CONTRACEPTIVE FACTS AND FAMILY PLANNING

Updates on Family Planning Methods

RONALDO R. SANTOS, MD, FPOGSDepartments of Obstetrics and Gynecology,FEU-NRMF and JRRMMC

MODULE 3

Is sex important?

WHO reports: 42 B coitus/year 115 million/day: 250,000/day 4.8 million/hr: 10,000/day 1,331 ejaculations / sec: 2.8

0

10

20

30

40

50

60

2000 2001 2004 2005 2006 2008

4749.8 49.4 49.3 50.6 50.7

32.3 33 35.1 36 35.9 34

14.7 16.814.2 13.2 14.8 16.7

Total Modern Trad

Contraceptive Prevalence Rate in the Phil. (2000 - 2008)

Contraceptive Use according to methods in the Phil among women 15 - 45 years

Effectiveness

Outline of Presentation

1. Understand the new methods of contraception

New generation progestogens Combined injectable contraception Extended and continuous use oral contraceptives Levonorgestrel intrauterine system Single rod implant Essure Frameless IUD Female condom Emergency contraception

Outline of Presentation

2. Understand the mechanism of action of the IUD

3. Define the following relationships: IUD and PID, Ectopic pregnancy Hormonal contraception and breast, cervical

and ovarian cancers DMPA and breast cancer LAM and breast cancer Calendar method and abortion

4. Apply the WHO Medical Eligibility Criteria

References:

Vern L. Katz, MD, Gretchen M. Lentz, MD, Rogerio A. Lobo, MD and David M. Gershenson, MD, Comprehensive Gynecology 5th ed, Mosby, an affiliate of Elsevier Inc., Philadelphia, PA, 2007

Berek, Jonathan S. Berek & Novak's Gynecology, 14th Edition, Lippincott Williams & Wilkins, 2007

John O. Schorge, MD, Joseph I. Schaffer, MD, Lisa M. Halvorson, MD, Barbara L. Hoffman, MD, Karen D. Bradshaw, MD, F. Gary Cunningham, MD, Editors, Williams Gynecology, Williams Gynecology, The McGraw-Hill Companies, Inc, 2008

Family Planning: A global Handbook for Providers, WHO Department of Reproductive Health and Research, Johns Hopkins Bloomberg School of Public Health/Center for Communication Programs, 2007

WHO Medical Eligibility Criteria for contraception, 4th ed, 2009 Cunningham, Leveno, Bloom, Hauth, Rouse, Spong, eds, Williams

Obstetrics 23rd ed, McGraw-Hill Companies, USA, 2010 The Philippine Clinical Standards Manual on Family Planning, Dept of

Health, 2006

New Progestins: Notable characteristics

Dienogest: antiandrogenic Drospirenone: antimineralocorticoid Trimegestone: highly progestational Nestorone: highly progestational and

antigonadotrophic Nomogestrol acetate: highly

antigonadotrophic

ClassificationPROGESTERONE DERIVATED TESTOSTERONE DERIVATED

17-OH PROG PREGNANE

19-NORPROGNON-PREGNANE

ESTRANE GONANES

OHprogesterone caproate

Nomegestrol acetate

Lynestrenol Norgestrel

OHprogesterone heptanoate

Demegestone Levonorgestrel Desogestrel

Gestonorone caproate

Promegestone Norethisterone Gestodene

Chlormadinone acetate

Nestorone Norethisterone acetate

Norgestimate

Medrogestone Trimegestone Ethinodiol diacetate

MPA Norgestrienone

CPA Dienogest

Dienogest

Anti-androgenic: 40% potency of cyproterone acetate

As OCP with EE 30 ug: Pearl index of 0.2

Also used for HRT in combination with estradiol valerate

Drospirenone

Derived from spirolactone

Antimineralocorticoid Competes with

aldosterone receptors 30% potency of

cyproterone acetate Available as

Yasmin: 30 ug EE Yasminelle: 20 ug EE Yas: 20 ug EE x 24 days

(2008) Indicated for PMDD

Trimegestone (TMG)

High progesterone receptor affinity

30x more potent than MPA

Used for HRT

Nomegestrol Acetate

20% potency of CPA Component of HRT Highly

antigonadotrophic: can be use for inhibition of ovulation

Nestorone

Not active orally but in target tissues only

Used in sustained release implants, vaginal rings or transdermal systems

Highly antigonadotrophic

Progestogens: Relative potencies

Sitruk-Ware R. Menopause 9:6, 2002Sitruk-Ware R. Menopause 9:6, 2002

McPhail index

NES 100 > LNG 10 > Progesterone 1

Ovulation inhibition

NES 30 > LNG 10 > Progesterone 1

TMG DSG NOMAc NET DrospirenoneTMG DSG NOMAc NET Drospirenone

MPA Norgestimate MPA Norgestimate

DSG MPA NET Drospirenone Norgestimate CPA Dienogest

DSG MPA NET Drospirenone Norgestimate CPA Dienogest

Progestational activity

0 20 40 60 80 100

CPA

DNG

DRSP

CMA

Muhn P. et al. Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Contraception 1995; 51: 99-110 Stölzer W. et al. Tierexperimentelle Charakterisierung des Gestagens Dienogest (STS 557). II. Antigonadotrope, gestagene, estrogene und antiandrogene Wirkungen. III Jenaer Symposium zur hormonalen Kontrazeption, 1985

Relative antiandrogenic potency (Hershberger test)

Highest antiandrogenic potency of CPA vs. other progestagens

Antiandrogenic potency

Continuous-Use Oral Contraceptives

Seasonale 150 µg

levonorgestrel and 30 µg ethinyl estradiol.

a pill every day for 84 days (12 weeks) and then take hormone-free pills for 7 days.

