Basics of Hormonal Basics of Hormonal ContraceptionContraception

Dr varsha deshmukhDr varsha deshmukhAss prof Ass prof GMC, AURANGABADGMC, AURANGABAD

ObjectivesObjectives

Discuss the available methods of hormonal Discuss the available methods of hormonal contraception.contraception.

Discuss efficacy, contraindications, and Discuss efficacy, contraindications, and instructions for use.instructions for use.

Explain different methods for reporting contraceptive failure rate.

Reading: Contraceptive Technology 18Reading: Contraceptive Technology 18 thth ed. ed. 391-494391-494

Categories of Categories of ContraceptivesContraceptives

E+P

COCs

Transdermal Patch

Vaginal Ring

P only

POP

DMPA

LNG-IUS

Implants

No hormones

CuT IUD

Barrier

Surgical

NFP

Contraceptive Contraceptive effectivenesseffectiveness Pearl indexPearl index Life-table Life-table

Pearl IndexPearl Index

Number of pregnancies x 1300NuPearl IndexPearl Indexmber of cycles

Pregnancy Rate (%) During 1Pregnancy Rate (%) During 1 stst Year of UseYear of Use

Hatcher: Contraceptive Technology, 18th Ed

% of Women Experiencing % of Women Experiencing an Unintended Pregnancy an Unintended Pregnancy

within the First Year of Usewithin the First Year of Use

% of Women % of Women Continuing Continuing Use at One Use at One

YearYearMethodMethod Typical UseTypical Use Perfect Perfect

UseUseNo MethodNo Method 8585 8585 4242

Male CondomMale Condom 1515 22 5353

Combined Pil l and POPCombined Pil l and POP 88 0.30.3 6868

Ortho Evra PatchOrtho Evra Patch 88 0.30.3 6868

Vaginal RingVaginal Ring 88 0.30.3 6868

DMPADMPA 33 0.30.3 5656

copper T IUDcopper T IUD 0.80.8 0.60.6 7878

levonorgestrel IUSlevonorgestrel IUS 0.10.1 0.10.1 8181

Female Steri l izationFemale Steri l ization 0.50.5 0.50.5 100100

Male Steri l izationMale Steri l ization 0.150.15 0.100.10 100100

Combined Oral Combined Oral ContraceptionContraception

Mechanism of actionMechanism of action Non-contraceptive benefitsNon-contraceptive benefits Indications/contraindicationsIndications/contraindications Counseling on use, startCounseling on use, start History of the pillHistory of the pill

COCsCOCs

80% of US women born after 1945 have 80% of US women born after 1945 have used OCs at some time.used OCs at some time.

Introduced 1960Introduced 1960– 11stst, 2, 2nd,nd, 3 3rdrd generation pills generation pills– Varying progestin componentVarying progestin component

failure rate failure rate – 0.3%, perfect use0.3%, perfect use– 8% typical first-year use8% typical first-year use

Effective, safe, rapidly reversible form of Effective, safe, rapidly reversible form of contraceptioncontraception

Mechanism of actionMechanism of action

Mostly a Mostly a progestinprogestin effect effect– Block LH surge, inhibiting ovulation. (breakthrough Block LH surge, inhibiting ovulation. (breakthrough

ovulation rate 2-8% depending on EE dose)ovulation rate 2-8% depending on EE dose)– Thicken cervical mucusThicken cervical mucus– Inhibit capacitation of spermInhibit capacitation of sperm– Slow tubal motilitySlow tubal motility– Distrupt transport of fertilized ovumDistrupt transport of fertilized ovum– Endometrial changes (atrophy, underlying vascular Endometrial changes (atrophy, underlying vascular

function and structure and alter the metalloprotein content) function and structure and alter the metalloprotein content) Estrogen (ethinyl estradiol or mestranol)

