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Hormonal Contraception

  • Vincenzina BruniEmail author
  • Metella Dei
  • Francesca Pampaloni
Living reference work entry
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Part of the Endocrinology book series (ENDOCR)

Abstract

The clinical approach to hormonal contraception is based on the integration of two points of view. On the one side we have to consider the specific needs and the biological characteristics of the girl or the woman asking for contraception, according to age, period of life, and personal physical or psychological vulnerability. On the other side, it is well documented that an appropriate choice of the formulation, maybe including therapeutic effects, facilitates the long-term adhesion to the method. This competence requires a thorough knowledge of the pharmacology of single preparations. Therefore a part of this chapter is the revision of the characteristics of various hormonal components of contraceptives in use. To follow is a synthesis of main contraindications, in agreement with current guidelines, and of therapeutic indications.

Keywords

Contraceptives Estrogens Progestins Specific needs Risks Benefits 

References

  1. Abrams LS, Skee DM, Natarajan J, Wong FA, Lasseter KC. Multiple-dose pharmacokinetics of a contraceptive patch in healthy women participants. Contraception. 2001;64(5):287–94.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Ahire D, Sinha S, Brock B, Iyer R, Mandlekar S, Subramanian M. Metabolite identification, reaction phenotyping, and retrospective drug-drug interaction predictions of 17-deacetylnorgestimate, the active component of the oral contraceptive norgestimate. Drug Metab Dispos. 2017;45:676–85.PubMedCrossRefPubMedCentralGoogle Scholar
  3. Algorta J, Diaz M, de Benito R, Lefebvre M, Sicard E, et al. Pharmacokinetic bioequivalence, safety and acceptability of Ornibel®, a new polymer composition contraceptive vaginal ring (etonogestrel/ethinylestradiol 11.00/3.474 mg) compared with Nuvaring® (etonogestrel/ ethinylestradiol 11.7/2.7 mg). Contraception. 2013;87:264–72.CrossRefGoogle Scholar
  4. André G. Actions of a 19-norprogesterone derivative on mammary gland: nomegestrol acetate. J Gynecol Obstet Biol Reprod (Paris). 2005;34(1 Pt 1):69–84.CrossRefGoogle Scholar
  5. Apter D, Gemzell-Danielsson K, Hauck B, Rosen K, Zurth C. Pharmacokinetics of two low-dose levonorgestrel-releasing intrauterine systems and effects on ovulation rate and cervical function: pooled analyses of phase II and III studies. Fertil Steril. 2014;101(6):1656–62.PubMedCrossRefPubMedCentralGoogle Scholar
  6. Apter D, Zimmerman Y, Beekman L, Mawet M, Maillard C, et al. Estetrol combined with drospirenone: an oral contraceptive with high acceptability, user satisfaction, well-being and favourable body weight control. Eur J Contracept Reprod Health Care. 2017;22(4):260–7.PubMedCrossRefPubMedCentralGoogle Scholar
  7. Arowojolu AO, Gallo MF, Lopez LM, Grimes DA. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. 2012;11(7):CD004425.Google Scholar
  8. Bateson D, Butcher BE, Donovan C, Farrell L, Kovacs G, et al. Risk of venous thromboembolism in women taking the combined oral contraceptive: a systematic review and meta-analysis. Aust Fam Physician. 2016;45(1):59–64.PubMedPubMedCentralGoogle Scholar
  9. Boozalis A, Tutlam NT, Robbins CC, Peipert JF. Sexual desire and hormonal contraception. Obstet Gynecol. 2016;127(3):563–72.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Byrne G. Prevalence and psychological sequelae of sexual abuse among individuals with an intellectual disability: a review of the recent literature. J Intellect Disabil. 2018;22(3):294–310.PubMedCrossRefPubMedCentralGoogle Scholar
