rogestogen - Only Contraceptives Bouquet of Choices

Progestogen only pills (POP) LNG, desogestrel,norethindrone & lynestrenol Failure rates 2-8% but under 1% during lactation Progestogen only injectables Depot MPA & norethisterone enanthate Failure rates 0.1-0.6% in first 12 months Progestogen only implants LNG (Norplant) & etonorgestrel (Implanon) Failure rates under 0.2% in first 12 months IMAP, IPPF Med Bull, 36(5):1, 2002

Progestogen - Only Pills Efficacy, Acceptability & Safety

Comparison of desogestrel 75 ug/day & LNG 30 ug/day Multicentric randomised study of 989 subjects for 13 consecutive treatment cycles DG users had higher incidence of amenorrhoea & infrequent bleeding with tendency to bleed less Pearl Index 0.14 with DG & 1.17 with LNG DG has superior efficacy with similar acceptability Coll Study Group, Eur J Cont Rep Health Care, 3:169, 1998

Progestogen - Only Pills Effects on Lactation

Comparison of desogestrel 75 ug/day with IUCD

use during lactation in 83 subjects Evaluation of quantity & constitution of milk Follow up of children up to 2.5 years No change in amount or constitution of milk No affection of growth & development Safe and effective contraceptive for lactating women

Bjaradottir et al, Br J Obs Gyn, 108(11):1174, 2001

Progestogen - Only Pills Effects on Lactation

Growth of the newborns
Length (cm)
80

Weight (kg)
10 9

Biparietal head circumference (cm)

50 45

70

8 7 40 35

60

6 5

Treatment periods

Treatment periods IUD Cerazette

Treatment periods

9910014_d/42

Bjaradottir et al, Br J Obs Gyn, 108(11):1174, 2001

Progestogen - Only Pills omparative Contraceptive Performance

Use of POPs (117), progesterone rings (187), Norplant (120) & CuT380A (122) during lactation
Initiation on day 56 postpartum All equally effective with pregnancy rates < 1% Normal breast feeding & infant growth Bleeding in first month in 50% For over 10 days from 0% with POPs to 7% with Norplant Lactational amenorrhoea 4-5 months longer with progestogen only methods Diaz et al, IPPF Med Bull, 32(2):1, 1998

Progestogen - Only Pills Perception of Traditional POPs

Concerns & disadvantages with LNG 30 ug Less effective than COCs - Inconsistent anovulation Reliance on cervical effect for contraception Slight increase in risk of ectopic pregnancy Unpredictable bleeding patterns causes discontinuation Dose related androgenic effects on carbohydrate metabolism, serum lipoprotiens & skin Promising development - Desogestrel 75 ug Organon, Cerazette Sc Brochure, 1999

Progestogen - Only Pills Ovulation Inhibition

Follicular rupture and maximum progesterone concentration
% of all cycles Follicular rupture + P > 30 nmol/l Follicular rupture + P = 10-30 nmol/l Follicular rupture + P < 10 nmol/l
P= Progesterone concentration
9910014_d/7

Desogestrel
(N=59)

LNG 30 ug
(N=57)

1.7% 1.7% 1.7%

28% 3.5% 1.7%

Rice et al, Hum Reprod, 14:982, 1999

Progestogen - Only Pills Ovulation Inhibition

Maximum progesterone concentration
Desogestrel 75 ug
treatment period Progesterone < 10 nmol/l 10-30 nmol/l > 30 nmol/l 7
(N=30)

LNG 30ug
treatment period 7
(N=29)

12
(N=29)

12
(N=28)

97% 3% 0%*

97% 0% 3%*

34% 28% 38%

50% 11% 39%

* p < 0.001 compared to levonorgestrel group

9910014_d/6

Rice et al, Hum Reprod, 14:982, 1999

Progestogen - Only Pills Contraceptive Efficacy

Excluding exposure during breast-feeding
Treatment Woman-years Pregnancies Pearl Index

