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.