Experts' view on the role of oestrogens in combined oral contraceptives: emphasis on oestetrol (E4).

Introduction: The evolution of contraception has been crucial for public health and reproductive well-being. Over the past 60 years, combined oral contraceptives (COCs) have remained an important part of the contraceptive landscape worldwide; continued development has worked toward maintaining efficacy and improving safety.

Methods: Seven global experts convened to discuss the clinical relevance of the oestrogen in COCs, focusing on the impact of the new oestrogen, oestetrol (E4).

Can initial vaginal bleeding patterns in etonogestrel implant users predict subsequent bleeding in the first 2 years of use?

Objectives: To evaluate if a simple method for characterizing vaginal bleeding patterns in etonogestrel contraceptive implant users can predict subsequent patterns and bleeding-related discontinuation over the first 2 years of use.

Study Design: We reanalyzed phase 3 study bleeding data for non-breastfeeding participants from the United States, Europe, Russia and Chile during the first 2 years of implant use to characterize and correlate bleeding patterns. We used 90-day reference periods with period 1.

A phase 2b multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of vaginal rings containing nomegestrol acetate or etonogestrel and 17β-estradiol in the treatment of women with primary dysmenorrhea.

Objective: To evaluate the effect of investigational vaginal rings containing nomegestrol acetate (NOMAC) plus 17β-estradiol (E2) or etonogestrel (ENG) plus E2 in women with moderate to severe primary dysmenorrhea.

Study Design: This was a Phase 2b randomized, placebo-controlled, multicenter, double-blind study. We randomized participants to one of five treatment groups: four hormonal rings and one placebo ring.

Phase II dose-finding study on ovulation inhibition and cycle control associated with the use of contraceptive vaginal rings containing 17β-estradiol and the progestagens etonogestrel or nomegestrol acetate compared to NuvaRing.

Purpose: To identify at least one contraceptive vaginal ring that effectively inhibits ovulation and demonstrates cycle control that is non-inferior to NuvaRing (Merck Sharp & Dohme B.V., The Netherlands) in terms of an unscheduled bleeding incidence, with a non-inferiority margin of 10%.

The effect of laquinimod, a novel immuno-modulator in development to treat Huntington disease, on the pharmacokinetics of ethinylestradiol and levonorgestrel in healthy young women.

Purpose: Laquinimod is an orally dosed immuno-modulator currently under development for Huntington's disease (HD). Preclinical findings suggest potential teratogenicity of laquinimod, thus the reproductive ability of females with HD treated with laquinimod needs to be closely managed. Because combined oral contraceptives (COC) are often used in this context, the pharmacokinetics of COC containing ethinylestradiol (EE) and levonorgestrel (LNG) in combination with laquinimod (0.

Psychometric validation of the dysmenorrhea daily diary (DysDD): a patient-reported outcome for dysmenorrhea.

Purpose: The objective of this study was to evaluate the psychometric properties of the Dysmenorrhea Daily Diary (DysDD), an electronic patient-reported outcome, in a sample of 355 women with primary dysmenorrhea enrolled in a phase IIb, multicenter, randomized, partially blinded, placebo-controlled trial for treatment of dysmenorrhea.

Methods: Subjects completed the DysDD over three menstrual cycles, one pre-treatment baseline cycle and two treatment cycles. The DysDD was administered alongside the Menstrual Distress Questionnaire (MDQ), the Short-Form 36 Version 2.

Pooled analysis of two randomized, open-label studies comparing the effects of nomegestrol acetate/17β-estradiol and drospirenone/ethinyl estradiol on bleeding patterns in healthy women.

Objectives: To obtain more precise and detailed information regarding the bleeding patterns of nomegestrol acetate (NOMAC)/17β-estradiol (E2) and drospirenone/ethinyl estradiol (DRSP/EE) and to identify whether baseline demographic characteristics were associated with unscheduled bleeding, absent scheduled bleeding, or amenorrhea.

Study Design: This analysis pooled results from two pivotal open-label, randomized trials that compared bleeding patterns of NOMAC/E2 and DRSP/EE. In the two studies 4317 women aged 18-50 years from 24 countries across the Americas, Europe, and Asia underwent treatment.

Efficacy and safety of the contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive in Chinese women: a 1-year randomised trial.