Desogestrel

600

0.17

LNG 30 ug

213

3*

1.41

* including one ectopic pregnancy

9910014_d/12

Coll Study Grp, Eur J Contracept Rep Health Care, 3:169, 1998

Progestogen - Only Pills Bleeding Patterns

Definitions over a 90 days reference period
Amenorrhea Infrequent B/S Frequent B/S Prolonged B/S
B/S = bleeding/spotting
9910014_d/15

no bleeding 1 or 2 B/S episodes 6 or more B/S episodes B/S episode > 14 days

Belsey et al, Contraception, 34:253, 1986. 1986

Progestogen - Only Pills Bleeding Patterns

Reference periods in efficacy study
Treatment days reference period 1 1 - 90 29 - 118 reference period 2 reference period 3 reference period 4
9910014_d/18

shifted reference period

91 - 180 181 - 270 271 - 360

Progestogen - Only Pills Bleeding Patterns

Shifted reference period 29 to 118 days
%
80 70 60 50 40 30 20 10 0
amenorrhea
9910014_d/21

Cerazette starters/switchers 30 g LNG starters/switchers

1-2 B/S episodes

3-5 B/S episodes

6 or more B/S episodes

prolonged

Coll Study Grp, Eur J Contracept Rep Health Care, 3:169, 1998.

Progestogen - Only Pills Bleeding Patterns

Reference period 4 271 to 360 days
%
80 70 60 50 40 30 20 10 0
amenorrhea
9910014_d/22

Cerazette starters/switchers 30 g LNG starters/switchers

1-2 B/S episodes

3-5 B/S episodes

6 or more B/S episodes

prolonged

Coll Study Grp, Eur J Contracept Rep Health Care, 3:169, 1998

Progestogen - Only Pills Nuances of Dose Scheduling

Traditional POPs have peak effect with in 4 hrs lasting up to just under 24 hrs Contraceptive protection lost if delay > 3 hrs in taking the next tablet Desogestrel 75 ug suppresses the HPO axis Dosage at regular 24 hr intervals Delay of up to 12 hrs does not affect efficacy & tablet not considered missed if taken with that time offering a greater margin of error Organon, Cerazette Sc Brochure, 1999

Type of progesteron Norethisterone Levonorgestrel Di norgestrel Etynodiol diacetate Disogestrel 350mcg 30mcg 75mcg 500mcg 75mcg

POP
Micronor Noriday Microval, Norgeston Neogest Femulen Cerazette

Indications
< 21 days post partum. 6wks-6mths postpartum partially or

fully BF Age> 35 and smoke BMI> 35 Multiple risk for CVS Those at risk of VTE, inc personal hx Hypt controlled with meds DM/ CHD/ valvular problems CIN/ endometrial ca/ ovarian ca F Hx Breast ca SCD

Contraindications
Uncontrolled hypertension
Active hepatitis/ decompensated cirrhosis/ liver tumours Mal absorption Current DVT Undiagnosed Genital tract bleeding Recent trophoblastic dx with high bHCG Current IHD

 Current breast Ca Past severe side effects Acute porphyria

 Missed pill: pill needs to be taken at same time of day. There is only 3

hour window period for missed pills. Contraception efficacy is restored after 2 days as compared to COC Cerazette- has a 12 hour window period. Vomiting within 2 hrs or severe diarrhoea decreases efficacy. Starting regimes- same as COC however additional method is needed for only 48hrs Drug interactions- Pop not affected by broad spectrum abx. However enzyme inducing drugs reduces efficacy.

Missed POP Pill/s

Missed POP pill/s
More than 3 hours late (27 hours after last pill) Cerazette?
Take the missed pill and continue as normal NO YES

Less than 3 hours late?

Take missed pill as soon as possible, Take rest of packet as normal And use extra precautions for the next 2 days

Less than 12 hours late?

More than 12 hours late?

Take missed pill as soon as possible and continue with packet as normal

Take missed pill as soon as possible, take the rest of the packet as normal. Use extra precautions until pills taken for 2 consecutive days

Vomiting & Diarrhoea

If vomiting within 3

hours of taking pill then absorption will be reduced and may be ineffective. Diarrhoea alone without vomiting has to be severe to reduce the absorption of the pill.

