CHAPTER 10 Family Planning OBGY R1 Lee Eun Suk NOVAK’S GYNECOLOGY

CHAPTER 10 Family Planning

OBGY R1 Lee Eun Suk

NOVAK’S GYNECOLOGY

Family Planning

The rapid growth of the human population in this century threatens the survival of all

At this present rate, the population of the world will double

in 47 years

That of many of the poorer countries of the world will double in about 20 years

Family Planning

For the individual and for the planet, reproductive health requires careful use of effective means

Prevent both pregnancy and sexually transmitted diseases

The contraceptive choices made by American couples in 1995

For couples older than 35 years of age Sterilization is the number one choice

For younger couples Oral contraceptives (OCs) are the most used methods The condom ranks second

T10.1

Family Planning Abortion is an obvious indicator of unplanned pregnanacy

Abortion ratios by age group indicate that the use of abortion Greatest for the youngest women Least for women in their late 20s and early 30s

Family Planning

Young people are much more likely to experience contraceptive failure

Their fertility - greater than of older women More likely to have intercourse without contraception

Efficacy of Contraception Factors affecting whether pregnancy will occur

The fecundity of both partners The timing of intercourse in relation to the time of ovulation The method of contraception used The intrinsic effectiveness of the contraceptive method The correct use the method

A pregnancy rate per year can be calculated using the Pearl formula Dividing the number of pregnancies by the total number of

months contributed by all couples, then multiplying the quotient by 1,200

Rates of pregnancy with different methods are best calculated by reporting two different rates derived from multiple studies

T10.2

Safety

Some contraceptive methods have associated health risks; Areas of concern are listed in Table 10.3

Most methods provide noncontraceptive health benefits in addition to contraception

Oral contraceptives reduce the risk for ovarian and endometrial cancer and ectopic pregnancy

Barrier methods and spermicides provide some protection against STDs, cervical cancer, and tubal infertility

T10.3

Cost

Intrauterine devices (IUDs) & subdermal implants Expensive initial investment Prolonged protection for a low annual cost

Sterilization & the long-acting methods The least expensive over the long term

T10.4

Nonhormonal Methods Coitus Interruptus

Lactation Amenorrhea

Periodic Abstinence or Natural Family Planning

Condoms

Vaginal Spermicides

Vaginal Barriers

Intrauterine Devices

Coitus Interruptus Withdrawal of the penis from the vagina before ejaculation

Advantages Immediate availability No cost Reduced the risk for STDs

Failure rate ( reported by The Oxford Study ) 6.7 per 100 woman-years The penis must be completely withdrawn both from the vagina and from the external genitalia

Lactation Amenorrhea Ovulation is suppressed during lactation The suckling of the infant

→ prolctin levels↑ → gonadotropin-releasing hormone (GnRH)↓ → luteinizing hormone (LH)↓ → follicular maturation↓

Another method of contraception should be used from 6 months after birth, or when menstruation resumes Progestin only OCs, implants, injectable contraception Barrier methods, spermicides, IUDs

The risk for the breast cancer↓


Couples attempt to avoid intercourse during the fertile period around the time of ovulation

A variety of methods The calendar method

The least effective The mucus method (Billings or ovulation method)

To predict the fertile period by feeling the cervical mucus The symptothermal method

The first day of abstinence is predicted either from the calendar, by subtracting 21 from the length of the shortest menstrual cycle in the preceding 6 months The end of the fertile period – by use of basal body temperature


Efficacy

3.1% probability of pregnancy in 1 year for the small proportion of couples who used the method perfectly

86.4% for the rest Vaginal infection increase vaginal discharge

↑ Complicating the use of the method Accurate advance prediction of the time of ovulation

↑ Facilitate both the use & efficacy


Risks

Conceptions resulting from intercourse remote from the time of ovulation

↑ Spontaneous abortion than contraceptions from midcycle intercourse

→ Malformations are not more common

Condoms

Latex rubber condoms 1840s due to vulcanization

Hold the seminal fluid → preventing its position in the vagina

Prelubricated with the spermicide ↑ More effective

The risks for condom breakage About 3%

Condoms

Sexually Transmitted Diseases

Latex condoms and other barrier methods ↓ the risk for STDs ↓ Gonorrhea, ureaplasma, and PID and its sequelae (tubal infertility) Chlamydia trachomatis , herpes virus type 2,HIV, and hepatitis B → did not penetrate Some protection from cervical neoplasia