  11. Cagnacci A, Ferrari S, Tirelli A, Zanin R, Volpe A. Route of administration of contraceptives containing desogestrel/etonogestrel and insulin sensitivity: a prospective randomized study. Contraception. 2009;80(1):34–9.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Caprio M, Antelmi A, Chetrite G, Muscat A, Mammi C, et al. Antiadipogenic effects of the mineralocorticoid receptor antagonist drospirenone: potential implications for the treatment of metabolic syndrome. Endocrinology. 2011;152(1):113–25.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Chang T, Davis MM, Kusunoki Y, Ela E, Hall KS, Barber JS. Sexual behavior and contraceptive use among 18 to 19 year old adolescent women by weight status: a longitudinal analysis. J Pediatr. 2015;167(3):586–92.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Chen S, Kumar N, Mao Z, Sitruk-Ware R, Diaz Brinton R. Therapeutic progestin segesterone acetate promotes neurogenesis: implications for sustaining regeneration in female brain. Menopause. 2018;25(10):1138–51.PubMedCrossRefPubMedCentralGoogle Scholar
  15. Choi YS, Cho S, Lim KJ, Jeon YE, Yang HI, et al. Effects of LNG-IUS on nerve growth factor and its receptors expression in patients with adenomyosis. Growth Factors. 2010;28(6):452–60.PubMedCrossRefPubMedCentralGoogle Scholar
  16. Collaborative Study Group on the Desogestrel-containing Progestin only Pill. A double-blind study comparing the contraceptive efficacy, acceptability and safety of two progestogen-only pills containing desogestrel 75 micrograms/day or levonorgestrel 30 micrograms/day. Eur J Contracept Reprod Health Care. 1998;3(4):169–78.CrossRefGoogle Scholar
  17. Cortessis VK, Barrett M, Brown Wade N, Enebish T, et al. Intrauterine device use and cervical cancer risk: a systematic review and meta-analysis. Obstet Gynecol. 2017;130(6):1226–36.PubMedCrossRefPubMedCentralGoogle Scholar
  18. Darlympe J, Booth J, Flowers P, Lorimer K. Psychosocial factors influencing risk-taking in middle age for STIs. Sex Transm Infect. 2017;93(1):32–8.CrossRefGoogle Scholar
  19. De Bastos M, Stegeman BH, Rosendaal FR, Van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, Dekkers OM. Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev. 2014;3(3):CD010813.Google Scholar
  20. De Seta F, Restaino S, De Santo D, Stabile G, Banco R, Busetti M, et al. Effects of hormonal contraception on vaginal flora. Contraception. 2012;86(5):526–9.PubMedCrossRefPubMedCentralGoogle Scholar
  21. Dehlendorf C, Krajewski C, Borrero S. Contraceptive counseling: best practices to ensure quality communication and enable effective contraceptive use. Clin Obstet Gynecol. 2014;57(4):659–73.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Dei M, Bruni V. Guida alla ginecologia dell’infanzia e adolescenza, cap. 20 Ed. Firenze: OEO; 2016.Google Scholar
  23. Dinger J, Do Minh T, Heinemann K. Impact of estrogen type on cardiovascular safety of combined oral contraceptives. Contraception. 2016;94(4):328–39.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Duijkers IJM, Hger-Mahn D, Drouin D, Colli E, Skouby S. Maintenance of ovulation inhibition with a new progestogen-only pill containing drospirenone after scheduled 24-h delays in pill intake. Contraception. 2016;93(4):303–9.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Engemise SL, Willets JM, Taylor AH, Emembolu JO, Konje JC. Changes in glandular and stromal estrogen and progesterone receptor isoform expression in eutopic and ectopic endometrium following treatment with the levonorgestrel-releasing intrauterine system. Eur J Obstet Gynecol Reprod Biol. 2011;157(1):101–6.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Fruzzetti F, Bitzer J. Review of clinical experience with estradiol in combined oral contraceptives. Contraception. 2010;81:8–15.PubMedCrossRefPubMedCentralGoogle Scholar
  27. Gaber TA. Significant reduction of the risk of venous thromboembolism in all long-term immobile patients a few months after the onset of immobility. Med Hypotheses. 2005;64(6):1173–6.PubMedCrossRefPubMedCentralGoogle Scholar