Drug Interactions
The effectiveness of COC, POP and EHC will be

reduced by interaction with drugs that are enzyme inducers

Broad spectrum antibiotics may reduce

effectiveness of COC by altering the bacterial flora of the bowel

Progesterone contraceptives include;

Progesterone implant
Progesterone injections Progesterone only pill (Minipill) Progesterone intrauterine system (Mirena) Emergency progesterone contraception

(within 72 hours on intercourse)

Progestin contraceptives
May be preferable in some situations: Absolute or relative contraindications to estrogen Side effects to estrogen-containing hormonal contraception Lactation Comfort and feasibility of formulations for long-term use

Emergency Contraception: Indications

Intercourse within past 72 hours without contraceptive

protection (independent of time in the menstruel cycle) Contraceptive method failure, misuse
Barrier method dislodgment / breakage Missed oral contraceptive pills Error in practicing coitus interruptus

Sexual assault Exposure to teratogens (e.g., cytotoxic drugs, live vaccine)

Recommended only as an emergency, individual event

treatment

ACOG Practice Bulletin 69. Obstet Gynecol. 2005; 106: 1443-1451.

Emergency Contraception Effectiveness

Method Number of pregnancies Reduction (%)

No treatment
Combined Progestin-only IUD insertion

80
20 10 1

75 88 99

If 1000 women have unprotected intercourse once in the second or third week of their cycle

Weismiller DG. Am Fam Physician. 2004; 70: 707-714.

Emergency Contraception Mechanism of Action

Mode of action varies according to the day of the

menstrual cycle which intercourse occurs and EC is administered Inhibit or delay ovulation Have effects after ovulation
Interference with sperm transport or penetration Impairment of corpus luteum

Endometrial changes may prevent implantation

Have no effect if taken after implantation

ACOG Practice Bulletin 69. Obstet Gynecol. 2005; 106: 1443-1451.

Progestin Only Emergency Contraception: Nor-Levo

Nor-Levo (Levonorgestrel 0.75 mg)

First Dose: Take one tablet within 72 hours of

unprotected intercourse
Second Dose: Take the remaining tablet 12 hours after

first dose (Traditional, two-dose administration)

Weismiller DG. Am Fam Physician. 2004; 70: 707-714.

Single vs. Two Dose Levonorgestrel: Efficacy

100

82%
80 60

77%

%
40 20 0 Single-Dose Levonorgestrel Two-Dose Levonorgestrel

Prevented pregnancies estimated to occur without treatment

von Hertzen H. WHO Multicentre Randomised Trial. Lancet. 2002; 360: 1803-1810.

Single-Dose vs. Two Dose Levonorgestrel: Effect of Treatment Delay on Efficacy

100

Pregnancies Prevented (%)

Single Dose LNG Two Dose LNG

80 60 40 20 0 1 to 3 4 to 5

Delay in Treatment After Intercourse (Days)

von Hertzen H. WHO Multicentre Randomised Trial. Lancet. 2002; 360: 1803-1810.

Single-Dose vs. Two Dose Levonorgestrel: Side Effects

40
Single-Dose Levonorgestrel Two-Dose Levonorgestrel 31 31

30

% 20
14 15 14

18

10
4 1 1 Diarrhea Fatigue 3

8 5 0

0
Nausea Vomiting Breast Tenderness Bleeding Menses Delay >7 Days

von Hertzen H. WHO Multicentre Randomised Trial. Lancet. 2002; 360: 1803-1810.

Hormonal Emergency Contraception: Contraindications

Suspected or confirmed pregnancy (WHO)
Food and Drug Administration-Relative (based on OC

labeling, but no data available)

Clotting problems, venous thromboembolism, ischemic

heart disease, stroke, migraine, liver tumors, breast cancer

No negative effects on fetal development

Grimes DA. Ann Intern Med. 2002; 137: 180-189.

Progestin-only pills
Desogestrel Levonorgestrel Norgestrel Norethisterone Ethynoidial

75 mg/day 30 mg/day 500 mg/day 350 mg/day 500 mg/day

(Cerazette) (Microval, Microlut) (Ovrette, Neogest) (Micronor) (Femulen)

diacetate

Routes of administration
Oral (POP + EHC)
Injectables (DMPA and NET-EN) Subdermal implant (Implanon)

IUS (Mirena)

Uptake GB 2007 49)

POP 6%
Injectable 3% Implant 2%

(women 15

IUS 3%

ONS Omnibus Survey

Metabolic effects of progestogens

Progestogen
Progesterone

Progestational Androgenic activity activity 1 + +

Norethisterone 4 Medroxyprog 4

Levonorgestrel 6
Desogestrel 8

++
+

Metabolic effects of oral progestogens

Negligible effect on haemostasis Negligible effect on lipid metabolism Negligible effect on carbohydrate metabolism