Latex allergy could lead to life-threatening anaphylaxis Nonlatex condoms of polyurethane and Tactylon are now available

Condoms

Female Condoms

Vaginal pouches made of polyurethane are available

Efficacy trials The pregnancy rate : only 2.6%

No signs of trauma, and the bacterial flora is not changed

Vaginal spermicides Nonionic surface-active detergents that immobilize sperm

Aerosol foams provided rapid dispersal throughout the vagina the best protection

Nonoxynol-9 ↓ the risk for bacterial vaginosis and other STDs, including HIV Toxic to the lactobacilli that normally colonize the vagina

vaginal colonization with bacterium Escherichia coli

Concerns about possible teratogenicity No greater risk for miscarriage, birth defects, or low birth weight

Vaginal Barriers

Vaginal diaphragm, cervix cap, vault cap, vimule (Fig. 10.4)

They are safe

The noncontraceptive benefit

Protection from STDs, tubal infertility & cervical neoplasia

F10.4

Vaginal Barriers

Diaphragm

Circular spring covered with fine latex rubber (Fig 10.5)

Coil-spring & flat –spring → flat oval compressed for insertion

Proper fitting & proper use are key to its effect Spermicide is always prescribed for use

Fig 10.5

Risks

↑The risks for bladder infection

Relative risk : 1.42, 2.83, and 5.68 for use 1, 3, or 5days in a week

→ Smaller-sized, wide-seal diaphragm or cervical cap

An study comparing cases of toxic shock with controls

No increased risk from diaphragm use

Cervical caps

Much smaller than the diaphragm Does not contain a spring in the rim Covers only the cervix with spermicide

Efficacy A first-year pregnancy rate of 11.3 per 100 women

Near perfect use → a first-year pregnancy rate of 6.1 per 100 The cap worn for more than 72 hours → pregnancy rate ↑

The failure rates with “perfect use” → higher than the diaphragm Parous women more failures than nulliparous women

Fitting Cervical caps

The cervical size is estimated and palpation

The cap is inserted by compressing it between finger and thumb and placing it through the introitus, dome outward

Before use, the cap is one-third filled with spermicidal jelly or cream

Cervical caps - Risks

Negative cervical cytology progressed to dysplasia in 4% Other studies - not found this effect In contrast, Koch - to be protected from dysplasia

Not associated with cystitis

Toxic shock – not reported

Intrauterine Devices

Very important worldwide but play a minor role in contraception for the U.S.

High-dose copper IUD : TCU380, or ParaGard Safe, long-term contraception with effectiveness equivalent to tubal steri

lization

The third copper IUDs T380A (ParaGard) : the progesterone-releasing T (Progestasert)

Bands of copper on the cross arms of the T Copper wire around the stem Total surface area of 380 mm of copper

Levonorgestrel-releasing T (Mirena)

Mechanism of Action

Formation of “biologic foam” within the uterine cavity Contains strands of fibrin, phagocytic cell & proteolytic enzymes

Copper IUDs → Release a small amount of the metal → Producing an even greater inflammatory response

Stimulate the formation of prostaglandin Smooth muscle contraction & inflammation

→ The altered intrauterine environment ↓ Sperm passage ↓ fertilization

Mechanism of Action

The natural progesterone in the Progestasert → endometrial atrophy

The levonorgestrel in the Mirena Much more potent than natural progesterone Blood levels of the hormone

Half of the levonorgestrel subdermal implant (Norplant) → Block ovulation

The IUD is not an abortifacient Contraceptive effectiveness

→ not depend on interference with implantation

Effectiveness

The copper T380A and the levonorgestrel T

Remarkably low pregnancy rates Less than 0.2 per 100 woman-years

Total pregnancies over a 7-year period The levonorgestrel T : 1.1 per 100 woman The copper T380A : 1.4 per 100 woman

Benefits

The ParaGard and the Mirena IUDs

Protect against ectopic pregnancy

Progesterone or levonorgestrel → Menstrual bleeding & clamping↓

Risks

Infection

The relative risk for PID Progestasert : 2.2 Copper 7 : 1.9 Saf-T-Coil : 1.3 Lippes Loop : 1.2

↑Risk was detectable within 4 months of insertion The rate of diagnosis of PID →1.6 cases per 1,000 women per year

