Updates in Contraception From The XVI World Congress of the International Federation of Gynecology and Obstetrics

David A. Grimes, MD

Disclosures

September 20, 2000

In This Article

Ovarian Activity With a Combination Injectable Contraceptive

Although once-a-month combined injectable contraceptives are highly effective, the precise mechanism of action is unclear. John Jain and his colleagues[23,24] at the University of Southern California in Los Angeles conducted a randomized controlled trial to examine ovarian suppression resulting from administration of 1 product (Lunelle), which is soon to be marketed in the United States. This injectable contains medroxyprogesterone acetate 25 mg plus estradiol cypionate 5 mg in each monthly dose. The comparison contraceptive was a low-dose combination oral contraceptive (Alesse) containing ethinyl estradiol 20 mcg and levonorgestrel 100 mcg.

Jain and associates evaluated 30 women with sequential vaginal ultrasound examinations to look for dominant follicles. Those who evidenced a dominant follicle were enrolled in the study after informed consent and then randomized to receive 2 months of the injectable or 2 months of the oral contraceptive. Of the 15 women randomized to the injectable, 14 completed the observations; 13 of the 15 assigned to the oral contraceptive completed the protocol.

Development of a large follicular space was infrequent with both groups. No women assigned to the injectable had a fluid-filled space of 30 mm in diameter or larger, whereas 1 of 13 who received the oral contraceptive did.

Assuming that 13-mm diameter is the minimum follicular size capable of ovulation, Jain and colleagues examined the proportions of women who developed follicular spaces of this magnitude. This occurred in only 7% of those receiving the injectable contraceptive, in contrast to 77% of those receiving the low-dose oral contraceptive. They concluded that this injectable contraceptive suppresses follicular development in the ovary to a greater extent than does the low-dose birth control pill tested.

An important caveat here is that follicular development does not predict contraceptive effect. For example, follicular recruitment and development can occur with today's low-dose combination oral contraceptives. However, ovulation seldom occurs.[25] Even if ovulation were to occur with low-dose pills, other contraceptive mechanisms, such as the effect on cervical mucus or endometrial histology, would still be operative. Thus, although this well-done trial shows powerful suppression of ovarian activity with the injectable contraceptive, the superior contraceptive performance is probably more related to its route of administration: a monthly injection. The wide disparity between theoretical and actual contraceptive effectiveness of combined oral contraceptives stems from problems with compliance. With injectable contraceptives, the theoretical and actual effectiveness rates tend to merge.

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