  28. Glisic M, Shahzad S, Tsoli S, Chadni M, et al. Association between progestin-only contraceptive use and cardiometabolic outcomes. A systematic review and meta-analysis. Eur J Prev Cardiol. 2018;25(10):1042–52.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Goshtazebi A, Subotic Brajic T, Scholes D, Lederer Goldberg TB, Berenson A, Prior JC. Adolescent use of combined hormonal contraception and peak bone mineral density accrual: a meta-analysis of international prospective controlled studies. Clin Endocrinol. 2019;90:517–24.CrossRefGoogle Scholar
  30. Graesslin O, Korver T. The contraceptive efficacy of Implanon: a review of clinical trials and marketing experience. Eur J Contracept Reprod Health Care. 2008;13:4–12.PubMedCrossRefPubMedCentralGoogle Scholar
  31. Grandi G, Cagnacci A, Volpe A. Pharmacokinetic evaluation of desogestrel as a female contraceptive. Expert Opin Drug Metab Toxicol. 2014a;10(1):1–10.PubMedCrossRefPubMedCentralGoogle Scholar
  32. Grandi G, Piacenti I, Volpe A, Cagnacci A. Modification of body composition and metabolism during oral contraceptives containing non-androgenic progestins in association with estradiol or ethinyl estradiol. Gynecol Endocrinol. 2014b;30(9):676–80.PubMedCrossRefPubMedCentralGoogle Scholar
  33. Hanjalic-Beck A, Schäfer WR, Deppert WR, Fischer L, Stein A, et al. Chlormadinone acetate suppresses prostaglandin biosynthesis in human endometrial explants. Fertil Steril. 2012;98(4):1017–22.PubMedCrossRefPubMedCentralGoogle Scholar
  34. Hardman SM, Gebbie AE. The contraception needs of the perimenopausal woman. Best Pract Res Clin Obst Gyn. 2014;28:903–15.CrossRefGoogle Scholar
  35. Hillard PJ. Menstrual suppression with the levonorgestrel intrauterine system in girls with developmental delay. J Pediatr Adolesc Gynecol. 2012;25(5):308–13.PubMedCrossRefPubMedCentralGoogle Scholar
  36. Ichioka M, Mita S, Shimizu Y, Imada K, Kiyono T, et al. Dienogest, a synthetic progestin, down-regulates expression of CYP19A1 and inflammatory and neuroangiogenesis factors through progesterone receptor isoforms A and B in endometriotic cells. J Steroid Biochem Mol Biol. 2015;147:103–1.PubMedCrossRefPubMedCentralGoogle Scholar
  37. Iversen L, Sivasubramaniam S, Lee AJ, Fielding S, et al. Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners’ Oral Contraception Study. Am J Obstet Gynecol. 2017;216(6):580 e1–9.CrossRefGoogle Scholar
  38. Jareid M, Thalabard JC, Aarflot M, Bovelstad HM, et al. Levonorgestrel-releasing Intrauterine System use is associated with a decreased risk of ovarian and endometrial cancer, without increased risk of breast cancer. Results from the NOWAC Study. Gynecol Oncol. 2018;149(1):127–32.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Jatloui TC, Whiteman MK, Jeng G, Tepper NK, et al. Intrauterine device expulsion after postpartum placement: a systematic review and meta-analysis. Contraception. 2018;132:895–905.Google Scholar
  40. Johanesson U, Sahlin L, Masironi B, Hilliges M, Blomgren B. Steroid receptor expression and morphology in provoked vestibulodynia. Am J Obstet Gynecol. 2008;198(3):311.e1–6.CrossRefGoogle Scholar
  41. Kluft C, Zimmerman Y, Mawet M, Klipping C, et al. Reduced hemostatic effects with drospirenone -based oral contraceptives containing estetrol vs. ethinyl estradiol. Contraception. 2016;95(2):140–7.PubMedCrossRefPubMedCentralGoogle Scholar
  42. Koulouri O, Conway GS. A systematic review of commonly used medical treatments for hirsutism in women. Clin Endocrinol. 2008;68(5):800–5.CrossRefGoogle Scholar
  43. Lenzi E, Pluchino N, Begliuomini S, Ninni F, Freschi L, et al. Effects of nomegestrol acetate administration on central and peripheral beta-endorphin and allopregnanolone in ovx rats. J Steroid Biochem Mol Biol. 2008;110(1–2):67–75.PubMedCrossRefPubMedCentralGoogle Scholar
  44. Lete I, Lapuente O. Contraceptive options for women with premenstrual dysphoric disorders: current insights and a narrative review. Open Access J Contracept. 2016;7:117–25.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Lethaby A, Wise MR, Weterings MA, Bofil Rodriguez M, Brown J. Combined hormonal contraceptives for heavy menstrual bleeding. Cochrane Database Syst Rev. 2019;2:CD000154.PubMedPubMedCentralGoogle Scholar