Cardiovascular risk of progestogens: case-control studies

WHO study (Contraception 1998) oral and injectable contraceptives no increased risk of MI, CVA or VTE Transnational study (EJCRHC 1999) POPs only no increased risk of MI, CVA or VTE

Cancer risk of progestogens

Breast 1996 Lancet meta-analysis: RR 1.17 for both POP and injectables but limited data Other 1991 WHO Collaborative Study of Neoplasia and Steroid Contraceptives for injectables: no increased risk for ovarian and cervical, RR 0.21 for endometrial

Hormones and functional ovarian cysts

Progestogen-only methods that disturb rather than inhibit ovulation tend to cause FOCs COC: incidence decreased Standard POP: incidence increased (Tayob 1985) Cerazette: no data Implanon: incidence increased* Injectables: incidence decreased IUS: some increase initially (Robinson 1989)
* A few women have their Implanon removed because of abdominal pain

Relative doses
COC
Desogestrel 150mg

POP
75mg 30mg 350mg

Levonorgestrel 150mg Norethisterone 500mg

POP mode of action

Ovarian suppression (not complete; but greater with

desogestrel) Cervical mucus thickening Endometrial (prevention of implantation) Tubal motility

POP effect on cervical mucus

Mid-cycle mucus reduced in quantity, thicker ->

reduced sperm penetration Effect maximal within 2 4 h Effect begins to wear off after 16 20 h

Effectiveness of POP
Progestogen
Etynodiol diacetate

Woman months
24,534

Pearl index
2.1 2.3 3.0

Norethisterone 26,173 Levonorgestrel 36,118

Vaginal Bleeding Patterns

90 days reference period
Definitions (Current WHO Criteria)

Amenorrhoea Infrequent B/S Normal Frequent B/S Prolonged B/S

no bleeding 1 or 2 B/S* episodes 3-5 B/S episodes 6 or more B/S episodes B/S episode > 14 days

* B/S = bleeding/spotting

Belsey EM, et al. Contraception 1986;34:253-60.

Bleeding patterns in women not using hormonal contraception

Normal 84.2%

Amenorrhoea
Infrequent B-S Frequent B-S Prolonged B-S

1.9%
10.9% 0% 0.05%

(Belsey et al. Contraception 1997; 55: 57-65)

Bleeding patterns on conventional POP

40% have regular periods
normal ovulatory cycles
least effectively contracepted

40% shorter cycles (< 24 days)

variable disruption of cycle: erratic bleeding functional ovarian cyst formation

20% amenorrhoea or long cycles (> 45 days)

ovulation suppressed very effective

75 g desogestrel daily Continuous regimen

 Cerazette

bleeding pattern

More variable bleeding pattern than LNG

Shift to less bleeding with time
more amenorrhoea more infrequent bleeding less bleeding/spotting episodes

Shift to less bleeding/spotting days

Risk of ectopic pregnancy with the POP

Levonorgestrel

1 ectopic in 250 woman years use Norethisterone 1 ectopic in 290 woman years use

Liukko et al 1977

Ectopic pregnancy with Cerazette

No ectopic pregnancies in trial of Cerazette (727

woman years of use) cf levonorgestrel POP

Collaborative Study Group EJCRHC 1998

Effect of POP on lactation

No change in duration of lactation
No change in volume of milk No change in composition of milk

Cerazette: efficacy study

Randomised, double-blind 12 month study comparing desogestrel 75mg and levonorgestrel 30mg 71 volunteers with regular cycles and known to be ovulatory Ultrasound, estradiol, progesterone, LH and FSH performed throughout 7th and 12th 28-day treatment periods
Rice at al Human Repro 1999; 14: 982

Ovulation
Defined as follicular rupture followed by a rise in

serum progesterone to > 30nmol/l

Ovulation on scan and max. serum progesterone

Deso N=59
Foll rupture + prog > 30 (%) 1 (1.7)

LNG N=57
16 (28) 2 (3.5) 1 (1.7)

Foll rupture + 1 (1.7) prog 10-30 (%) Foll rupture + prog < 10 (%) 1 (1.7)

Efficacy study
The difference between the desogestrel and

levonorgestrel groups for a maximum progesterone level > 30 nmol/l is statistically significant (p < 0.001) for both assessment periods

Multicentre trial
Randomised double-blind study
Duration 1 year Desogestrel POP: 979 women

Levonorgestrel POP: 327 women

1/3 of participants breast-feeding at start of study Collaborative Study Group 1998

Contraceptive efficacy
excluding exposure during breast-feeding
Treatment Woman-years Pregnancies Pearl Index (95% CI) 0.17 (0.004-0.93) 1.41 (0.29-4.12)

Desogestrel

600

LNG

213

Collaborative Study Group. Eur J Contracept Reprod Health Care 1998;3:169-78.

