Advances in Contraception

, Volume 8, Supplement 1, pp 5–12 | Cite as

Noncontraceptive benefits of modern low-dose oral contraceptives

  • I. H. Thorneycroft
Article

Abstract

Most oral contraceptive formulations in current use contain 50 μg or less of ethinyl estradiol and 1 mg or less of the various progestins: norethindrone (0.5–1 mg), norgestrel (0.3–0.5 mg), or levonorgestrel (0.05–0.25 mg) [1].

The new generation of progestins-norgestimate, desogestrel and gestodene—are derived from levonorgestrel, the biologically active enantiomer of norgestrel. These steroids have specific metabolic and pharmacologic activity that allow oral contraception at lower doses than previous progestins.

Desogestrel and norgestimate are both prodrugs and must undergo hepatic and gastrointestinal metabolism to become biologically active compounds. Gestodene is immediately and completely bioavailable [2].

For the new formulations containing less than 50 μg of ethinyl estradiol, the incidence of complications has decreased. With most of the early medical problems identified, current research can now focus on other aspects of oral contraception such as compliance and OC use failure. Prominent non-contraceptive health benefits have been observed in OC users and represent new directions for future research. When the risk-benefit ratio of OC use is evaluated in healthy women today, it clearly favors the benefits. However, these will not be fully realized without an increase in method compliance.

Keywords

Estradiol Oral Contraceptive Levonorgestrel Ethinyl Estradiol Oral Contraception 

Resumé

La plupart des contraceptifs oraux d'usage courant contiennent 50 μg ou moins d'éthinyloestradiol et 1 mg ou moins de progestatifs variés: norethindrone (0.5–1 mg), norgestrel (0.3–0.5 mg), ou levonorgestrel (0.05–0.25 mg) [1].

Les nouvelles générations de progestatifs (norgestimate, desogestrel et gestodène) sont des dérivés du lévonorgestrel, l'éniantomère actif du norgestrel. Ces stéroides ont une activité métabolique et pharmacologique spécifique qui permet une contraception orale à des doses plus faibles que celles des progestatifs plus anciens.

Le desogestrel et le norgestimate sont l'un et l'autre des prodrogues. Ce sont les métabolismes hépatique et gastrointestinal qui en font des composés actifs. Le gestodène est immédiatement et complètement biodisponible [2].

Pour les nouvelles formulations contenant moins de 50 μg d'éthinyloestradiol, le taux de complications a diminué. La plupart des problèmes initiaux étant identifiés, la recherche actuelle peut se focaliser maintenant sur d'autres aspects de la contraception orale tels que le taux de conformation à la prescription médicales et l'échec des contraceptifs oraux. Des bienfaits non contraceptifs notables pour la santé ont été observés chez les utilisatices de contraceptifs oraux et ont ouvert de nouvelles voies de recherche. Quand le rapport avantage-risque des contraceptifs oraux sur la santé des femmes aujourd'hui est calculé, il est clairement en faveur des avantages. Cependant, ces avantages ne seront jamais pleinement réels sans une amélioration du taux de conformation à la prescription médicale.

Resumen

La mayoría de las formulaciones de anticonceptivos orales (AO) que se emplean actualmente contienen 50 μg o menos de etinil estradiol y 1 mg o menos de diversas progesteronas: noretindrone (0.5–1 mg), norgestrel (0.3–0.5 mg), o levonorgestrel (0.05–0.25 mg) [1].

La nueva generación de progesteronas-norgestimate, desogestrel y gestodén-se derivan del levonorgestrel, enantiómero biológicamente activo del norgestrel. Estos esteroides tienen una actividad metabólica y farmacológica específica que permite una formulación anticonceptiva oral a dosis menores que las progesteronas anteriores.

Desogestrel y norgestimate son ambos profármacos y deben pasar por el proceso de metabolismo hepático y gastrointestinal para llegar a ser compuestos biológicamente activos. La biodisponibilidad del gestodén es inmediata y completa [2].

En el caso de las nuevas formulaciones que contienen menos de 50 μg de etinil estradiol, la incidencia de complicaciones ha disminuido. Al haverse identificado la mayoría de los problemas médicos que ocurrían al principio, las actuales investigaciones pueden concentrarse ahora en otros aspectos de los AO, tales como cumplimiento y fracaso en el uso de AO. Se han observado claros beneficios no anticonceptivos para la salud entre las usuarias de AO, que representan nuevas vías a seguir en futuras investigaciones. Al evaluarse la relación riesgo-beneficio del uso de AO en mujeres saludables en la actualidad, los beneficios son claramente mayores. Sin embargo, no se concretarán plenamente si no se registra un aumento en el cumplimiento con el método.

