Contraceptives

Contraceptives Dr. Entisar Al-Mukhtar

Interference with ovulation is the most common pharmacologic intervention for prevention of pregnancy.

Major classes of contraceptives
1. Combination oral contraceptives (COCPs):
• Containing a combination of an estrogen & a progestin are the most common type of oral contraceptive (OC).
• Monophasic combination pills contain a constant dose of estrogen & progestin.
• Triphasic OC mimic the natural female cycle & most contain a constant dose of estrogen with increasing doses of progestin given over 3 successive 7-day periods.
• A combination of estradiol valerate & dienogest is available as a four-phasic OC.
• With most OCs, active pills are taken for 21-24 days, followed by 4 to 7 days of placebo, for a total regimen of 28 days.
• Withdrawal bleeding occurs during the hormone-free (placebo) interval.
Note: Ethinyl estradiol is the most common estrogen in COCPs & the most common progestins are norethindrone, norethindrone acetate, levonorgestrel, desogestrel, norgestimate & drospirenone.
• COCPs are highly effective.
• An extended-cycle contraception (84 active pills followed by 7 days of placebo) results in less frequent withdrawal bleeding.
• A continuous OC product (active pills taken every day) is also available.

2. Transdermal patch contraceptive:
• An alternative to COCPs.
• Containing ethinyl estradiol & norelgestromin (progestin). worn
• One patch is applied each week for 3 weeks to the abdomen, upper torso, or buttock. At week 4 (patch free) withdrawal bleeding occurs.
• Its efficacy is comparable to that of the OC, but it is less effective in women weighing > 90 kg.
• Contraindications & adverse effects are similar to those of OC.
• Risk of adverse events such as thromboembolism with the transdermal patch is greater than that seen with OC.

3. Vaginal ring:
• Containing ethinyl estradiol & etonogestrel.
• A ring is inserted into the vagina & left for 3 weeks, at week 4 (ring free) withdrawal bleeding occurs.
• Efficacy, contraindications & adverse effects like those of COCPs.

4. Progestin-only pills (mini-pill):
• Usually containing, norethindrone, & are taken daily on a continuous schedule.
• less effective than COCPs & may produce irregular menstrual cycles more frequently.
• Used for patients who are breastfeeding (unlike estrogen, progestins do not affect milk production), intolerant to estrogen, smokers, or have other contraindications to estrogen.

5. Injectable progestin:
• Medroxyprogesterone acetate is available in both IM & SC formulations injected every 3 months.
• Medroxyprogesterone acetate adverse effect: weight gain, amenorrhea, return to fertility may be delayed for several months.
• It should not be continued for more than 2 years because patients may predispose to osteoporosis and/or fractures.

6. Progestin implants:
• An etonogestrel containing implant (4-cm capsule) placed subdermally in the upper arm, it provides about 3 years of contraception.
• Implant is nearly as reliable as sterilization, & the effect is reversible after surgical remove.
• Side effects include irregular menstrual bleeding & headaches.
7. Progestin intrauterine device:
• A Levonorgestrel-releasing intrauterine system, it is a highly effective contraceptive, provides long-term contraception (3 - 5 years)>
• Suitable for women who having contraindications to estrogen.
• Should be avoided in patients with pelvic inflammatory disease or a history of
ectopic pregnancy.
8. Postcoital (emergency) contraception:

Risk of pregnancy is 15%, 30%, 12%, and near zero if a coitus without effective contraception (unprotected intercourse) occurs 3 days before ovulation, 1 or 2 days before ovulation, day of ovulation and 1 or 2 days after ovulation respectively.
• Reduces the chance of pregnancy to between 0.2 & 3 %.
• High doses of levonorgestrel (eg. 0.75 mg) or high doses of ethinyl estradiol (100 ?g) plus levonorgestrel (0.5 mg) are administered as soon as possible preferably within 72 hours of unprotected intercourse (the “morning-after pill”). A second dose should be taken 12 hours after the first dose.
• A newer progestin-only regimen consists of a one-time dose of 1.5 mg levonorgestrel.
• An alternative emergency contraceptive is the progesterone agonist/antagonist ulipristal, it is indicated within 5 days of unprotected intercourse.

Mechanism of action
Estrogen provides a negative feedback on the LH & FSH release, thus preventing ovulation. Progestin also thickens the cervical mucus, thus hampering the transport of sperm. Withdrawal of the progestin stimulates menstrual bleeding during the placebo week.
Adverse effects:
Determined by the specific compounds & combinations used.
• Breast fullness, fluid retention, headache & nausea are most common with estrogens. Increased BP may also occur.
• Progestins may cause depression, changes in libido, hirsutism, and acne.
• Although rare, thromboembolism, thrombophlebitis, MI, and stroke may occur with use of OCs especially among smoker women over age 35.
• Cervical cancer incidence may be increased with OCs, because women are less likely to use additional barrier methods of contraception that reduce exposure to human papillomavirus (the primary risk factor for cervical cancer). [Note: OCs are associated with a decreased risk of endometrial & ovarian cancer.]

Contraindications:
1. Cerebrovascular & thromboembolic disease, estrogen-dependent neoplasms, liver disease, and pregnancy.
2. COCPs should not be used in heavy smokers patients over the age of 35.

Drug interactions:
1. Drugs like rifampin & bosentan induce metabolism of OCs reducing their efficacy (avoid concurrent use, or use an alternate barrier method of contraception).
2. Antibiotics that alter the normal GI flora may reduce enterohepatic recycling of the estrogen (in OCs), thus, an alternate method of contraception is needed.