Evolution of Evolution of Contraception: Contraception:

Potions to ProgestinsPotions to ProgestinsJennifer McDonald DOJennifer McDonald DO

BasicsBasics• 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

Pregnancy PreventionPregnancy Prevention

Lactational Amenorrhea (LAM)

•Typical use 95%• Perfect use 98%

Natural Family Planning• 78-88%

No method• 15%

Ancient “Technology”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

““Modern” ContraceptionModern” 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

Development of Non-Development of Non-hormonal Meanshormonal 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)

Barrier MethodsBarrier Methods• Condoms (male & female)

• Diaphragm (used by <2% of women)• Cervical cap (no longer available in the

US)• Contraceptive sponge

Progestin Only OptionsProgestin Only OptionsInjection

Depo Provera

Intrauterine DevicesMirena – good for up to 5 yearsProgestasert – inserted yearly

ImplantsImplanon – good up to 3 years

Mechanism of Action Mechanism of Action Progestin Only Forms Progestin Only Forms

• Blocks LH • Maintains thickness of cervical mucous

• Reduces mobility of fallopian tubes• Changes uterine lining making it

unfavorable for implantation

Side Effects Progestin OnlySide Effects Progestin Only• Headache• Vaginitis

• Breast pain• Weight gain

• Acne

Most disappear within a few months of starting

Depo ProveraDepo 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

Depo Provera cont.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)

Implanon 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)

ImplanonImplanon• 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

ImplanonImplanonAdvantages

• 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 irregularitiesInfrequent bleeding (27%)

Amenorrhea (18%)Prolonged bleeding (15%)Frequent bleeding (7%)

• Weight gain

Progesterone IUDsProgesterone 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

IUD Mechanism of ActionIUD Mechanism of Action

Mirena & Cycle EffectsMirena & Cycle Effects

Who Shouldn’t Use the IUDWho 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

Oral ContraceptivesOral 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

Estrogen PharmacokineticsEstrogen Pharmacokinetics

Naturally occurring estrogens

• Readily absorbed by GI tract, skin and mucous

membranes• Also fairly well absorbed

when given IM• Partially inactivated by

P450 system

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

Progesterone Progesterone PharmacokineticsPharmacokinetics

• 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 EffectsEdema/depression/Increase LDL:HDL

Disadvantages of EstrogenDisadvantages 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

Contraindications to Contraindications to Estrogen Containing Estrogen Containing

ContraceptivesContraceptives• 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

OCs – Noncontraceptive OCs – Noncontraceptive BenefitsBenefits

• 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)

OCs – DisadvantagesOCs – Disadvantages

• No protection against STDs• Increase in thromboembolic events

• Compliance issues• Nausea/weight gain/breast tenderness• May precipitate migraine headaches

Oral ContraceptivesOral Contraceptives• Combination pills

• Progestin only pills• Post-coital (Emergency)

contraception

Mechanism of ActionSuppression of ovulation by feedback

inhibition of endogenous estrogen

Combination FormulationsCombination Formulations• Estrogen prevents

ovulation• Progestin prevents

implantation and makes cervical mucus impenetrable to sperm

• Perfect use efficacy 99%

• Rapid return to fertility on discontinuation

Ethinyl estradiol* Estrogen in 99% of all

OCPs

MonophasicTriphasic

Extended Cycle

Ortho EvraOrtho 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

Nuva RingNuva 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

Progestin Only PillsProgestin Only Pills• “Mini-pill”

• Safe in breast feeding• Ovulation not necessarily affected

• Must be taken at the same time every day to ensure effectiveness

Improper CounselingImproper 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

Emergency ContraceptionEmergency 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

Emergency ContraceptionEmergency ContraceptionPreven 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)

Nutrition & Hormonal Nutrition & Hormonal ContraceptionContraception

Hormonal Contraception & Hormonal Contraception & CancerCancer

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

Uterine Cancer• Reduces risk by 40-

50%

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

Surgical SterilizationSurgical 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%

Essure Tubal OcclusionEssure 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%

EssureEssure

Essure Follow-upEssure Follow-up

Normal HSG Abnormal HSG

Dye spillage

Essure AdvantagesEssure 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

Essure DisadvantagesEssure 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

Natural Family PlanningNatural Family PlanningFertility 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

Ovulation MethodOvulation MethodBillings Method

• Monitoring cervical secretions• Avoid unprotected intercourse during preovulatory days until the 4th day after

the “peak” secretions day (last day of watery discharge)

SymptothermalSymptothermal• Observation of cervical secretions as well

as taking basal body temperatures• Avoidance during peak fertility days

Standard DaysStandard 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