1 Contraception Update & New Developments – May 2008 E Stephen Searle MRCGP, MFPH, FFFP Clinical Director/Consultant in Contraception & Sexual Health,

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Contraception Update & New Developments – May 2008

E Stephen Searle MRCGP, MFPH, FFFP

Clinical Director/Consultant in Contraception & Sexual Health, N Derbyshire

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Content of talk

• Yaz, Evra, NuvaRing

• IUDs/IUS

• Esure

• Peri-menopausal contraception

• Injectables, esp osteoporosis. Implant

• Contraception at time of TOP

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satisfaction

• 25% never start Rx contraception

• 30% discontinue within 1 month

• 65-80% missed 1+ pill per month

• Offer ‘Quick-start regime’ – start on day of presentation regardless of day of cycle. Advise back-up method x 1 wk. & return if menses late

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Future methods

• NuvaRing – planned Sept 2008

• Yaz – planned ?Sept 2008

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NuvaRingDesign, composition and use

• 1 ring per cycle

• Regimen:– 3 weeks of ring-use– 1 ring-free week

• Daily release:– 15 µg ethinylestradiol– 120 µg etonogestrel

• 1 ring per cycle

• Regimen:– 3 weeks of ring-use– 1 ring-free week

• Daily release:– 15 µg ethinylestradiol– 120 µg etonogestrel

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NuvaRingPharmacokinetics and dynamics

02040

6080

100120

140160

0 7 14 21

Days

EE

Con

cent

ratio

n (p

g/m

l)

NuvaRing®

Patch

Pill

Based on data from various sources, no direct comparative data

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Contraceptive efficacyNuvaRing European study

Pregnancies Cycles Pearl Index

95% CI

6 12 109 0.65 0.24–1.41

Roumen et al, Hum Reprod, 2001;16:469–75

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NuvaRingCompliance: Ring V’s COC

• Compliance was higher in the NuvaRing group:

• > 85% of women in the NuvaRing group

complied to prescribed regimen

• 75% of women in the Microgynon group

complied to prescribed regimen

i

Scientific communication ESC 2004

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NuvaRingConcomitant antibiotic use

0 1 0 0 2 0 0 3 0 0 4 0 0 5 0 00

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

2 5 0 0 N u v a R i n g a lo n e( c o n t r o l )

N u v a R i n g + a m o x i c i l l i n( i n t e r a c t i o n )

H o u r s a f t e r N u v a R i n g i n s e r t i o n

Ser

um E

NG

leve

l(p

g/m

L)0 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0

0

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

2 5 0 0N u v a R i n g a lo n e ( c o n tr o l)N u v a R i n g p lu s d o x y c y c li n e( i n te r a c t i o n )

H o u r s a f t e r N u v a R in g in s e r t io n

Ser

um E

NG

leve

l(p

g/m

L)

Amoxicilline Doxycycline

Scientific communication ESC 2004

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Incidence of local adverse events (n=1145)

Vaginal discharge 5.3%

Vaginitis 5.0%

Device-related events 3.8%

Treatment-relatedAdverse event

Vaginal discomfort 2.2%

Roumen et al, Hum Reprod, 2001;16:469–75

Irregular bleeding with Nuvaring Comparison with a COC

Scientific communication ESC 2004

0

10

20

1 2 3 4 5 6 7 8 9 10 11 12

Cycle

Inci

dence

of

irre

gula

r

ble

edin

g (

%)

NuvaRing (n=512)

30 EE/150 LNG (n=512)

*

**

* / * * Statistically significant differences

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NuvaRing Effect of on body weight

-0.4

-0.2

0

0.2

0.4

0.6

NuvaRing 30 EE/150 LNG

Mean

ch

an

ge f

rom

baseli

ne (

kg

)

(n=121) (n=126)

Bjarnadóttir et al, Am J Obstet Gynecol, 2003

Cycle 3

Cycle 3

Cycle 6

Cycle 6

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Storage• Prior to dispensing to the user, store refrigerated 2–

8°C (36–46°F).

• After dispensing to the user, NuvaRing® can be stored for up to four months at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Avoid storing NuvaRing® in direct sunlight or at temperatures above 30°C (86°F).

NuvaRing® Package Insert

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Yasmin

• Drospirenone 3mg, EE 30mcg• Good for fluid retension/bloating• Acne (1st try oestrogenic COC, tetracycline.

