THE LATEST DEVELOPMENT ON FEMALE CONTRACEPTION

Dr Pansy W.Y. Lam

Definitions:
Pearl Index number of pregnancy in 100 women in 1 year Cumulative pregnancy rate in number of years Failure rate~ Pregnancy rate

Various methods of contraception

Combined Pills (COC) Contraceptive Injection Contraceptive implant Transdermal Patch Progestogen only pills Intra-uterine Systems (LNG-IUD) Condoms Spermicides Diaphragms Intra-uterine Devices (IUD) Sterilization - male and female Natural family planning

Efficacy of various contraceptive methods commonly used in US & Western Europe

Reliability Very high Very high Highvery high Reasonable Unreliable Contraception type Combined oral contraceptives Transdermal patch Mini-pill (progesterone only) Male condom Coitus interruptus (Withdrawal) Pearl Index* 0.032.36 ~1.0 0.44.3 714 1040

*The total number of unplanned pregnancies which occur per 100 womanyears of use 1. The Gallup Organization Inc. 2004; 2. Skouby 2004; 3. Leidenberger 1998; 4. Baltzer et al. 1985; 5. Ortho-McNeil Pharmaceutical Inc. 2001; 6. Ortho-McNeil Pharmaceutical Inc. 2002

Combined OC pills Actions

Pearl index of 0.1 Inhibit FSH and LH secretions thus preventing ovulation Thicken cervical mucus to prevent sperm penetrating uterus Endometrial thinning to prevent fertilized egg implantation

Combined OC pills Other uses

Good cycle regulator Menorrhagia - reduce mean menstrual blood loss Dysmenorrhoea Endometriosis Premenstrual syndrome PCOS Acne

Categorization of Combined OC pills

Categories 1st generation 2nd generation

Estrogen dose/day 50ug/day 20 - 35ug/day

Progestogen levonorgestrel levonorgestrel or norgestrel desogestrel and gestodene Drospirenone (DRSP)

3rd generation

20 - 30ug/day

New generation

20 - 30ug/day

Combined OC pills Preparation

Monophasic 21, 21/7, 22/6, 24/4, 84/7 Biphasic 2 types of combined E+P Triphasic 3 types of combined E+P No advantage in biphasic and triphasic preparations

Estrogens Side effects dose dependent

Coagulation- stroke, DVT ( especially in smoker) Lipid problem ( inc HDL and lower LDL) Breast tenderness Water retention and weight gain Depression-serotonin reduction GIT condition- nausea and vomiting Photosensitive Breast cancer? Liver tumour risk?

Pharmacological Profile of Progestogens

Progestogenic Antiandrogenic activity Progesterone Drospirenone Cyproterone acetate Desogestrel Dienogest Gestodene Levonorgestrel Norgestimate + + + + + + + + activity (+) + + + Antimineralocorticord activity + + (+) Glucocorticord activity (+) -

+ effect, (+) negligible at therapeutic dosages, - no effect

Risks of Oral Contraceptives: Nonfatal Venous Thromboembolism

100
Estimated Average Risk/ 100,000 Women/Year

80 60
60

40 20 0
5
Healthy Non-OC Users 25 (3rd generation) 15 (2nd generation) Users of OCs Pregnant Women

Food and Drug Administration. FDA Talk Paper. Nov. 24, 1995.

Cardiovascular Mortality Risk with Smoking and Age in COC Users

Cases per 100,000 Woman-Years

30 25 20 15 10 5 0

Oral contraceptive nonuser Oral contraceptive user

Attributable Risk/100,000 User-Years

Nonsmoker Smoker 0.06 1.73 < 35 years of age

Nonsmoker Smoker 3.03 19.4 35 years of age

Sherif K. Am J Obstet Gynecol. 1999;180(Pt 2):S343-S348. 2):S343-

Cardiovascular Risk
On the basis of a large EU surveillance study in > 58,600 women followed-up for over 142,400 women years, the European Agency for the Evaluation of Medicinal Products has concluded COCs are safe and highly effective at preventing pregnancy, and that there is no reason for women currently using any brand of a COC to stop taking the medication - 2007

