Old - Jim - Contraception

Front 1

Ghazi's Summary:

On the market:
_ estrogens
_ progestins

Options: (2)

-Point of estrogen is:

Routes? (6)

Back 1

On the market:
2 estrogens
5 progestins

Options:
Progestin only
Combination (Estrogen+Progestin)

-Point of estrogen (ethinyl estradiol) is to prevent breakthrough bleeding
-By taking a combination pill, women can choose not to have a monthly bleed - just maintaining a thin lining

Oral
Oral Chewable
Transdermal (patch - not on breast!)
Injection
Vaginal
Implants

Front 2

Non-contraceptive uses?

Back 2

-Acne
-Pre-menstrual dysphoric d/o

Off-label: Painful period, irrgular periods

Front 3

What causes contraception?

Back 3

Progesterone

Front 4

What are two synthetic contraceptive Rxs made from Testosterone?

Back 4

Norethynodrel
Norethisterone

[C///C on 17th carbon to protect in digestion]

=Progestins (1950-60)
Stimulate uterine lining to be secretory! (Like progesterone)

No androgenic activity.

Front 5

Estrogen in pill ...

Back 5

... ethinyl estradiol
... to prevent bleeding

Front 6

Change in pill for 1960 to today?

Back 6

Much lower Progestins AND Estrogen

Front 7

Progestogens:

Back 7

... inhibit ovulation

Norethindrone acetate

ethynodial diacetate

desogestrel

norgestimate

drospirenone

Front 8

Drugs Affecting Mixed Function Oxidases? (4)

non-drug mech?

Back 8

Rifampin
St. John's Wort
Griseofulvin
Dilantin

OR heavier person

=> faster metabolism of steroids => pill failure

Front 9

How do OCPs work? (4)

Back 9

Direct effect on follicle maturation/ovulation (Progestagen inhibits LH and FSH release!!! Estrogen does too, but would need very high dose. (Side note: Endogenous estradiol is also knocked out, testosterone reduced))

Impaired Tubal motility

Altered endometrial lining (thin - progestin effect)

Thickened cervical mucus

Front 10

How to prescribe pill?

Back 10

Medical hx

Reproductive, menstrual, sexual hx
- pill masks menstrual d/os with 'artificial cycle' (eg amenorrhea), but does not adversely effect reproductive performance

List meds

Blood pressure

Front 11

Starting OCPS?

Back 11

Begin on first day of menses or first Sunday after onset - not a big deal, but will prevent irregular bleed

Effective after 7 days (usually tell people 1 month)

Front 12

Pill free interval

Back 12

Arbitrary

Reassurance of withdrawal bleeding 'cycle intact' - even though it's not a real cycle

Indicates that there is no pregnancy

BUT less efficacious, + side effects (pain, headaches, swelling) + peak in endogenous estradiol

Front 13

Continuous OCP

Back 13

BP, Weight, Hb no different

You can give any monophasic pill for >21 days - though breakthrough bleed may eventually occur

Mircette - 21 active pills, 5 ethinyl estradiol, 2 inert

Lo Estrin - 24 active pills

YAZ - same

Seasonale - Combination pill - 84 days, 7 days off (or do it yourself)

Lybrel - 365 days

Front 14

Advantage of non-oral routes?
Disad?

Back 14

Less fluctuation
-less vasomotor adverse events - headaches

vaginal- may thicken mucosa (reduce HIV)


Disad: May give too much - higher side effects (eg venous thrombosis - not known)

Front 15

Depro-provera?
Norplant?
Jadelle?
Implanon?

Back 15

Implantable/injectable - once you place it - tough to remove. Scarring.

Depro-provera - 3 months - Bone loss concern!
Norplant - 5 years - Removed from market!
Jadelle - not in USA
Implanon - 3 yrs

Front 16

Lunelle

Back 16

-Bleeding episodes occur appx. 3 weeks after each injection.
-Requires monthy injection (28 days).
-Recall of this product by Pharmacia/Pfizer occurred in October 2002 because of quality control problems with prefilled syringes. This product is not currently available in the USA.