– Cycle control– acts to inhibit follicular growth by decreasing FSH

PharmacologyPharmacologyProgestins

19-nortestosterone

Estranes Gonanes

Norethindrone

Norethindrone Acetate

Ethynodiol diacetate

PharmacologyPharmacology

19-nortestosterone

Gonanes

Norgestrel*

Gestodene

Desogestrel

Norgestimate

Estranes

Progestins

*dextro-norgestrel inactive

levo-norgestrel active

PharmacologyPharmacologyProgestins

19-nortestosterone

Estranes Gonanes

Norethindrone

Norethindrone Acetate

Ethynodiol diacetate

Norgestrel*

Gestodene

Desogestrel

Norgestimate

17α-acetoxyprogesterone

Pregnanes

MegaceMPA

PharmacologyPharmacologyProgestins

19-nortestosterone

Estranes Gonanes

Norethindrone

Norethindrone Acetate

Ethynodiol diacetate

Norgestrel*

Gestodene

Desogestrel

Norgestimate

17α-spironolactone

Drospirenone

17α-acetoxyprogesterone

Pregnanes

MegaceMPA

Metabolic Effects of Estrogen and ProgestinMetabolic Effects of Estrogen and Progestin

EstrogenEstrogen Progestin ProgestinProteinProtein ↑↑ Globulin synthesis* Globulin synthesis* ↓↓ SHBG SHBG

LipidsLipidsHDL cholesterolHDL cholesterol ↑↑ ↓↓LDL cholesterolLDL cholesterol ↓↓ ↑↑

Total cholesterol Total cholesterol ↑↑ ↓↓TriglyceridesTriglycerides ↑↑ ↓↓

* Including many clott ing factors, angiotensinogen, and SHBG* Including many clott ing factors, angiotensinogen, and SHBG

Other benefits- gynOther benefits- gyn ImprovesImproves

– dysmenorrheadysmenorrhea– menstrual blood lossmenstrual blood loss– PMSPMS– fibroidsfibroids– anovulatory bleedinganovulatory bleeding– Mittelschmerz painMittelschmerz pain– Ovarian cystsOvarian cysts– menstrual migrainesmenstrual migraines– Androgen sensitivity/excess conditionsAndrogen sensitivity/excess conditions– PID severityPID severity– EndometriosisEndometriosis– AnemiaAnemia

Decreased risk uterine/ovarian cancerDecreased risk uterine/ovarian cancer Decreased risk benign breast conditionsDecreased risk benign breast conditions

Other benefits – non-gynOther benefits – non-gyn

Possible decrease risk of rheumatoid Possible decrease risk of rheumatoid arthritisarthritis

Increased bone mineral density.Increased bone mineral density. LipidsLipids Possible decrease colorectal cancer Possible decrease colorectal cancer

risk, risk, seizure, asthma, (when related to seizure, asthma, (when related to

menses)menses)

DisadvantagesDisadvantages

General: General: – Daily use Daily use – expense expense – storage storage – no STI protectionno STI protection

Health complications Health complications with COCswith COCs Myocardial Infarction (MI)Myocardial Infarction (MI) StrokeStroke Venous Thromboembolism (VTE)Venous Thromboembolism (VTE) HypertensionHypertension

Health complications Health complications with COCswith COCs MIMI

– arterial thrombosisarterial thrombosis– Low-dose (<50mcg EE) has no significant Low-dose (<50mcg EE) has no significant

increase in risk in healthy women – 1.3increase in risk in healthy women – 1.3– Role of other risk factorsRole of other risk factors

Smoking (75% attributable)Smoking (75% attributable) Underlying atherosclerotic CVDUnderlying atherosclerotic CVD AgeAge

Health complications Health complications with COCs (cont)with COCs (cont) StrokeStroke

– No increase in low risk womenNo increase in low risk women– High risk =High risk =

Migraine with aura (OR 3.0)Migraine with aura (OR 3.0) Smokers (RR 7.6)Smokers (RR 7.6) HTN (RR 25.7)HTN (RR 25.7)

Health complications Health complications with COCs (cont)with COCs (cont) VTEVTE

– Estrogen increases liver production of various Estrogen increases liver production of various clotting factors and platelet activityclotting factors and platelet activity

– Rate per 100,000:Rate per 100,000: Baseline: 4-5Baseline: 4-5 Low-dose OC: 12 – 20Low-dose OC: 12 – 20 Pregnancy: 40 – 60Pregnancy: 40 – 60

– Significant increases most common with risk Significant increases most common with risk factors: thrombophilia factors: thrombophilia

Health complications Health complications with COCs (cont)with COCs (cont) HypertensionHypertension

– Increase angiotensin IIIncrease angiotensin II– E and P enhance aldosterone activity -> E and P enhance aldosterone activity ->

fluid retention and increased BPfluid retention and increased BP– 3-5mm rise common3-5mm rise common– Should normalize after discontinuation. If Should normalize after discontinuation. If

not, HTN workup warranted.not, HTN workup warranted.