Summary on Cerazette
Differences between DSG and LNG POP effectiveness

in this small trial were not statistically significant (underpowered) No other available trials comparing Cerazette with another POP No trials comparing Cerazette with COC

2 RCTs: Progestin-only pills

1: Progestin-only vs. placebo
1: Progestin-only vs. progestin-only, timing of

start

Velasquez, 1976
N = 20 women Mexico 12 NET (progestin only) on PP days #1-14 8 identically packaged placebos Outcomes No differences in milk volume, infant growth or milk composition during 14 days of the study

ACOG Recommendations for Hormonal Contraception if used

POPs to start 2-3 weeks postpartum DMPA to start at 6 weeks postpartum COCs, if prescribed, should not be started

before 6 weeks postpartum, and only when lactation is well established and the infant's nutritional status well-monitored
ACOG bulletin: Breastfeeding: Maternal and infant aspects 7/00

ACOG Practice bulletin 2000

Progestin-only preparations are safe and

preferable forms of hormonal contraception for lactating women. Combination OCs are not recommended as the first choice for breastfeeding mothers because of the negative impact of contraceptive doses of estrogen on lactation. Level A evidence

The use of hormonal contraception in women with

coexisting medical conditions, ACOG, 7/00

Cochrane Review 2003

Evidence from RCTs is limited and of poor

quality No established link between hormonal contraception and milk quality/quantity Evidence inadequate to make recommendations regarding hormonal contraceptive use for breastfeeding women
Hormonal contraception & lactation

POPs: Mechanisms of Action

Suppress ovulation
Reduce sperm transport in upper genital tract (fallopian tubes) Change endometrium making implantation less likely

Thicken cervical mucus (preventing sperm penetration)

65

POPs: Contraceptive Benefits

Effective when taken at the same time every day (0.055 pregnancies per 100 women during the first year of use) Immediately effective (< 24 hours) Pelvic examination not required prior to use Do not interfere with intercourse Do not affect breastfeeding Immediate return of fertility when stopped

66

POPs: Contraceptive Benefits

continued
Few side effects
Convenient and easy-to-use Client can stop use

Can be provided by trained nonmedical staff

Contain no estrogen

67

POPs: Limitations

Cause changes in menstrual bleeding pattern Some weight gain or loss may occur User-dependent (require continued motivation and daily use) Must be taken at the same time every day Forgetfulness increases method failure Resupply must be available Effectiveness may be lowered when certain drugs for epilepsy (phenytoin and barbiturates) or tuberculosis (rifampin) are taken Do not protect against STDs (e.g., HBV, HIV/AIDS)

68

Who Can Use POPs

Women: Of any reproductive age Of any parity including nulliparous women Who want effective protection against pregnancy Who are breastfeeding (6 weeks or more postpartum) and need contraception Who are postpartum and not breastfeeding Who are postabortion

69

Who Can Use POPs continued

Women: Who have blood pressure < 180/110, blood clotting problems or sickle cell disease With moderate to severe menstrual cramping Who smoke (any age, any amount) Who prefer not to or should not use estrogen Who want a progestin-only contraceptive but do not want injections or implants Who should not use progestin-only IUDs

70

POPs: Who May Require Additional Counseling

Women: Who cannot remember to take a pill every day at the same time Who cannot tolerate any changes in their menstrual bleeding pattern

71

POPs: Who Should Not Use (WHO Class 4)

POPs should not be used if woman:
Is pregnant (known or suspected)

Source: WHO 1996.

72

POPs: Conditions Requiring Precaution (WHO Class 3)

POPs are not recommended unless other methods are not available or acceptable if woman:
Is breastfeeding (< 6 weeks postpartum)
Has unexplained vaginal bleeding (only if

serious problem suspected) Has breast cancer (current or history) Is jaundiced (active, symptomatic)
Source: WHO 1996.
73

POPs: Conditions Requiring Precaution (WHO Class 3) continued

POPs are not recommended unless other methods are not available or acceptable if woman:
Is taking drugs for epilepsy (phenytoin and barbiturates)

or tuberculosis (rifampin) Has severe cirrhosis Has liver tumors (adenoma and hepatoma) Has had a stroke Has ischemic heart disease (current and history of)

Source: WHO 1996.

