Evolution of Contraception: Potions to Progestins

1. Evolution of Contraception: Potions to Progestins Jennifer McDonald DO

2. Basics • 48% pregnancies in the US are unintended • Age group with second highest rate of unintended pregnancy is women 40-44 • Half of all unintended pregnancies end in abortion • 45% of abortions occur in women 25-30 years old and 24% occurred >30 years old

3. Pregnancy Prevention

4. Lactational Amenorrhea (LAM) • Typical use 95% • Perfect use 98% • Natural Family Planning • 78-88% • No method • 15%

5. Ancient “Technology” • Vaginally administered honey • Drinking the water used to wash the dead • “Sponges” made from crocodile dung or fermented dough • Lemon wedges over the cervix • Middle Ages women died of lead, arsenic, mercury, or strychnine poisoning after drinking for theoretical contraceptive or abortifacient effects • Earwax of a mule worn as an amulet to ward off pregnancy

6. “Modern” Contraception • 1930s Austrian physiologist suggested extracts of ovarian hormones could inhibit fertility • Researched hampered by unavailability of hormones • 1960s FDA approved first oral contraceptive • Estimates suggest that by the end of their reproductive years 80% of US women will have used OCs for an average of 5 years

7. Development of Non-hormonal Means • First IUD made of silk suture in 1929 reported a 3% pregnancy rate • 1930s rings wrapped in silver wire 1.6% pregnancy rate • 1960s first copper IUDs introduced • 1980s litigation involving Dalkon Shield led to decrease in IUD use • Today IUDs used by 2% US women • 2 available forms: Progesterone (Mirena/Progestasert) and copper (Paraguard)

8. Barrier Methods • Condoms (male & female) • Diaphragm (used by <2% of women) • Cervical cap (no longer available in the US) • Contraceptive sponge

9. Progestin Only Options Injection Depo Provera Intrauterine Devices Mirena – good for up to 5 years Progestasert – inserted yearly Implants Implanon – good up to 3 years

10. Mechanism of Action Progestin Only Forms • Blocks LH • Maintains thickness of cervical mucous • Reduces mobility of fallopian tubes • Changes uterine lining making it unfavorable for implantation

11. Side Effects Progestin Only • Headache • Vaginitis • Breast pain • Weight gain • Acne Most disappear within a few months of starting

12. Depo Provera • FDA approval for contraception in 1991 • Given as an IM injection every 11-13 weeks • Suppresses ovulation • Depresses ovarian steroidogenesis • Estradiol can dip into menopausal ranges leading to increased bone mineral resorption • Continuous use should not exceed 2 years (not lifetime) • Menstrual changes • 50% amenorrheic by 12 months • 75% amenorrheic by 24 months

13. Depo Provera cont. • Weight gain more variable than with other methods • Return to fertility can be delayed (median 9-10 months) • May be used in breast feeding • May be used in women with contraindications to estrogen containing products (eg. Smokers over 35, thrombophilias)

14. Implanon • Available in Europe and Asia for 8 years and used by 2 million women • Easier insertion and removal than its predecessor Norplant • 99% efficacious (Pearl index 0.38)

15. Implanon • Single 4 cm rod implant (Etonogestrel) • Implanted subdermally in the upper arm • No meaningful effects on lipids, carbohydrate metabolism, liver function, blood pressure, thyroid or adrenal function

16. Advantages Dysmenorrhea relief in 88% of women Safe in breast feeding High efficacy No abortifacient properties Long term use Does not suppress estradiol levels Disadvantages Requires minor surgical procedure Lack of protection against STDs Bleeding irregularities Infrequent bleeding (27%) Amenorrhea (18%) Prolonged bleeding (15%) Frequent bleeding (7%) Weight gain Implanon

17. Progesterone IUDs • Introduced in the US 2002 • Approved for 5 years of use • 5 year failure rate 0.7% • Actions primarily local (thickens cervical mucous) • Ovulation not usually impaired • Rapid return to fertility • Long term effects on endometrium • By 12 months bleeding reduced 70-90% • Majority of women amenorrheic at one year • Useful in patients with dysmenorrhea and menorrhagia Copper Mirena

18. IUD Mechanism of Action

19. Mirena & Cycle Effects

20. Who Shouldn’t Use the IUD • History of pelvic inflammatory disease • Copper allergy (Copper IUDs only) • Multiple sexual partners • Uterine abnormalities • Untreated infections of the cervix or uterus • History of ectopic pregnancy

21. Oral Contraceptives • Combination of ethinyl estradiol and one of several progestins or progestin alone Mechanism of Action • Inhibit the LH surge needed for ovulation (progestin) • Modulating GnRH release/FSH production (estrogen) • Alter cervical mucous • Induce atrophic changes in the endometrium

22. Estrogen Pharmacokinetics • Synthetic estrogen analogs • Well absorbed by GI tract, skin and mucous membranes • Fat soluble stored in adipose tissue • Prolonged action and higher potency than natural estrogens • Naturally occurring estrogens • Readily absorbed by GI tract, skin and mucous membranes • Also fairly well absorbed when given IM • Partially inactivated by P450 system

23. Progesterone Pharmacokinetics • Rapidly absorbed after administration by any route • Short half life • Almost completely metabolized after one passage through the liver • Synthetic progestins less rapidly metabolized • Adverse Effects • Edema/depression/Increase LDL:HDL

24. Disadvantages of Estrogen • Even for healthy users slight increase of blood clots • For smokers over the age of 35 this risk is dramatically increased • Contraindicated in women with history of certain forms of cancer