Then Dianette x 6/12)• Mild hypertension <140/90• PMS: RCT Xover v’s placebo yasmin signif

better• £14.70 x3 x21

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Yaz

• EE 20mcg

• 24 active pills then x4 placebo pills

• Launch ? Sept 2008

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IUDs

• Cu T 380 now approved for 12 yrs in USA

• Failure rate virtually stable up to 15 yrs

• Cu IUDs may be left in-situ x20 yrs

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IUDs & infection

• Single dose of doxy. prophylactically at insertion only results in signif reduction of PID in areas of high GC, Chlamydia prevalence

• ALOs less likely with IUS (2.9%) than IUDs (up to 20%)

• No link between IUD use & CIN. Even a Hx of Ca Cx is WHO 2 for continuing IUD. WHO 4 for insertion while awaiting diagnosis

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IUDs & HIV

• No effect on viral shedding

• No increased risk of transmission or other infection (still rec. condoms)

• WHO 2 for HIV

• WHO 3 for insertion with AIDS

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IUD/IUS & gynae pathology

• Cu IUD reduces endometrial Ca by 50%, increased protection with duration of use

• IUS good for endometriosis

• IUS may reduce fibroid related problems, surgery & size

• Spotting may take longer to settle in women with menorrhagia esp if also have fibroids

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HPV vaccine

• Catch-up vac still useful in women who’ve had HPV as only 5% of young women have had exposure to >1 type, so still get protection from other types.

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Evra

• = ‘cilest in a patch’

• Weekly patch x 3 then PFI x 7/7

• Better compliance than pills

• No 1st pass through liver, consider for GI disease/malabsorption

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How do we choose?- Nottingham Evra Audit

0

5

10

15

20

25

30

35

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Should modern women accept having menstruation?

• ‘Menses should be optional & convenient’

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Peri-menopausal contraception

• Oldest reported spontaneous preg. – 57 yr old in Portland

• “COC & Depo are methods of choice in osteoporotic women” – combined with osteoporosis Rx

• Measuring FSH on COC – OK at end of PFI

• Can abandon contraception from 55th year

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Progestogen-Only

Injectable Contraceptives

January 2003

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• What are the advantages of injectables – Depo & Noristerat?

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Advantages of DMPA

• Almost 100% effective, up to 14/52

• Does not require day to day motivation

• Non intercourse related

• No oestrogenic side effects or health risks

• Protective against PID & Endometrial Ca

• Does not inhibit lactation

• Protective in sickle cell (SS) disease

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Depo Provera and Cancer

• Breast cancer 1.2 (0.96 - 1.5)

• Cervical cancer 1.1 (0.96 - 1.3)

• Ovarian cancer 1.1 (0.6 - 1.8)

• Endometrial cancer 0.2 (0.1 - 0.8)

WHO studies 1991-2

RR 95% CI

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Disadvantages of DMPA

• (Injection cannot be removed once given)

• Menstrual disturbance

• Delay in return of fertility

• Weight gain

• (Androgenic side effects eg. acne - rare)

• ? osteoporosis

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Depo Guidelines

Contraception & Sexual Health Service

Guideline for Injectable Contraception

(Progestogen Only) - First Visit

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Depo & osteporosis SUMMARY

• Special Warnings and Precautions etc: Loss of bone mineral density, increasing with length of use. A risk: benefit assessment should be performed, especially in young or adolescent women and if use is anticipated to be long term (ie 2 years or longer). In adolescents and women with significant lifestyle and/or medical risk factors for osteoporosis, other methods of contraception should be considered before using Depo-Provera.

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Depo Provera and Arterial disease

• Reduction in HDL (15% approx)

• Impairment of arterial endothelial function

• Sorenson MB et al. Circulation 2002; 106: 1646-1651

• WHO Epidemiological study – no increased risk

• WHO Contraception 1998; 57: 315-324

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Contraception at time of TOP

• Talk to ALL women about LARC

• IUD/IUS fit at time of STOP or MTOP:– WHO 1 for 1st trimester TOP– WHO 2 for 2nd trimester (<24/40) STOP or MTOP

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Bleeding patterns with Implanon® All studies

0

10

20

30

40

50

60

1 2 3 4 5 6 7 8

Three-monthly assessments

Per

cen

tage

Amenorrhoea Infrequent bleedingFrequent bleeding Prolonged bleeding

Br J Fam Plann 1999;24

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BODY Wt. Comparative 2 yr study N=180

• METHOD CHANGE in Wt

• Implanon +2.6%

• Norplant +2.9%

• Cu IUD +2.4%

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Cerazette

• Desogestrel

• As effective as COC

• 12 hr rule

• No oestrogen risks or S/E

• Frequently used, often 1st choice POP or even 1st choice OC but for ?bleeding