74

POPs: Conditions for Which There Are No Restrictions

Blood pressure (< 180/110)
Diabetes (uncomplicated or < 20 years duration) Pre-eclampsia (history of)

Smoking (any age, any amount)

Surgery (with or without prolonged bed rest) Thromboembolic disorders Valvular heart disease (symptomatic or asymptomatic)

75

POPs: When to Start

Day 1 of the menstrual cycle Anytime you can be reasonably sure the client is

not pregnant Postpartum:

after 6 months if using lactational amenorrhea

method (LAM) after 6 weeks if breastfeeding but not using LAM immediately or within 6 weeks if not breastfeeding
76

Postabortion (immediately)

POPs: Side Effects Which May Require Management

Amenorrhea (absence of vaginal bleeding

77

or spotting) Bleeding or spotting Heavy or prolonged bleeding Lower abdominal/pelvic pain (with or without symptoms of pregnancy) Weight gain or loss (change in appetite) Headache Nausea/dizziness/vomiting

POPs: Management of Amenorrhea

Evaluate for pregnancy, especially if amenorrhea

occurs after period of regular menstrual cycles If not pregnant, counsel and reassure client Do not attempt to induce bleeding with COCs

78

POPs: Management of Bleeding or Spotting

Prolonged spotting (> 8 days) or moderate bleeding: Reassurance Check for gynecologic problem (e.g., cervicitis) Short-term treatment:
COCs (30-50 g EE) for 1 cycle1, or Ibuprofen (up to 800 mg 3 times daily x 5 days)

1Remind

client to expect bleeding after completing COCs.

79

POPs: Management of Prolonged or Heavy Bleeding

Bleeding twice as long or twice as much as normal: Carefully review history and check hemoglobin (if available) Check for gynecologic problem Short-term treatment:
COCs (30B50 Fg) for 1 cycle1, or Ibuprofen (up to 800 mg 3 times daily) x 5 days

1Remind

client to expect bleeding after completing COCs.

80

POPs: Management of Prolonged or Heavy Bleeding

continued
If bleeding not reduced in 3B5 days, give:
2 COC pills per day for the remainder of her cycle

followed by 1 pill per day from a new packet of pills, or High dose estrogen (50 g EE COC, or 1.25 mg conjugated estrogen) for 14B21 days

81

POPs: Drug Interactions

Most interactions relate to increased liver metabolism of levonorgestrel:
Rifampin (tuberculosis) Anti-epilepsy (seizures):

Barbiturates, phenytoin, carbamzepine (but not valproic acid)

Griseofulvin (long-term use only)

82

POPs: Client Instructions

Take 1 pill at the same time each day. Take first pill on first day of your menstrual

83

period. If you start POPs after the first day of your menstrual period, but before the seventh day, use a backup method for the next 48 hours. Take all pills in pack. Start a new pack on the day after you take last pill. If you vomit within 30 minutes of taking pill, take another pill or use a backup method if you have sex during next 48 hours.

POPs: Client Instructions continued

If you take a pill more than 3 hours late, take it as soon

as you remember. Use a backup method if you have sex during the next 48 hours. If you forget to take 1 or more pills, you should take the next pill when you remember. Use a backup method if you have sex during the next 48 hours. If you miss 2 or more menstrual periods, you should go to the clinic to check to see if you are pregnant. Do not stop taking pills unless you know you are pregnant.

84

POPs: General Information

Changes in menstrual bleeding patterns are

85

common, especially during first 2 or 3 cycles. They are often temporary and rarely a risk to health. Other minor side effects may include weight gain, mild headaches and breast tenderness. These symptoms are not dangerous and gradually disappear. Certain drugs (rifampin and most anti-epilepsy drugs) may reduce effectiveness of POPs. Tell your provider if you start any new drugs.

