The National Procedures Institute – 2001

E.J. Mayeaux, Jr., M.D., FAAFP

Associate Professor of Family Medicine

Clinical Associate Professor of Obstetrics and Gynecology

Louisiana State University Medical Center

1. Of all the scientific advances, effective contraception is arguably the one that has most empowered women to be equal partners in society. It has also given men and women unprecedented control over such major life considerations as when and how families are created and reared.

1. Physicians are responsible for educating patients and prescribing the most effective forms of contraception.
2. Pregnancy during adolescence is a tremendous personal and worldwide public health issue.

1. In 1996, more than a half-million females under the age of twenty gave birth, with two thirds of these pregnancies being unintended. ¹

1. Physicians must make opportunities to discuss this sensitive and potentially embarrassing issue with patients, since patients are often reluctant to broach the subject themselves.

1. Depot medroxyprogsterone acetate or DMPA (Depo-Provera) can be given every three months to provide reversible contraception.

1. It has been used by more than 90 million women worldwide and provides 12 weeks of contraception per injection (14 weeks with >90 percent efficacy).
2. Almost as effective as sterilization.
3. It is not a sustained release system, but relies on peak serum concentrations high enough to allow for 3 months of efficacy.
4. Fecundity usually returns in 4 - 9 months, but may take longer than 1 year. ^{2, 3}
5. There is probably no increase in congenital abnormalities when contraception failure occurs. ³
6. DMPA mechanisms of action

1. inhibition of ovulation due to LH suppression
2. thickening of cervical mucus
3. endometrial atrophy
4. decreased motility of the fallopian tubes 2, 3

1. Good choice for women who cannot consistently use user-dependent birth control (such as adolescents).
2. Useful for women who cannot tolerate or have contraindications to estrogen-containing products
3. Good for women who are contemplating but have not decided on sterilization.
4. Good method for patients who require very effective user-independent contraception because of conditions such as HIV, cancer or Accutane treatment, mental retardation, endometriosis, hemoglobinopathies, hepatic disease, cardiovascular disease, menorrhagia, psychosis, or renal disease.
5. Progestin-only contraceptives such as the mini-pill, Depo-Provera, and the Norplant system are ideal for breast-feeding women

1. They are nearly 100 percent effective during lactation, do not affect the quantity or quality of the breast milk, and may be started immediately postpartum.
2. A recent review found that progesterone withdrawal may be responsible for lactogenesis, so delaying contraceptives until postpartum day three may optimize support of lactation. ⁴

1. Table 1 compares the theoretic and actual failure rates of commonly available contraceptive methods.
2. Progestins do not affect seizure activity. The high levels of progestins may raise the seizure threshold.

1. Patients with known hypersensitivity to the drug

1. undiagnosed abnormal gynecological bleeding
2. pregnancy
3. active liver disease
4. liver tumors
5. suspected or active breast cancer

1. The product insert also lists active thrombophlebitis or thromboembolic disorders as contraindications.

1. These problems are worsened by estrogens, but usually not by progestins, and these patients have been safely treated with Depo-Provera.
2. Clinical judgment must be exercised in deciding if these patients may actually be good candidates for this form of contraception.

1. The dose is 150 mg IM every three months.
2. The injection should be given within five days of the onset of menses. If given beyond this time, an alternate birth control method should be used for two to four weeks.
3. If re-injection is delayed more than two weeks, a pregnancy test should be done before therapy is given. ³
4. DMPA may also be given six weeks postpartum. It is excreted in breast milk but causes no other changes in the milk, and infants exposed and studied demonstrated no adverse effects. ^{3, 5}
5. Some authors recommend giving DMPA immediately postpartum. However, this may increase the incidence of bleeding or spotting. ³
6. Because of the higher bioavailability and decreased likelihood of measurement errors, the 150 mg/ml concentration or the prefilled syringe should be used for contraception, not the 400 mg/ml concentration. ^{2, 3, 5}
7. The injection is given deeply in the gluteal or deltoid muscles by a Z-track technique using a 21 or 23 gauge needle. Do not rub the injection site.

1. Irregular bleeding and spotting is common during the first few months of use. ^{2, 5}

1. If severe, a 10- to 21-day course of oral estrogen may decrease or eliminate this problem. ⁵
2. Amenorrhea becomes more common with time.
3. 50% who use this method of contraception will have amenorrhea by one year. ^{2, 5}

1. Weight gain may be a problem throughout use, with an average of five pounds gained in the first year. ⁵

1. Some comparative studies have not shown significant weight gain compared to controls or users of other methods such as IUDs. ^{6, 6a}
2. However, one well designed study demonstrated a 6.2 lb and 11.8 lb weight gain at 1 and 2 years respectively. ^6b

1. Concern has been raised that long-term use of DMPA may adversely affect bone mineral density. ^6c This could increase the risk of osteoporosis.
2. Less common side effects include headaches, bloating, dizziness, mood changes, and palpitations. ^{3, 5}

1. There may be a small impairment in glucose metabolism that is probably not clinically significant, and LDL and total cholesterol may increase. ^{3, 5}
2. Other advantages and disadvantages are shown in Table 6.