Source: Dinger JC., et al. The safety of a drospirenone-containing OC. Contraception 2007;75:344-354 drospirenone2007;75:344-

Combined OC pills Contraindications

Hypertension, DM, Hyperlipidaemia Potential high risk age >35 Venous Thrombotic Embolism Stroke Breast cancer risk controversial Liver tumour risk- controversial Varicose Precaution in smoker

New preparation with low estrogen pills (20mcg daily)

low estrogen pills Increase problems of BTB and spotting Risk of failure with missed pills increased Alternative contraception if in doubt recommended e.g. take other drugs, missed pills frequently New regimes of 24/4 and 84/7 regimes Side effects varies due to different types of progestogen (Drosperinone, Dienogest)

New 24/4 regime with Drospirenone Contraindications and precautions

?Increase non-fatal venous thromboembolism actively being investigated the same as those for other low-dose combined oral contraceptives
In addition, should not be used in women with conditions that predispose to hyperkalemia, e.g. renal insufficiency, hepatic dysfunction and adrenal insufficiency

Women who are taking daily long-term medications that may increase serum potassium levels
Such agents include angiotensin converting enzyme (ACE) inhibitors, angiotensinII receptor antagonists, potassium-sparing diuretics, potassium supplementation, heparin, aldosterone antagonists and non-steroidal anti-inflammatory drugs (NSAIDs)

Other new preparation

Seasonale: Levonorgestrel-015mg + ethinylestradiol-30mcg Extended cycle regime- 84 days with 7 pill-free days Pearl Index- 1.0 HWY Less PMS Precaution with estrogen related condition attention with smoker / DM/ hypertension More spotting can occur

Other new prepapration

Dienogest (DNG) with estradiol valerate (E2V) Dynamic-estrogen step down and progestogen step up sequence good cycle control DNG- strong progestogenic and low androgenic effect Highly endometrial selective Low estrogenic and androgenic

Dienogest (DNG) with Estradiol Valerate (E2V) Reliable contraception- Pearl Index- 0.42 Shorter withdrawal bleeding duration Less irregular spotting Lighter period - useful for abnormal menstrual bleeding Well tolerated -Satisfactory rate- 79.5%

DNG/E V preparation
2

Less metabolic effect including haemostatic parameters- Prothrombin and D-Dimer Inc HDL and lower LDL No change to CHO metabolism Less acne Better vaginal surface cell maturation Same endometrial stimulation and FSH suppression effects (as other low dose OCP) Well tolerated -Satisfactory rate- 79.5%

OC Discontinuation: Impact of Side Effects

In a study of 1657 women not desiring pregnancy, 32% new starters and 16% switchers discontinued OCs due to side effects within 6 months*. Most common side effects leading to OC discontinuation (n=293):
Bleeding irregularities Nausea Weight gain Mood change Breast tenderness Headache 12% 7% 5% 5% 4% 4%

Managing expectations
*Excluding

women who discontinued to pursue pregnancy or were no longer in a sexual relationship Rosenberg J, Waugh MS. Am J Obstet Gynecol. 1998;179:577-582.

Progestogen only pills (Mini-pill) Mechanism

Progestogen effect Thinning of endometrium Thicken cervical mucus ?may prevent ovulation for some pills Take it same time each day even when menstruating Loss the contraceptive effect if 3 hours late, ?longer in newer drugs (Cerazette)

Progestogen only pills (mini-pills) Applications

breastfeeding diabetics women who smoke Women who could not use combined OC pills e.g. blood pressure has gone up on the Pill older women.

Side effects
Irregular period Secondary amenorrhoea sometimes May be ectopic if get pregnant (ectopics are said to be rarer with Cerazette) May increase pigmentation Breast pain Sometimes nausea, headache, dizziness, depression and weight change.