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References

  1. 1.
    HatcherRA, StewartF, TrussellJ, KowallD, GuestF, StewartGK, GatesW. Contraceptive Technology 1990–1992. 15th ed. New York: Irvington Publishers; 1990.Google Scholar
  2. 2.
    ShenfieldGM, GriffinJM. Clinical pharmacokinetics of contraceptive steroids: an update. Clin Pharmacokinet. 1991;20(1):15–37.PubMedGoogle Scholar
  3. 3.
    American College of Obstetricians and Gynecologists. Oral Contraceptives. ACOG Technical Bulletin no. 106. July 1987.Google Scholar
  4. 4.
    MeadeTW, GreenbergG, ThompsonSG. Progestogens and cardiovascular reactions associated with oral contraceptives and a comparison of the safety of 50- and 30-μg oestrogen preparations. BMJ. 1980;280:1157–61.PubMedGoogle Scholar
  5. 5.
    ThorogoodM. The epidemiology of cardiovascular disease in relation to the estrogen dose of oral contraceptives: an historical perspective. Adv Contracept. 1991;7(suppl 3):11–21.PubMedGoogle Scholar
  6. 6.
    DaumeE. Influence of modern low-dose oral contraceptives on hemostasis. Adv Contracept. 1990;6(suppl):51–68.PubMedGoogle Scholar
  7. 7.
    General discussion. Adv Contracept. 1990;6(suppl):75–9.Google Scholar
  8. 8.
    DalyL, BonnarJ. Comparative studies of 30 μg ethinyl estradiol combined with gestodene and desogestrel on blood coagulation, fibrinolysis, and platelets. Am J Obstet Gynecol. 1990;163:430–7.PubMedGoogle Scholar
  9. 9.
    CroftP, HannafordPC. Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners' oral contraception study. BMJ. 1989;298:165–8.PubMedGoogle Scholar
  10. 10.
    HirvonenE, Idänpään-HeikkiläJ. Cardiovascular death among women under 40 years of age using low-estrogen oral contraceptives and intrauterine devices in Finland from 1975 to 1984. Am J Obstet Gynecol. 1990;163:281–4.PubMedGoogle Scholar
  11. 11.
    EngelH-J, EngelE, LichtlenPR. Coronary atherosclerosis and myocardial infarction in young women-role of oral contraceptives. Eur Heart J. 1983;4:1–8.Google Scholar
  12. 12.
    ClarksonTB, AdamsMR, KaplanJR, ShivelyCA, KoritnikDR. From menarche to menopause: coronary artery atherosclerosis and protection in cynomolgus monkeys. Am J Obstet Gynecol. 1989;160:1280–5.PubMedGoogle Scholar
  13. 13.
    WagnerJD, StClairRW, SchwenkeDC, ShivelyCA, AdamsMR, ClarksonTB. Regional differences in arterial low density lipoprotein metabolism in surgically postmenopausal cynomolgus monkeys: effects of estrogen and progesterone replacement therapy. Arteriosclerosis and Thrombosis. 1992;12:717–26.PubMedGoogle Scholar
  14. 14.
    GodslandIF, CrookD, SimpsonR, ProudlerT, FeltonC, LeesB, AnyaokuV, DevenportM, WynnV. The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism. N Engl J Med. 1990;323(2):1375–81.PubMedGoogle Scholar
  15. 15.
    NotelovitzM, FeldmanEB, GillespyM, GudatJ. Lipid and lipoprotein changes in women taking low-dose, triphasic oral contraceptives: a controlled, comparative, 12-month clinical trial. Am J Obstet Gynecol. 1989;160:1269–80.PubMedGoogle Scholar
  16. 16.
    SkoubySO, PetersenKR, JespersenJ. The influence of new low-dose oral contraceptives on metabolic variables. Adv Contracept. 1991;7(suppl 2):77–88.PubMedGoogle Scholar
  17. 17.
    SilverbergSG, MakowskiEL. Endometrial carcinoma in young women taking oral contraceptive agents. Obstet Gynecol. 1975;46:503–6.PubMedGoogle Scholar
  18. 18.
    SchlesselmanJJ. Oral contraceptives and neoplasia of the uterine corpus. Contraception 1991;43(6) 557–79.PubMedGoogle Scholar
  19. 19.
    Oral contraceptive use and the risk of ovarian cancer. The Centers for Disease Control Cancer and Steroid Hormone Study. JAMA. 1983;249:1596–9.Google Scholar
  20. 20.
    Combined Oral Contraceptives and Liver Cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Int J Cancer. 1989;43:254–9.Google Scholar
  21. 21.
    BrintonLA, VesseyMP, FlavelR, YeatesD. Risk factors for benign breast disease. J Epidemiol. 1981;113(3):203–14.Google Scholar
  22. 22.
    VesseyMP, Villard-MackintoshL, McPhersonK, YeatesD. Mortality among oral contraceptive users: 20 year follow up of women in a cohort study. BMJ. 1989;299:1487–91.PubMedGoogle Scholar
  23. 23.
    PaulCH, SkeggDCG, SpearsGFS, KaldorJM. Oral contraceptives and breast cancer: a national study. BMJ. 1986;293:723–6.PubMedGoogle Scholar
  24. 24.
    Long-term oral contraceptive use and the risk of breast cancer. The Centers for Disease Control Cancer and Steroid Hormone Study. JAMA. 1983;249:1591–5.Google Scholar
  25. 25.
    OlssonH, MollerTR, RanstamJ. Early oral contraceptive use and breast cancer among premenopausal women: final report from a study in southern Sweden. J Natl Cancer Inst. 1989;81:1000–4.PubMedGoogle Scholar
  26. 26.
    GrimesDA. Neoplastic effects of oral contraceptives. Int J Fertil. 1991;36(suppl 1):19–24.PubMedGoogle Scholar
  27. 27.
    PaterA, BayatpourM, PaterMM. Oncogenic transformation by human papillomavirus type 1b deoxyribonucleic acid in the presence of progesterone or progestins from oral contraceptives. Am J Obstet Gynecol. 1990;162:1099–03.PubMedGoogle Scholar
  28. 28.
    BrintonLA. Oral contraceptives and cervical neoplasia. Contraception. 1991;43:581–95.PubMedGoogle Scholar
  29. 29.
    OryHW. The noncontraceptive health benefits from oral contraceptive use. Fam Plann Perspect. 1982;14(4):182–4.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1992

Authors and Affiliations

  • I. H. Thorneycroft
    • 1
  1. 1.Department of Obstetrics and GynecologyUniversity of South AlabamaMobileUSA

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