Lybrel: no menstruation pill

90 ug Levonorgestrel

20 ug ethinyl estradiol

365 days without pill-free interval

Extended use OCP

Goal: to prevent menstruation

Rationale: Amenorrhea leads to a reduction in: Premenstrual syndrome Dysmenorrhea

Combined Injectables

Monthly injection of Estrogen/Progestin: less bleeding problems, better compliance Earlier return to fertility

Cyclofem/Cyclo-Provera Feminena/Lunelle/Lunella: 5 mg estradiol and 25 mg MPA

Mesigyna/Norigynon: 5 mg estradiol and 50 mg Norethisterone enanthate

Norifam

rationale

Negative effects in progestin injectables bleeding pattern disruption (Goldberg, 2007)

return to fertility: 9 – 10 months (Schwallie 1974; Pardthaisong 1980; Kaunitz 2000)

Regular cyclic endometrial shedding for combined estrogen – progesterone prep. (Kaunitz, 2000).

Composition: Norifam

Estradiol valerate 5 mg

NaturalLess potent than ethinyl estradiol

Norethisterone enanthate 50 mgo Available as

Noristerat

Indication: Contraception

Mechanism of Action:How does it prevent pregnancy

Inhibition of ovulation

Motility of the endometrium and fallopian tube is altered

Cervical mucus thickens preventing entry of sperms

Pharmacokinetics

Injected intramuscularly every month Elevated estradiol levels for 7 – 11 days Predominance of progesterone in the 2nd

half of the cycle Inhibits follicle maturation for 30 days Inhibit ovulation and corpus luteum

formation for 60 days

Sang, Contraception, 1994 Apr;49(4):361-85.

Monthly Injectable (Lunelle)

MPA/E2C injection: 25 mg of medroxyprogesterone acetate and 5 mg of estradiol cypionate

Monthly intramuscular injection Contraindications the same as oral

contraceptive pills

Kaunitz AM., Obstet Gynecol Clin North Am. 2000 Dec;27(4):741-80.

DMPA-SC

Lower dose: 104 mg Subcutaneous

injection every 3 months

Pre-filled Uniject syringe

Self administered

The NuvaRing

releases 120 µg of etonogestrel and 15 µg of ethinyl estradiol per day

1 ring every 3 weeks, 13 rings in a year

Pearl index of 0.65 (95% confidence interval 0.24-1.41)

32-40 US$ Nestorone 150 ug in one

ring, x 3 wks, remove, reinserted, cycle repeated.

Can be removed for 3 hrs if bothersome during sex

Otho-Evra Patch

150 µg of the progestin norelgestromin and 20 µg of the estrogen ethinyl estradiol per day.

Weekly patch x 3 followed by patchless week

square patch, each side about 4.45 centimeters (1.75 inches) long, resembling a light brown bandage

Spray-On Contraceptives

Nestorone Metered Dose Transdermal System, a daily progestin-only spray-on contraceptive, began in Australia in 2004.

In a clinical trial a Nestorone gel applied to the skin daily for three months suppressed ovulation in 83% of participants applying 1.2 mg per day

Phase II studies

Implants

Levonorgestrel: Jadelle, 2 rods of 140 mg, 5 years effectiveness

Etonogestrel: Implanon, 1 rod, 3 years effectiveness

Nestorone: ST 1435, 1 rod, 2 years

Levonorgestrel - IUS

Levonorgestrel: 20 ug/day

5 years effective Indicated for DUB Some bleeding problems Mirena, Femilis

Standard Days Method

Natural FP method Color-coded beads:

Cycle beads Fertile period: 8 to

19 days For women with

cycles 26-32 days only

12/100 pregnancies

How to Use

Day 1

Pre-ovulation (infertile)

Fertile days (D8 –D19)

Post-ovulation (infertile)

TwoDay method

Based on cervical secretions Q1) “Did I notice secretions today?” and

Q(2) “Did I notice secretions yesterday? 14/100 pregnancies

Emergency Contraception

Taken within 72 hours after unprotected intercourse

Plan B: 0.75 mg of levonorgestrel (postinor) Yuzpe: 100 ug of EE and 1 mg norgestrel or

0.5 levonorgestrel taken 12 hours apart IUD insertion MOA: inhibition or delay of ovulation,

alteration of the endometrium, sperm penetration, and tubal motility

Established pregnancies are not harmed.

