Category:Hormonal contraceptives

A hormonal contraceptive is a medicine that prevents pregnancy by interrupting the endocrine signals of the female reproductive cycle. The category includes the combined estrogen-progestin contraceptives (oral pills, transdermal patches, vaginal rings) that suppress ovulation by negative feedback on the hypothalamic-pituitary-gonadal axis, the progestin-only contraceptives that act principally by thickening cervical mucus and altering endometrial receptivity (oral pills, injectable depot medroxyprogesterone, the etonogestrel subdermal implant, the levonorgestrel intrauterine systems), and the emergency contraceptive preparations used after unprotected intercourse (levonorgestrel high-dose, ulipristal acetate, and intrauterine copper).

The development of the hormonal contraceptive is a twentieth-century clinical-pharmacology story with social consequences out of proportion to the technical content. The biological premise was established by the early 1930s: synthetic progestational steroids would suppress ovulation if given by mouth in sufficient quantity. The synthesis problem (described under sex hormones) was solved by Russell Marker's diosgenin extraction in the 1940s and by Carl Djerassi and Luis Miramontes's synthesis of norethindrone on 15 October 1951. The clinical-trial problem was solved by Gregory Pincus and John Rock, funded by the contraceptive advocate Margaret Sanger and the heiress Katharine McCormick, at the Worcester Foundation for Experimental Biology and in clinical trials in Puerto Rico from 1956.^[1] The combination of norethynodrel (a closely related Searle progestin) and mestranol was approved by the U.S. Food and Drug Administration as Enovid in 1957 for menstrual-irregularity indications and in 1960 for contraception. The contraceptive pill changed female participation in the workforce, in higher education, and in public life within a decade of its introduction, and is conventionally cited as among the most consequential medicines of the twentieth century.

The pharmacology has been progressively refined toward lower estrogen doses and toward more selective progestin chemistry. The original Enovid contained 150 micrograms of mestranol; contemporary combined oral contraceptives contain 20 to 35 micrograms of ethinylestradiol (the more potent synthetic estrogen that displaced mestranol in the 1960s), or the bioidentical estradiol valerate or estetrol in newer formulations. The progestin component has evolved through "generations": the first-generation norethindrone and norethynodrel (1950s-1960s), the second-generation levonorgestrel and norgestrel (1970s, lower androgen activity, lower thrombotic risk), the third-generation desogestrel and gestodene and norgestimate (1980s, marketed for reduced androgenic side effects but later associated with a higher venous-thromboembolism risk than the second-generation), the fourth-generation drospirenone (a spironolactone analogue with antimineralocorticoid and antiandrogen activity), and the newest dienogest and nomegestrol acetate.

The progestin-only branch of the category was developed for women in whom estrogen was contraindicated (breast-feeding, history of venous thromboembolism, migraine with aura, smoker over age 35). The progestin-only oral pill ("mini-pill") of norethindrone or norgestrel requires more precise daily dosing than the combined pill because of the narrower contraceptive margin; the newer drospirenone-only and desogestrel-only mini-pills have a wider window. The injectable depot medroxyprogesterone acetate (Depo-Provera, every-three-months intramuscular or subcutaneous) was approved in the United States in 1992. The etonogestrel subdermal implant (Implanon and the radiopaque Nexplanon) was approved in 2006 and provides three years of contraception with a single insertion. The progestin-releasing intrauterine systems (the Mirena released in 1990 in Finland, the smaller and lower-dose Kyleena, Liletta, and Skyla) provide three to seven years of contraception with the additional benefit of substantial reduction in menstrual bleeding.

The non-hormonal IUDs (the copper-containing ParaGard, in use since 1976) and the modern barrier methods are not hormonal contraceptives and are not collected here, although they share clinical indication. The clinical comparison among contraceptive methods is conventionally expressed as the Pearl Index (pregnancies per 100 women per year of use) under typical use and perfect use; long-acting reversible contraceptives (LARC: the IUDs and implants) have Pearl Indices below 1 under both typical and perfect use, whereas the combined oral contraceptive has a perfect-use Pearl Index near 0.3 and a typical-use Pearl Index of approximately 7 (reflecting missed pills and other adherence failures). The shift in clinical recommendation toward LARC as first-line contraception for adolescents and for postpartum women, supported by the Contraceptive CHOICE Project and similar real-world studies, reflects this efficacy and adherence advantage.

By formulation:

• Combined estrogen-progestin contraceptives:
  • Oral (combined oral contraceptive, COC): a long list of brand-name combinations, classified by estrogen content (low-dose 20-35 mcg ethinylestradiol or its newer equivalents) and progestin generation
  • Transdermal patch: norelgestromin/ethinylestradiol (Ortho Evra/Xulane), weekly
  • Vaginal ring: etonogestrel/ethinylestradiol (NuvaRing), monthly; segesterone acetate/ethinylestradiol (Annovera), annual reusable
• Progestin-only contraceptives:
  • Oral mini-pill: norethindrone (Micronor, Nor-QD), norgestrel, drospirenone (Slynd), desogestrel
  • Depot injection: medroxyprogesterone acetate (Depo-Provera, 150 mg IM every 12 weeks; the subcutaneous Depo-SubQ Provera 104, 104 mg every 12 weeks)
  • Subdermal implant: etonogestrel (Nexplanon, 3 years)
  • Levonorgestrel intrauterine systems: Mirena (52 mg, 7 years), Kyleena (19.5 mg, 5 years), Liletta (52 mg, 8 years), Skyla (13.5 mg, 3 years)
• Emergency contraception:
  • Levonorgestrel high-dose (Plan B One-Step), single 1.5 mg oral dose
  • Ulipristal acetate (Ella, 30 mg oral, effective up to 5 days after intercourse, partial progesterone-receptor antagonist)
  • Copper intrauterine device (non-hormonal but listed here for the clinical-decision context)

The boundary of this category is "medicine prescribed primarily for the prevention of pregnancy through hormonal action." The copper IUD is not a hormonal contraceptive and is mentioned only for the clinical-decision context. The non-hormonal medicines used in family planning (the spermicides nonoxynol-9, the diaphragm and cervical-cap fittings) are not in this category. The medicines used in medical abortion (mifepristone combined with misoprostol) are not contraceptives and are listed under sex hormones and under prostaglandin analogues. The medicines used in assisted reproduction (clomifene, the gonadotropins, the GnRH agents) are not contraceptives. The medicines used for menstrual symptoms when contraception is not the indication (combined oral contraceptive for dysmenorrhoea, for menorrhagia, for endometriosis, for the management of polycystic ovary syndrome) are cross-indexed under those indications but their underlying pharmacology is the same as that of the contraceptive use.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.