  46. Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ. 2009;339:b2890–4.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Lidegaard Ø, Løkkegaard E, Jensen A, Skovlund CW, Keiding N. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med. 2012;366(24):2257–66.PubMedCrossRefPubMedCentralGoogle Scholar
  48. Lopez JM, Chen M, Mullins S, et al. Steroidal contraceptives and bone fractures in women: evidence from observational studies. Cochrane Database Syst Rev. 2012;8:CD009849.Google Scholar
  49. Louw-du Toit R, Perkins MS, Snoep JL, Storbeck KH, Africander D. Fourth-generation progestins inhibit 3β-Hydroxysteroid dehydrogenase type 2 and modulate the biosynthesis of endogenous steroids. PLoS One. 2016;11(10):e0164170.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Martínez F, Ramírez I, Pérez-Campos E, Latorre K, Lete I. Venous and pulmonary thromboembolism and combined hormonal contraceptives. Systematic review and meta-analysis. Eur J Contracept Reprod Health Care. 2012;17(1):7–29.PubMedCrossRefPubMedCentralGoogle Scholar
  51. Maxwell L, Devries K, Zionts D, Alhusen JL, et al. Estimating the effect of intimate partner violence on women’s use of contraception: a systematic review and mea-analysis. PLoS One. 2015;10(2):e0118234.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Meresman GF, Augé L, Barañao RI, Lombardi E, Tesone M, Sueldo C. Oral contraceptives suppress cell proliferation and enhance apoptosis of eutopic endometrial tissue from patients with endometriosis. Fertil Steril. 2002;77:1141–7.PubMedCrossRefPubMedCentralGoogle Scholar
  53. Merki-Feld GS, Apter D, Bartfai G, Grandi G, Haldre K, et al. ESC expert statement on the effects on mood of the natural cycle and progestin-only contraceptives. Eur J Contracept Reprod Health Care. 2017;22(4):247–9.PubMedCrossRefPubMedCentralGoogle Scholar
  54. Milanes-Skopp R, Nelson AL. Transdermal contraceptive patches: current status and future potential. Expert Rev Clin Pharmacol. 2009;2(6):601–7.PubMedCrossRefPubMedCentralGoogle Scholar
  55. MMWR. US Medical eligibility criteria for contraceptive use. Recomm Rep. 2016;65:3. www.cdc.gov/MMWR
  56. Nappi ER, Kaunitz AM, Bitzer J. Extended regimen combined oral contraception: a review of evolving concepts and acceptance by women and clinicians. Eur J Contracept Reprod Health Care. 2016;21(2):106–15.PubMedCrossRefPubMedCentralGoogle Scholar
  57. Noboa S, Le Gal G, Lacut K, Mercier B, Leroyer C, EDITH Collaborative Study Group, et al. Family history as a risk factor for venous thromboembolism. Thromb Res. 2008;122(5):624–9.PubMedCrossRefPubMedCentralGoogle Scholar
  58. Oelkers W. Antimineralocorticoid activity of a novel oral contraceptive containing drospirenone, a unique progestogen resembling natural progesterone. Eur J Contracept Reprod Health Care. 2002;7(Suppl 3):19–26.PubMedPubMedCentralGoogle Scholar
  59. Paris F, Balaguer P, Rimbault F, Gaspari L, Sultan C. Molecular actions of norgestimate: new developments. Gynecol Endocrinol. 2015;31(6):487–90.PubMedCrossRefPubMedCentralGoogle Scholar
  60. Pecchioli Y, Oyewumi L, Allen LM, Kives S. The utility of routine ultrasound in the diagnosis and management of adolescents with abnormal uterine bleeding. J Pediatr Adolesc Gynecol. 2017;30(2):239–42.PubMedCrossRefPubMedCentralGoogle Scholar
  61. Pluchino N, Lenzi E, Merlini S, Giannini A, Cubeddu A, et al. Selective effect of chlormadinone acetate on brain allopregnanolone and opioids content. Contraception. 2009;80(1):53–62.PubMedCrossRefPubMedCentralGoogle Scholar
  62. Quint EH, O’Brien RF. Menstrual management for adolescents with disabilities. Pediatrics. 2016;138(1):e20160295.PubMedCrossRefPubMedCentralGoogle Scholar
  63. Raps M, Helmerhost F, Fleischer K, Thomassen S, Rosendaal F, et al. Sex hormone binding globulin as a marker for the thrombotic risk of hormonal contraceptives. J Thromb Haemost. 2012;10(6):992–8.PubMedCrossRefPubMedCentralGoogle Scholar
  64. Regidor PA, Colli E, Schidler AE. Drospirenone as estrogen-free pill and hemostasis: coagulatory study results comparing a novel 4 mg formulation in a 24 + 4 cycle with desogestrel 75 μg per day. Gynecol Endocrinol. 2016;32(9):749–51.PubMedCrossRefPubMedCentralGoogle Scholar