Objectives: The aim of the study was to assess the efficacy and tolerability of the monthly vaginal ring (NuvaRing; 15 μg ethinylestradiol [EE] and 120 μg etonogestrel per day) compared with a monophasic (21/7) combined oral contraceptive (COC) containing 30 μg EE and 3 mg drospirenone in healthy Chinese women aged 18-40 years.

Methods: This was a phase III, open-label, randomised multicentre trial conducted in China. Participants received NuvaRing or COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-free/pill-free period).

Comparative analysis of the effects of nomegestrol acetate/17 β-estradiol and drospirenone/ethinylestradiol on premenstrual and menstrual symptoms and dysmenorrhea.

Objectives: To compare premenstrual and menstrual symptoms in healthy women using nomegestrol acetate/17β-estradiol (NOMAC/E2) and drospirenone/ethinylestradiol (DRSP/EE) via the Moos Menstrual Distress Questionnaire Form C (MDQ-C).

Methods: Women completed the MDQ-C at baseline and after completion of cycles 1, 3, 6 and 13, for the premenstrual (four days before most recent flow) and menstrual (most recent flow) phases in two randomized controlled trials. Treatment effects of NOMAC/E2 and DRSP/EE on the t-scores of eight MDQ-C symptom domains from 3522 women were examined, and the effects of both treatments on the score for cramps from 1779 women with moderate to severe cramps at baseline.

Efficacy, safety, and tolerability of a monophasic oral contraceptive containing nomegestrol acetate and 17β-estradiol: a randomized controlled trial.

Objective: To estimate the efficacy, cycle control, tolerability, and safety of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-estradiol (E2) in comparison with drospirenone and ethinyl E2.

Methods: In a randomized, open-label, comparative multicenter trial, healthy women (n=2,281; age 18-50 years) at risk for pregnancy and in need of contraception were allocated in a 3:1 ratio to receive nomegestrol acetate (2.5 mg) and 17β-E2 (1.

Efficacy and tolerability of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in a 24/4 regimen, in comparison to an oral contraceptive containing ethinylestradiol and drospirenone in a 21/7 regimen.

Objectives: The primary objective was to assess the efficacy, cycle control and tolerability of a monophasic combined oral contraceptive (COC) containing nomegestrol acetate (NOMAC) and 17β-oestradiol (E2). Effects on acne were evaluated as a secondary objective. Results were compared to those of a COC containing drospirenone (DRSP) and ethinylestradiol (EE).

Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17 beta-oestradiol on ovarian function in comparison to a monophasic combined oral contraceptive containing drospirenone and ethinylestradiol.

Objective: To compare the effects on ovarian activity of two oral contraceptives containing nomegestrol acetate (NOMAC)/17 beta-oestradiol (E2) or drospirenone (DRSP)/ethinylestradiol (EE).

Methods: In this open-label, randomised, six-cycle study, 32 subjects using NOMAC/E2 (2.5-1.

Ovulation incidence with oral contraceptives: a literature review.

Background And Methodology: Combined oral contraceptives (COCs) provide reliable and convenient contraception, although contraindications and tolerability issues may limit their use in some women. Progestogen-only pills (POPs) may be more suitable for some women, however, traditional POPs do not have the same contraceptive efficacy as COCs. A literature search was performed in order to assess the incidence of ovulation with available COCs, traditional POPs and with a desogestrel POP [Cerazette, 75 microg desogestrel (DSG)].

The effects of Implanon on menstrual bleeding patterns.

Objectives: To evaluate an integrated analysis of bleeding patterns associated with use of the subdermal contraceptive implant Implanon (etonogestrel, Organon, part of Schering-Plough) and to provide physician guidance to optimize patient counselling.

Methods: Data from 11 clinical trials were reviewed (N = 923). Assessments included bleeding-spotting records, dysmenorrhoea, and patient-perceived reasons for discontinuation.

The contraceptive efficacy of Implanon: a review of clinical trials and marketing experience.

Objectives: To evaluate the contraceptive efficacy of the etonogestrel-releasing implant Implanon as assessed in international studies and during nine years of marketing experience.

Methods: The analysis included 11 international studies and data collected during nine years of marketing experience (1998--2007). Seven of these studies were noncomparative; the four other studies included the 6-rod levonorgestrel implant system or an intrauterine device as a comparator.

Maintenance of ovulation inhibition with the 75-microg desogestrel-only contraceptive pill (Cerazette) after scheduled 12-h delays in tablet intake.