Transdermal Patch
Ethinyl estradiol 20mcg + norelgestromin 150mcg daily release One patch per week for 3 weeks, one patch-free week per cycle Apply to body including abdomen, buttock, outer arm, upper torso, exclude breast Failure rate 0.3% perfect user and 0.9% typical user

Transdermal patch Side effects and disadvantage

All the side effects of COC pills Slightly increased risk of VTE Vs COC pills Skin irritation May come out and loss adhesiveness

Contraceptive injections
Progestogens only Combined estrogen + Progestogen

Contraceptive Injections (Progestogens only)

12-wk injection: Depo-Provera (DMPA) 8-wk injection: Noristerat or NET-EN (norethisterone) Intramuscular injections Cumulative pregnancy rate: 0.1-0.7 % in first year, <0.4% after second year First injection at Day 1-5 of period OR abstinence or barrier method for 7 days

Actions of Contraceptive Injections

Prevents ovulation Thickens cervical mucus to prevent sperm penetration Endometrial thinning to prevent implantation

Advantages
No increased risks of stroke, VTE and MI No need to take a pill everyday with risks of missing pills No interference with sex. Used when breast-feeding. Reduce premenstrual tension, heavy periods and pain. Used by those who cannot take combined pill. Some protection against pelvic infection with mucous plug in the cervix which may prevent bacterial ascending infection

Progestogen only injections Disadvantages

Once given, cannot be removed and side effects may last >3 months Irregular bleeding in first few months, may be heavy and prolonged Weight gain, fluid retention, increase in acne and breast discomfort Long-acting drug may not ovulate after 6-8 months or rarely 2 yr, not related to the length of time used After the first few months, periods become lighter than usual or even no periods at all (7 in 10 women after the injection for a year).

Pregestogen only injection Side effects

Stopped due to menstrual disturbance, fluid retention, weight gain, acne, breast discomfort Late return of fertility Reduced BMD slightly (no evidence of increased osteoporotic fracture risk) recovery after stopping, reassessed every 2 year C/I :no period for six months, risk of osteoporosis, heavy drinker, anorexia nervosa

Combined monthly injectables (Cyclofem)

Cyclofem, Mesigyna, Lunelle, Chinese injectable No. 1 Monthly injection of every 30 days Effectiveness (Cyclofem)
Correctly used - 1% in one year Typically used (missed or delayed injeiton) 3% in one year

Action: prevents ovulation + thicken cervical mucous

Combined monthly injectables (Cyclofem)

Mechanism: combine E+P Contraceptive effects of estrogen + progestogen Side effects of risks of OC pills Medroxyprogesterone 50mg micmic effects of Depo-provera

Side effects and disadvantages

Hypertension Smoker >35 Severe headache or migraine Breast tenderness, dizziness, weight gain Bleeding disorders scanty, irregular, prolonged or no period at all 1-3 months to have period return to normal status

Contraceptive implants
A tube of 40mm long and 2mm wide Progestogen <1 per 1000 women in one year Acts like progestogen injection
Prevent ovulation Thicken cervical mucus Endometrium thinning

Contraceptive implants Advantages

3 years Can breast feed Reduce dysmenorrhoea No missed pills

Contraceptive implants Disadvantages

Insert under LA Wound site problem such as infection Removed under LA, not immediately reversible Side effects of progestogen Menstrual problems:
Prolonged heavy flow in the beginning Irregular flow Secondary amenorrhoea

Fluid retention, weight gain Breast pain Other problems Injection time might be forgotten Difficult to locate after years, new type has barium filled more easily located

Intrauterine device
Intrauterine device Copper IUCD Intrauterine system Hormonal IUCD

Copper IUDs Action

Copper IUDs prevent fertilization by immobilizing sperms and prevent implantation by changing endometrial lining Does not affect ovulation or the menstrual cycle.