Essure – Microcoil

FEMALE CONDOM

New Methods

Lower doses of Ethinyl Estradiol: safer Newer Progestins: other non-

contraceptive benefits New routes of administration:

compliance New technology: effectiveness

ASSOCIATIONS AND RELATIONSHIPS

Mechanics:

5 groups of 5 members each Identify your team with a innovative name for a

new contraceptive Objective: to earn points Group earn points if they answer the questions

correctly The group with the highest points wins Each member of the team can only answer a

maximum of 2 questions Decision of the judge is final I am the judge

Relationships, Associations

IUD and: Abortion PID Ectopic pregnancy

COC and: VTE, MI and CVA Breast, cervical and ovarian cancer

DMPA and Breast cancer Calendar method and abortion

GROUPINGS

PRACTICE: HOW MANY DAYS BEFORE OVULATION CAN SEXUAL ABSTINENCE PREVENT PREGNANCY?A. 2B. 3C. 5D. 7

Contraception: General

Because sperm may survive 5 to 7 days in the female genital tract, even a week's abstinence around the time of actual ovulation offers no guarantee against pregnancy

Ovulation can occur even in the absence of menstruation.

Pregnancies have occurred after a single act of coitus 7 days before apparent ovulation indicated by basal body temperature.

PRACTICE 2: BASED ON THE GRAPH, WHICH OF THE FOLLOWING COITAL POSITION IS ASSOCIATED WITH PRETERM DELIVER WITH PROM?

A. FEMALE SUPERIORB. MALE SUPERIORC. SIDE BY SIDED. REAR ENTRY

51Ekwo et al, ACOG 168:1, 1993

Risk of Preterm Delivery with PROM as to Coital Position

0

1

2

3

4ODD’S RATIO ACCORDING TO COITAL POSITION

Clinical vs. Statistical Significance

STATISTICAL SIGNIFICANCE◦ Hypothesis testing: expressed as

probabilities or P value◦ Confidence interval: expressed as a

range of values CLINICAL SIGNIFICANCE

◦ If RR = 1: no association◦ If RR > 1: harm◦ If RR < 1: protection

Relationship of Coitus to Pregnancy Outcome

SEXUAL ACTIVITY

PRETERM DELIVERY WITH PROM

TERM WITH PROM

PRETERM DELIVERY WITHOUT PROM

FEMALE SUPERIOR

1.50 (0.80-2.82) 0.88 (0.41-1.67) 1.08 (0.51-2.29)

MALE SUPERIOR 1.84 (1.05-3.22) 1.59 (0.93-2.71) 2.05 (1.20-3.50)

SIDE BY SIDE 1.19 (0.71-1.98) 0.84 (0.48-1.36) 1.19 (0.71-2.01)

REAR ENTRY 1.40 (0.72-2.72) 0.88 (0.43-1.79) 1.06 (0.55-2.01)

ORGASM 1.91 (1.12-3.23) 1.12 (0.70-1.79) 0.93 (0.60-1.41)

Ekwo et al, ACOG 168:1, 1993

IUD

It is approved for up to 10 years of continuous use.

The levonorgestrel T is approved in the United States for 5 years of use, although studies through 7 years of use show no loss of efficacy

Sivin I, Stern J. Health during prolonged use of levonorgestrel 20 micrograms/d and the copper TCu 380A intrauterine contraceptive devices: a multicenter study. Fertil Steril 1994;61:70–77.)

1. WHAT IS THE MAIN MECHANISM OF ACTION OF IUD AS A CONTRACEPTIVE METHOD?

A.Prevents implantationB.Inhibits ovulationC.Impairs sperm and egg

motilityD.Thickens cervical mucus

Mechanism of Action:

Intrauterine devices cause the formation of biologic foam within the uterine cavity that contains strands of fibrin, phagocytic cells, and proteolytic enzymes.

Copper IUDs continuously release a small amount of the metal, producing an even greater inflammatory response.

All IUDs stimulate the formation of prostaglandins within the uterus, consistent with both smooth muscle contraction and inflammation.

Scanning electron microscopy studies of the endometrium of women wearing IUDs show alterations in the surface morphology of cells, especially of the microvilli of ciliated cells

There are major alterations in the composition of proteins within the uterine cavity, and new proteins and proteinase inhibitors are found in washings from the uterus

The altered intrauterine environment interferes with sperm passage through the uterus, preventing fertilization.

IUD and MOA

Sperm can be obtained by laparoscopy in washings from the fallopian tubes of control women at midcycle; fewer sperm are present in the tubal washings from women wearing IUDs (57Stanford JB, Mikolajczyk RT. Mechanism of action of the intrauterine device: update and estimation of post fertilization effect. Am J Obstet Gynecol 2002;187:1699-1708).

Ova flushed from the tubes at tubal sterilization showed no evidence of fertilization in women wearing IUDs (58Alvarez F, Guiloff E, Brache V, et al. New insights on the mode of action of intrauterine devices in women. Fertil Steril 1989;49:768-773.

studies of serum β-human chorionic gonadotropin levels in women wearing IUDs do not indicate pregnancy (59Segal S, Alvarez-Sanchez F, Adejeuwon CA, et al. Absence of chorionic gonadotropin in sera of women who use intrauterine devices. Fertil Steril 1985;44:214-218).

The contraceptive effectiveness does not depend on interference with implantation, although this phenomenon also occurs and is the basis for using copper IUDs for emergency contraception.

The IUD is not an abortifacient.

New Insights on MOA of IUD

Ova Fertilized0

10

20

30

40

50

60No IUD IUD 115 women using

no contraception vs. 56 with IUDs for surgical sterilization

Tubal flushings 48 and 120 hrs after midcycle LH peak

Alvarez F, et al, Fertil Steril. 1988 May;49(5):768-73.

