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Contraceptives
Estrogen and Progestin as contraceptives
16
Medical
Undergraduate 4
03/22/2009
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Term
Menstrual Cycle: Follicular Phase
 Definition
  • FSH stimulates follicular maturation
    • follicle matures and secretes estrogen
      • estrogen causes endometrium to thicken
      • estrogen stimulates cervix to secrete a mucus that allows sperm to pass thru cervix to reach egg
      • estrogen causes mid-cycle surges of FSH, LH; LH surge causes folicular rupture and release of egg from ovary (ovulation)
Term
Menstrual Cycle: Luteal Phase
 Definition
  • ruptured follicle develops into corpus luteum which secretes progesterone (and estrogen)

Progesterone:

– limits the endometrial proliferation

– causes cervix to secrete a thick mucus that hinders penetration of cervix by sperm
Term

Contraceptives

WHat are they?

How they work?

Definition
  • Combination pills contain estrogen and progestin : inhibit ovulation by 99% and is 99.9% effective
  • “Minipills” contain only progestin: inhibit ovulation by 60% and is 99% effective
  • Estrogen and progestin each feedback to inhibit GnRH, FSH, LH:
    • suppression of FSH prevents development of follicle
    • suppression of LH prevents mid-cycle LH surge
    • thus, ovulation is blocked

– progestin makes cervical mucus that prevents sperm penetration

– progestin changes endometrium, impairing implantation of egg
Term

Contraceptives: Monophase

 

 Definition
  • Fixed doses of Estrogen and Progestesin
  • can be take as followed...
    • 21/7: 21 consequetive days and 7 days off
    • 84/7: 84 consequetive days and 7 days off
      • The idea is to reduce the number of periods u get, esp important for anemic pts bc its not good to lose alot of blood
    • 24/4: 24 days and 4 days off
Term
Contraceptives: Biphasic
 Definition
  • Fixed estrogen dose but
  • Progestin dose is low in first half and high in second half
  • it is trying to mimic the follicular phase where progestin lvls are very low and then in the luteal phase where progestin levels are high
Term
Contraceptives: triphasic
 Definition
  • estrogen is fixed
  • the cycle is divided into 3 seven day periods
    • first seven days take low progestin dose
    • second seven days take medium progestin dose
    • third seven days take high progestin dose
  • It is trying to mimic the normal progestin rhythm
Term

Contraceptive: Mini pills

 

 Definition
  • contains only progestin
  • fixed low doses (lower than combos) taken daily
  • a 28 day course
Term
What happens when miss a dose of contraceptive medication?
 Definition
  • Combination therapy
    • since we are blocking the HP axis, it will take a couple of days for it to turn back on, so missing a couple of doses will not increase chance of conception
  •  Mini pill
    • since we are only directly acting on the endometrium to secret mucus that prevents implantation, the HP axis is still working
    • so if miss a dose, there is no more mucus and the HP will release FSH and LH causing an increase chance of conception
    • if pt is not taking medicaiton at the same time everyday, it increases her chances of conception.
Term
Types of estrogen used in Contraceptives
 Definition
  • most are used a low doses (35mcg or less)
    • Ethinyl estradiol
    • mestranol
Term
Types of progestin used in contraceptives
 Definition

• desogestrel

• drosperinone (also a mineralocorticoid receptor antagonist)

• ethynodiol

• levonorgestrel

• norethindrone

• norgestimate

• norgestrel

 
Term
Plan B: Emergency contraceptive
Definition
  • Levonorgestrel
  • prevents implantation by causing the endometirum to secrete mucus
  • 2 doses taken q12h
  • 80% effective
  • taken the sooner, the better
Term
Non-oral Contraceptives
 Definition

Combination products

• transdermal: OrthoEvra

• intravaginal: NuvaRing

 

Progestin-only

• intramuscular: Depo-Prover (medroxyprogesterone)

– Every 3 months

 

• intrauterine devices: release progestin into the uterus

Term
Additional benefits of contraceptives
 Definition
  • Reduced risk of ovarian cancer and ovarian cysts
    • due to reduced ovarian stimulation
    • Persists 10-20 years after discontinue
  • Reduced risk of uterine cancer; used to treat endometriosis
    • progestin effect on reducing endometrial proliferation
    • Persists after discontinue
  • Reduced risk of colorectal cancer
  • More regular menstrual cycles: less anemia
  • Some indicated to treat acne
    • Estrogen increases synthesis of sex hormone binding globulin, causing a decrease in free testosterone levels
Term
Adverse Effects due to Estrogen
 Definition
  •  Increased risk of MI, stroke, PE, DVT
    • Especially in those with pre-existing HTN, DM, or heavy smokers over the age of 35
    • Risks greatest in first year of use
    • Risks gone after discontinue
  • Small increased risk of breast cancer
    •  but less advanced, more treatable form
    •  risk gone 10 years after stop using
  • Small increased risk of cervical cancer
    • Related to HPV status
  • Increased risk of cancer and genital abnormalities in offspring if used during pregnancy
  •  Breast tenderness
  • Headaches, nausea, edema, bloating
  • Increased blood pressure
  • Reduced breast milk production
Term

Estrogen Drug-Drug Interactions

Definition
  • P450 inducers increase metabolism of estrogens
    • Phenytoin, St. John’s wort
  • tetracyclines, ampicillin reduce intestinal bacteria that are involved in enterohepatic recycling of estrogens, and increase excretion of estrogens
    •  Backup contraception necessary
Term

Adverse Effects due to Progestin

Definition
  • Androgenic component of some progestins
    • can cause acne, hirsutism, weight gain, increased pigmentation
    • norgestrel or levonorgestrel have the most androgenic activity
    •  desogestrel or drosperinone have the least androgenic activity
  • Spotting or breakthrough bleeding due to unstable endometrium
    • usually decreases with use
    • if occurs in early cycle, increase estrogen component
    • if occurs in late cycle, increase progestin component
    • If occurs mid-cycle, increase estrogen and progestin component
  • Unfavorable effect on lipids bone
    • ↑ cholesterol, ↑ LDL, ↓ HDL
  • ↓Bone Density
  • ↓ glucose tolerance
  • MR activation: sodium and water retention
    • Nausea, vomiting, headache, depression, mood changes
    • Harmful to fetus
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