1. Problems NOT associated with DMPA

1. There is no association with breast cancer ⁷, liver cancer ⁸, ovarian cancer ⁹, or hypertension ⁵, and it may lower the risk of endometrial cancer. ^{3, 10}
2. There is no change in clotting parameters at three months and no increase in thrombosis at 15 months. ²
3. An association was found in beagles between Depo-Provera use and breast cancer. Human studies have shown NO significant association. In fact, it has been found that any high-dose progesterone will give these dogs tumors. ^{3, 5, 11}

1. Injectable medroxyprogesterone acetate (MPA) and estradiol cypionate (E2C) (Lunelle, Pharmacia & Upjohn) was FDA approved in October 2000 for monthly injections for reversible contraception.
2. Each 0.5ml dose contains MPA 25 mg and E2C 5 mg.
3. It is almost as effective as sterilization (0 to 0.2 pregnancies per 100 woman years use), and gives good cycle control and good return to fertility. Its failure rate is between 0.1 and 1%.
4. Its side-effect profile is similar to low-dose oral contraceptives.
5. Return of fertility within 6 months in >50% of women studied; within 1 year in 83% of women studied.
6. Dosing - Once-a-month dosing; administered IM injection every 28-30 days (not to exceed 33 days)

1. Lunelle, when administered at the recommended dose to women every month inhibits the secretion of gonadotropins, which, in turn, prevents follicular maturation and ovulation. Although the primary mechanism of this action is inhibition of ovulation, other possible mechanisms of action include thickening and a reduction in volume of cervical mucus (which decrease sperm penetration) and thinning of the endometrium (which may reduce the likelihood of implantation).

1. Provides women with 99 percent effectiveness for an entire month without having to take a pill daily and requiring "nothing to put in place" before sex.
2. Many of Lunelle's potential side effects, similar to those of the pill, are advantageous: more regular periods as well as less menstrual cramping, acne, premenstrual tension, and menstrual flow, and reduced risks of rheumatoid arthritis and iron deficiency anemia.
3. We won't know for certain what the long term effects of taking Lunelle are until it's been in use for some time, but it is "assumed" that, like the pill, Lunelle will also protect against ovarian and endometrial cancers, pelvic inflammatory disease, non-cancerous growths of the breasts, ovarian cysts, and osteoporosis (thinning of the bones).

1. While taken it once a month, Lunelle has to be administered by injection.
2. It does not protect against sexually transmitted diseases.
3. Cost: about $30 to $35 per month,plus $15 for the injection, part of which may be covered by your insurance (in comparison, the pill usually costs about $15 to $45 per month).

1. LUNELLE is contraindicated in women with known or suspected pregnancy; thrombophlebitis, or thromboembolic disorders; current or history of deep-vein thrombophlebitis or thromboembolic disorders; cerebral vascular or coronary artery disease; undiagnosed abnormal vaginal bleeding; in women who are heavy smokers (15 or more cigarettes per day) and are over age 35; a history of liver dysfunction or disease; known or suspected estrogen-dependent neoplasia; severe hypertension; diabetes with vascular involvement; headaches with focal neurological symptoms; or valvular heart disease.
2. Cigarette smoking increases the risk of serious cardiovascular side effects from contraceptives containing estrogen; this risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use LUNELLE should be strongly advised not to smoke.

1. In the U.S. clinical trial, weight gain was the most common adverse event leading to discontinuance (5.7% of patients).
2. During any given injection interval, approximately 75% of women experienced a single withdrawal bleeding episode, without additional breakthrough bleeding or spotting, during that interval. In any given injection interval, approximately 15% of women experienced no bleeding and 10% experienced bleeding or spotting at various times in that injection interval.
3. Adverse events leading to discontinuation: Hormone related: (bleeding , breast pain) 8.6% vs 2.8% with OC, weight 5.8% vs .9% with OC, emotional changes 4.4% vs 2.8% with pills, others like headaches or edema 4.6% vs 1.6%,overall Less than 2% of women reported serious adverse events.
4. Overall adverse effects HA: 17% in both groups, breast tenderness 14% in Lunelle, 4.4 in OC group. Weight change 13.9% lunelle, and 3.5 in pill use, dysmenorrhea, 12.6% vs 10%, emotional labiality 9.2% vs 4.7%, nausea 7.7% vs 9.4%.
5. No difference in glucose tests, rates of anemia, or liver or renal function in women on Lunelle verses women on oral contraceptives. Remember these studies looked at healthy women. Consult your physician
6. Total cholesterol is reduced by about 11 points, with HDL reduced about the same as with OC s, less impact on clotting factors in Lunelle users than OC.

1. Beginning with the second month after the last injection, the cumulative percentage of women who became pregnant was 1.4% at the end of the first month (3 months total), 52.9% after 6 months(9 months), and 82.9% after 1 year(14 months); 94.8% of the pregnancies ended in a live birth.
2. The time to achieving pregnancy was not correlated with the woman's age, weight, or number of injections administered.

1. The patient must use an alternative form of contraception, and get a pregnancy test before the next injection may be administered.

MPA/E2C Patient Satisfaction

2. Patient satisfaction was very high, and similar to oral contraceptive use with over 90% feeling comfortable with administration and feeling like it fits nicely into life style.

1. Patient satisfaction is often dependent on good counseling.
2. Most patients are highly satisfied if they are tolerant of menstrual changes, and amenorrhea may be considered an advantage by some. ³
3. Patient education should cover likely menstrual changes, other side effects, the need for compliance, and cost.
4. Warn patients about possible delayed return to fertility.

1. The consequences of an unplanned pregnancy in adolescence can be severe, affecting physical, psychological, financial, and social aspects of both the patient’s life and her child’s.

1. The morbidity associated with teenage pregnancy is well recognized, and the cost of care for the adolescent and her child is often assumed by society.
2. In 1996, more than 500,000 births in the United States were to mothers under age twenty.

1. The use of depot medroxyprogesterone acetate injections (Depo-Provera) in teenagers can be highly effective.

1. Patient compliance is limited to keeping appointments, which can be a problem in some adolescent populations.
2. If the patient has no other complaint when presenting for an injection and is not in need of a pelvic examination or Papanicolaou smear, a system should be in place to allow quick, convenient service for the patient.