2. WHICH OF THE FOLLOWING STATEMENTS BEST DESCRIBE THE ASSOCIATION OF IUD AND PID?A. CURRENT IUD USE IS A RISK FACTOR FOR PIDB. PID IS ASSOCIATED WITH IUD INSERTIONC. IUD IS THE CAUSE FOR CHRONIC PIDD. INCIDENCE OF PID IS DIRECTLY PROPORTIONAL TO DURATION OF IUD USE

IUD

Increased risk was detectable only within 4 months of insertion of the IUD.

A still larger, prospective World Health Organization study revealed that PID increased only during the first 20 days after insertion.

Thereafter, the rate of diagnosis of PID was about 1.6 cases per 1,000 women per year, the same as in the general population

Farley TMM, Rosenberg MJ, Rowe PJ, et al. Intrauterine devices and pelvic inflammatory disease: an international perspective. Lancet 1992;339:785-788.

3. IS IUD A RISK FACTOR FOR ECTOPIC PREGNANCY?

A.NoB.Yes, only if compared to other

contraceptive methodsC.Yes, only if compared to non-

contraceptive userD.Yes, compared to other contraceptive

methods and to non-contraceptive users

IUD

Ectopic Pregnancy: If pregnancy occurs in an IUD wearer, it will be ectopic in about 5% of cases. This is because the fallopian tubes are less well protected against pregnancy than is the uterus.

Compared with women using no contraception, however, women wearing either the copper T380A or the levonorgestrel T have an 80% to 90% reduction in the risk of ectopic pregnancy (53), which is a greater reduction than that seen for users of barrier methods.

Both the copper T 380A and the levonorgestrel T protect against ectopic pregnancy.

IUD and pregnancy

In case of pregnancy and the strings of the IUD are not visible, an ultrasound examination should be performed to localize the IUD and determine whether expulsion has occurred.

If the IUD is present, there are three options for management: Therapeutic abortion Ultrasound-guided intrauterine removal of the IUD Continuation of the pregnancy with the device left in place

No recommendation on the time of insertion

Combined Oral Contraception

Typically, they are administered for 21 days beginning on the Sunday after a menstrual period, then discontinued for 7 days to allow for withdrawal bleeding that mimics the normal menstrual cycle.

Alternatively, OCs can be started on the first day of menstruation.

The 28-day version provides placebo tablets for the last 7 days of the cycle so the user simply takes one pill a day and starts a new pack as soon as the first pack is completed.

COC

Ovulation can be inhibited by estrogen or by progestin alone. Pharmacologic synergism is exhibited when the two

hormones are combined and ovulation is suppressed at a much lower dose of each agent.

Combination OCs, patches, and the NuvaRing suppress basal follicle-stimulating hormone FSH and LH. They diminish the ability of the pituitary gland to synthesize gonadotropins when it is stimulated by the hypothalamic GnRH (89).

Ovarian follicles do not mature, little estradiol is produced, and there is no midcycle LH surge. Ovulation does not occur, the corpus luteum does not form, and progesterone is not produced.

This blockade of ovulation is dose related.

4. HOW CAN THE RISK OF VTE AMONG USERS OF COC BEST DESCRIBED?

A.No clinical nor statistical riskB.Both Clinical and statistical riskC.Clinically significant risk onlyD.Statistically significant risk only

COC and thrombosis

The absolute risk of thrombosis in COC users taking pills containing 30 to 35 µg EE is 3 per 10,000 per year, compared with 1 per 10,000 reproductive-aged women not using OCs and 6 per 10,000 in pregnancy (106 Farmer RDT, Preston TD. The risk of venous thromboembolism associated with low oestrogen oral contraceptives. J Obstet Gynaecol

1995;15:195-200). Thrombosis risk is apparent by 4 months after starting estrogen-

containing OCs and does not increase further with continued use. Risk is highest during the first year of use (107Sazelenko JK, Nace MC,

Alving B. Women with thrombophilia: assessing the risks for thrombosis with oral contraceptives or hormone replacement therapy. Semin Thromb Hemost 1998;24(suppl 1):33–39.

).

Hormonal Contraception and VTE National Cohort Study in Denmark: 1995-

2005 Full article available

71

Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C., BMJ. 2009 Aug 13;339:b2890. doi: 10.1136/bmj.b2890.

Hormonal contraception and risk of venous thromboembolism: national follow-up study.Study

Healthy Danish women 15-49 years, from 1995-2005, 10.4 M woman –years

NON USERS OC USERS0

1

2

3

4

5

6

7

3.01

6.29VTE RISK RATIO / 10,000 WOMEN-YEARS

72

Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C., BMJ. 2009 Aug 13;339

Hormonal contraception and risk of venous thromboembolism: national follow-up study.Study Healthy Danish women 15-49 years, from 1995-2005, 10.4 M woman –

years

NON USER < 1 1-4 >40

1

2

3

4

5

VTE RATE RATIO ACCDG TO DURATION OF USE IN YEARS

73

Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C., BMJ. 2009 Aug 13;339

Hormonal contraception and risk of venous thromboembolism: national follow-up study.Study

Healthy Danish women 15-49 years, from 1995-2005, 10.4 M woman –years

LEVO NORETH NORGE DESO GST DRSP CPA0

1

2

3 VTE RATE RATIO ACCDG TO TYPE OF PROGESTINS

74

van Hylckama Vlieg A, et al. BMJ. 2009 Aug 13;339:b2921. doi:0.1136/bmj.b2921.

