Women’s Health InitiativeAugust 19, 2014

Cleve Ziegler, M.D

CME Speaker: Bayer, Schering-Plough (Merck), Bayer,

Wyeth (Pfizer)

Advisory Board: Bayer, GSK, Schering-Plough (Merck)

Physiology of Menstruation Anthropology of Menstruation Cultural Attitudes Toward Menstruation Update In New Contraceptive Methods Concept of Extended Cycle Contraception

and Menstrual Suppression

Normal Physiological Process Pathological Entity

Ridding the body of toxins

Sign of fertility and femininity

Physiological anemia and reduction in cardiovascular disease

Dysmenorrhea Menorrhagia Endometriosis Ovarian cancer Breast cancer Premenstrual

syndrome Migraine headache Epilepsy

Finer LG. Perspect Sex Reprod Health. 2006; Moreau C. Contraception. 2007. Frost JJ. In Brief. 2008.

UnintendedPregnanciesEach Year

Unintended Pregnancies

Using Contraception

Time Magazine, May 3, 2010.

Nancy Gibbs, Time Executive Editor

“Arriving at a moment of social

and political upheaval,

the Pill became a handy proxy

for wider trends:

the rejection of tradition,

the challenge to institutions,

the redefinition of women’s roles”

Unintended Pregnancy in First Year of Contraceptive Use*

Trussell J. Contraception 2004; 70: 89-96.

85

2 0.3 0.3 0.3 0.6 0.1 0.5

85

15

8 83

0.8 0.1 0.50

10

20

30

40

50

60

70

80

90

No Method Condom COC and POP Patch / Ring DMPA Copper IUD LNG-IUS FemaleSterilization

Perfect Use

Typical Use

85

2 0.3 0.3 0.3 0.6 0.1 0.5

85

15

8 83

0.8 0.1 0.50

10

20

30

40

50

60

70

80

90

No Method Condom COC and POP Patch / Ring DMPA Copper IUD LNG-IUS FemaleSterilization

Perfect Use

Typical Use

Wo

men

wit

h U

nin

ten

ded

Pre

gn

anc

yw

ith

in F

irst

Yea

r o

f U

se

(%)

COC=combined oral contraceptive; POP= progestin only pill; DMPA=depot medroxyprogesterone; LNG-IUS=levonorgestrel releasing intrauterine system

*not head-to-head comparison of contraceptive methods

1

4

6

7

8

10

23

28

38

39

63

0 10 20 30 40 50 60 70

Cervical Cap

Diaphragm

Female Condom

Rhythm

Withdrawal

IUD

Injection

Female Sterilization

Condom

Male Sterilization

Pill

Values in %*Based on Respondents Familiar with Method

Fisher WA et al. JOGC 2004;June :580-590.

DMPA=depot medroxyprogesteroneBack et al. J Obstet Gynaecol Can 2009;31(7):627–640.

Column totals may exceed 100% as women were allowed to choose more than one method.Base: Women aged 15-50 who have had vaginal intercourse in the previous 6 months, n=2,341

0 10 20 30 40 50 60

Condom

Combined oral contraceptive

Male/Female sterilization

Withdrawal

Intrauterine device/system

Rhythm

Natural family planning

Injection:DMPA

% of women

Cultural Preferences Geographic Trends

21/7 Phasic 21/7 Phasic

Estrogen (µg)

160

140

120

80

60

40

20

0

Mestranol

Ethinyl Estradiol

1960 1970 1980 19902000Year of Introduction

Thorneycroft IH. Infert Clin North Am. 2000;11:515-529.

Most serious cardiovascular adverse events associated with

all COCs

Farley et al., Contraception 1996; 57(3)211-30.

Venous thrombo-embolism

StrokeMyocardialinfarction

Dinger Contraception 2007

Non Pregnant Non UsersNon Pregnant Non Users

OC UsersOC Users

Pregnant WomenPregnant Women

BMI: body mass index *Risk estimates based on 115 VTEs in 116,708 WY of exposureDinger, EURAS Study, Presentation EC Prague 2008.

4

171

18 21

53

27

137

111

216

271

0

100

200

300

No Ris

k Fac

tor

Obe

sity

(BM

I 30+

)

Age 4

0+

VTE H

isto

ry**

BMI 3

0+; A

ge 4

0+

BMI 2

5+; H

ist.*

*

BMI3

0+; H

ist.

Age 4

0+; H

ist.

BMI2

5+;A

ge40+

;His

t.

BMI3

0+;A

ge40+

;His

t.

VT

E/1

0,0

00

WY

1 Risk Factor 2 Risk Factors 3 Risk Factors

Impact of Multiple Risk Factors on VTE Risk During OC Use

** Family or personal history of VTEBased on EURAS study results: not yet published

1. Preferential prescribing of new preparations to new users

2. Most VTE in first 6 months, newer users at higher risk

3.Preferential prescribing of new drugs to higher risk patients because of perceived “safety”.

4. Preferential prescribing of drospirenone to hyperandrogenic women who have underlying vascular disease

1 ring per cycle Regimen:

◦3 weeks of ring-use◦1 ring-free week

Daily release:◦15 µg ethinylestradiol◦120 µg etonogestrel

-500

0

500

1000

1500

2000

0 5 10 15 20

Time after insertion (days)

Eto

noge

stre

l (pg

/mL)

0

10

20

30

40

50

60

Eth

inyl

estr

adio

l (pg

/mL)

EtonogestrelEthinylestradiol

Css OC

Css OC

Pharmacokinetic profilePharmacokinetic profile NuvaRing and 30 EE/150 DSG COCNuvaRing and 30 EE/150 DSG COC

Timmer & Mulders, Clin Pharmacokinet, 2000;39:233–42

D’Arcangues et a., Contraception. 2007; 75: S2-S7

Prevalence of IUD use in women aged 15-49, married or in union (2005)

Intrauterine system (IUS) Releases up to 20 μg/day

of levonorgestrel (progestin)

No estrogen 5 years of treatment

Indications Contraception

Mirena provides contraception througha combination of 3 main actions:

Minor effect

on ovarian function

2- Inhibition of sperm function

1- Thickening of cervical mucus

3- Prevention of endometrial growth

Normal menstrual cycle

Days of cycle

Menstrual cycle in awoman with Mirena

Endometrium in resting stateResulting in scanty bleeding

1. Use 2nd generation pill with lowest estrogen dose as first choice

2.If adverse effects occur, switch to 3rd or 4th generation pill.

3.Patients at high risk for VTE should use progestin only pill, DMPA, or IUS.

4.Use 2nd generation pill in older women