Estrogens In the United States, most OCs contain either of two estrogens: mestranol or ethinyl estradiol (EE). Mestranol is EE with an extra methyl group. It requires bioactivation in the liver, where the methyl group is cleaved, releasing the active agent, EE. Oral contraceptives with 35 μgof EE provide the same blood levels of hormone as do OCs containing 50 μgof mestranol. (115). Estradiol cypionate and estradiol valerate are esters of natural 17 β-estradiol also in use for contraception.
Ovulation can be inhibited by estrogen or by progestin alone. Pharmacologic synergism is exhibited when the two hormones are combined and ovulation is suppressed at a much lower dose of each agent. Combination OCs, patches, and the NuvaRing suppress basal follicle-stimulating hormone (FSH) and LH. They diminish the ability of the pituitary gland to synthesize gonadotropins when it is stimulated by hypothalamic GnRH (116). Ovarian follicles do not mature, little estradiol is produced, and there is no midcycle LH surge. Ovulation does not occur, the corpus luteum does not form, and progesterone is not produced. This blockade of ovulation is dose related. Newer low-dose OCs do not provide as dense a block and allow somewhat higher baseline FSH and LH levels than higher dose formulations (117). This makes ovulation somewhat more likely to occur if pills are missed or if the patient takes another medication that reduces blood levels of the contraceptive steroids.
Highly effective contraception can be provided by progestin alone, thus avoiding the risks of estrogen. The mode of action of progestin-only contraceptives is highly dependent on the dose of the compound (118). With low levels of progestin in the blood, ovulation will occur part of the time. At moderate levels of progestin in the blood, normal basal levels of FSH and LH are present, and some follicle maturation may occur. At higher blood levels as seen with DepoProvera, the basal FSH is reduced, and there is less follicular activity, less estradiol production, and no LH surge.
Transdermal Hormonal The patch (OrthoEvra), which adheres to the user’s skin, and the vaginal NuvaRing both contain
Contraception combinations of EE and a potent progestin. Both provide sustained release of the steroids and result in relatively constant serum levels that are less than the peak levels seen with OCs but sufficient to prevent ovulation.
Hormonal Implants With the levonorgestrel subdermal implants there is some follicular maturation and estrogen production, but LH peak levels are low and ovulation is often inhibited. In the first year of use, ovulation is believed to occur in about 20% of cycles. The proportion of ovulatory cycles increases with time, probably as a result of the decline in hormone release. By the fourth year of use, 41% of cycles are ovulatory. The more potent progestin released by the etonogestrel implant is even more effective at preventing ovulation (119). The mechanisms of action of low-dose progestins include effects on the cervical mucus, endometrium, and tubal motility. The scant, dry cervical mucus that occurs in women using implants inhibits sperm migration into the upper tract. Progestins decrease nuclear estrogen receptor levels, decrease progesterone receptors, and induce activity of the enzyme 17-hydroxysteroid dehydrogenase, which metabolizes natural 17 β-estradiol (118).