Levonorgestrel Gestodene Desogestrel Lynestrenol Norethisterone Cyproterone Norgestimate Drospirenone0

5

10

15

20

25

3.6 5.6 7.3 5.6 3.9 6.8 5.9 6.3

Risk (OR, 95% CI) of VTE associated with type of progestogen in combined OCs

MEGA: Venous thromboembolism increased with OC use irrespective of progestin type Study 1524 Premenopausal women <50 years old vs 1760 controls

MEGA study: multiple environmental and genetic assessment of risk factors for venous thrombosis-study.

Risk of venous thromboembolism* by population characteristics

*Cases of non-fatal venous thromboembolism.

OC users with Fac-tor V Leiden

Pregnant women

OC users

Non-OC users

0 50 100 150 200 250 300 350 400

230

60

35

8

Estimated average risk/100,000 women/year

75FDA. FDA Talk Paper. 1995. Ridker PM, et al. JAMA. 1997 Apr 23-30;277(16):1305-7.

76Ridker PM, et al. J Am Med Assoc 1997;277:1305–7.

Prevalence in Asian women of Factor V Leiden mutation is lowStudy of the ethnic distribution of Factor V Leiden mutation in 4047 men and women

White

Blacks

Asians

Hispanics

Native Americans

0 1 2 3 4 5 6

4.85

1.23

0.45

2.21

1.25

Prevalence of Factor V Leiden mutation, %

4. WHICH OF THE FOLLOWING CONDITIONS HAS THE GREATEST ATTRIBUTABLE RISK TO AN ISCHEMIC CARDIOVASCULAR EVENT AMONG OCP USERS?

A.Age > 35 but < 50B.Controlled hypertensionC.BMI > 30D.25 sticks of cigarettes/day

COC and Vascular events

Past use of OCs does not increase risk for subsequent myocardial infarction (123Stampfer MJ, Willett WC, Colditz GA, et al. A prospective study of past use of oral contraceptive agents and risk of cardiovascular diseases.

N Engl J Med 1988;319:1313-1317.

Smokers taking OCs had seven times the risk of ischemic (thrombotic) stroke when compared with smokers who did not use OCs, and hypertensive women had 10-fold increased risk if they took OCs, but a fivefold risk if they did not (129World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Ischaemic stroke and combined oral contraceptives: results of an international, multicenter, case control study. Lancet 1996;348:505-510).

COC and MI

After adjusting for age, illness, smoking, ethnicity, and body mass index, risk for myocardial infarction was not increased by OC use (OR, 1.14; CI 95%, 0.27 to 4.72).

Of heart attack victims, 61% smoked; only 7.7% were current users of OCs.

In a later study, the same investigators pooled results from the California study with a similar study from Washington State.

The results were the same. Current users of low-dose OCs had no increased risk for myocardial infarction after adjustment for major risk factors and sociodemographic factors (122Sidney S, Siscovick DS, Petitti DB, et al. Myocardial infarction and use of low dose oral

contraceptives: a pooled analysis of 2 U.S. studies. Circulation 1998;98:1058-1063).

Ischemic Stroke Risk With Oral Contraceptives:A meta-analysisStudy 73 Studies published from January 1960 through November 1999

81

Leslie Allison Gillum, BA, JAMA, July 5, 2000—Vol 284, No. 1

HPN NO HPN Hx OF HPN NO HX of HPN01234567 RISK RATIO OF OC USERS

Risk of Myocardial Infarction among women < 50 years old: effect of smoking

0

10

20

30

Rel

ativ

e R

isks

Non smoker1-24 sticks +25sticks/day

Never smoked Past smoker Current smoker

COC and stroke

Similarly, a study from Denmark found that women with diabetes had a fivefold increase risk for stroke, which increased to 10-fold if they took OCs (132 Lidegaard O. Oral contraceptives, pregnancy and the risk of cerebral thromboembolism: the influence of diabetes, hypertension, migraine and

previous thromboembolic disease. BJOG 1995;102:153-159). Unfortunately, these data were not limited to low-

estrogen OCs. Oral estrogen alone has no adverse effect on glucose

metabolism, but progestins exhibit insulin antagonism .

84

Risk of myocardial infarction in current OC users by smoking status

Heavy smokers defined as: *10 cigarettes/day; **15 cigarettes/day; ***25 cigarettes/day.

WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1997 Apr 26;349(9060):1202-9. Croft P, Hannaford P. BMJ. 1989 Jan;298(6667):165-8. Rosenberg L, et al. Am J Epidemiol 1990 Jun;131(6):1009-16.

Current user, nonsmoker

Never user, heavy smoker

Current user, heavy smoker

Current user, nonsmoker

Never user, heavy smoker

Current user, heavy smoker

Never user, heavy smoker

Current user, heavy smoker

-49

1

51

101

151

201

251

301

4 11.1

87

0.9 3.320.8 8.7

30

Risk (RR, 95% CI) of MI with OC use and smoking status

WHO (Europe). 1997* Croft P (RCGP). 1989** Rosenberg L. 1990***

85Margolis KL,et al. Fertil Steril 2007 Aug;88(2):310-6.

