Endometrial histology following 1 year of a continuous daily regimen of levonorgestrel 90 mu g/ethinyl estradiol 20 mu g
ABSTRACT The objective of this study was to evaluate the effect of a continuous daily regimen of levonorgestrel (LNG) 90 micro g/ethinyl estradiol (EE) 20 micro g on endometrial histology.
This was a substudy of a large phase 3 trial conducted in six sites in North America. Healthy and sexually active women aged between 18 and 49 years took LNG 90 micro g/EE 20 micro g daily for 1 year. Results from endometrial biopsies performed at pretreatment baseline and those after at least 6 months of treatment were compared.
Of the 146 participants, 93 had a baseline biopsy and completed at least six pill packs. Before treatment, 56 subjects (60%) had an endometrial biopsy with findings classified as "weakly proliferative or proliferative." During the last on-therapy visit, 48 subjects (52%) had an endometrium categorized as "other," which included primarily an inactive or benign endometrium (n=42). No hyperplasia or malignancy was observed during the study.
The results of a 1-year continuous regimen of LNG 90 micro g/EE 20 micro g were shown to have a good endometrial safety profile.
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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.Patient Preference and Adherence 11/2009; 3:131-43. · 1.49 Impact Factor
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ABSTRACT: Oral contraceptives are classically given in a cyclic manner with 21 days of active pills followed by 7 days of placebo. In the past 4 years, new oral contraceptives have been introduced which either shorten the placebo time, lengthen the active pills (extended cycle), or provide active pills every day (continuous). These concepts are not new; extended and continuous pills were first studied in the 1960s and 1970s and have been provided in an off-label manner by gynecologists to treat menstrual disorders, such as menorrhagia and dysmenorrhea, and gynecologic disorders, such as endometriosis. Now that extended and continuous combined oral contraceptives are available for all patients, it is critical for providers to understand the physiology, dosing, side effects, and benefits of this form of oral contraceptive. This article reviews the history and the potential uses of the new continuous combined oral contraceptive.Therapeutics and Clinical Risk Management 11/2008; 4(5):905-11. · 1.47 Impact Factor
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ABSTRACT: BACKGROUND: Previous studies report association of contraceptives with moderate increase in urinary tract infection among sexually active premenopausal women. The aim of our study was to find out whether the use of hormonal contraceptives has any effect on microbiota of the vagina in the contraceptives users in Khairpur Sindh Pakistan. METHODS: A prospective study in woman population of Khairpur Sindh Pakistan aged 20--30 years and 31--40 years, using Hormonal contraceptives was carried out. High vaginal swab samples (n = 100) were collected from the test populations as well as control group (n = 100) and investigated for vaginal microbial flora using standard microbiological and biochemical techniques. RESULTS: Vaginal swabs culturing from hormonal contraceptives users in the age group 20--30 years showed statistically insignificant Candida sp (10 % samples), and statistically significant (p < 0.05) Staphylococcus saprophyticus. (18 % samples), Streptococcus agalactiae (23 % samples), Escherichia. coli (28 % samples) and Lactobacillus fermentum (32 % samples). In the age group 31--40 years, statistically significant percentage of samples (p < 0.05) showed Lactobacillus fermentum (28 %), Candida sp (24 %), and E. coli, (24 %) where statistically insignificant samples showed Staphylococcus saprophyticus (13 %) and Streptococcus agalactiae (11 %). CONCLUSIONS: The use of hormonal contraceptives alters the normal microbiota of vagina in women according to the age. Lactobacillus fermentum appeared as the predominant species followed by E. coli among the age group of 20--30 years and, Lactobacillus fermentum, Candida sp and E. coli as predominant among women of age group 31--40 years when compared to corresponding control groups. An inverse relationship between E. coli and Lactobacillus fermentum was observed in the women aged 20--30 years.BMC Urology 08/2012; 12(1):22. DOI:10.1186/1471-2490-12-22 · 1.94 Impact Factor