Progestins Used in Combined Hormonal Contraceptives

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The development of progestins in combined hormonal contraceptives represents a continuous effort to balance contraceptive efficacy, cycle control, and metabolic effects. First-generation progestins, exemplified by norethindrone and norethindrone acetate, provided metabolically neutral profiles with minimal impact on lipids and glucose metabolism. Despite their androgenic structural origins, these progestins demonstrated good cycle control when balanced with appropriate estrogen levels. However, their relatively short 8-hour half-life became problematic as contraceptive formulations moved toward lower hormone doses, leading to increased breakthrough bleeding that compromised user satisfaction.

Second-generation progestins such as norgestrel and levonorgestrel addressed the potency and duration limitations of earlier formulations, offering enhanced contraceptive efficacy and longer action profiles. Levonorgestrel’s exceptional potency and extended activity made it ideal for various delivery systems, including emergency contraception, progestin-only pills, and hormonal intrauterine devices. However, increased androgenicity with these formulations prompted the development of third-generation progestins designed to minimize androgenic effects while maintaining contraceptive effectiveness. Norgestimate and desogestrel emerged as solutions, with norgestimate earning FDA approval for acne treatment, expanding the noncontraceptive benefits available to users.

Modern progestin development has moved beyond traditional androgenic scaffolding to create novel compounds with unique properties. Drospirenone, derived from spironolactone, offers antimineralocorticoid effects and appears in various formulations, including stand-alone progestin-only pills with improved ovulation suppression. Dienogest provides antiangiogenic properties that complement shorter-acting estrogens, while segesterone acetate enables extended-use vaginal ring applications. This diverse progestin portfolio, representing 65 years of contraceptive evolution, provides clinicians with numerous options to match individual patient needs, preferences, and treatment goals while optimizing contraceptive efficacy and user satisfaction.