  65. Riggs M, Klebanoff M, Nansel T, Zhang J, Schwebke J, Adrews W. Longitudinal association between hormonal contraceptives and bacterial vaginosis in women of reproductive age. Sex Transm Dis. 2007;34(12):954–9.PubMedPubMedCentralGoogle Scholar
  66. Roach RE, Helmerhorst FM, Lijfering WM, Stijnen T, Algra A, Dekkers OM. Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke. Cochrane Database Syst Rev. 2015;8:CD011054.Google Scholar
  67. Rutanen EM. Insulin-like growth factors and insulin-like growth factor binding proteins in the endometrium. Effect of intrauterine levonorgestrel delivery. Hum Reprod. 2000;15(Suppl 3):173–81.PubMedCrossRefPubMedCentralGoogle Scholar
  68. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JT, et al. Classification and pharmacology of progestins. Maturitas. 2003;46(S1):S7–S16.PubMedCrossRefPubMedCentralGoogle Scholar
  69. Silverman JG, Mc Cauley HL, Decker MR, Miller E, Reed E, Raj A. Coercive forms of sexual risk and associated violence perpetrated by male partners of female adolescents. Perspect Sex Reprod Health. 2011;43(1):60–5.PubMedCrossRefPubMedCentralGoogle Scholar
  70. Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update. 2006;12(2):169–78.PubMedCrossRefPubMedCentralGoogle Scholar
  71. Stanczyk FZ, Archer DF. Gestodene: a review of its pharmacology, potency and tolerability in combined contraceptive preparations. Contraception. 2014;89(4):242–52.PubMedCrossRefPubMedCentralGoogle Scholar
  72. Stegeman BH, de Bastos M, Rosendaal FR l FR, van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, Dekkers OM. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ. 2013;347:f5298.PubMedPubMedCentralCrossRefGoogle Scholar
  73. TepperNK BSL, Whiteman MK, Monsour M, et al. Postpartum venous thromboembolism: incidence and risk factors. Obstet Gynecol. 2014;123(5):987–96.CrossRefGoogle Scholar
  74. Tosti C, Biscione A, Morgante G, Bifulco G, Luisi S, Petraglia F. Hormonal therapy for endometriosis: from molecular research to bedside. Eur J Obstet Gtnecol Reprod Biol. 2017;209:61–6.CrossRefGoogle Scholar
  75. Trémollieres F1. Oral combined contraception: is there any difference between ethinyl-estradiol and estradiol? Gynecol Obstet Fertil. 2012;40(2):109–15.CrossRefGoogle Scholar
  76. UK Medical Eligibility Criteria. 2016. www.fsrh.org/ukmec
  77. WHO. Medical eligibility criteria for contraceptive use. 2015. www.who.int/reproductivehealth/publications/MEC
  78. Widman L, Choukas- Bradley S, Noar SM, Nesi J, HìGarrett MA. Parent- adolescent sexual communication and adolescent safer sex behavior: a meta-analysis. JAMA Pediatr. 2016;170(1):52–61.PubMedPubMedCentralCrossRefGoogle Scholar
  79. Xu H, Wade JA, Peipert JF, Zhao Q, Madden T, Secura GM. Contraceptive failure rates of etonogestrel subdermal implants in overweight and obese women. Obstet Gynecol. 2012;120:21.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Yamamoto T, Yoshiji S, Yasuda J, Shiroshita K, Kitawaki J, Fujii M, Urabe M, et al. Aromatization of norethindrone in ethinylestradiol in human adult liver. Endocrinol Jpn. 1986;33(4):527–31.PubMedCrossRefPubMedCentralGoogle Scholar
  81. Zigler RE, McNicholas C. Unscheduled vaginal bleeding with progestin-only contraceptive use. Am J Obstet Gynecol. 2017;216(5):443–50.PubMedCrossRefPubMedCentralGoogle Scholar
  82. Zoller B, Li X, Sundquist J, Sundquist K. Age- and gender-specific familial risks for venous thromboembolism: a nationwide epidemiological study based on hospitalizations in Sweden. Circulation. 2011;124:1012–20.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Vincenzina Bruni
    • 1
    Email author
  • Metella Dei
    • 2
  • Francesca Pampaloni
    • 3
  1. 1.University of FlorenceFlorenceItaly
  2. 2.Italian Society Pediatric Adolescent GynecologyFlorenceItaly
  3. 3.Pediatric and Adolescent Gynecology Unit Careggi Hospital FlorenceFlorenceItaly

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