Copper IUDs Advantages and disadvantages

No side effects of hormones May increase mean menstrual blood loss May increase ascending infection, vaginal fungal infection Failure may result in ectopic pregnancy

Intrauterine systems / Hormonal IUCDs

Intrauterine device Hormonal effect of progestogen
Endometrial thinning Thicken cervical mucus

Intrauterine systems Advantages and disadvantages

Originally designed for treating menorrhagia, menstrual blood loss could be reduced dramatically Prolonged spotting in first 3-6 months after insertion can be troublesome Risk of ectopic pregnancy if failure still present Prolonged secondary amenorhoea can be worrying Reversal of fertility difficult to predict

Female Barrier Methods

Female condom Diaphragm Cervical cap

Female condom
5% pregnancy rate Advantages Prevents the spread of STD, including HIV and AIDS. No hormonal side effects. Can be used by people with latex sensitivities. It can be pre-lubricated and it can be used with oil and water-based lubricants. Disadvantages: Sometimes difficult to insert or use. Does not contain spermicide. Can break or leak. More expensive than male condoms.

Cervical cap
The cervical cap is a rubber cap shaped like a thimble, which fits over the cervix Advantages: Placed days or hours before sex The cap also uses less spermicide than the diaphragm Disadvantages: No means of protecting from STD Left for a few days with spermicide may cause odour Occasionally the cap can become dislodged during intercourse rendering it ineffective

Diaphragm
A rubber cap that looks like a cervical cap inserted in the vagina and placed over the cervix with spermicide Advantages: 5 % pregnancy if used probably Disadvantages: Does not stop the spread of STDs Slight risk of Toxic Shock Syndrome May experience difficulty with urinating.

Safety Period / Natural Family Planning

2-20% failure rate Calender charting Mucus monitoring
Dry day, ~5 days after period Wet day (thick sticky discharge) cervical opening

Basal body temperature increased only 1F during ovulation

Current Prevalence of Contraception in Hong Kong

70 60

50

40

1987 1992 1997 2002

30

2007

20

10

0 Male condom Female sterilization Intra-uterine Device (IUD) Oral contraceptive Rhythm

1987 1992 1997 2002 2007

Female Intra-uterine Oral Male condom sterilization Device (IUD) contraceptive 32.2 16.8 5.6 20.3 40.0 21.9 5.9 19.8 44.4 22.9 5.9 16.3 54.3 16.8 10.4 9.4 63.1 8.9 11.7 8.4

Rhythm 6.7 5.9 3.5 3.4 2.9

* Sources: KAP Survey conducted by FPA in 1987-2007

Comparison of Contraceptive Methods

Failur e Rate Combined Oral Contraceptive Intra-uterine System (IUS) 0.2 3 0 0.2 Need to be removed by physician X Waiting period of 6 to 12 months Need to be removed by physician X Efficac y Reversible Convenienc e Weight Gain

DRSP causes no signif weight gain X

Sterilization Contraceptive Injection Intra-uterine Device (IUD) Condom Natural Family Planning

01 01

X X

0.3 2 2 - 15 2 - 20

X X X

Source: Guillebaud J. Contraception Today 1997, 3rd Edition

Efficacy of various contraceptive methods commonly used in US & Western Europe

Reliability Very high Very high Highvery high Reasonable Unreliable Contraception type Combined oral contraceptives Transdermal patch Mini-pill (progesterone only) Male condom Coitus interruptus (Withdrawal) Pearl Index* 0.032.36 ~1.0 0.44.3 714 1040

*The total number of unplanned pregnancies which occur per 100 womanyears of use 1. The Gallup Organization Inc. 2004; 2. Skouby 2004; 3. Leidenberger 1998; 4. Baltzer et al. 1985; 5. Ortho-McNeil Pharmaceutical Inc. 2001; 6. Ortho-McNeil Pharmaceutical Inc. 2002

Conclusion
All E+P preparations have similar risks and side effects COC still the best drug if hormones are not contraindicated Progestogens only pills have their advantages but bleeding problems IU devices can be very useful and long term Barrier method, if probably used, effective and less side effects with some protection of STD

Suggestion
Individualize recommendation Know your client Discuss Make agreements

Thank You!! Thank You!!