25. Contraindications to Estrogen Containing Contraceptives • Migraine with aura • Smokers over the age of 35 • History of thromboembolic disease • Coronary artery disease • Diabetes or hypertension with vascular disease or older than 35 • Lupus erythematosus • Hypertriglyceridemia

26. OCs – Noncontraceptive Benefits • Lower incidence of endometrial and ovarian cancers • Fewer ovarian cysts • Decreased risk of ectopic pregnancy • Minimize acne • Regulation of menses – lighter flow • Reduction in dysmenorrhea • Reduction in symptomatic fibrocystic breast disease • Decrease upper genital tract infection (PID)

27. OCs – Disadvantages • No protection against STDs • Increase in thromboembolic events • Compliance issues • Nausea/weight gain/breast tenderness • May precipitate migraine headaches

28. Oral Contraceptives • Combination pills • Progestin only pills • Post-coital (Emergency) contraception Mechanism of Action Suppression of ovulation by feedback inhibition of endogenous estrogen

29. Combination Formulations • Estrogen prevents ovulation • Progestin prevents implantation and makes cervical mucus impenetrable to sperm • Perfect use efficacy 99% • Rapid return to fertility on discontinuation Monophasic Triphasic Extended Cycle Ethinyl estradiol* Estrogen in 99% of all OCPs

30. Ortho Evra • Introduced in 2002 • Combination estrogen/progestin • Inhibits ovulation similar to OCPs • Each worn for 1 week at a time for 3 consecutive weeks • Fourth week is patch free • Return to fertility within one month • Weight > 198 pounds associated with higher pregnancy rates

31. Nuva Ring • Introduced in mid-2002 • Combination therapy • Half the estrogen dose than traditional oral contraceptives • Inserted at the top of the vagina • Slow, continuous release of hormone over a 3 week period • Return of fertility within one month

33. Progestin Only Pills • “Mini-pill” • Safe in breast feeding • Ovulation not necessarily affected • Must be taken at the same time every day to ensure effectiveness

34. Improper Counseling • 42% women will discontinue method without consulting health care provider • Poor compliance • 47% users miss one or more pills/cycle • 22% miss two or more

35. Emergency Contraception • High dose estrogen/progestin administered within 72 hours of unprotected intercourse • Two doses 12 hours apart • Single mechanism of action not identified • Inhibition or delay of ovulation • Histologic/biochemical changes in the endometrium • Alterations in tubal transport • 98% patients will menstruate by 21 days after treatment

36. Emergency Contraception • Preven Emergency Contraceptive Kit • Plan B • High incidence of nausea & vomiting • Effectiveness rate 75% • If 100 women had unprotected intercourse in the middle two weeks of their cycle 8 would become pregnant. Use of emergency contraception would reduce this number to 2 (75% reduction)

37. Nutrition & Hormonal Contraception

38. Hormonal Contraception & Cancer • Ovarian Cancer • Reduces risk by 30-50% • Even in women with genetic predisposition • Believed to be due to progestin component • Protection after 5 years of use and persists for up to 20 years • Cervical Cancer • Unknown whether increased risk arises from true oncogenic effect or discontinued condom use and risk taking behavior (increased risk of HPV acquisition) • Breast Cancer • Studies conflicting • Risk was higher with older higher dose pills • Study in 2002 no association between Ocs and breast cancer after 15 years of use • Uterine Cancer • Reduces risk by 40-50%

39. Surgical Sterilization • One of most common methods of contraception in the US (25%) • In every case should be considered permanent • Patency of fallopian tube disrupted by excision, ligation, cauterization, or occlusion by rings or clips • 10 year failure rates range from 0.75% to 3.65% • Male sterilization involves disruption of vas deferens • First year failure rate 0.15%

40. Essure Tubal Occlusion • Available in the US since 2002 • Micro-insert composed of stainless steel inner coil, nitinol elastic outer coil and PET fibers • Inserted in the proximal section of each fallopian tube under hysteroscopic guidance • Elicits an intended benign occlusive tissue response • Clinical trials 2 year failure rate 0%

41. Essure

42. Essure Follow-up Dye spillage Abnormal HSG Normal HSG

43. Essure Advantages • Non-incisional • Non-hormonal • Can be performed without general anesthesia • Rapid recovery - discharged 45 minutes after and 92% returned to work the next day • Highly effective • Available to patients with not eligible for invasive sterilization

44. Essure Disadvantages • Chance that both micro-inserts can not be placed (14% in clinical trials) - 83% were placed on second attempt • Must rely on back-up contraception for 3 months • Removal of inserts requires surgery and may result in hysterectomy

45. Natural Family Planning Fertility Awareness Methods • Basal body temperature • Ovulation method • Symptothermal Success based on: • Method’s accuracy in determining fertile days • Ability to comply with method diligently • Couple’s ability to avoid intercourse on fertile days

46. Ovulation Method Billings Method • Monitoring cervical secretions • Avoid unprotected intercourse during preovulatory days until the 4th day after the “peak” secretions day (last day of watery discharge)

47. Symptothermal • Observation of cervical secretions as well as taking basal body temperatures • Avoidance during peak fertility days

48. Standard Days • Based on physiology of the menstrual cycle & functional life span of the sperm and ovum • Best for women with cycle length between 26 and 32 days • Pregnancy only likely on Days 8-19 • Intercourse 5 days prior to ovulation 4% probability • 2 days preceding ovulation 25-28% • 24 hours after 8-10% • Day after 0% • 5% Failure rate • 12% Typical use failure rate