Exposure to sexually transmitted pathogens More important determinant of PID than the wearing of an IUD PID with actinomycosis → only in women wearing an IUD

Risks

Pelvic Inflammatory Disease

When PID is suspected in IUP-wearing woman

→ The IUD should be immediately removed

→ High-dose antibiotic therapy should be started

Risks

Ectopic Pregnancy

In 5% of IUD wearers

d/t the fallopian tubes are less well protected against pregnancy than uterus

Copper T380A or levonorgestrel T

Compared with women using no contraception

→ 80% to 90% reduction in the risk for ectopic pregnancy Greater reduction than that seen for users of barrier methods

Risks

Fertility

↑Twofold in the risk for infertility associated with tubal factors

The Oxford Study : giving birth just as promptly after IUD removal

Exposure to sexually transmitted pathogens → Confers risk for infertility

IUD – Clinical Management

Contraindications to IUD use

Pregnancy A history of PID Undiagnosed genital bleeding Uterine anomalies Large fibroid tumors Chronic immune suppression Copper allergy and Wilson’s disease

Clinical Management

Insertion The cervix is exposed with a speculum The uterine cavity should be measured with a uterine sound A paracervical block

→10mL of 1% lidocaine mixed with atropine (0.5mg) Use of a tenaculum for insertion is mandatory to prevent perforation With the ParaGard and the Progestasert, the outer sheath of the inserter

is withdrawn a short distance to release the arms of the T → gently pushed inward again to elevate the now-opened T against the fundus

With the Mirena IUD, insertion is somewhat different The inserter tube loaded with the IUD is introduced into the uterus Until the preset sliding flange on the inserter is 1.5 to 2cm from the external

os of the cervix

Clinical Management

Intrauterine Devices in Pregnancy

IUD should be removed as soon as possible To prevent later septic abortion, premature rupture of the memb- ranes & premature birth

Options for management (if the IUD is present) Therapeutic abortion Ultrasound-guided intrauterine removal of the IUD Continuation of the pregnancy with the device left in place

If the IUD is not in a fundal → Ultrasound-guided intrauterine removal of the IUD

If the IUD is in a fundal → Continuation of the pregnancy with the device left in place

IUD – Duration of Use

Progestasert Replaced at the end of 1 year

Copper T380A Approved for 10 years

Levonorgestrel T Approved for 5 years

Actinomyces-like particles should be found Removal of the IUD Treatment with oral penicillin

IUD – Choice of Devices

Copper T380A & levonorgestrel T Protection for many years Low pregnancy rates ↓Risk for ectopic pregnancy

Progestasert Must be replaced annually Risk for infection with each insertion Increasing cost ↑Risk for ectopic pregnancy ↓ The amount of menstrual bleeding & dysmenorrhea

Hormonal Contraception


Female sex steroids , Synthetic estrogen Synthetic progesterone (progestin) , Progestin only

Combination OCs The most widely used hormonal contraception Administered for 21days beginning on the Sunday after a menstrual peri

od → discontinued for 7 days to allow for withdrawal bleeding

Progestin-only formulations Take every day without interruption


Injectable progestins Estrogen-progestin combinations Subdermal implants releasing progestin Experimental vaginal ring

Release either estrogen-progestin or progestin alone Silastic ring

Worn in the vagina release steroid hormones Absorbed at a constant rate Containing levonorgestrel or combinations of levonorgestrel and estroge

n

Hormonal Contraception - Steroid Hormone Action

Progestins Progestins are synthetis compounds that mimic the effect of natural progesterone but differ from it structurally Three classes

Estranes ┓ 19-nor progestin & used in oral contraceptives in US Gonanes ┛ Pregnane (or 17-acetoxy compounds)

Similar to progesterone → bound by the progesterone receptor Medroxyprogesterone acetate (Provera) : major injectable progestin

Some directly bound to the receptor( levonorgestrel, norethindrone) Require bioactivation ( i.e. desogestrel )

Three newer progestins Norgestimate , desogestrel, and gestodene → little androgenic effect

Hormonal Contraception - Steroid Hormone Action

Estrogens

In the United States, OCs contain either of two estrogens Mestranol or ethinyl estradiol Mestranol requires bioactivation releasing the active agent EE

OCs with 35µg of EE provide the same blood levels of hormone as do OCs containing 50 µg of mestranol

