1 / 34

Safety of Oral Contraceptives for Women

Safety of Oral Contraceptives for Women. M. Meyers and B. Spizziri. Are Current Oral Contraceptives Safe For All Women?. History. 1940s Russel Marker Wild yams (diosgenin a plant steroid) Synthetic progesterone 1956 Drug trial “Enovid 10”

weston
Download Presentation

Safety of Oral Contraceptives for Women

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Safety of Oral Contraceptives for Women M. Meyers and B. Spizziri

  2. Are Current Oral Contraceptives Safe For All Women?

  3. History • 1940s • Russel Marker • Wild yams (diosgenin a plant steroid) • Synthetic progesterone • 1956 • Drug trial “Enovid 10” • 150µg mestranol (estrogen), 10mg norethynodrel (Progestin) • Nausea, dizziness, stomach pain, and vomiting • 1962 • Obvious Side Effects • Death due to stroke and blood clots • 1970s-Present • Decrease dose of hormones • Variety of hormonal configurations(40+)

  4. Human Menstrual Cycle Hormones, Temperature & Ovulation

  5. Hypothalamus and Pituitary Hormones • Progestin and estrogen have (-) feedback GnRH at hypothalamus. • FSH has an estrogen effect and LH has the progestin effect at the pituitary.

  6. Types of Oral Contraceptives • Combination Oral Contraceptive (COC) • Progestin Only Contraceptive (POC)

  7. Hormones Involved in Combined Oral Contraceptives (COCs) • Estradiol • Synthetic • Estrogen • Progesterone • Anti-estrogen effects • Synthetic • Progestin

  8. Progestin Derivatives 1st Generation Norethindrone Norethynodrel-derivative of Norethindrone 2nd Generation Norgesterl Levonorgestrel 3rd Generation Desogestrel Norgestimate Gestodene Estrogen Derivatives Mestranol Ethinyl Estradiol Combined Oral Contraceptive Generations (Robinson 1994)

  9. Binding Affinity Differs by progestin Half-Life Progestin – 17-deacetyl norgestimate - 12 – 30 hours Estrogen Ethinyl estradiol - 6 - 14 hours Peak serum concentrations 2h after administration Rapid Decline Estrogen and Progestin (Robinson 1994)

  10. Combination Oral Contraceptive • Combination Oral Contraceptive (COC) • Ethinylestradiol • Estrogen Component • Dose - 20 - 40 micrograms • Monophasic • Multiphasic • 2nd and 3rd generation progestins • Progestin component • Dose- 0.15-1.5 mg • Fixed • Biphasic • Triphasic • Normal schedule is 21d on COC with a 7d gap. (Sherif 1999)

  11. Current COCs • Lower Estrogen dose than 1960’s • 50-150 µg vs. 20-40µg of estrogen • Required amount is less than original dose. • More effective • New 2nd and 3rd generation progestins • 10mg vs. 0.15-1.5mg • Required amount is less than original dose • More effective • Occurrence of serious side effects decreased due to lower dose of estrogen and progestin.

  12. COCs Prevent Pregnancy • Prevent ovulation • Progestin effects: • Suppresses LH secretion • Thickens cervical mucus preventing/hindering sperm transport • Thins endometrium preventing ovum implantation • Interferes with secretory/peristaltic function inside fallopian tubes • Estrogenic effects • Inhibits ovulation by suppressing FSH and LH • Alters endometrium secretions • (Sheriff 1999)

  13. Progestin-only Oral Contraceptive • “Minipills”/POC • Norethindrone (Norlutin) or Norgestrel (Orvette) • lower dose of progestin • Norethindrone 0.3 to 0.6 mg • levonorgestrel 0.03 to 0.0375 mg • 28 day active hormone cycle • Does not always supress GnRH. • Ovulation can occur • Efficacy dependent on cervical mucus and endometrial effects • 6-10% ectopic pregnancies among users • Not as common • Recommended for: • Breast-feeding mothers • Smokers • Older women • Other health problems (ContraceptINFO 2006)

  14. Risk Factors… • Venous Thromboembolism • Myocardial Infarction/Stroke • Migraine • Bone Health • Gall Bladder Disease • Breast Cancer • Fertility

  15. Venous Thromboembolism • Venous Thromboembolism (VTE) • Formation of a blood clot in the veins which can travel from the site where it formed and block blood flow at another location Types: • Deep venous thrombosis (DVT) • Pulmonary Embolism (PE) • Caused by DVT in deep veins of lower extremities and clot travels to lungs (Cornell 2006)

