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Benagiano G, Carrara S, Filippi V. Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives. Patient Prefer Adherence. 2009;3:131-43doi: 10.2147/ppa.s3692.
Benagiano, G., Carrara, S., & Filippi, V. (2009). Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives. Patient preference and adherence, 3131-43. https://doi.org/10.2147/ppa.s3692
Benagiano, Giuseppe, et al. "Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives." Patient preference and adherence vol. 3 (2009): 131-43. doi: https://doi.org/10.2147/ppa.s3692
Benagiano G, Carrara S, Filippi V. Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives. Patient Prefer Adherence. 2009 Nov 03;3:131-43. doi: 10.2147/ppa.s3692. PMID: 19936155; PMCID: PMC2778424.
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Patient Prefer Adherence. 2009 Nov 03;3:131-43. doi: 10.2147/ppa.s3692.

Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives.

Patient preference and adherence

Giuseppe Benagiano, Sabina Carrara, Valentina Filippi

Affiliations

  1. Department of Gynaecology and Obstetrics, Sapienza University, Rome, Italy.

PMID: 19936155 PMCID: PMC2778424 DOI: 10.2147/ppa.s3692

Abstract

The progestational steroid norgestrel was synthesized and tested between 1960 and 1965 through an international cooperation between Wyeth, USA and Schering, Berlin. It is a mixture of two "enantiomers," with only one form (designated as levonorgestrel) biologically active. When taken orally, it is rapidly absorbed, not subjected to a "first-pass" effect and is approximately 90% bioavailable, with a circulating half-life around 15 hours. Its contraceptive action is exerted at the central (hypothalamic) and peripheral (cervical mucus and endometrium) levels. Levonorgestrel (LNG), alone or in combination with ethinyl estradiol (EE), is the most widely employed contraceptive progestin: it is used in combined oral contraceptives, progestogen-only pills, long-acting contraceptive implants, intrauterine contraceptive systems and in emergency contraception. It is also the steroid of choice for new oral contraceptive regimens aimed at reducing the frequency of bleeding episodes. This novel approach, already tried more than 30 years ago, gained interest around the year 2000 when surveys of women's attitudes toward monthly menstrual bleeding started to show a major change: more and more women declared that they would welcome a hormonal contraceptive method that reduced bleeding episodes to 4, 2 or even 1 per year. At this point, while the debate on the significance and "usefulness" of menstruation went on, attention focused on new regimens. The first new modality consisted of changing the 7-day medication-free interval, either shortening it to fewer than 7 days, or by the administration of low-dose estrogens during the interval between packages. Then, continuous administration regimens started to be investigated. This, however, did not happen suddenly, since, in specific situations, doctors had for years empirically utilized various continuous administration regimens. The first extended-cycle oral contraceptive regimen introduced in clinical practice is an 84-day regimen that results in bleeding only 4 times a year. A commercial product specifically packed for continuous use is now available in Europe and contains 30 mug EE and 150 mug LNG. In a variation of this regimen, after administration of the same combination for 84 days, women are given 7 pills containing 10 mug EE. A 6-monthly regimen has also been tested in a small study using EE 20 mug plus LNG 100 mug taken with and without a hormone-free interval. Women in the continuous group reported significantly fewer bleeding days requiring protection and were more likely to have amenorrhea; in addition they also reported significantly fewer days of bloating and menstrual pain. A yearly regimen is now being developed. Each pill of this novel formulation contains EE 20 mug and LNG 90 mug to be taken continuously for 364 days (13 cycles) per year. A phase III trial has now evaluated safety, efficacy and menses inhibition. At the end of the 1-year trial amenorrhea was present in 58.7% of the women and a complete absence of bleeding in 79.0%. Overall, the number of bleeding and spotting days per pill pack declined with time and adverse events and discontinuations were comparable to those reported for cyclic oral contraceptive regimens.

Keywords: amenorrhea; continuous administration; levonorgestrel; menstruation; oral contraceptive

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