Antifertility Effects Combination Oral Contraception

Suppress basal follicle-stimulating hormone (FSH) and LH

↓ Ability of the pituitary gland to synthesize gonadotropines

→ Ovarian follicles do not mature → Little estradiol is produced → There is no midcycle LH surge → Ovulation does not occur

Antifertility Effects

Progestin-only Preparations Progestin-only “minipill”→ 0.3mg of norethindrone per day (Micronor)

40% of cycles : ovulatory 25% : inadequate luteal function 18% : follicular maturation without ovulation 18% : complete suppression of follicle

At moderate blood levels of progestin Normal basal levels of FSH and LH Some follicle maturation → estradiol trigger LH releasing However, no answering LH surging & no ovulation

At higher blood levels of progestin FSH↓ & Follicular activity↓ → Estradiol producton↓ & no LH surge

Antifertility Effects Hormonal Implants

Release levonorgestrel (Norplant) In the first year of use, ovulation occurs in about 20% of cycles The proportion of ovulatory cycles increases with time

Mechanism Low-dose progestins include effects on the cervical mucus , endometrium & t

ubal motility → sperm migration↓

Nuclear estrogen receptor levels↓& progesterone receptor ↓ → Activity of the enzyme 17-hydroxysteroid dehydrogenase ↑ that metabolizes natural estradiol 17β

Antiprogesterone mefipristone (RU486) → Given before ovulation it can be delayed for several days

Oral contraceptives

Combination OCs Pregnancy rates as low as two to three per 1,000 women per year, when

used consistently

Progestin-only OCs Less effective Three to four per 1,000 women per year

Injectable progestins & implants Much less subject to user error Comparable to pregnancy rates after tubal sterilization

Oral contraceptives - Metabolic Effects and safety

Venous Thrombosis Older studies linked OC use to venous thrombosis & embolism,

cerebral vascular accidents, and heart attack

More recent studies found a much lower risk

Other obvious predisposing causes of thrombosis → Contraindications to OC use

Previous thrombosis Preexisting vascular disease Coronary artery disease Leukemia Cancer Serious trauma


Venous Thrombosis

Estrogens affect procoagulant & anti-coagulant systems Fibrinolysis (anticoagulant) is increased as much as coagulant Balance at increased levels of production & destruction of fibrinogen

The lower estrogen dose reduces the risk for a thromboembolic event when compared with higher-dose

Smokers taking low-dose OCs ↑ Activation of the coagulation system than nonsmoker


The absolute risk for thrombosis in OC users taking pills containing 30 to 35 ㎍ EE is 3 per 10,000 per year

Compared with 1 per 10,000 reproductive-aged women not using OCs & 6 per 10,000 in pregnancy

Thrombosis risk is apparent by 4 months after starting estrogen-containing OCs

Not increase further with continued use

Risk is highest during the first year of use


Thrombophilia

Hemostatic variables in women given lower-dose OCs who had previous thrombosis with OCs and compared with no thrombosis

( Bloemenkamp and colleagues) ↑Factor VII,VIII, and protein C ↓Antithrombin III, activated protein C sensitivity ratio, and protein S Women who had previous thrombosis with OCs → pronounced changes

Factor V Leiden Genetic variation : 3% to 5% of the white population Mutation in the factor V protein, inhibiting cleavage of the protein by activated

protein C Risk for thromboembolic episode : 27.2 per 10,000 woman-years


Thrombophilia

OCs containing newer agents ( i.e., prodestins, desogestrel,or gestodene ) → Modest increased risk for venous thrombosis than older progestins

Lewis and colleagues Attrition of susceptibles & adverse selection Venous thrombosis attributable to OCs during the initial months of use↑ Compared new users to women already taking OCs for some time without inci

dent → risk ↑

A large European study of thrombosis with different OCs Apparent risk for thrombosis was lowest with the first low-does pills introduce

d & highest with those recently introduced


Ischemic Heart Disease

Ischemis heart and stroke Major causes of death blamed on OC use in the past

Principal determinants of risk Advancing age & cigarette smoking

With the higher-does OCs used in the 1980s Smoking had a profound effect on risk Smoking 25 or more cigarettes per day had a 30-fold increased risk for myocardial infarction if they used OCs , compared with nonsmokers not usi

ng OCs



Use of OCs is now much safer Because most women are taking low-dose pills Physicians prescribe selectively, excluding women with major cardiovascular ri

sk factors Nearly all current users took OCs with less than 50 ㎍ of EE

Current users of low-dose OCs had no increased risk for myocardial infarction (California study and a study from Washington State)

