Oral contraceptives/ Hormonal contraception

Most oral contraceptives contain a combination of 2 types of hormones: an estrogen and a progestin. Both of these hormones are naturally found in women’s bodies. There are many different types of estrogens and progestins, and different types of pills contain different combinations, but they all work similarly. Some pills contain only progestin, sometimes called the “mini-pill.”

1. Oral contraceptives Dr. Chavan P. R. Pharm D

2. Definition Contraception is the prevention of pregnancy following sexual intercourse by inhibiting sperm from reaching a mature ovum (i.e., methods that act as barriers or prevent ovulation) or by preventing a fertilized ovum from implanting in the endometrium (i.e., mechanisms that create an unfavorable uterine environment). Method failure (perfect-use failure) is a failure inherent to the proper use of the contraceptive alone. User failure (typical use failure) takes into account the user’s ability to follow directions correctly and consistently.

3. THE MENSTRUAL CYCLE

4. Nonpharmacologic Therapies Of Contraception Periodic abstinence The abstinence (rhythm) method is not well accepted Relatively high pregnancy rates and Necessitates avoidance of intercourse for several days in each cycle.

5. Barrier Techniques The effectiveness of the diaphragm depends on its function as a barrier and on the spermicidal cream or jelly placed in the diaphragm before insertion. The cervical cap, smaller and less messy than the diaphragm, fits over the cervix like a thimble. Caps can be inserted 6 hours prior to intercourse, and women should not wear the cap for longer than 48 hours to reduce the risk of toxic shock syndrome.

6. Condoms made in the United States from latex rubber -impermeable to viruses, but about 5% are made from lamb intestine - not impermeable to viruses. Mineral oil–based vaginal drug formulations (e.g., Cleocin vaginal cream, Premarin vaginal cream, Vagistat 1, Femstat , and Monistat Vaginal suppositories) can decrease barrier strength of latex by 90% in 60 seconds. Condoms with spermicides - no longer recommended since no additional protection against pregnancy or sexually transmitted diseases (STDs) and may increase vulnerability to human immunodeficiency virus (HIV). The female condom (Reality) covers the labia as well as the cervix, thus it may be more effective than the male condom in preventing transmission of STDs. However, the pregnancy rate is reported to be 21% in the first year of use.

7. Pharmacologic Therapies Of Contraception Spermicides Spermicide -Implanted Barrier Techniques Hormonal Contraception Transdermal Contraceptives Contraceptive Rings Long-Acting Injectable and Implantable Contraceptives Injectable Progestins Subdermal Progestin Implants Intrauterine Devices

8. Oral contraceptives Oral contraceptives ( birth control pills ) are medications that prevent  pregnancy . Oral contraceptives are hormonal preparations that may contain combinations of the hormones estrogen and progestin or progestin alone. Combinations of estrogen and progestin prevent pregnancy by inhibiting the release of the hormones luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the  pituitary gland  in the brain. LH and FSH play key roles in the development of the egg and preparation of the lining of the uterus for implantation of the embryo. Progestin also makes the uterine  mucus  that surrounds the egg more difficult for sperm for penetration and  fertilization  also can inhibits  ovulation  (release of the egg).

9. Hormonal Contraception Mechanism of Action Hormonal contraceptives contain either a combination of synthetic estrogen and synthetic progestin or a progestin alone.

10. Components Ethinyl Estradiol (EE) And Mestranol . Mestranol must be converted to EE in the liver to be active. Most combined oral contraceptives (OCs) contain estrogen at doses of 20 to 50 mcg of EE daily. The contraceptive ring produces one-half the serum concentration of EE derived from a 30-mcg OC.

11. Considerations with Oral Contraceptive Use The recommendation of the American College of Obstetricians and Gynecologists is to allow provision of hormonal contraception after a simple medical history and blood pressure measurement. OCs offer several Noncontraceptive benefits, The transdermal patch may cause less breast discomfort and dysmenorrhea than OCs. Progestins show estrogenic and antiestrogenic properties as progestins are metabolized to estrogenic substances.

12. Androgenic properties occur because of the structural similarity of the progestin to testosterone. Progestins include desogestrel , drospirenone , ethynodiol diacetate , norgestimate , norethindrone , norethindrone acetate, norethynodrel , norgestrel , and levonorgestrel , the active isomer of norgestrel . The patch contains norelgestromin , the active metabolite of norgestimate . The vaginal ring contains etonogestrel , the metabolite of desogestrel .

13. Advantages of OCs 1. Highly effective if used correctly. 2. Rapid return of fertility after stoppage. 3. Suitable for nulligravida and newly married couples. 4. Completely controlled by the woman and can be stopped at any time unlike other methods (IUD & Implants). 5. No need to do any thing at the time of intercourse.

14. Non contraceptive benefits of OCs Regulation of the cycle with ↓ amount & duration. So it helps in prevention & ttt of iron def. anemia. ↓risk of epithelial ovarian tumors. ↓Incidence of functional ovarian cysts. ↓ risk of ectopic pregnancy. ↓risk of developing PID. ↓risk of endometrial cancer. ↓spasmodic dysmenorrhea and PMS. ↓risk of benign breast lesions.