  16. VTE and COCs • A 1995 study found COC users have 3-4 fold increase risk of VTE.(Sheriff 1999) • Highest risk in first year of use • Highest risk with 3rd generation progestins • 50 fold increase of VTE if individual is a carrier for coagulation Factor V. Leiden mutation when using 3rd generation COCs • A 2002 study found 1st generation COC users had a higher risk than 2nd or 3rd generation users.(Lidegaard 2002) • Duration of Use • VTE risk decreased with decreasing estrogen dose

  17. VTE • Studies provide similar results: • 2nd generation safer than 3rd generation • Additional risk factors • Family history • Excessive weight (BMI > 30) • Smoking • Factor V. Leiden mutation • Translates 1-2 additional cases/yr/10,000 users • Highest risk associated with 1st generation users. • (Jick 2006, Middledorp 2005, Spitzer 1996, Sherif1999)

  18. Myocardial Infarction (MI)/ Stroke • 2 fold increased risk of Ischemic Stroke with any COC. • COCs with dose greater than 50μg Ethinyl estadiol have greatest risk. • Conflicting results between risks with 2nd or 3rd generation COCS • Carriers of Factor V. Leiden mutation had 13 fold increase risk. (Kemmeren 2002, Semin Reprod Med 2001, Tanis 2001, Martinelli 2006)

  19. Additional Risk Factors for MI/Stroke • Increased Risks with COCs: • Smoking • Age >30 (2-3 fold) • Hyptertension (10 fold) • Estrogen Level (>30µg) • Hypercholesterolemia • Obesity • Migraines if over 35y • POCs do not cause a risk of myocardial infarction or stroke. (Kemmerman 2001, Sherif 1999, Loder 2005)

  20. Migraine • Estrogens are vasodilators causing migraines in some women. • Migraines are thought to be associated with estrogen withdrawal period. • Dose and progestin generation does not influence migraines. • Occurrence highest in women >35y. • Migraines are linked to a stroke. (Sherif 1999, Loder 2005)

  21. Bone Mass • COC users <18y may gain less BMD. • Decreased estrogen exposure. • Loss of bone mineral content. • Increases risk of fracture. • Limited studies in women under 30. (WHO 2005)

  22. Gall Bladder Disease • Oral contraceptives have little effect on development of gallbladder disease. • Use of COCs can cause gall bladder attacks • COC association is unknown • Hormones may increase cholesterol saturation and decrease gall bladder motility • Decreased motility causes gallstone formation (ContraceptINFO 1997)

  23. Risk of Breast Cancer • Increased risk if used <45y (20-40x)? • Increased risk if 20-29 or <35? • Greatest risk is in women <35 with recent COCs • Increased risk if used >35y • due to increase risk of breast cancer with age • Conflicting results for type or generation of progestin. • 50x higher risk with >35 μg estrogen dose. • With breast cancer, COC users have increased rate of tumor growth • POCs have lower risk. (Bhathena 2006, Althuis 2003, Yankaskas 2005, Huiyan 2006)

  24. Fertility • Fertility Problems • 58% 1st cycles are ovulatory • Cycles can take up to one year to normalize. • Oral contraceptives do not cause permanent infertility. (Gnoth 2002)

  25. Benefits • Prevention of: • Bone loss • 12% increase in BMD vs. control >18y • Greatest protection with 10 yrs use • Due to estrogen dose • 25μg (WHO 2005)

  26. Benefits • Treatment of: • Acne • Hirsutism • How? • Decreases bio-available testosterone • Decreases ovarian and adrenal androgen secretion • Decrease 5-reductase activity

  27. Benefits • COC regulate: • Irregular cycles • Dysmenorrhea • Menorrhagia • Amenorrhea

  28. Benefits • Pelvic inflammatory disease (PID) • COCs increasing the thickness of cervical mucus. • Preventing bacteria from moving up the reproductive system. • Decreasing menstrual flow, limiting the opportunity for bacteria to grow in the upper reproductive tract. • Ectopic pregnancy • Less likely • High contraceptive efficacy

  29. Ovarian and Endometrial Cancer • Ovarian cancer • 10 to 12 percent decrease in risk after 1 year of use • 50 percent decrease after 5 years of use • Regardless of generation or dose • Endometrial Cancer • Decreases with length of use • Protection continues after discontinuation (Hankinson 1992)

  30. Breast Cancer Benefits • Long term COC use reduces: • Benign breast disease • Fibroadenoma (tumor) • Fibrocystic disease (lumps) • Decreased risk following discontinuation after 10y use (Yankaskas 2005)

  31. Summary: • Are Oral Contraceptives Safe for All Women? • Family history • Age • Nursing mothers • Smoking • BMI • Other Health Problems

  32. Questions……..

  33. Chemical Structures of Progestin Components Progesterone Norethindrone 19-Nortestosterone Norgestimate

  34. Chemical Structure of Estrogen Components Mestranol Estradiol Ethinyl Estradiol

More Related