Adjustment for major risk factors and sociodemographic factors Age, illness, smoking, ethnicity, and body mass index

After adjustment → risk for myocardial infarction was not increased



One study of so-called third-generation OCs

OCs containing the new progestins desogetrel or gestodene → myocardial infarction↓than OCs with similar estrogen dose

Myocardial infarction risk is strongly increased among smokers →Smokers who used OCs containing the new progestins → less likely to have myocardial infarction than the older OCs


Oral contraceptive and Stroke

OC use appeared to be linked to risk for both hemorrhagic & thrombotic stroke (1970s)

New information shows no risk for women who are healthy

Petitti and colleages study Hypertension, diabetes, obesity, current smoking, and black race → strongly associated with stroke risk Neither current nor past OC use was associated with stroke

WHO study European women using low-dose OC → no increased risk for either type of stroke, thrombotic or hemorrhagic European women using high-dose OC → risk↑


Oral contraceptive and Stroke

Smokers and women with hypertension and diabetes Increased risk for cardiovascular disease whether or not use OCs

WHO study ( if they use low-dose OCs )

Smokers taking OCs → 7 times the risk for ischemic (thrombotic) stroke Hypertension → 10-fold increased risk (if they took OCs) The current U.S. practice of limiting OC use by women older than 35 years of

age to nonsmokers without other vascular risk factor is prudent


Blood Pressure Dose-related effect on blood pressure Older high-dose pills → 5% higher than 140/90mmHg Estrogen → renin substrate↑ → BP ↑

Glucose Metabolism Progestins exhibit insulin antagonism → insulin level ↑ The effect is related to androgenic potency of the progestin & dose

Lipid Metabolism Androgens & estrogens → competing effects on hepatic lipase Estrogens → LDL↓ & HDL↑ TG ↑ Androgens → LDL ↑ & HDL ↓


Other Metabolic effects

Estrogen in OCs

Circulating-thyroid-bind globulin ↑

Total thyroxine (T4) ↑ & triiodothyronine (T3) resin uptake↓

The results of actual of TFT → normal by free T4 & radioiodine tests

Oral contraceptives and Neoplasia Endometrial Cancer and Ovarian cancer

Combination OCs reduced the risk for subsequent endometrial cancer and ovarian cancer

A recent study found that as little as 1 year of OC use was protective & continued use reduced risk by 7% per year

Benefit persisted for 15 years after last use , with little diminution

50% reduction in ovarian cancer risk was observed for women who took OCs for 3 to 4 year

80% reduction was seen with 10 or more years use

Oral contraceptives and Neoplasia Cervical cancer

A weak association between OC & squamous cancer of the cervix Risk factors

Early sexual intercourse Exposure to human papillomavirus

If a woman already has HPV, OC use does not further increase her risk for cervical neoplasia

Among women who are HPV negative, OC use doubles the risk of having such a lesion

Adenocarcinoma of the cervix Rare but not easily detected → incidence↑ Doubling of risk with OCs use

Oral contraceptives and Neoplasia Breast Cancer

Generally, no increase in overall risk is found from OC use

Some studies → the risk may increase in women OC use Used OCs For many year Nulligravid Young at the time of diagnosis Continue using OCs in their 40s

Progestin-only OCs → protective effect

OC users who developed breast cancer were more likely to be diagnosed in early stages & less likely to have LN involvement

Oral contraceptives and Neoplasia Breast Cancer (Collaborative Group’s study)

Diagnosed while women were taking OCs Less advanced than those in women who had never used OCs

Greater risk in women who started OC use before 20 years of age Breast cancer is rare before 20 years of age No increase in actual numbers

A term pregnancy → short-term increase in breast cancer risk Growth-enhancing effects of estrogen The effects of OCs may promote growth of existing cancers

Oral contraceptives and Neoplasia Liver Tumors

OCs implicated as a cause of benign adenomas of the liver

Newer low-dose product → less risk

No association between OC use & subsequent liver cancer

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CHAPTER 10 Family Planning OBGY R1 Lee Eun Suk NOVAK’S GYNECOLOGY