15. May protect from colorectal cancer. May ↓ Incidence of fibroid. Improvement of Rhumatoid arthritis. Treatment of Dysfunctional uterine bleeding. Treatment of Endometriosis. Treatment of PMS. Treatment of spasmodic dysmenorrhea . Postponing of menstruation for social or religious causes. Treatment of hirsutism .

16. Disadvantages of OCs Increased risk of cardiovascular problems Must be taken as per defined schedule No protection against STIs Have some associative side effects Increased health risk with smoking Lower effectiveness in obese patient Need a prescription Unreliable for women with irregular menstrual cycle

17. Specific considerations Women over 35 Years of Age CHCs containing less than 50 mcg EE are an acceptable form of contraception for nonsmoking women up to the time of menopause. Studies have not demonstrated an increased risk of myocardial infarction (MI) or stroke in healthy, nonsmoking women older than 35 years of age using low-dose OCs.

18. Smoking Women Women over 35 years who smoke and take OCs have an increased risk of MI The WHO states that smoking 15 or more cigarettes per day by women over 35 years is a contraindication to the use of CHCs, and that the risks generally outweigh the benefits even in those who smoke fewer than 15 cigarettes per day. Progestin-only contraceptive methods should be considered for women in this group.

19. Hypertension CHCs, even those with less than 35 mcg estrogen, can cause small increases in blood pressure (6 to 8 mm Hg) in both normotensive and hypertensive women. In women with hypertension, OCs have been associated with an increased risk of MI and stroke. Use of CHCs is acceptable in women younger than 35 years with well-controlled and monitored hypertension. Hypertensive women with end-organ disease or who smoke should not use CHCs. Progestin-only pills and depot medroxyprogesterone acetate (DMPA) are choices for women with hypertension.

20. Diabetes The new progestins are believed to have little, if any, effect on carbohydrate metabolism. Nonsmoking women younger than 35 years with diabetes, but no vascular disease, can safely use CHCs, but diabetic women with vascular disease or diabetes of more than 20 years’ duration should not use OCs.

21. Dyslipidemia Generally, synthetic progestins decrease high-density lipoprotein (HDL) and increase low-density lipoprotein (LDL). Estrogens decrease LDL but increase HDL and triglycerides. Most low-dose CHCs (with the possible exception of levonorgestrel pills, which may reduce HDL levels in some patients) have no significant impact on HDL, LDL, triglycerides, or total cholesterol. However, the mechanism for the increased incidence of cardiovascular disease in CHC users is believed to be thromboembolic and thrombotic changes, not atherosclerosis.

22. Women with controlled dyslipidemias - can use low-dose CHCs, with periodic monitoring of fasting lipid profiles. Women with uncontrolled dyslipidemia (LDL greater than 160 mg/ dL , HDL less than 35 mg/ dL , triglycerides greater than 250 mg/ dL ) and additional risk factors (e.g., coronary artery disease, diabetes, hypertension, smoking, or a positive family history) - should use an alternative method of contraception.

23. Thromboembolism Estrogens have a dose-related effect in the development of venous thromboembolism (VTE) and pulmonary embolism. This is especially true in women with underlying hypercoagulable states or who have acquired conditions (e.g., obesity, pregnancy, immobility, trauma, surgery, and certain malignancies.) The risk of VTE in women using low-dose OCs (less than 50 mcg EE with norethindrone or levonorgestrel ) was four times the risk in nonusers. However, this risk is less than the risk of thromboembolic events during pregnancy.

24. OCs containing desogestrel have been associated with a 1.7 to 19 times higher risk of VTE than OCs containing levonorgestrel . CHCs are contraindicated in women with a history of thromboembolic events and in those at risk due to prolonged immobilization with major surgery unless they are taking anticoagulants. Emergency contraception (EC) has not been associated with an increased risk of thromboembolic events.

25. Migraine Headache Women with migraines may experience a decreased or increased frequency of migraine headaches when using CHCs. CHCs may be considered for healthy, nonsmoking women with migraines if they do not have focal neurologic signs; however, women of any age who have migraine with aura should not use CHCs. Women who develop migraines (with or without aura) while receiving CHCs should immediately discontinue their use.

26. Breast Cancer A U.S. study found no association between overall breast cancer and current or past OC use. Although some studies have found differences in risk of breast cancer based on the presence of BRCA1 and BRCA2 mutations, the most recent cohort study found no association with lowdose OCs and the presence of either mutation. The choice to use CHCs should not be affected by the presence of benign breast disease or a family history of breast cancer with either mutation. The WHO precautions state that women with recent personal history of breast cancer should not use CHCs, but that CHCs can be considered in women without evidence of disease for 5 years.