POPs: Warning Signs

Return to clinic if any of the following occur:
Delayed menstrual period after several months of

regular cycles (may be sign of pregnancy) Severe lower abdominal pain Heavy or prolonged bleeding Migraine headaches

86

Kathryn Grifo, BSN, RN Marcie Woznick, BSN, RN

ANP III University of North Florida

Introduction
History of the progestin-only pill (POP) Developed in mid 1960s Safety concerns with estrogen Four generations of POPs Classification varied Availability in the United States - $30/month norethindrone 0.35 mg Micronor, NorQD, camilla, errin, nora-BE

Physiologic Effect of POPs

Thickening of cervical mucus Makes sperm penetration challenging Tubal motility and cilia are slowed
Suppression of LH surge Dose dependent & relative to the individual Endometrial changes Secretory phase

Pharmacokinetics
Serum peak: 1 2 hrs
Half-Life: 5 14 hrs Rapid decrease in effects after 20 hrs Considered missed dose if > 3 hrs late Metabolism: hepatic Excretion: urine

Contraindications
Hypersensitivity to norethindrone or other

components of pill Undiagnosed vaginal bleeding Severe hepatic disease Breast CA Pregnancy

Administration

Start on first day of menses One pill daily - No placebo pills Same time every day very important** Use backup method until 1st pack is completed One missed dose (> 3 hrs) Take ASAP & resume schedule Use backup method for 48 hrs Multiple missed doses Consider alternative contraceptive method

Efficacy
Perfect Use 99% 0.5 pregnancies per 100 women Typical Use 92% 3 pregnancies per 100 women Discontinuation Rate of

POPs & COPs

Approximately 68%

Prescriptive Purposes
Oral Contraception Estrogen contraindications Emergency contraception Postpartum/post-abortion Lactation considerations

Estrogen Contraindications
Cardiovascular risk factors HTN (up to stage 1), smokers, obestiy (class 1) Hx MI, CVA, DVT, PE, HTN (stage 2 & 3) hyperlipidemia (class 2) Presence of venous thromboembolism (class 3) Estrogen triggered migraines Hypersensitivity to estrogen Postpartum women

Emergency Contraception
Plan B: levonorgestrel 1.5 mg po once
Mechanism of action Delays or blunts LH surge and, therefore, ovulation is delayed or prevented Does not terminate existing pregnancy** FDA approved behind the counter access to women

> 18 yoa in 2006

Postpartum
Ovulation may occur 25

Post-abortion
Ovulation may occur 14

days after birth Women are at risk for venous thrombosis POPs may be started immediately (class 3) or up to 6 weeks postpartum (class 1) Lactation considerations exist

days after 1st trimester abortion/miscarriage Women at increased risk for venous thrombosis POPs may be started immediately or within 2 weeks (class 1)

Lactation Considerations
Lactation delays ovulation Anovulation most likely with Exclusive breastfeeding < 6 mo postpartum Amenorrhea POPs preferred OCP Does not seem to affect milk composition/quantity No apparent impact on infant

Lactation Considerations
Timing of postpartum POP initiation still under

debate
Effects on lactation Effects on infant

Manufacturer's initiation recommendations 6 weeks postpartum if breastfeeding only 3 weeks postpartum if breastfeeding & using formula

Positive & Negative Attributes

Negative Unscheduled uterine Positive bleeding Minimal or no effect on If pregnancy occurs, more coagulation, blood likely to be ectopic pressure, or lipid profiles Weight gain & headaches Acne rare Ovarian cysts Easily reversible Narrow administration window Obese pts without comorbidities, endometrial & ovarian CA, uterine fibroids (class 1)

Unscheduled Uterine Bleeding

Most common reason for D/C of all OCPs POPs have unpredictable effect on ovulation No evidence suggests a decrease in

contraceptive protection Amenorrhea

Pregnancy vs anovulation

Unscheduled Uterine Bleeding

Management Options Patient education Importance of timely administration Estrogen therapy Short term use D/C POP and start combination OCP Mifepristone Low dose decreases length/quantity of episodes Not readily available for this specific purpose

Patient Education
Possible side effects Irregular bleeding is not correlated with decreased

efficacy
r/o pregnancy

To the frequency of unscheduled uterine bleeding

take pill at same time daily

Patient Education
When to take a pregnancy test late/missed pills >45 days since LMP Experiencing symptoms of pregnancy Multivitamin Calcium/vitamin D supplementation Use a condom to protect against STIs

Patient Education
ACHES Abdominal pain Chest pain Headache Eye problems or visual changes Swelling or severe pain of legs