Contains 25mg medroxyprogesterone acetate and 5mg of estradiol cypionate.

No dose adjustment needed for BMI. Grace period of 5 days.

Return to ovulation 60 days after last injection (small study of 14 women).

Front 17

Side Effects

Dose relation?

Back 17

Nausea/vomiting

Headaches

Breast enlargement and tenderness

Bloating

Breakthrough bleeding

Weight gain(?) (Gallo,MF etal Obstet/Gynecol Feb.2004:meta-analysis:ocp use does not cause weight gain.)

Acne(?)-OCPs are approved to treat acne


Not related to dose at low levels - Pills containing lower doses of estrogen and progestin did cause higher rates of breakthrough bleeding.

Front 18

Risk of Cancer?

Back 18

No.

No increased risk due to:

Duration of use
Estrogen dose (30 mcg to 50 mcg)
Black or white race
Initiation of use at young age (less than 20)
Family history of breast cancer
(mother, sister, daughter)


(2) Reduced risk of colon cancer

(3) Ovarian cancer (lifetime risk 1.7%) => Reduced risk! Longer use has bigger reduction)

(4) Reduced risk of endometrial cancer

(5)Cervical intraepithelial neoplasia (CIN - on Pap smear) risk increases!

Front 19

Cardiovascular risk?

Back 19

Real. 3x risk. correlates well with the estrogen content in the OCP.

No increased risk of stroke!

10% chance that a DVT will result in PE.
10% chance that a PE will result in death.
Average risk for DVT is 4/100,000 women per year.
DVT risk on OCPs is 12/100,000 women per year.
DVT risk from pregancy is 60/100,000 women per year.

Front 20

Migraines?

Back 20

2x risk of stroke

8x of risk with pill

=> (16x risk. Working with low numbers - 3/100k=> 24/100k, but real risk)

Front 21

MI?

Back 21

MI risk for OCP use - not sure.

1/100k normally
Smoking=> 3/100k
High smoking=> 21/100k

Don't give OCPs to >35yo who smokes


Risk of MI is very low in young women.

Risk of MI in women younger than 24 yrs. of age is 0.2/100,000 women/year.

Risk of MI in women 40 – 44 yrs of age is 30/100,000/year.

Several studies have identified no risk in MI (in nonsmokers) who use OCPs.

Front 22

Should Screening for Factor V Leiden Mutation Be Performed Before Prescribing an OCP?

Back 22

To prevent one death identify > 70,000 women with Factor V


So NO.

Front 23

Old Emergency contraception?

New?

Back 23

Old: Yupze -- within 72 hours (at any tie in cycle)

100mg EE2 and 0.5mg levonorgestrel

Chance of conceiving 1.9% vs 7.2%


New: Plan B
Contains 0.75 mg levonorgestrel.

Take first dose within 72 hours of unprotected intercourse.

Take second dose 12 hours later.

(Alternative: Ovrette: 20 pills as first dose and 20 pills as second dose.)

Note: Antiemetics (Bonine,Benadryl,Dramamine etc) taken 30 min to 60 min before first dose minimizes nausea.

Front 24

Emergency Contraception Caveats

Back 24

Appears safe for women older than 35 who smoke.
No known medical contraindications exist.
Drug interaction may exist (Rifampin).
Pretreatment laboratory tests not required.
Consider prophylactic prescribing.
Remember to recommend/use antiemetics.

Front 25

Male Contraception

Back 25

Testosterone enanthate (l00mg IM q week) given with levonorgestrel 500mcg po/qd resulted in 94% of subjects being oligospermic (less than 3 million sperm/ml of ejaculate) after six months of treatment.
Oligospermic men are unlikely to cause a pregnancy ie 1.4 failures/l00 person years.
Hormonal contraception for men may require 3-6 months of therapy before oligospermia is reached but is reversible.
Increased apoptosis of germ cells may be major mechanism of action.
Clinical trials are ongoing.