Low-dose OC use not associated with increased myocardial infarction riskStudy 48,321 Swedish women, aged 30–49 years, followed for

mean of 11 years

Most current users were taking low-dose estrogen and second- or third-generation progestins

Results

Former users Current users0.2

0.6

1

1.4

1

0.700000000000001

Risk (RR, 95% CI) of fatal and nonfatal MI in OC users vs non-users

5. WHICH OF THE FOLLOWING THYROID CONDITIONS IS COC CONTRAINDICATED?

A.HYPERTHYROIDISMB.HYPOTHYROIDISMC.BOTHD.NEITHER

COC and thyroid function tests The estrogen in OCs increases circulating

thyroid-binding globulin, thereby affecting tests of thyroid function that are based on binding, increasing total thyroxine (T4) levels, and decreasing triiodothyronine (T3) resin uptake.

The results of actual thyroid function tests, as measured by free T4 and radioiodine tests, are normal (138Mishell DR Jr, Colodyn SZ, Swanson LA. The effect of an oral

contraceptive on tests of thyroid function. Fertil Steril 1969;20:335-339).

6. IN WHICH GROUP OF COC USERS HAS THE GREATEST RELATIVE RISK OF BREAST CANCER ? A.Positive family history of breast

cancerB.> 4 year use prior to FFTP (first

full term pregnancy)C.35-40 years of ageD.Caucasian pill users

COC and breast cancer

A meta-analysis of 54 studies of breast cancer and hormonal contraceptive use reanalyzed data on 53,297 women with breast cancer and 100,239 controls from 25 countries, representing about 90% of the epidemiologic data available worldwide at that time Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiologic studies. Lancet 1996;347:1713-1727.

Current use of OCs was associated with a very small but statistically stable 24% increased risk (RR, 1.24; 95% CI, 1.15-1.33).

COC and breast cancer

The risk fell rapidly after discontinuation, to 16% 1 to 4 years after stopping and to 7% 5 to 9 years after stopping.

Risk disappeared 10 years after cessation (RR, 1.01; 95% CI, 0.96-1.05).

Results did not differ in any important way by ethnic group, reproductive history, or family history.

Since the meta-analysis was published, subsequent studies have found no increased risk. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and risk of breast cancer. N Engl J Med 2002;346:2025-2032

Use of oral contraceptive pills does not lead to an increased risk of breast cancer

0

1000

2000

3000

4000

nu

mb

er

of

cases

Breast Cancer Normal

OCP None

OR = 0.91 (95%CI 0.90-0.91)

Marchbanks, PA, et al. Oral contraceptive and the risk of breast cancer. NEJM 2002 June, 346(26):2025-2032

92

Lynn Rosenberg, et al, Amer J Epid Vol 169, No. 4, Dec 2008

Odd’s Ratio for invasive Breast cancer for OCP user accdg to duration of useStudy 907 cases with incident invasive breast cancer and 1,711 controls

from 1993 to 2007

NON USER 1-4 5-9 10-14 >150

0.5

1

1.5

2

2.5

3

3.5

ODD.’S RATIO ACCDG TO DURATION OF USE

93

CHRIS KAHLENBORN, MD; et al, Mayo Clin Proc. 2006;81(10):1290-1302

Odd’s Ratio for Premenopausal invasive Breast cancer among OCP user

Study Meta-Analysis: 34 studies after 1980, < 50 years old

NON USER OVERALL B4FFTP AFFTP0

0.20.40.60.8

11.21.41.61.8

ODD.’S RATIO

7. WHICH OF THE FOLLOWING RELATIONSHIP BETWEEN HORMONAL CONTRACEPTION AND CERVICAL CANCER HAS NO EVIDENCE?

A.OCP has a causal relationship to cervical cancer

B. Increasing risk of cervical cancer according to duration of use of OCP among HPV positive women

C.HPV maybe a confounder

COC and other genital cancer Combination OCs reduce the risk of subsequent

endometrial cancer and ovarian cancer (139,140). Two-year use of OCs reduces the risk of endometrial

cancer by 40%, and 4 or more years of use reduces the risk by 60%.

Another study found a 50% reduction in ovarian cancer risk for women who took OCs for 3 to 4 years and an 80% reduction with 10 or more years of use (141).

There was some benefit from as little as 3 to 11 months of use. Benefit continues for at least 15 years from last use (125,127,142).

COC and cervical cancer

A systematic review of 28 epidemiologic studies of cervical cancer in OC users compared with those who never used OCs reported summary relative risks of 1.1 (95% CI 1.1-1.2) at less than 5 years of pill use, 1.6 (1.4-1.7) at 5 to 9 years, and 2.2 (1.9-2.4) at 10 or more years (146 Smith JS, Green J, Berrington de Gonzales A, et al. Cervical cancer and use of hormonal contraceptives: a systematic

review. Lancet 2003;363:1159-1167). A critique of this study argued that causation is not proved

because few of the studies cited adequately control for the key behavioral factors of partners, use of barrier contraception, and adequacy of cervical cancer screening (147 Miller K, Blumenthal P, Blanchard K. Oral contraceptives and cervical cancer: critique of a recent review.

Contraception 2004;69:347-351).

97

Smith JS, et al,, Lancet. 2003 Apr 5;361(9364):1159-67.