Health Complications Health Complications with COCswith COCs Slight increases inSlight increases in

– Benign liver tumorsBenign liver tumors– Chlamydia cervicitisChlamydia cervicitis– Cervical dysplasiaCervical dysplasia

Health Complications Health Complications with COCs (cont)with COCs (cont) Do NOT increase:Do NOT increase:

– Glucose metabolism/DiabetesGlucose metabolism/Diabetes– Gallbladder disease unless preexistingGallbladder disease unless preexisting– Choestatic jaundiceChoestatic jaundice– Hepatic carcinomaHepatic carcinoma

Probably do not increase:Probably do not increase:– Breast cancerBreast cancer

Absolute Absolute contraindicationscontraindications Breastfeeding < 6wk ppBreastfeeding < 6wk pp Smoke > 15 cig/day; >35 yoSmoke > 15 cig/day; >35 yo Uncontrolled HTNUncontrolled HTN History of DVT/PEHistory of DVT/PE ThrombophiliaThrombophilia Heart disease, MI, CVAHeart disease, MI, CVA Migraine with auraMigraine with aura Breast cancerBreast cancer

Pil l init iation methodsPil l init iation methods

Quick-startQuick-start– Day of visitDay of visit– Reasonably sure not pregnantReasonably sure not pregnant– 7 days back-up7 days back-up– Remind that menses may be delayed or irregularRemind that menses may be delayed or irregular– More successful at getting women started on the pills.More successful at getting women started on the pills.

First-day startFirst-day start– In regularly ovulating, normal mensesIn regularly ovulating, normal menses

Sunday startSunday start– Back up needed for 7 days. Back up needed for 7 days. – Not usually recommended.Not usually recommended.

Patterns of Pil l usePatterns of Pil l use

Monthly cycling 21/7Monthly cycling 21/7 Multiphasic PreparationsMultiphasic Preparations

– Alters the dosage of both the estrogen and Alters the dosage of both the estrogen and progestin components periodically throughout the progestin components periodically throughout the pill-taking schedulepill-taking schedule

Reduction in pill-free intervalsReduction in pill-free intervals– Using a 4-day pill-free interval is associated with Using a 4-day pill-free interval is associated with

greater ovarian suppression.greater ovarian suppression. Extended cycle regimens (bicycling, tricycling)Extended cycle regimens (bicycling, tricycling)

– 42 – 84 active followed by 7 inactive pills42 – 84 active followed by 7 inactive pills– Seasonale, SeasoniqueSeasonale, Seasonique

Continuous useContinuous use

Transdermal Contraceptive Transdermal Contraceptive PatchPatch

Ortho-McNeil Pharmaceutical 2001

Transdermal Transdermal Contraceptive PatchContraceptive Patch Advantages:Advantages:

– Similar indication profile as COCs.Similar indication profile as COCs.– Similar non-contraceptive benefitsSimilar non-contraceptive benefits– Once-weekly dosingOnce-weekly dosing– Visible Visible

DisadvantagesDisadvantages– VisibleVisible– Similar to COCSimilar to COC– No STI protectionNo STI protection– Local skin irritationLocal skin irritation

Patch and VTE?Patch and VTE?

Hype: “Hype: “Birth control patch linked to higher Birth control patch linked to higher fatality ratefatality rate”-Associated Press July 20, 2005”-Associated Press July 20, 2005

Findings:Findings:– 2/3 case-control studies do not show increased 2/3 case-control studies do not show increased

risk in patch users vs. pill usersrisk in patch users vs. pill users– 1 study that does show risk has selection bias. All 1 study that does show risk has selection bias. All

patch users were new users, pill users could be patch users were new users, pill users could be continuing userscontinuing users

Jick, S Contraception 2007; 76:4-7Jick, S Contraception 2006; 73: 223-226Cole, J Obstetrics and Gynecology 2007; 9(1):339-346

Van den Heuvel et al, Contraception. 2005 72(3) 168-74.

