Hormonal Contraception by Injection, Implantation or Transdermal Routes

Steroid sex hormones may be injected intramuscularly to provide a depot that, depending on the drug, dosage, and formulation, may provide contraception for 1 month, 6 months, or even 1 year. A pure progestin may be used, or the injection may consist of a combination of a progestin with an estrogen. Most of these regimens prevent ovulation by suppression of anterior pituitary function.

The compound that has been most widely used worldwide for contraception is medroxyprogesterone acetate (Depo-Provera). The most extensively evaluated regimen consists of 150 mg every 90 days. This results in marked interference with the midcycle production of LH. Ovulation is suppressed, although small amounts of FSH may be produced and some ovarian follicle development may occur. Because of the marked imbalance of estrogen and progesterone produced as a consequence of pituitary suppression, the endometrium usually is atrophic, and uterine bleeding is either irregular or absent for months. For example, in sharp contrast to Norplant (an implantable contraceptive that releases levonorgestrel), about 60% of users of the injection method of progestin administration experience amenorrhea after 1 year of use. Nonetheless, contraceptive effectiveness is very high. Published failure rates of 0.3% in the first year of use indicate that this injectable form of birth control is one of the most effective available. After the injections are discontinued, there may be considerable delay in reestablishment of regular ovulation and corresponding true menstrual bleeding. However, fertility rates are essentially normal at about 18 months after discontinuation.

Approximately a twofold increased risk of premenopausal breast cancer among women under 35 years of age using medroxyprogesterone was reported in one study, although the overall risk of breast cancer in older postmenopausal users was not elevated. Whether or not this constitutes a significant risk requires confirmation in other studies.

Bone mineral density may be reduced among those who receive injections of medroxyprogesterone. Changes in bone density appear similar to those seen during lactation. Subgroups of long-term users of Depo-Provera may experience a decrease in spinal bone density that appears to be reversible following discontinuation. Side effects other than irregular bleeding that may be encountered are weight gain, headache, nervousness, abdominal discomfort, dizziness, and fatigue. An advantage of the drug is that its use is independent of coitus or a daily activity like pill taking; a disadvantage is the need for injections every 3 months.

Norplant, which is a system that contains 36 mg of levonorgestrel in each of 6 Silastic rods, is another form of progestin contraception. The Silastic rods, which are placed subdermally in the inner aspect of the upper arm, provide contraceptive protection for up to 5 years. Efficacy is high and first-year pregnancy rates are only 0.2% with cumulative 5-year rates of 3.9%. As with most progestins, pregnancy protection is likely for many women because of ovulation inhibition. However, since a significant number of women may ovulate while using the Norplant system, other mechanisms such as thickening of the cervical mucus are also of importance.

Major potential health sequelae have not been identified in association with use of Norplant, but side effects are fairly common. Some degree of menstrual irregularity such as increased flow or spotting has been reported in up to 60% of Norplant users in the first year. However, the occurrence of such side effects is time-dependent, with the rate declining by about 50% after 1 year. Headache is cited as the reason for discontinuation of Norplant in about 20% of women. Weight change and mastalgia are also reported with varying frequency among users. Like medroxyprogesterone, a significant advantage of the system is long-term effectiveness in a method that is independent of coitus or a daily activity, eg, taking a pill. The disadvantage is the requirement that a health care provider place and remove the rods via a minor surgical procedure.

In the summer of 2000, the FDA approved a once-a-month injectable combination contraceptive containing 25 mg of medroxyprogesterone acetate and 5 mg estradiol cypionate (Lunelle). This monthly injectable method combines the convenience and contraceptive efficacy of long-acting steroids with cycle control, return to fertility, and a side effect profile more typical of combination low-dose oral contraceptives.

Three additional hormonal contraceptives methods have recently become available: The transdermal patch (Ortho Evra, Ortho-McNeil Pharmaceuticals, Inc.), the vaginal ring, (NuvaRing, Organon, Inc.) and a single rod implant system (Implanon, Organon, Inc.). The patch, measuring 20 cm2, delivers 150 ug norelgestromin (the primary active metabolite of norgestimate) and 20 ug ethinyl estradiol daily into the circulation. It is applied once per week for 3 consecutive weeks followed by 1 week off. The contraceptive efficacy is similar to that of oral contraceptives, but compliance may be better relative to that with oral contraceptives. One disadvantage is that it may be less effective in women at or above 198 lb.

The vaginal ring is a flexible plastice device, measuring approximatley 2 inches in diameter. It is inserted for a 3 week period, then removed for 1 week during which time withdrawal bleeding is expected. The ring releases 120 ug of the etonogestrel (the major metabolite of desogestrel) and 15 ug of ethinyl estradiol daily into the circulation. The contraceptive efficacy of the ring is comparable to that of combination oral contraceptives. The ring can be expelled if improperly placed, while removing tampons, or during straining. If the ring is left out of the vagina for more than 3 hours, then adequate protection may not occur and backup protection is required until the ring has been in place continuously for 7 days.

The single rod implant measures 40 mm long and 2 mm in diameter and releases 60 ug of etonogestrel daily. It has been shown to prevent ovulation in most women for 3 years. Adverse effects are similar to those of other progestin only methods. A change in bleeding pattern was the most frequent adverse event causing discontinuation according to one study. Weight gain was also significant in one study where the mean BMI increased by 3.5%. An advantage to the single rod system is that it allows for faster and easier insertion and removal than the six capsule system.

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Provided by ArmMed Media
Revision date: July 3, 2011
Last revised: by Janet A. Staessen, MD, PhD