pill.
     •Classified by estrogen level
          •Low dose (20 mcg)
          •Regular dose (30-35 mcg)
          •High dose (50 mcg)
     •Alter the level of hormones
     once during the menstrual cycle.
     •Same amount of estrogen but
     halfway through the cycle,
     progestin is increased.
     •3 different doses of hormones.
     •Depending on brand, estrogen
     may increase.
   Progesterone-Only
     • Evonid
     • Minipill
   Monophasic
     • Yasmin
   Biphasic
     • Necon
   Triphasic
     • Cyclessa (100 ug, 125 ug,
       or 150 ug desogesterl)
     • Ortho Tri-Cyclen Lo
     • Tri-Norinyl
 Mifepristone          (aka RU-486)
  • It is a competitive receptor antagonist in the presence of
      progesterone at the progesterone receptor.
  •   It causes the decidual degeneration which leads to trophoblast
  •   Results in decreased production of Human chronic
      gonadotropin (hCG), which causes decreased production of
      progesterone by the corpus luteum.
  •   Since pregnancy is dependant on progesterone production by
      the corpus lutenum, pregnancy is terminated.
  •   In addition it increases prostagladin release from the uterine
      lining, increasing uterine contractions and enhances the uterus’
      sensitivity to prostagladin.
 Methotrexate
  • Blocks enzyme necessary for DNA synthesis,
   which inhibits the growth of placental
   trophoblastic cells.
 Misoprostol
  • Synthetic protaglandin E1 analogue.
  • Used in combination with Mifepristone and
  • Softens and dilates the cervix.
  • Binds to myometrial cells to cause uterine
    contractions which cause expulsion of the
 Plan-B
  • Consists of two doses of the “minipill” (.75 mg
   levonorgestrel per pill) separated by 12 hours.
 Preven   (“Yuzpe”)
  • A two 2-pill doses of a high-dose oral
   contraceptive (.25 mg of levonorgestrel and .05
   mg of ethinyl estradiol per pill) separated by 12
 Vaginal   rings
  • Nuvaring
 Transdermal
  • Contraceptive patches
  • Nestorone gel
 Intrauterine
  • Progestasert
  • Mirena
 Intramuscular
  • Gravibinon
 Subcutaneous
  • Norplant
 Stillin clinical trials.
 Stopping the secretion of a man’s
  reproductive hormones in the brain and
  the testes to reduce or block sperm is the
  ultimate goal.
 Blood clots
 Heart attacks
 Stroke
 Cancer
 Depression
 Nausea
 Dizziness
 Stomach upset
 Headache
 Looking  at reducing the risks involved
  with taking the pill.
 Using natural products.
 Vaccines
   Matthiesson, Kati L. and McLachlan Robert. Male hormonal
    contraception:concept in sight? Human Reproduction Update, Vol.12,
    No.4 pp. 463–482, 2006
   Ferro, Valerie and Mann, Jamie. Recent Developments in Female
    Hormonal Contraception. Current Women’s Health Reviews, 2005, 1,
   Benagiano, Giuseppe, Bastianelli, Carlo and Farris Manuela.
   Orme, M.L’E. The Clinical Pharmacology of Oral Contraceptive Steroids.
    Br. J. clin. Pharmac. (1982), 14, 31-42
   Mears, Eleanor. Clinical Trials of Oral Contraceptives. British Medical
    Journal. Nov. 4. 1961