OCP use and Cervical Cancer

Study Meta-Analysis: 28 studies, 12531 cases

NON USER < 5 5-9 >100

0.5

1

1.5

2

2.5

3

RELATIVE RISKS ACCDG TO DURATION OF USE

98

Smith JS, et al,, Lancet. 2003 Apr 5;361(9364):1159-67.

OCP use and Cervical Cancer: HPV POSITIVE

Study Meta-Analysis: 28 studies, 12531 cases

NON USER < 5 5-9 >100

0.51

1.52

2.53

3.54

4.5

RELATIVE RISKS ACCDG TO DURATION OF USE

COC and Cervical Cancer

Individual data for 16,573 women with cervical cancer and 35,509 without cervical cancer were reanalysed centrally

The relative risk of cervical cancer is increased in current users of oral contraceptives and declines after use ceases

Cancer and COC

No additional cancer risk in a cohort of UK women

oral contraception was not associated with an overall increased risk of cancer

COC and Liver Cancer

There are case reports of hepatocellular carcinoma in young women with no risk factors other than long-term OC use (157).

However, a large study from six countries in Europe found no association between use of OCs and subsequent liver cancer (158Oral contraceptives and liver cancer: results from the Multicentre International Liver Tumor Study (MILTS). Contraception 1997;56:275–284.).

8. WHO WILL BENEFIT MOST FROM LACTATION AMENORRHEA METHOD IN THE PREVENTION OF BREAST CANCER?

A. Positive history of breast cancerB. AsiansC. Obese womenD. Breast feeding for 24 months

Lactation Amenorrhea:

Ovulation is suppressed during lactation. The suckling of the infant elevates prolactin levels and reduces

gonadotropin-releasing hormone (GnRH) from the hypothalamus, reducing luteinizing hormone (LH) release and thus inhibiting follicular maturation (10 Knobil E, Neil JD, Ewing LI, et al (eds). The physiology of reproduction. New York, NY: Raven Press, 1988:2323-2349.

Breastfeeding reduces the mother's lifetime risk of breast cancer. In a very large study in Korea, 13 to 24 months of lactation

reduced the risk of breast cancer by 30%, and there was a clear trend of decreasing breast cancer risk with increasing duration of lactation (14 Lee SY, Kim MT, Kim SW, et al. Effect of lifetime lactation on breast

cancer risk: a Korean women's cohort study. Int J Cancer 2003;105:390-393).

111

Lee SY,, et al, Int J Cancer. 2003 Jun 20;105(3):390-3.

Lactational Amenorrhea Method and Reduction in Breast Cancer Risk

Study Cohort Study: 110,604 premenopausal Korean Women, 57,440 breast fed, 4,584 breast fed > 24 months, 6 years follow-up

NON USER 1-2 years > 2 years0

0.2

0.4

0.6

0.8

1

1.2

RELATIVE RISKS ACCDG TO DURATION OF USE

LAM and Breast Cancer

Risk of breast cancer is reduced only in patients with family history of breast cancer

No reduction in the general population

113

Stuebe AM, Arch Intern Med. 2009 Aug 10;169(15):1364-71.

Lactational Amenorrhea Method and Reduction in Breast Cancer Risk

Study Cohort Study: 60,075 women, 608 incident cases, 357,556 person-years of follow-up

NON USER BREASTFED 1ST DEGREE0

0.2

0.4

0.6

0.8

1

1.2

HAZARD RATIO

9. IS THERE A RELATIONSHIP BETWEEN THE CALENDAR METHOD AND ABORTION?A. Of course NOT!B. Yes, it is directly proportional to the

remoteness of coitus to ovulation dayC. Yes, it is highest when sex is

consummated 3 days after ovulation day

D. Yes, the fear of pregnancy creates a hostile intra-uterine environment

Timing of intercourse and Abortion Conceptions resulting from

intercourse remote from the time of ovulation more often lead to spontaneous abortion than conceptions from midcycle intercourse However, malformations are not more common

Guerrero R, Rojas OI. Spontaneous abortion and aging of human ova and spermatozoa. N Engl J Med 1975;293

INJECTABLE HORMONAL CONTRACEPTION

Depomedroxyprogesterone acetate (DMPA), a suspension of micro crystals of a synthetic progestin, was approved for contraception in 1992. A single 150-mg intramuscular dose will suppress ovulation in most women for 14 weeks or longer (188).

Persistent irregular bleeding can be treated by adding low-dose estrogen temporarily; for example, conjugated estrogens, 1.25 mg per day, can be given for 10 to 21 days at a time.

Irregular bleeding with DMPA may be related to the down regulation of endometrial estrogen receptors it produces.

The FDA has issued a black box warning proposing that DMPA treatment be limited to 2 years at a time unless the patient has no other good options for contraception.

10. IS DMPA CARCINOGENIC?A. No, it is not carcinogenicB. It can cause breast cancerC. It can cause ovarian cancerD. It can cause both breast and

ovarian cancer

DMPA and Breast Cancer

The risk of breast cancer during the first 4 years of use appears to be slightly increased, but there is no relation to long-term use and no overall increase in breast cancer risk; hence, any causal relationship between DMPA and breast cancer is unlikely

Chilvers C. Breast cancer and depot-medroxyprogesterone acetate: a review. Contraception 1994;49:211-222).

Breast cancer and depot-medroxyprogesterone acetate: a multinational study. WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Lancet. 1991 Oct 5;338(8771):833-8.