Background: In contrast to traditional progestagen-only pills (POPs), the desogestrel-only pill Cerazette consistently inhibits ovulation. This study was performed to test the hypothesis that desogestrel alone will keep inhibiting ovulation even when pills are taken 12 h late, indicating that delays in tablet intake of up to 12 h do not jeopardize contraceptive efficacy.

Methods: Women aged between 19 and 40 years with confirmed ovulation were admitted to this open-label pharmacodynamic study.

Ovarian function during and after treatment with the new progestagen Org 30659.

Objective: To evaluate ovarian function during 21 days of oral administration of different doses of Org 30659, a novel selective progestagenic steroid.

Design: Randomized, double-blind, dose-finding study.

Settings: Three centers in Austria, Sweden, and the United Kingdom.

Implanon contraceptive implants: effects on carbohydrate metabolism.

The objective of the study was to assess the possible differences in effects of Implanon and Norplant implants on carbohydrate metabolism. This is a 2-year open randomized study of 80 implant (Implanon and Norplant) acceptors. Oral glucose tolerance test (OGTT) was performed before implant insertion and at 6, 12, and 24 months after implant insertion.

Effect of Implanon use on selected parameters of thyroid and adrenal function.

In this article, the effects of Implanon implant use on thyroid and adrenal function was compared with those of Norplant implants. In this 2-year open randomized study of 80 implant acceptors, we found that both implants may induce minimal changes in thyroid hormones and cortisol levels, possibly secondary to alterations in the respective binding globulins in the serum. These alterations in thyroid and adrenal function would have no clinical significance in healthy women.

The effects of Implanon on lipid metabolism in comparison with Norplant.

This open, randomized study was intended to assess the effects of the new single-rod contraceptive implant (Implanon) containing etonogestrel on lipid metabolism in Indonesian women, in comparison with the six-rod implant Norplant, containing levonorgestrel. The effects of both products were compared with a control group using an intrauterine device (IUD) over a 3-year period. A total of 135 healthy volunteers of childbearing potential, aged 22 to 41 years, were enrolled in Jakarta, Indonesia.

A pilot efficacy study with a single-rod contraceptive implant (Implanon) in 200 Indonesian women treated for < or = 4 years.

In this 4-year open-label, noncomparative, single-center pilot efficacy study, the contraceptive efficacy, safety, bleeding pattern and acceptability of Implanon was studied in 200 sexually active women of proven fertility in Indonesia. All subjects received the single-rod subdermal implant Implanon, which contains 68 mg etonogestrel (3-keto-desogestrel), with an initial release rate of 67 micrograms etonogestrel/day. Contraceptive efficacy was analyzed by calculation of the pregnancy rate, bleeding patterns were determined by the 90-day reference period method, and acceptability by the discontinuation rate.

A 4-year pilot study on the efficacy and safety of Implanon, a single-rod hormonal contraceptive implant, in healthy women in Thailand.

Objective: To investigate the contraceptive efficacy, safety and acceptability of a new single-rod, progestogen-only contraceptive implant (Implanon).

Methods: In an open, non-comparative pilot study, 100 healthy women received a contraceptive implant containing the progestogen etonogestrel (3-ketodesogestrel) for 2 years with an optional extension up to 4 years.

Results: Subjects were exposed to Implanon for 296.

A randomized controlled double-blind study of the effects on hemostasis of two progestogen-only pills containing 75 microgram desogestrel or 30 microgram levonorgestrel.

The effects of two progestogen-only pills containing either 75 microgram desogestrel (DSG) or 30 microgram levonorgestrel (LNG) on hemostasis were investigated in a double-blind, randomized, controlled study of seven treatment cycles in 78 healthy women. DSG reduced factor VII activity (p < 0.05) and prothrombin fragment 1+2 (p < 0.

The combined oral contraceptive pill: what advice should we give when tablets are missed?

Despite more than 30 years' experience with the pill, being by far the most thoroughly studied drug ever, we must conclude that there still is a remarkable paucity of data that would allow us to assess unambiguously its margins of efficacy. The physiological studies on which we must rely encompass limited numbers of subjects and are unlikely to include sufficient representatives of the vulnerable minority of women that really matter. Even though we realise that this vulnerable minority is there, we still cannot do better than to hypothesise about their characteristics, let alone identify them in advance.

Effects of loading on the synthesis of proteoglycans in different layers of anatomically intact articular cartilage in vitro.

The anatomically intact articular cartilage (approximately equal to 2.5 cm2) of whole bovine sesamoid bones was cultured on its bone support. A load of 5 kg was applied intermittently at 0.