Progestogen-only pills (POPs), colloquially known as "mini pills", are a type of oral contraceptive that contain synthetic progestogens (progestins) and do not contain estrogens. They are primarily used for the prevention of undesired pregnancy, although additional medical uses also exist. Progestogen-only pills differ from combined oral contraceptive pills (COCPs), which consist of a combination of progestins and estrogens.
Terminology Progestogen-only pills, progestin-only pills, and progesterone-only pills refer to the same class of synthetic hormone medications. The phrase progestogen-only pill is used by the World Health Organization and much of the international medical community. The phrase progestin-only pills is typically used in the United States and Canada. Despite sometimes being referred to as progesterone-only pills, these medications do not contain progesterone but instead one of several chemically related compounds. For example, the medication Opill contains the synthetic hormone norgestrel, which has some distinct chemical differences despite producing a similar physiological effect.
Available formulations
Progestogens share the common feature of being able to bind to the body's progesterone receptors and enact a physiological effect similar to naturally occurring progesterone. Still, there are differences between progestogens, and various organizational systems exist to categorize the progestogen hormones used in oral contraception medications.
By Generation - based on when it became available for use, each synthetic hormone can be grouped into 1 of 4 generations of medications. A medication's generation is not necessarily a reflection of safety or efficacy. By Additional Receptor Activity - each medication may act upon other receptors such as androgen receptors, estrogen receptors, glucocorticoid receptors, and mineralocorticoid receptors. Additional interactions may be positive, increasing activity at a given receptor, or negative, decreasing activity at a given receptor. The overall profile of these additional actions for each medication can be used to describe and contrast progestogens.
In the United States, progestogen-only pills are available in 350-μg norethisterone, 4-mg drospirenone, and 0.075-mg norgestrel formulations. Norgestrel is FDA-approved for over-the-counter availability. Norethindrone and drospirenone are available by prescription.
Medical uses Progestogen-only pills are one management option for the suppression of menstruation to avoid pregnancy. With "perfect use," the efficacy of progestogen-only pills in avoiding unintended pregnancy is greater than 99%, meaning that less than 1 out of every 100 patients will experience undesired pregnancy within the first year of use. "Perfect use" means that an individual uses their contraceptive pill at the same time every day without missing a scheduled dose. Assuming "typical use," the theoretical efficacy of progestogen-only pills in avoiding undesired pregnancy falls to around 91-93%, meaning that approximately 7 to 9 out of every 100 patients will experience an unintended pregnancy within the first year of use. "Typical use" means that an individual uses their contraceptive pill at inconsistent times day to day and/or misses scheduled doses. The study reporting the "typical use" failure rate failed to differentiate COCPs and POPs as distinct medications and instead studied them as a combined group, decreasing the validity of this finding. The results were published before the widespread use of progestogen-only pills other than norethindrone and may not be applicable to formulations that have since been developed. Reported efficacy varies between types of progestogen-only pills. For example, norgestrel has a reported failure rate of 2%, and drosperinone has a reported failure rate of 1.8%. Some progestogen-only formulations, such as those containing norethindrone, were thought to have a shorter duration of effect than COCPs. As a result, current guidelines recommend no more than 27 hours between doses to ensure effectiveness, creating a 3-hour window of variability. However, a more recent meta-analysis suggested that there is actually a significantly longer half-life for many of the now available progestogen-only pill formulations. For example, norgestrel and drosperinone, in particular, appear to have a longer window of efficacy. More variation in dose timing may still effectively prevent pregnancy. Although the 3-hour window is still widely respected, some researchers have expressed their belief that an update to these guidelines may be beneficial.
Mechanism of action Depending on the specific progestogen and its corresponding dose, the contraceptive effect of progestogen-only pills is enacted through combinations of the following mechanisms:
Thickening the cervical mucus. This reduces sperm viability, sperm penetration, and decreases the likelihood of fertilization. Inhibition of ovulation through an action on the hypothalamic-pituitary-gonadal axis. For a low-dose formulation, this may occur inconsistently in ~50% of cycles. Intermediate-dose formulations, such as the progestogen-only pill Cerazette (desogestrel), much more consistently inhibit ovulation in 97–99% of cycles. Alteration of the endometrial lining of the uterus through modification of the structure of endometrial glands and their corresponding secretary patterns, as well as causing the endometrial lining to thin out (atrophy). Overall, the endometrium becomes less suitable for implantation of a fertilized egg and the likelihood of a viable pregnancy decreases. Reduction of fallopian tube motility leading to a slowing of the transport of eggs and sperm through the reproductive tract. The process of fertilization, as well as implantation, are both time-sensitive events. Disruption of the normal movement of these reproductive cells plays a role in preventing a viable pregnancy, although the magnitude of this role is likely less significant than previously mentioned mechanisms of action.
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