27. Systemic Lupus Erythematosus OCs do not increase the risk of flare among women with stable systemic lupus erythematosus (SLE) and without antiphospholipid / anticardiolipin antibodies. CHCs should be avoided in women with SLE and antiphospholipid antibodies or vascular complications. Progestin-only contraceptives can be used in these women

28. General Considerations for Oral Contraceptives Monophasic OCs Biphasic OCs Triphasic pills Extended-cycle pills Continuous combination regimens Third generation OCs The progestin-only “ minipills ” Quick-start method First-day start method Sunday start method

29. General Considerations for Oral Contraceptives With perfect use - >99% efficacy Typical use - 8% of women may experience unintended pregnancy. Monophasic OCs - same amounts of estrogen and progestin for 21 days, followed by 7 days of placebo. Biphasic and triphasic pills - variable amounts of estrogen and progestin for 21 days and are followed by a 7-day placebo phase.

30. Extended-cycle OCs - increase the number of hormone-containing pills from 21 to 84 days, followed by a 7-day placebo phase, resulting in four menstrual cycles per year. Continuous combination regimens - OCs for 21 days, then very-low-dose estrogen and progestin for an additional 4 to 7 days. Third generation OCs - newer progestins (e.g., desogestrel , drospirenone , gestodene , and norgestimate ), no estrogenic effects and are less androgenic, fewer side effects (e.g., less likelihood or severity of acne).

31. Drospirenone may also cause less weight gain compared to levonorgestrel . The progestin-only “ Minipills ” - Less effective than combination OCs but can cause irregular and unpredictable menstrual bleeding - Must be taken every day of the menstrual cycle -Associated with more ectopic pregnancies than other hormonal contraceptives.

32. In the “quick-start” method for initiating OCs, the woman takes the first pill on the day of her office visit (after a negative urine pregnancy test). In the first-day start method, women take the first pill on the first day of the next menstrual cycle. The Sunday start method was used for many years, whereby the first pill was taken on the first Sunday after starting the menstrual cycle.

33. Choice of an Oral Contraceptive In women without coexisting medical conditions, an OC containing 35 mcg or less of EE and less than 0.5 mg of norethindrone is recommended. Adolescents, underweight women (<110 lb [50 kg]), women older than 35 years, and those who are perimenopausal may have fewer side effects with OCs containing 20 to 25 mcg of EE. With missed dose - risk of bleeding & contraceptive failure Women weighing more than 160 lb (72.7 kg) may have higher contraceptive failure rates with low-dose OCs and may benefit from pills containing 35 to 50 mcg of EE.

34. Progestin-only method includes minipills , DMPA, and the levonorgestrel intrauterine system It is recommonded for Women with migraine headaches, History of thromboembolic disease, Heart disease, Cerebrovascular disease, SLE with vascular disease, and Hypertriglyceridemia Women older than 35 years who are smokers or are obese, or who have hypertension or vascular disease

35. Missed Dose Advice Chart

36. Managing Side Effects Many symptoms occurring in the first cycle of OC use (e.g., breakthrough bleeding, nausea, bloating), improve by the second or third cycle of use. Women should be instructed to immediately discontinue CHCs if they experience warning signs often called ACHES (abdominal pain, chest pain, headaches, eye problems, and severe leg pain).

37. Drug Interactions Rifampin reduces the efficacy of OCs. Case reports have shown a reduction in EE levels when CHCs are taken with tetracyclines and penicillin derivatives. Women who develop breakthrough bleeding during concomitant use of antibiotics and CHCs should be told to use an alternate method of contraception during the period of concomitant use.

38. Proper awareness about the small risk of interactions with antibiotics, and consideration of appropriate additional nonhormonal contraceptive agents should be made. Phenobarbital, carbamazepine , and phenytoin potentially reduce efficacy of OCs, and many anticonvulsants are known teratogens . The use of condoms in conjunction with high-estrogen OCs or intrauterine devices (IUDs) may be considered for women taking these drugs.

39. Discontinuation of the Oral Contraceptive, Return of Fertility Women are advised to allow two to three normal menstrual periods after discontinuing CHCs before becoming pregnant. The average delay in ovulation after discontinuing OCs is 1 to 2 weeks. No data showing miscarriage or fetal abnormalities with pregnancy after discontinuation of OCs

40. Emergency Contraception Plan B considered as emergency contraception that contains two tablets, each containing 0.75 mg levonorgestrel . The first tablet is to be taken within 72 hours of unprotected intercourse (the sooner, the more effective); the second dose is taken 12 hours later. It is available without a prescription for women at least 18 years old and for those less than 18 years old by prescription. It is sold only in pharmacies and must be kept behind the counter.

41. The FDA approved regimens for EC (first dose within 72 hours of unprotected intercourse and a followup dose 12 hours later) ✓ Ovral (two tablets/dose) ✓ Nordette , Levlen , Levora , Lo/ Ovral , Triphasil , Tri- Levlen , or Trivora (four tablets/dose) ✓ Alesse or Levlite (five tablets/dose) In addition, progestin-only pills can be used as EC ( Ovrette [20 tablets/dose]). Common side effects of EC are nausea, vomiting, and irregular bleeding.

42. Evaluation Of Therapeutic Outcomes Annual blood pressure monitoring. Glucose monitoring in patients with a history of glucose intolerance or diabetes mellitus. Annual cytologic screening Symptomatic assessment e.g., Breakthrough bleeding, amenorrhea, weight gain, and acne.

43. Thank you