Contraceptive Vaginal RingContraceptive Vaginal Ring

www.contraceptiononline.com

Vaginal Contraceptive Vaginal Contraceptive RingRing

– 0.12mg/day etonogestrel (the metabolite of desogestrel)0.12mg/day etonogestrel (the metabolite of desogestrel)– 15 15 µµg/day ethinyl-estradiolg/day ethinyl-estradiol

3 weeks in /1 week ring-free3 weeks in /1 week ring-free less BTB than OCsless BTB than OCs Advantages Advantages

– rapid return to ovulation rapid return to ovulation – lower doses of hormones, lower doses of hormones, – ease and convenience, ease and convenience, – improved cycle control.improved cycle control.

Same contraindications as OCsSame contraindications as OCs

Progestin-only Progestin-only contraceptioncontraception Describe the advantages and limitations of Describe the advantages and limitations of

progestin only contraception. progestin only contraception. List the administration methods of progestin List the administration methods of progestin

only contraception. only contraception. Discuss the factors relevant to prescribing Discuss the factors relevant to prescribing

injectable progestin only contraception. injectable progestin only contraception. Describe the Implanon contraceptive device Describe the Implanon contraceptive device

and for whom it is appropriate. and for whom it is appropriate.

Progestin Only Progestin Only ContraceptivesContraceptivesOral pillOral pill 19731973Injectable suspensionInjectable suspension

IntramuscularIntramuscular 1968 (1992 U.S.)1968 (1992 U.S.)SubcutaneousSubcutaneous 20052005

Subdermal ImplantSubdermal Implant6 LNG6 LNG 199019902 LNG2 LNG 199619961 ENG1 ENG 2001 (2006 U.S)2001 (2006 U.S)

Intrauterine System (LNG)Intrauterine System (LNG) 20022002

Mechanism of ActionMechanism of Action

Ovulation inhibition by decreased Ovulation inhibition by decreased GnRH pulse frequency.GnRH pulse frequency.

Suppression of midcycle LH and FSH Suppression of midcycle LH and FSH surgesurge

Thickened and decreased cervical Thickened and decreased cervical mucusmucus

Endometrial changes (atrophic Endometrial changes (atrophic endometrium)endometrium)

Progestin-only Pil lsProgestin-only Pil ls

NorethindroneNorethindrone– MicronorMicronor– Nor-QDNor-QD

NorgestrelNorgestrel– OvretteOvrette

Slightly less effective than COCSlightly less effective than COC Highly sensitive to user errorHighly sensitive to user error

Depot Medroxyprogesterone Depot Medroxyprogesterone AcetateAcetate

150 mg intramuscular q 3 mos150 mg intramuscular q 3 mos– DeltoidDeltoid– GlutealGluteal

104mg subcutaneous q 3 mos104mg subcutaneous q 3 mos Contraceptive level of progesterone Contraceptive level of progesterone

maintained for 14 weeksmaintained for 14 weeks DMPA is not a “sustained-release” systemDMPA is not a “sustained-release” system

– Relies on high peaks of progestin to Relies on high peaks of progestin to inhibit ovulation and thicken mucusinhibit ovulation and thicken mucus

DMPA - ? disadvantagesDMPA - ? disadvantages

6-9 month delay in return to fertility6-9 month delay in return to fertility Weight gainWeight gain

– Normal weight women do not have Normal weight women do not have increased weight gainincreased weight gain

– MPA stimulates appetiteMPA stimulates appetite Bone loss Bone loss

– similar to lactationsimilar to lactation– reversible reversible – smoking may be a risk factor.smoking may be a risk factor.– No evidence for increased fracture riskNo evidence for increased fracture risk

ImplanonImplanon

3-year implant3-year implant 68 mg etonorgestrel68 mg etonorgestrel Highly effectiveHighly effective Irregular menstrual profileIrregular menstrual profile Endogenous estrogen Endogenous estrogen

present, bones protectedpresent, bones protected Easier removal than Easier removal than

NorplantNorplant Requires provider trainingRequires provider training

www.implanon-usa.com

Questions ?Questions ?