BONUS: WHAT IS MAIN DRAWBACK OF A MALE HORMONAL CONTRACEPTIVE?

A. Negative feedback is not complete

B. Poor metabolic resultsC. Risk of liver cancerD. All of the above

MALE HORMONAL CONTRACEPTION

The same negative feedback of sex steroids that can block ovulation in women will also suppress spermatogenesis in men, but it will produce loss of libido and potentially extinguish sexual performance

Asian men virtually always achieve azospermia or oligospermia when treated with testosterone undecanoate, 500 to 1,000 mg monthly, whereas only 86% of white men achieved oligospermia or azospermia with similar testosterone regimens (218Wang C, Swerdloff RS.

Male hormonal contraception. Am J Obstet Gynecol 2004;190:S60-S68. However, pregnancy has occurred in partners of androgen-treated

oligospermic men with sperm counts as low as 3 million/mL (219 Wallace EM, Aitken RJ, Wu FC. Residual sperm function in oligozoospermia induced by testosterone enanthate administered as a potential steroid male contraceptive. Int J Androl 1992;15:416-424.

Male Hormonal Contraception Combining testosterone with a progestin allows a lower dose

of the androgen with efficacy comparable to use of testosterone alone.

One promising regimen combined injections of testosterone undecanoate with norethindrone enanthate given at 6-week intervals.

This regimen produced azospermia in 90% of subjects (220). Adverse lipid changes have been noted with DMPA and androgen combinations, raising concern about vascular disease with prolonged use.

Liver cancer is also a concern with long-term androgen therapy (221).

WHO MEC 2009

WHO Categories for Temporary Methods

WHO 1 Can use the method. No restriction on use

WHO 2 Can use the method. Advantages outweigh theoretical or proven harm

WHO 3 Should not use the method unless a doctor or nurse makes a clinical judgement that the client can safely use it

WHO 4 Should not use the method. Condition represents an unacceptable health risk.

Simplified 2-Category System

WHO Category

With Clinical Judgement With Limited Clinical Judgement

1 Use the method in any circumstances

Use the method

2 Generally use the method

3 Use of the method not usually recommended unless other, more appropriate methods are not available or acceptable

Do not use the method

4 Method not to be used

Importance of Selected Procedures for Providing Family Planning Methods

A.Essential and mandatoryB.Contributes substantially to safe and

effective use, but implementation maybe considered within the public health and / or service context

C.Does not contribute substantially to safe and effective use

D.No materially related to either good routine preventive health or to the safe and effective use of the method

Procedures before COC use

PELVIC EXAM CBLOOD PRESSURE READING 2BREAST EXAM BY PROVIDER CHEMOGLOBIN TEST CSTD risk assessment CSTD screening by lab test CCERVICAL CANCER SCREENING CRoutine, mandatory lab tests (eg. Cholesterol, FBS, LFT) CProper infection-prevention procedures CSpecific COUNSELLING points for FP methods ACOUNSELLING about change in menses A

CASES

Case 1:

32 year old G1P1 sought consult for contraception. Her mother is a breast cancer survivor. Menses are irregular but no dysmenorrhea. BP 120/80, Uterus is slightly enlarged due to 3x3 cms myoma found on ultrasound. What can be given to address her concerns?

Case 2:

V.N. is 42 years old, G5P4 with on and off BP elevations. No antihypertensive drugs taken. Non –smoker. Her blood sugar is controlled with regular medications. Menstruation is regular at 28-30 days cycle. She wants to take the pills. What is your advise?

Case 3:

24 year old, G2P2, DMPA user for 1 year before her husband left abroad for work sough consult for contraceptive advise. She used to have vaginal spotting while on DMPA. Her husband would be coming home for just 2 months. What is your recommendation?

Case 4

19 year old, nulligravida, with an OFW partner, comes come for 2 weeks. She, however, has vaginal discharge. What is her recommended method of contraception?

Case 5

42 years old, G3P3 is on COC for the past 4 years. Her vital signs are normal. She is concerned about VTE because of her varicose veins. Can she continue the COC? If not, what method is recommended?

Case 6

38 years old, G5P5, had just delivered by forceps delivery under epidural anesthesia. She had requested for BTL during the prenatal check-up. Her pregnancies were complicated by pre-eclampsia, severe. What will be your course of action?

Case 7

32 year old, G1P1, s/p partum 2 weeks, asks for contraceptive advise. She wants to go back to work but would want to continue breast feeding. What would be your advise?

Case 8

21 years old, nulligravida, had an unprotected intercourse 2 days ago. She requested for emergency contraception. She had tried EC 2x. What will be your advise?

Case 9

24 year old, G1P1, sought consult in a health center, manned by a midwife. She had controlled hypertension. Can she take the pills? If NO, what would you recommend?

Case 10

34 year old, G1P1, is diagnosed case of mental retardation. Her parents requested that she be ligated. She would usually leaves the house for days without information on her whereabouts. She does not remember the father of her child. What is your recommendation?

Learning Objectives: Strategies Learning objective 1: Lecture – 1 hr Learning objective 2 & 3: Interactive

lecturettes – 1 hr Learning objective 4: Problem solving,

Case discussion – 2 hours Learning objective 5: small group

Writeshop: course content of a FP method class